Memorial Health University Medical Center

Evaluation of trauma care must be an integral part of any system designed for care of seriously injured patients. However, outcome review should offer comparability to national standards or norms. The TRISS method offers a standard approach for evaluating outcome of trauma care. Anatomic, physiologic, and age characteristics are used to quantify probability of survival as related to severity of injury. TRISS offers a means of case identification for quality assurance review on a local basis, as well as a means of comparison of outcome for different populations of trauma patients. Methods for calculating statistics associated with TRISS are presented. The Z and M statistics are explained with the nonstatistician in mind. We feel this article is a source for those interested in developing or upgrading trauma care evaluation.

Steroid hormones are made from cholesterol, primarily derived from lipoproteins that enter cells via receptor-mediated endocytosis. In endo-lysosomes, cholesterol is released from cholesterol esters by lysosomal acid lipase (LAL; disordered in Wolman disease) and exported via Niemann-Pick type C (NPC) proteins (disordered in NPC disease). These diseases are characterized by accumulated cholesterol and cholesterol esters in most cell types. Mechanisms for trans-cytoplasmic cholesterol transport, membrane insertion, and retrieval from membranes are less clear. Cholesterol esters and "free" cholesterol are enzymatically interconverted in lipid droplets. Cholesterol transport to the cholesterol-poor outer mitochondrial membrane (OMM) appears to involve cholesterol transport proteins. Cytochrome P450scc (CYP11A1) then initiates steroidogenesis by converting cholesterol to pregnenolone on the inner mitochondrial membrane (IMM). Acute steroidogenic responses are regulated by cholesterol delivery from OMM to IMM, triggered by the steroidogenic acute regulatory protein (StAR). Chronic steroidogenic capacity is determined by CYP11A1 gene transcription. StAR mutations cause congenital lipoid adrenal hyperplasia, with absent steroidogenesis, potentially lethal salt loss, and 46,XY sex reversal. StAR mutations initially destroy most, but not all steroidogenesis; low levels of StAR-independent steroidogenesis are lost later due to cellular damage, explaining the clinical findings. Rare P450scc mutations cause a similar syndrome. This review addresses these early steps in steroid biosynthesis.

Over the last 15 years, substantial progress has been made in understanding the potential and the limitations of the CA 125 assay. More than 2000 papers have been published concerning laboratory and clinical studies of CA 125. The original CA 125 assay utilized the OC 125 antibody that recognizes the CA 125 epitope on a high molecular weight glycoprotein. Despite repeated attempts, the gene encoding the peptide component has not yet been cloned. Monoclonal antibodies have been raised against other epitopes expressed by this molecule, leading to the development of the CA 125-II assay that exhibits less day-to-day variation. Using either assay, elevated levels of CA 125 are detected in a number of benign conditions, including endometriosis. CA 125 is most consistently elevated in epithelial ovarian cancer, but can be expressed in a number of gynecologic (endometrial, fallopian tube) and non-gynecologic (pancreatic, breast, colon and lung) cancers. The best established application of the CA 125 assay is in monitoring ovarian cancer. The rate of decline in CA 125 during primary chemotherapy has been an important independent prognostic factor in several multivariate analyses. Persistent elevation of CA 125 at the time of a second look surgical surveillance procedure predicts residual disease with > 95% specificity. Rising CA 125 values have preceded clinical detection of recurrent disease by at least 3 months in most, but not all studies. Given the modest activity of salvage chemotherapy, this information has not yet impacted on survival. Rising CA 125 during subsequent chemotherapy has been associated with progressive disease in more than 90% of cases. CA 125 may serve as an effective surrogate marker for clinical response in phase II trials of new drugs. CA 125 levels can aid in distinguishing malignant from benign pelvic masses, permitting effective triage of patients for primary surgery. Early detection of ovarian cancer remains the most promising application of CA 125. An algorithm has been developed that estimates the risk of ovarian cancer (ROC) based upon the level and trend of CA 125 values. A major trial has been initiated that uses the ROC algorithm to trigger transvaginal sonography and/or subsequent laparotomy. Such a trial could demonstrate improvement in survival through early detection. This strategy should provide adequate specificity, but sensitivity for early stage disease may not be optimal. In the future, improved sensitivity may be attained using multiple markers and neural network analysis. Most serum tumor markers have been proteins or carbohydrates, but lipid markers such as lysophosphatidic acid deserve evaluation. Genomic and proteonomic technologies should identify additional novel markers.

