The fetal cardiovascular response to increased placental vascular impedance to flow determined with 4-dimensional ultrasound using spatiotemporal image correlation and virtual organ computer-aided analysis.

OBJECTIVE: We sought to determine if increased placental vascular impedance to flow is associated with changes in fetal cardiac function using spatiotemporal image correlation and virtual organ computer-aided analysis. STUDY DESIGN: A cross-sectional study was performed in fetuses with umbilical artery pulsatility index >95th percentile (abnormal [ABN]). Ventricular volume (end-systole, end-diastole), stroke volume, cardiac output (CO), adjusted CO, and ejection fraction were compared to those of 184 normal fetuses. RESULTS: A total of 34 fetuses were evaluated at a median gestational age of 28.3 (range, 20.6-36.9) weeks. Mean ventricular volumes were lower for ABN than normal cases (end-systole, end-diastole) with a proportionally greater decrease for left ventricular volume (vs right). Mean left and right stroke volume, CO, and adjusted CO were lower for ABN (vs normal) cases. Right ventricular volume, stroke volume, CO, and adjusted CO exceeded the left in ABN fetuses. Mean ejection fraction was greater for ABN than normal cases. Median left ejection fraction was greater (vs right) in ABN fetuses. CONCLUSION: Increased placental vascular impedance to flow is associated with changes in fetal cardiac function.

Insulin glargine dosing before next-day surgery: comparing three strategies.

STUDY OBJECTIVE: To evaluate three evening insulin glargine dosing strategies for achievement of target (100-179 mg/dL; 5.5 - 9.8 mmol/L) and widened (80-249 mg/dL; 4.4 - 13.7 mmol/L) preoperative fasting blood glucose (FBG) ranges on the day of surgery. DESIGN: Prospective, randomized, open trial. SETTING: Preoperative units at two sites of a suburban hospital system. PATIENTS: 401 adult, ASA physical status 3 and 4 patients with type 1 and type 2 diabetes, undergoing elective noncardiac surgery. INTERVENTIONS: Patients were divided into two groups according to absence of daily rapid-acting/short-acting insulin (insulin glargine-only group) or presence of daily rapid-acting/short-acting insulin (insulin glargine plus bolus group). Subjects were then randomized to three evening insulin glargine dosing strategies: (a) take 80% of usual dose, (b) call physician for dose, or (c) refer to dosing table, based on self-reported usual FBG and insulin regimen. In the prehospital setting, patients administered the instructed insulin glargine dose on the evening before surgery. MEASUREMENTS: Venous blood glucose values were recorded in the preoperative holding area on the day of surgery. MAIN RESULTS: No significant differences in target preoperative FBG achievement were detected among strategies in the insulin glargine-only group (n = 174) or the insulin glargine plus bolus group (n = 227). In widened preoperative FBG achievement, no significant difference was noted among strategies in the insulin glargine-only group. In the insulin glargine plus bolus group, fewer subjects following the dosing table had FBG > 249 mg/dL (> 13.7 mmol/L; P = 0.031). CONCLUSIONS: Target preoperative FBG achievement was similar among strategies in both insulin glargine groups. An insulin glargine adjustment strategy based on usual glycemic control may better prevent severe preoperative hyperglycemia in patients receiving basal/bolus regimens.

Comparison of insulin pump therapy (continuous subcutaneous insulin infusion) to alternative methods for perioperative glycemic management in patients with planned postoperative admissions.

BACKGROUND: Patients with diabetes who use insulin pumps [continuous subcutaneous insulin infusion (CSII)] undergo surgeries that require postoperative hospital admission. There are no defined guidelines for CSII perioperative use. METHODS: This retrospective single-institution study identified type 1 and type 2 diabetes subjects by electronically searching 2005-2010 anesthesia preoperative assessments for "pump." Surgical cases (n = 92) were grouped according to intraoperative insulin delivery method: (a) CSII continuation of basal rate with/without correctional insulin bolus(es) (n = 53); (b) conversion to intravenous insulin infusion (n = 20); and (c) CSII suspension with/without correctional insulin bolus(es) (n = 19). These groups were compared on mean intraoperative blood glucose (BG) and category of most extreme intraoperative BG. RESULTS: Differences were found on baseline characteristics of diabetes duration (p = .010), anesthesia time (p = .011), proportions receiving general anesthesia (p = .013), and preoperative BG (p = .033). The conversion group had the longest diabetes duration and anesthesia time; it had a higher proportion of general anesthesia recipients and a higher mean preoperative BG than the continuation group. There was no significant difference in mean BG/surgical case between continuation (163.5 ± 58.5 mg/dl), conversion (152.3 ± 28.9 mg/dl), and suspension groups (188.3 ± 44.9 mg/dl; p = .128). The suspension group experienced a greater percentage of cases (84.2%) with one or more intraoperative BG > 179 mg/dl than continuation (45.3%) and conversion (40%) groups Figure 1 groupings (p = .034). CONCLUSIONS: In this limited sample, preliminary findings are consistent with similar intraoperative glycemic control between CSII continuation and CSII conversion to intravenous insulin infusions. Continuous subcutaneous insulin infusion suspension had a greater rate of hyperglycemia. Preoperative differences between insulin delivery groups complicate interpretations of findings.

Functional results of posterior tibial tendon reconstruction, calcaneal osteotomy, and gastrocnemius recession.

BACKGROUND: This study aimed to assess and provide prospective outcome data following reconstruction of Stage II posterior tibial tendon insufficiency, as well as evaluate the effect of reconstruction with gastrocnemius recession on plantarflexion strength. METHODS: A prospective evaluation of 24 patients undergoing reconstruction for Stage II posterior tibial tendon insufficiency was granted IRB approval. The reconstructive procedures consisted of a flexor digitorum longus transfer, medial displacement calcaneal osteotomy, lateral column lengthening, and gastrocnemius recession. Patients were asked to complete multiple outcome measures preoperatively, 6 months, 1 year, and 2 years postoperatively. A dynamometer was utilized to evaluate peak torque plantarflexion preoperatively, 6 months, and 1 year postoperatively. RESULTS: In the study, 14 patients completed preoperative surveys, and 23 patients had 2-year followup. Patients were highly satisfied with the results of their surgery. All outcome measures showed statistically significant improvement. Improvement was seen at 6 months, but results continued to improve at the 1-year mark. By the second year, improvement largely reached a plateau. Biodex testing showed no loss of plantarflexion strength after reconstruction and gastrocnemius recession. CONCLUSION: Reconstruction of the flexible adult acquired flatfoot with FDL transfer, double calcaneal osteotomy, and gastrocnemius recession yielded excellent functional results for the treatment of Stage II posterior tibial tendon insufficiency. Plantarflexion weakness was not found to be a concern. A good functional outcome can be anticipated after the early postoperative period. However, it should be expected to take at least 1 year for maximal benefit.

Fetal cardiac ventricular volume, cardiac output, and ejection fraction determined with 4-dimensional ultrasound using spatiotemporal image correlation and virtual organ computer-aided analysis.

OBJECTIVE: The objective of this study was to quantify fetal cardiovascular parameters using spatiotemporal image correlation (STIC) and virtual organ computer-aided analysis (VOCAL). STUDY DESIGN: A cross-sectional study was performed in normal pregnancies (19-42 weeks) to evaluate ventricular volume, stroke volume (SV), cardiac output (CO), and ejection fraction (EF). The CO was also expressed as a function of estimated fetal weight and biometric parameters. RESULTS: The following results were found: (1) 184 STIC datasets; (2) with advancing gestation, ventricular volume, SV, CO, and adjusted CO increased, whereas EF decreased; (3) right ventricular (RV) volume was larger than the left ventricular (LV) volume in systole (0.50 vs 0.27 mL; P < .001) and diastole (1.20 vs 1.03 mL; P < .001); (4) there were no differences between the LV and RV in SV, CO, or adjusted CO; and (5) LV EF was greater than the RV EF (72.2 vs 62.4%; P < .001). CONCLUSION: Normal fetal cardiovascular physiology is characterized by a larger RV volume and a greater LV EF, resulting in similar LV and RV SV and CO.