BACKGROUND: Blunt injury to the carotid or vertebral vessels (blunt cerebrovascular injury [BCVI]) is diagnosed in approximately 1 of 1,000 (0.1%) patients hospitalized for trauma in the United States with the majority of these injuries diagnosed after the development of symptoms secondary to central nervous system ischemia, with a resultant neurologic morbidity of up to 80% and associated mortality of up to 40%. With screening, the incidence rises to 1% of all blunt trauma patients and as high as 2.7% in patients with an Injury Severity Score of >or=16. The Eastern Association for the Surgery of Trauma organization Practice Management Guidelines committee set out to develop an EBM guideline for the screening, diagnosis, and treatment of BCVI. METHODS: A computerized search of the National Library of Medicine/National Institute of Health, Medline database was performed using citations from 1965 to 2005 inclusive. Titles and abstracts were reviewed to determine relevance, and isolated case reports, small case series, editorials, letters to the editor, and review articles were eliminated. The bibliographies of the resulting full-text articles were searched for other relevant citations, and these were obtained as needed. These papers were reviewed based on the following questions: 1. What patients are of high enough risk, so that diagnostic evaluation should be pursued for the screening and diagnosis of BCVI? 2. What is the appropriate modality for the screening and diagnosis of BCVI? 3. How should BCVI be treated? 4. If indicated, for how long should antithrombotic therapy be administered? 5. How should one monitor the response to therapy? RESULTS: One hundred seventy-nine articles were selected for review, and of these, 68 met inclusion criteria and are excerpted in the attached evidentiary table and used to make recommendations. CONCLUSIONS: The East Practice Management Guidelines Committee suggests guidelines that should be safe and efficacious for the screening, diagnosis, and treatment of BCVI. Risk factors for screening are identified (see ), screening modalities are reviewed indicating that although angiography remains the gold standard, multi-planar (>or==8 slice) CT angiography may be equivalent, and treatment algorithms are evaluated. It is noted that change in the diagnosis and management of this injury constellation is rapid due to technological advancement and the difficulties inherent in performing randomized prospective trials in this patient population.

We performed a three-phase genome-wide association study (GWAS) using cases and controls from a genetically isolated population, Ashkenazi Jews (AJ), to identify loci associated with breast cancer risk. In the first phase, we compared allele frequencies of 150,080 SNPs in 249 high-risk, BRCA1/2 mutation-negative AJ familial cases and 299 cancer-free AJ controls using chi(2) and the Cochran-Armitage trend tests. In the second phase, we genotyped 343 SNPs from 123 regions most significantly associated from stage 1, including 4 SNPs from the FGFR2 region, in 950 consecutive AJ breast cancer cases and 979 age-matched AJ controls. We replicated major associations in a third independent set of 243 AJ cases and 187 controls. We obtained a significant allele P value of association with AJ breast cancer in the FGFR2 region (P = 1.5 x 10(-5), odds ratio (OR) 1.26, 95% confidence interval (CI) 1.13-1.40 at rs1078806 for all phases combined). In addition, we found a risk locus in a region of chromosome 6q22.33 (P = 2.9 x 10(-8), OR 1.41, 95% CI 1.25-1.59 at rs2180341). Using several SNPs at each implicated locus, we were able to verify associations and impute haplotypes. The major haplotype at the 6q22.33 locus conferred protection from disease, whereas the minor haplotype conferred risk. Candidate genes in the 6q22.33 region include ECHDC1, which encodes a protein involved in mitochondrial fatty acid oxidation, and also RNF146, which encodes a ubiquitin protein ligase, both known pathways in breast cancer pathogenesis.