Infectious organisms on Papanicolaou smears should not influence the diagnosis of atypical squamous cells of undetermined significance.

BACKGROUND: Atypical squamous cells of undetermined significance (ASCUS) remain the center of diagnostic controversy and patients' stress despite recent advances in cervical cancer screening and the introduction of human papilloma virus (HPV) testing. The role of infectious agents in the induction of such changes is not well understood. AIM: We aim at reviewing the effect of the different infectious organisms in Papanicolaou (PAP) smears on the ASCUS diagnosis. MATERIAL: 133 ASCUS cases associated with variable infectious organisms (ASCUS-infection group) with secondary HPV testing and appropriate follow-up studies were reviewed. A control group of 310 ASCUS cases without any organisms (ASCUS-only group) was selected for comparison. RESULTS: The ASCUS-infection group had a significantly higher proportion of HPV-positive tests than the ASCUS-only group (p = 0.0027). There was no significant difference on follow-up PAPs and biopsies between the two groups (p = 0.4272). They showed an overall mean of 75% negative, 20% low-grade lesions, and 5% high-grade lesions/carcinoma in situ on follow-up. CONCLUSION: Our study demonstrates no significant effect of infections on the cytological changes diagnostic of ASCUS. The cytologist should make this diagnosis neglecting any background infections even when predominant.

A radiographic analysis of the effects of glenosphere position on scapular notching following reverse total shoulder arthroplasty.

BACKGROUND: Multiple biomechanical studies have analyzed the potential influence of inferior glenosphere tilt on scapular notching in reverse total shoulder arthroplasty (RTSA). The purpose of this study was to clinically determine the likelihood of scapular notching in a series of shoulders, with the glenospheres placed in neutral versus inferior tilt. METHODS: From a database of all RTSA performed by the senior author, shoulders with a Delta III-type prosthesis and minimum 12-month follow-up (71 shoulders) were included. Notching in shoulders with neutrally placed glenosphere base plates (Group 1) was compared to notching with 10-15° inferiorly tilted base plates (Group 2). The prosthesis-scapular border angle (PSBA) was also defined and used to determine whether the radiographically quantified amount of inferior tilt was predictive of scapular notching independent of group assignment. RESULTS: There were no significant differences in the grade of notching or incidence of notching between groups 1 and 2 after adjusting for length of follow-up and prosthesis selection. The PSBA was also not predictive of scapular notching. CONCLUSION: Despite previous biomechanical studies' predictions that inferiorly tilting the glenosphere might reduce inferior scapular neck impingement and subsequent scapular notching, our data showed no difference at 1-year follow-up.

Study of intraocular pressure after 23-gauge and 25-gauge pars plana vitrectomy randomized to fluid versus air fill.

PURPOSE: To determine if a difference in intraocular pressure (IOP) exists after small-gauge pars plana vitrectomy randomized to fluid versus 80% sterile air fill. METHODS: Ninety-two eyes undergoing 23-gauge and 25-gauge transconjunctival pars plana vitrectomy were randomized to fluid versus air fill, and IOP was measured at 5 different time points. RESULTS: There is no difference in the mean IOP for eyes undergoing small-gauge pars plana vitrectomy randomized to fluid versus air fill after vitrectomy. Using 23-gauge instrumentation, the mean immediate and 2-hour postoperative IOPs were statistically lower than the mean preoperative IOP. The mean Postoperative Day 1 and Week 1 IOPs were statistically higher than the mean immediate postoperative IOP. Using 25-gauge instrumentation, the mean IOP was not statistically different at any time points in the 2 groups. When comparing 23-gauge with 25-gauge instrumentation, the immediate postoperative IOP was statistically lower and the rate of suture closure for sclerotomies was higher for 23-gauge vitrectomy. CONCLUSION: When performing 23-gauge or 25-gauge pars plana vitrectomy, there was no difference in mean IOP for fluid- versus air-filled eyes. However, the mean IOP in the immediate postoperative period was statistically lower, and there was a higher rate of suture closure for 23-gauge compared with 25-gauge instrumentation.