Letters1 December 1996Coma from the Health Food Store: Interaction between Kava and AlprazolamJoenie C. Almeida, MD and Edwin W. Grimsley, MDJoenie C. Almeida, MDMemorial Medical Center, Savannab, GA 31403. and Edwin W. Grimsley, MDMemorial Medical Center, Savannab, GA 31403.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-125-11-199612010-00023 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Millions of Americans use drugs sold in health food stores, yet most of these agents are unregulated. The potential for drug interactions is great. We report an interaction between kava and alprazolam that caused a semicomatose state.A 54-year-old man was hospitalized at our center in a lethargic and disoriented state. His medications included alprazolam, cimetidine, and terazosin. His vital signs and results of laboratory studies were normal. His alcohol level was negative, and a drug screen was positive for benzodiazepines. He became more alert after several hours and stated that he had been taking a “natural ...References1. Singh YN. Kava: an overview. J Ethnopharmacol. 1992; 37:13-45. Google Scholar2. Schelosky L, Raffauf C, Jendroska K, Poewe W. Kava and dopamine antagonism [Letter]. J Neurol Neurosurg Psychiatry. 1995; 58:639-40. Google Scholar3. Davies LP, Drew CA, Duffield P, Johnston GA, Jamieson DD. Kava pyrones and resin: studies on GABAA, GABAB and benzodiazepine binding sites in rodent brain. Pharmacol Toxicol. 1992; 71:120-6. Google Scholar4. Jussofie A, Schmiz A, Hiemke C. Kavapyrone enriched extract from Piper methysticum as modulator of GABA binding site in different regions of rat brain. Psychopharmacology (Berlin). 1994; 116:469-74. Google Scholar Author, Article, and Disclosure InformationAuthors: Joenie C. Almeida, MD; Edwin W. Grimsley, MDAffiliations: Memorial Medical Center, Savannab, GA 31403. 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BACKGROUND: Most gynecologists determine therapy based on current International Society of Gynecologic Pathologists (ISGP)/World Health Organization classification of endometrial hyperplasia, the reproducibility of which has been questioned. The Gynecologic Oncology Group (GOG) initiated a protocol to assess the efficacy of hormonal therapy of atypical endometrial hyperplasia (AEH). Primary goals of the first phase (Part A) were to prospectively determine reproducibility of referring institution's pathologist's diagnosis of AEH by a panel of 3 gynecologic pathologists and to determine reproducibility of diagnoses by panel members. METHODS: Three hundred six women were entered on this protocol with a referring institution's pathologist diagnosis of AEH based on biopsy or curettage. Available slides were assessed independently and interpreted by each of a panel of 3 gynecologic pathologists who used International Society of Gynecologic Pathologists (ISGP)/World Health Organization criteria. The majority diagnosis was based on diagnostic concordance by at least 2 of the 3 panelists. RESULTS: The referring institution's pathologist's diagnosis of AEH was supported by the majority of the panel in only 38% of cases. Overall kappa value for the panel diagnosis of AEH was 0.28. The majority diagnosis was adenocarcinoma in 29%, cycling endometrium in 7%, and nonatypical hyperplasia in 18% of cases. Unanimous agreement for any diagnosis was reached among all 3 of the panel in 40% of cases. For the panel, paired kappa values for any diagnosis ranged 0.34-0.43, with an overall kappa value of 0.40. CONCLUSION: Reproducibility of referring institution's pathologists' diagnosis of AEH by a panel of gynecologic pathologists is poor. Both underestimation and overestimation of the severity of the lesion are very common. The level of reproducibility among subspecialist panel members for diagnosis of AEH in these specimens also is poor. Better criteria and better sampling are needed to improve reproducibility of this diagnosis, particularly if it is to be used for clinical decisions.

Image-guided surgery has recently been described in the literature as a useful technology for improved functional endoscopic sinus surgery localization. Image-guided surgery yields accurate knowledge of the surgical field boundaries, allowing safer and more thorough sinus surgery. We have previously reviewed our initial experience with The InstaTrak System. This article presents a multicenter clinical study (n=55) that assesses the system's capability for localizing structures in critical surgical sites. The purpose of this paper is to present quantitative data on accuracy and performance. We describe several new advances including an automated registration technique that eliminates the redundant computed tomography scan, compensation for head movement, and the ability to use interchangeable instruments.