A radiographic analysis of the effects of prosthesis design on scapular notching following reverse total shoulder arthroplasty.

BACKGROUND: Scapular notching is a well-recognized complication of reverse total shoulder arthroplasty (RTSA). This paper analyzes the effects of prosthesis design on scapular notching in RTSA. METHODS: From a database of all RTSA performed by the senior author, shoulders with minimum 12-month follow-up were included (65 shoulders). Notching in shoulders with a prosthesis neck-shaft angle of 155° and no center-of-rotation (COR) offset (group 1) was compared to notching in shoulders with a neck-shaft angle of 143° and 2.5-mm COR offset (group 2). P values less than .05 were considered significant. RESULTS: The notching grade was significantly higher in group 1 than in group 2, even after statistically adjusting for differences in length of follow-up (P = .0081). The incidence of notching in group 1 at 60.7% was significantly higher than the 16.2% incidence in group 2 (P = .0107). CONCLUSION: Using prostheses with a smaller neck-shaft angle and increased COR offset can significantly reduce scapular notching in RTSA at 1 year, possibly improving prosthesis survival.

Mitochondrial gene expression changes in normal and mitochondrial mutant cells after exposure to ionizing radiation.

Mitochondrial DNA (mtDNA) contains 13 genes that encode proteins of the oxidative phosphorylation complex that are involved in ATP generation. Leber's optic atrophy and Leigh's syndrome are diseases that are caused by point mutations in the mitochondrial genome and that have phenotypes associated with energy deprivation. We hypothesized that energy deficiency from mitochondrial mutations in these cells leads to radiation hypersensitivity. Here we compared mitochondrial gene expression for the 13 mitochondrial protein-coding genes in two mitochondrial mutant cell lines, GM13740 (Leigh's syndrome) and GM10744 (Leber's optic atrophy) and a normal human lymphoblastoid cell line (GM15036) after X irradiation (0-4 Gy) 0 to 24 h postirradiation. Changes in gene expression were compared with cellular radiosensitivity. Statistically significant differences between Leigh's syndrome and normal cells were found in mitochondrial gene expression for all radiation doses and times that were commensurate with changes in radiation sensitivity. The data suggest that Leigh's syndrome cells have an impaired ability to repair radiation-induced DNA damage that results in radiation hypersensitivity. This may be attributable to mitochondrial dysfunction from reductions in mitochondrial gene expression and ATP generation, since Leigh's optic atrophy cells exhibit a mutation in the ATPase6 gene, which is an important component of Complex V of ATP synthase. In contrast, the mutation of the Leber's cells conferred radioresistance, which might be attributed to the mutation in the ND4 gene in the mitochondrial genome. The altered sensitivity of mitochondrial mutant cells to ionizing radiation can lead to decreased DNA repair, which may put individuals with mtDNA mutations at greater risk for cancer and other diseases.

Bystander effects induced by chemicals and ionizing radiation: evaluation of changes in gene expression of downstream MAPK targets.

Radiation-induced bystander effects have been evaluated extensively, including the involvement of the mitogen-activated protein kinase (MAPK) pathways. However, few studies have examined the ability of chemicals to induce bystander effects, and the molecular mechanisms involved in chemical bystander effects have not been investigated. We have previously demonstrated the ability of mitomycin C (MMC) and phleomycin (PHL) to induce bystander effects in normal human lymphoblastoid cells. Here, we demonstrate changes in the expression of MAPK target genes following bystander exposure to MMC or PHL or ionizing radiation. The expression changes of 18 genes, which code for proteins that are downstream targets of MAPK proteins, were evaluated at various time points following direct or bystander exposure to MMC, PHL and ionizing radiation. The 18 genes were analysed as groups belonging to one of the seven possible combinations of the three MAPK pathways. We observed statistically significant changes in expression of several genes following exposure to each agent. However, when the expression changes were analysed in the bystander cells alone, significant increases in expression of MAPK target genes were observed for MMC- and radiation-induced bystander effects but not for PHL. PHL is an acknowledged radiomimetic agent; however, in the present study, PHL responses did not resemble those of radiation. These results provide evidence for bystander-induced changes in MAPK proteins and downstream targets and suggest that the bystander effects are a part of a general stress response.

Glaucoma tube shunt implantation through the ciliary sulcus in pseudophakic eyes with high risk of corneal decompensation.

PURPOSE: To summarize our clinical experience with implanting Baerveldt glaucoma tube shunts through the ciliary sulcus in eyes with a posterior chamber intraocular lens and shallow anterior chambers, corneal transplants, guttata or edema. PATIENTS AND METHODS: A retrospective interventional nonrandomized noncomparative case series. Main outcome measure was postoperative corneal status. Secondary outcome measures included postoperative intraocular pressure (IOP), visual acuity and complications. RESULTS: Thirty-six eyes of 32 patients were identified through chart review. Follow-up period was 21.8+/-16.6 months (mean+/-standard deviation, range: 4.0 to 58.5 mo). At final visit, all 23 preoperative clear native corneas and 6 of 7 corneal transplants remained clear. Thus, of the 30 preoperative clear corneas, only 1 decompensated. Preoperative IOP was 27.9+/-11.8 mm Hg (range: 12 to 59 mm Hg), reduced postoperatively to 10.1+/-3.9 mm Hg (range: 2 to 21 mm Hg, P=0.0001), a reduction of 58.2%+/-19.3% (range: 5.0% to 95.4%). Final IOP was >or=5 and

Comparison of Rosenbaum pupillometry card using red and blue light to Colvard and Iowa pupillometers.

PURPOSE: To compare four scotopic pupil measuring techniques to determine whether a statistically significant difference exists among the techniques for each observer or between the observers for each technique. METHODS: Cross-sectional study performed on 200 eyes of 100 healthy individuals. Two observers performed pupillometry four times per pupil using the Rosenbaum card with red light, Rosenbaum card with blue light, Iowa pupillometer, and Colvard pupillometer. All measurements were recorded in scotopic conditions with each examiner masked to the other's results. RESULTS: Both examiners measured mean pupil diameters > 6.0 mm for all modalities except the Colvard device whose mean measurements were the smallest. The Iowa pupillometer and Rosenbaum card with red light produced the largest pupil measurements and were the most similar for both observers. The mean pupil diameter obtained by observer 1 was smaller compared with observer 2 while using the Rosenbaum card with blue light, but this was not significant (P = .2574). The mean pupil diameter obtained by observer 1 was larger compared with observer 2 while using the Colvard pupillometer and this was statistically different after adjusting for eye color (P = .0370). The mean pupil diameters of blue irides and brown irides are significantly higher than the measurements obtained for hazel irides (P = .0271 and P = .0445, respectively). CONCLUSIONS: Due to the complex interaction among observer, pupillometry technique, and iris color, one cannot compare the four techniques to each other with the same observer, nor can one compare the two observers irrespective of the technique.

Involvement of MAPK proteins in bystander effects induced by chemicals and ionizing radiation.