The objective of this study was to evaluate the effect of pharmacogenetics-guided treatment on patients diagnosed with depression and/or anxiety, in a diverse set of clinical settings, as compared to the standard of care. The trial design followed a prospective, randomized, subject- and rater-blinded approach enrolling 685 patients from clinical providers specializing in Psychiatry, Internal Medicine, Obstetrics & Gynecology, and Family Medicine. The NeuroIDgenetix® test uses a genetic variant panel of ten genes, along with concomitant medications, to make medication management recommendations based on gene-drug and drug-drug interactions for over 40 medications used in the treatment of depression and anxiety. Pharmacogenetic testing was performed at the initial screening visit and baseline patient assessments were determined using the 17-item Hamilton Rating Scale for Depression (HAM-D17) and the Hamilton Rating Scale for Anxiety (HAM-A). Following enrollment and randomization, pharmacogenetic results for subjects assigned to the experimental group were provided to physicians to guide treatment selection, while control subjects were treated according to the usual standard of care. HAM-D17 and HAM-A assessments were collected at 4 weeks, 8 weeks, and 12 weeks after baseline to assess the efficacy of therapeutic selection. In patients diagnosed with depression, response rates (p = 0.001; OR: 4.72 [1.93–11.52]) and remission rates (p = 0.02; OR: 3.54 [1.27–9.88]) were significantly higher in the pharmacogenetics-guided group as compared to the control group at 12 weeks. In addition, patients in the experimental group diagnosed with anxiety showed a meaningful improvement in HAM-A scores at both 8 and 12 weeks (p = 0.02 and 0.02, respectively), along with higher response rates (p = 0.04; OR: 1.76 [1.03–2.99]). From these results, we conclude that pharmacogenetic-guided medication selection significantly improves outcomes of patients diagnosed with depression or anxiety, in a variety of healthcare settings.

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States. Although there has been a statistically significant improvement in 5-year survival, in 2005 more than 16,000 women were expected to die of this disease. To date, there is no reliable method to screen for ovarian cancer; therefore, the majority of cases are diagnosed with advanced disease. For early ovarian cancer, appropriate surgical staging and adjuvant chemotherapy for selected cases will result in survival rates of 90-95%. For advanced ovarian cancer, survival depends primarily on the success of the initial surgical procedure. Patients with complete cytoreduction to microscopic disease are often cured with adjuvant chemotherapy. There is growing evidence that these patients with microscopic residual disease are excellent candidates for intraperitoneal chemotherapy, and this mode of chemotherapy delivery may be their best opportunity for cure. Patients with optimal cytoreduction also may benefit from intraperitoneal chemotherapy, but cure is less likely. For patients with suboptimal cytoreduction, intravenous chemotherapy with a combination of carboplatin and paclitaxel is the current standard therapy. Most of these patients will experience recurrence of the cancer, with small chance of cure. Salvage chemotherapy is important in ovarian cancer because many patients respond to several salvage regimens. Because of the high response rate of ovarian cancer, even after relapse, it is probably better to consider 10-year survival as the ideal end point. Finally, new biologic agents, in combination with traditional surgery and chemotherapy, may result in further improvement in survival for patients with ovarian cancer.