Many studies have examined bystander effects induced by ionizing radiation, however few have evaluated the ability of chemicals to induce similar effects. We previously reported the ability of two chemicals, mitomycin C (MMC) and phleomycin (PHL) to induce bystander effects in normal human lymphoblastoid cell lines. The focus of the current study was to determine the involvement of the MAPK proteins in bystander effects induced by physical and chemical DNA damaging agents and to evaluate the effects of MAPK inhibition on bystander-induced caspase 3/7 activation. The phosphorylation levels of the MAPK proteins ERK1/2, JNK, and p38, were measured from 1 to 24h following direct or bystander exposure to MMC, PHL or radiation. We observed transient phosphorylation, at early time points, of all 3 proteins in bystander cells. We also evaluated the effect of MAPK inhibition on bystander-induced caspase 3/7 activity to determine the role of MAPK proteins in bystander-induced apoptosis. We observed bystander-induced activation of caspase 3/7 in bystander cells. Inhibition of MAPK proteins resulted in a decrease in caspase 3/7 activity at the early time points, and the caspase activity increased (in the case of ERK inhibition) or returned to basal levels (in the case of JNK or p38 inhibition) between 12 and 24h. PHL is considered to be a radiomimetic agent, however in the present study PHL behaved more like a chemical and not like radiation in terms of MAPK phosphorylation. These results point to the involvement of MAPK proteins in the bystander effect induced by radiation and chemicals and provide additional evidence that this response is not limited to radiation but is a generalized stress response in cells.

Behavioral predictors of weight regain after bariatric surgery.

BACKGROUND: After bariatric surgery, a lifelong threat of weight regain remains. Behavior influences are believed to play a modulating role in this problem. Accordingly, we sought to identify these predictors in patients with extreme obesity after Roux-en-Y gastric bypass (RYGB). METHODS: In a large tertiary hospital with an established bariatric program, including a multidisciplinary outpatient center specializing in bariatric medicine, with two bariatric surgeons, we mailed a survey to 1,117 patients after RYGB. Of these, 203 (24.8%) were completed, returned, and suitable for analysis. Respondents were excluded if they were less than 1 year after RYGB. Baseline demographic history, preoperative Beck Depression Inventory (BDI), and Brief Symptom Inventory-18 scores were abstracted from the subjects' medical records; pre- and postoperative well-being scores were compared. RESULTS: Of the study population, mean age was 50.6 +/- 9.8 years, 147 (85%) were female, and 42 (18%) were male. Preoperative weight was 134.1 +/- 23.6 kg (295 +/- 52 lb) and 170.0 +/- 29.1 kg (374.0 +/- 64.0 lb) for females and males, respectively, p < 0.0001. The mean follow-up after bariatric surgery was 28.1 +/- 18.9 months. Overall, the mean pre- versus postoperative well-being scores improved from 3.7 to 4.2, on a five-point Likert scale, p = 0.001. A total of 160 of the 203 respondents (79%) reported some weight regain from the nadir. Of those who reported weight regain, 30 (15%) experienced significant regain defined as an increase of > or =15% from the nadir. Independent predictors of significant weight regain were increased food urges (odds ratios (OR) = 5.10, 95% CI 1.83-14.29, p = 0.002), severely decreased postoperative well-being (OR = 21.5, 95% CI 2.50-183.10, p < 0.0001), and concerns over alcohol or drug use (OR = 12.74, 95% CI 1.73-93.80, p = 0.01). Higher BDI scores were associated with lesser risk of significant weight regain (OR = 0.94 for each unit increase, 95% CI 0.91- 0.98, p = 0.001). Subjects who engaged in self-monitoring were less likely to regain any weight following bariatric surgery (OR = 0.54, 95% CI 0.30-0.98, p = 0.01). Although the frequency of postoperative follow-up visits was inversely related to weight regain, this variable was not statistically significant in the multivariate model. CONCLUSIONS: Predictors of significant postoperative weight regain after bariatric surgery include indicators of baseline increased food urges, decreased well-being, and concerns over addictive behaviors. Postoperative self-monitoring behaviors are strongly associated with freedom from regain. These data suggest that weight regain can be anticipated, in part, during the preoperative evaluation and potentially reduced with self-monitoring strategies after RYGB.

Antibody concentrations to Abeta1-42 monomer and soluble oligomers in untreated and antibody-antigen-dissociated intravenous immunoglobulin preparations.

Cognitive improvement in Alzheimer's disease (AD) patients treated with intravenous immunoglobulin (IvIg) has been attributed to its antibodies to amyloid beta (Abeta). We compared the concentrations of specific antibodies to soluble Abeta1-42 conformations, namely Abeta1-42 monomer and Abeta1-42 soluble oligomers, between three IvIg preparations, Gamunex, Gammagard, and Flebogamma. To determine specific antibody concentrations to these Abeta1-42 conformations, nonspecific binding of the IvIg preparations to the Abeta reverse sequence, Abeta42-1, was subtracted. These antibodies were measured in untreated IvIg preparations and also after they were treated to dissociate antibody-antigen complexes, because this procedure has been reported to increase the detectable levels of serum anti-Abeta antibodies. Antibody levels to Abeta1-42 monomer were significantly higher in untreated Gamunex than in the other two IvIg preparations, and antibody-antigen dissociation increased the measured anti-Abeta monomer concentrations in Gamunex and Gammagard. Dissociated Gamunex and Gammagard had higher anti-Abeta monomer levels than Flebogamma. Generally similar results were found for antibodies to soluble Abeta1-42 oligomers, with the exception that after antibody-antigen dissociation, only Gammagard had significantly higher antibody levels than Flebogamma. These differences in antibody concentrations to Abeta1-42 conformations (particularly to Abeta1-42 soluble oligomers, thought to be the most neurotoxic conformation of soluble Abeta) and the increased availability of these antibodies after antibody-antigen complex dissociation have important implications for IvIg treatment of AD patients.

Argatroban dosage requirements and outcomes in intensive care versus non-intensive care patients.

STUDY OBJECTIVE: To compare the outcomes of reduced-dose argatroban therapy in patients in the intensive care unit (ICU) with those of non-ICU patients. DESIGN: Retrospective medical record review. SETTING: Large, academic, tertiary care hospital. PATIENTS: Thirty-eight ICU patients and 43 non-ICU patients who received the institutional protocol of argatroban 0.8 microg/kg/minute and 1.2 microg/kg/minute, respectively, between March 2004 and September 2005. MEASUREMENTS AND MAIN RESULTS: Data on patient demographics, argatroban dosing, heparin-induced thrombocytopenia antibody results, activated partial thromboplastin times (aPTTs), new thrombotic events, and major bleeding events were extracted from medical records. Time-weighted mean +/- SD doses of argatroban were 0.82 +/- 0.3 microg/kg/minute for ICU patients and 1.25 +/- 0.29 microg/kg/minute for non-ICU patients. Mean aPTT ratios were similar between groups: 2.07 +/- 0.53 for ICU patients and 2.00 +/- 0.45 for non-ICU patients. More than 70% of all aPTT ratios were therapeutic. More than 95% of patients in both groups achieved a therapeutic aPTT ratio during therapy. Fewer ICU patients than non-ICU patients had all therapeutic aPTT ratios during argatroban therapy (29% vs 51%, p=0.07). Thrombotic events occurred in six (16%) ICU patients versus none of the non-ICU patients (p=0.009). Thrombotic events occurred in 4 (31%) of the 13 ICU patients with confirmed heparin-induced thrombocytopenia. Major bleeding occurred in four (11%) ICU patients versus none of the non-ICU patients (p=0.04). CONCLUSION: Both ICU and non-ICU patients require less than the manufacturer-recommended initial dosage of argatroban. However, ICU patients appear to be at an increased risk for bleeding and thrombotic events despite their attainment of therapeutic aPTTs.

An exploratory study of resident burnout and wellness.