BACKGROUND: The National Surgical Quality Improvement Program (NSQIP) began with the Veterans Affairs system to reduce morbidity and mortality by evaluating preoperative risk factors, postoperative occurrences, mortality reports, surgical site infections, and patient variable statistics. Our institution enrolled in NSQIP July 2006. The Surgical Care Improvement Project (SCIP) was developed to reduce surgical complications, including surgical infections. We began instituting SCIP protocols in July 2007. STUDY DESIGN: This is a retrospective review of the NSQIP data collected by our NSQIP nurse. The colorectal surgical site infection (SSI) data pre- and post-institution of SCIP guidelines are analyzed. Data from the July 2006 to June 2007 and July 2007 to June 2008 reports are compared. Rates of SCIP compliance are analyzed. RESULTS: There were 113 colorectal cases in the July 2006 to June 2007 NSQIP report. The rate of superficial SSI was 13.3%, with an expected rate of 9.7% (p = 0.041). The observed-to-expected ratio was 1.39. Compliance with SCIP was 38%. There were 84 colorectal cases in the July 2007 to June 2008 NSQIP report. The rate of superficial SSI was 8.3%, with an expected rate of 10.25% (p = 0.351). The observed-to-expected ratio was 0.81. Compliance with SCIP measures was 92%. CONCLUSIONS: Participation in NSQIP can identify areas of increased morbidity and mortality. Our institution was a high outlier in superficial SSI in colorectal patients during the first NSQIP evaluations. SCIP guidelines were instituted and a statistically significant reduction in our rates of SSI was realized. As our compliance with SCIP improved, our rates of superficial SSI decreased. Reduction in superficial SSI decreases cost to the patient and decreases length of stay.

Steroid hormones are essential for carbohydrate metabolism, stress management, and reproduction and are synthesized from cholesterol in mitochondria of adrenal glands and gonads/ovaries. In acute stress or hormonal stimulation, steroidogenic acute regulatory protein (StAR) transports substrate cholesterol into the mitochondria for steroidogenesis by an unknown mechanism. Here, we report for the first time that StAR interacts with voltage-dependent anion channel 2 (VDAC2) at the mitochondria-associated endoplasmic reticulum membrane (MAM) prior to its translocation to the mitochondrial matrix. In the MAM, StAR interacts with mitochondrial proteins Tom22 and VDAC2. However, Tom22 knockdown by siRNA had no effect on pregnenolone synthesis. In the absence of VDAC2, StAR was expressed but not processed into the mitochondria as a mature 30-kDa protein. VDAC2 interacted with StAR via its C-terminal 20 amino acids and N-terminal amino acids 221–229, regulating the mitochondrial processing of StAR into the mature protein. In the absence of VDAC2, StAR could not enter the mitochondria or interact with MAM-associated proteins, and therefore steroidogenesis was inhibited. Furthermore, the N terminus was not essential for StAR activity, and the N-terminal deletion mutant continued to interact with VDAC2. The endoplasmic reticulum-targeting prolactin signal sequence did not affect StAR association with the MAM and thus its mitochondrial targeting. Therefore, VDAC2 controls StAR processing and activity, and MAM is thus a central location for initiating mitochondrial steroidogenesis. Background: Steroidogenic acute regulatory protein (StAR) fosters cholesterol into the adrenal and gonadal mitochondria to initiate steroidogenesis. Results: Voltage-dependent anion channel 2 (VDAC2) knockdown ablated pregnenolone synthesis and StAR processing into the mitochondria. Conclusion: Interaction between StAR and VDAC2 is critical for steroidogenesis. Significance: VDAC2 is a crucial regulator for initiating steroidogenesis.

BACKGROUND: The focused assessment for the sonographic examination of the trauma patient (FAST) is a rapid diagnostic test that sequentially surveys for hemopericardium and then the right upper quadrant (RUQ), left upper quadrant (LUQ), and pelvis for hemoperitoneum in patients with potential truncal injuries. The sequence of the abdominal part of the examination, however, has yet to be validated. The objectives of this multicenter study were as follows: (1) to determine where hemoperitoneum is most frequently identified on positive FAST examinations; and (2) to determine if a relationship exists between that areas and the organs injured. METHODS: Ultrasound registries from four Level I trauma centers identified patients who had true-positive FAST examinations. Demographic data, areas positive on the FAST, and organs injured were recorded; injuries were classified as multiple, single solid organ (liver or spleen), isolated hollow viscus, or retroperitoneal. Relationships between positive locations on the FAST examinations and the associations of organs injured to areas positive were assessed using McNamara's chi2 test; a p value < 0.05 was considered statistically significant. RESULTS: The RUQ was the most common site where hemoperitoneum was detected, and this was statistically significant compared with either the LUQ or the pelvis. Also, statistically significant correlations (p < 0.001) were observed between positive RUQ areas on the FAST and multiple injuries, single solid organ (liver or spleen) injury, and retroperitoneal injuries. CONCLUSION: Blood is most often found on the FAST in the RUQ area in patients with multiple intraperitoneal injuries or isolated injury to the liver, spleen, or retroperitoneum, but not when there is injury to a hollow viscus.