PURPOSE: Physicians have a higher rate of burnout compared with the general population, and burnout's origin can be traced to residency training. Little evidence exists documenting the causes of burnout, and there is even less evidence on protective factors. The goal of this exploratory study was to determine which resident-identified stressors are associated with the presence of burnout and which resident-identified wellness factors are associated with the absence of burnout. METHOD: In the fall of 2006, residents from 13 specialties completed a demographics questionnaire, a survey of factors that promote burnout and wellness, and the Maslach Burnout Inventory. RESULTS: From a pool of 395 residents, 150 (38%) completed the questionnaires. Of 32 burnout factors, 27 were significantly associated with at least one burnout scale. Pessimism was the only burnout factor associated with all three burnout scales; 11 other burnout factors were associated with at least two burnout scales. Of 29 wellness factors, 25 were significantly associated with at least one burnout scale, indicating a lack of burnout. Use of prescription medications was the only wellness factor associated with all three burnout scales, indicating low burnout. Thirteen other wellness factors were associated with at least two of the scales. CONCLUSIONS: Significantly more research is needed to further define and measure wellness. Program directors should consider multiple burnout and wellness factors associated with burnout (or its absence) when designing treatment interventions. The aim should be to identify and bolster wellness factors that protect from burnout while minimizing the stressors that cause it.

Contrast volume reduction with superior vena cava catheter-directed coronary CT angiography: comparison with peripheral i.v. contrast enhancement in a swine model.

OBJECTIVE: Conventional MDCT angiography uses a traditional peripheral i.v. approach for contrast injection; however, we describe our experience with a superior vena cava (SVC) catheter approach for coronary artery MDCT angiography as a potential means of decreasing iodinated contrast volume. CONCLUSION: Central SVC contrast injection can decrease the contrast volume by 50% while maintaining coronary attenuation similar to that of peripheral i.v. injection. This approach has potential in reducing the contrast volume on coronary MDCT angiography studies and therefore the risk of contrast-induced nephropathy in certain high-risk patients. Further studies with higher injection rates and faster scan acquisition are needed for defining a lower contrast volume threshold.

Phlebotomy improves therapeutic response to interferon in patients with chronic hepatitis C: a meta-analysis of six prospective randomized controlled trials.

Prospective randomized controlled trials (RCTs) comparing phlebotomy and interferon (IFN) treatment to IFN alone in patients with chronic hepatitis C (CHC) have suggested a benefit for the phlebotomy group. However, statistical significance was achieved in only one of these trials. We performed a meta-analysis of RCTs comparing phlebotomy and IFN to IFN alone for the treatment of CHC. The MEDLINE database and Cochrane registry of controlled trials were searched using the key words "phlebotomy" and "treatment of hepatitis C." Reference lists of review articles discussing the interaction between iron and CHC, and prospective RCTs comparing phlebotomy plus IFN therapy to IFN alone were searched to identify additional RCTs that compared phlebotomy plus IFN to IFN alone. Peto odds ratios with their 95% confidence intervals and Forrest plots were generated for each variable to assess the relationships among the studies that had provided that information. Statistical analysis was performed using Comprehensive META-Analysis version 2.0. Six prospective RCTs were identified: all used sustained viral response (SVR) as an endpoint. The three largest RCTs excluded patients with cirrhosis. Two RCTs specifically included only patients with either high ferritin or high hepatic iron content. IFN treatment regimes varied. Length of treatment varied between 6 and 12 months. The phlebotomy plus IFN group and the IFN group did not differ with respect to the percentage of patients with cirrhosis or genotype 1. SVR was attained in 50/182 (27%) patients in the phlebotomy plus IFN group, compared to 22/185 (12%) patients in the IFN group. Peto odds ratio for SVR in phlebotomy plus IFN group was 2.7; 95% CI 1.6-4.5, P < 0.0001. All five RCTs published in manuscript form showed a trend towards a benefit from the phlebotomy plus IFN in attaining SVR, and the results of the meta-analysis were not dependent on any single RCT, since excluding any single RCT did not change the results. Phlebotomy improves the SVR in response to IFN treatment in patients with CHC. Confirmation of this will require RCT with detailed pre-treatment iron studies and appropriately powered to demonstrate a statistically significant benefit.