The Tridimensional Personality Questionnaire (TPQ) was developed to measure a variety of personality variants on three biosocial dimensions, harm avoidance (HA), novelty seeking (NS), and reward dependence (RD), which are thought to be related to serotonin (5-HT), dopamine (DA), and norepinephrine (NE) function, respectively. Patients with eating disorders have been reported to have abnormalities in all of these systems, as well as personality variants described by these dimensions. We therefore administered the TPQ to 147 patients with DSM-III-R defined eating disorders (110 bulimia nervosa [BN], 27 with anorexia nervosa [AN], and 10 with BN+AN) and compared their scores to those of 350 female controls. When significant, post hoc Bonferroni t tests were performed using alpha = 0.05. All subtypes of eating disorder patients scored significantly higher on HA than controls (p < or = .0001, analysis of variance. Only patients with BN (+/- AN) had significantly higher degrees of NS (p < or = .0001), particularly on the impulsiveness subscale (NS2), although this may, in part, be due to age. No significant differences in total RD were found, although BN patients scored lower on RD3 (attachment vs. detachment) and higher on RD4 (dependence vs. independence) than controls. In addition, AN patients had significantly higher RD2 (persistence vs. irresoluteness) subscale scores. These data support a theory of 5-HT dysregulation in both types of eating disorders and suggest that further research be done on the role of DA and NE in BN.

Mammalian telomeres consist of TTAGGG repeats organized in nucleosomes and associated with a six-protein complex known as shelterin, which preserves telomere structure and protects chromosome ends from the cellular DNA damage response. Recent studies have found that telomeres are transcribed into telomeric UUAGGG repeat-containing RNA (TERRA) starting from subtelomeric regions. TERRA binding at telomeres appears to be involved in cis-based mechanisms of telomeric chromatin organization and maintenance. A number of histone methyltransferases (HMTs) are known to influence telomeric chromatin status; however, the regulatory mechanisms of telomere transcription are poorly understood. Here, we show that the histone 3/lysine 4 (H3/K4) HMT and the transcriptional regulator MLL associate with telomeres and contribute to their H3/K4 methylation and transcription in a telomere length-dependent manner. In human diploid fibroblasts, RNA interference-mediated MLL depletion affects telomere chromatin modification and transcription and induces the telomere damage response. Telomere uncapping through either TRF2 shelterin protein knockdown or exposure to telomere G-strand DNA oligonucleotides significantly increases the transcription of TERRA, an effect mediated by the functional cooperation between MLL and the tumor suppressor p53. In total, our findings identify a previously unrecognized role of MLL in modifying telomeric chromatin and provide evidence for the functional interaction between MLL, p53, and the shelterin complex in the regulation of telomeric transcription and stability.

BACKGROUND: Evidence from clinical trials of early pulsed field ablation (PFA) systems in treating atrial fibrillation has demonstrated their promising potential to reduce complications associated with conventional thermal modalities while maintaining efficacy. However, the lack of a fully integrated mapping system, a staple technology of most modern electrophysiology procedures, poses limitations in lesion creation and workflow options. A novel variable-loop PFA catheter integrated with an electroanatomic mapping system has been developed that allows for real-time nonfluoroscopic procedural guidance and lesion indexing as well as feedback of tissue-to-catheter proximity. AdmIRE (Assessment of Safety and Effectiveness in Treatment Management of Atrial Fibrillation With the Bosense-Webster Irreversible Electroporation Ablation System), a multicenter, single-arm, Food and Drug Administration investigational device exemption study, evaluated the long-term safety and effectiveness of this integrated PFA system in a large United States-based drug-refractory symptomatic paroxysmal atrial fibrillation patient population. METHODS: Using the PFA catheter with a compatible electroanatomic mapping system, patients with drug-refractory symptomatic paroxysmal atrial fibrillation underwent pulmonary vein isolation. The primary safety end point was primary adverse event within 7 days of ablation. The primary effectiveness end point was a composite end point that included 12-month freedom from documented atrial tachyarrhythmia (ie, atrial fibrillation, atrial tachycardia, atrial flutter) episodes, failure to achieve pulmonary vein isolation, use of a nonstudy catheter for pulmonary vein isolation, repeat procedure (except for one redo during blanking), taking a new or previously failed class I or III antiarrhythmic drug at higher dose after blanking, or direct current cardioversion after blanking. RESULTS: At 30 centers, 277 patients with paroxysmal atrial fibrillation (61.5±10.3 years of age; 64.3% male) in the pivotal cohort underwent PFA. More than 25% of the procedures were performed without fluoroscopy. Median (Q1, Q3) pulmonary vein isolation procedure, fluoroscopy, and transpired PFA application times were 81.0 (61.0, 112.0), 7.1 (0.00, 14.3), and 31.0 (24.8, 40.9) minutes, respectively. The primary adverse event rate was 2.9% (8 of 272), with the most common complication being pericardial tamponade. The 12-month primary effectiveness end point was 74.6%. The 1-year freedom from atrial fibrillation, atrial tachycardia, or atrial flutter recurrence rate after blanking was 75.4%. Substantial improvements in quality of life were observed as early as 3 months after the procedure, concurrent with a reduction in multiple health care use measures. CONCLUSIONS: AdmIRE confirmed the safety and effectiveness of the variable-loop PFA catheter, with short procedure and PFA application times and low fluoroscopy exposure. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05293639.

Acetabular fractures with medial displacement patterns, particularly medial displacement of the quadrilateral surface, may be technically challenging to treat. Minimal bone stock, limited anatomic access, and difficulty in obtaining stable internal fixation in the true pelvis contribute to the surgical challenge of open reduction and internal fixation. Applying a medial buttress plate across the quadrilateral plate below the iliopectineal line in the true pelvis can be a helpful adjunct to internal fixation in these fractures. The quadrilateral plate is approached from the opposite side of the injury through a standard ilioinguinal approach or a modified Stoppa approach. An undercontoured plate is secured posteriorly along the sciatic buttress posterior to the joint and the quadrilateral plate and anteriorly on the posterior surface of the pubic ramus. By resisting medial secondary redisplacement, this technique adds to stable fixation for acetabular fractures involving medial displacement, particularly of the quadrilateral plate.

PURPOSE: To evaluate the efficacy and toxicity of erlotinib plus bevacizumab in patients with metastatic breast cancer (MBC), targeting the epidermal growth factor receptor (EGFR/HER1) and the vascular endothelial growth factor (VEGF) pathway. EXPERIMENTAL DESIGN: Thirty-eight patients with MBC were enrolled and treated at two institutions with erlotinib, a small molecule EGFR tyrosine kinase inhibitor (150 mg p.o. daily) plus bevacizumab, an anti-VEGF antibody (15 mg/kg i.v. every 3 weeks). Patients had one to two prior chemotherapy regimens for metastatic disease. The primary end point was response rate by Response Evaluation Criteria in Solid Tumors criteria using a Simon 2-stage design. Secondary end points included toxicity, time to progression, response duration, and stabilization of disease of > or = 26 weeks. Correlative studies were done on tumor tissue, including EGFR expression and mutation analysis. RESULTS: One patient achieved a partial response for 52+ months. Fifteen patients had stable disease at first evaluation at 9 weeks; 4 of these patients had stable disease beyond 26 weeks. Median time to progression was 11 weeks (95% confidence interval, 8-18 weeks). Diarrhea of any grade was observed in 84% of patients (grade 3 in 3%); 76% experienced grade 1 or 2 skin rash, and 18% developed hypertension (grade 3 in 11%). The level of EGFR expression was not predictive of response to therapy. CONCLUSIONS: The combination of erlotinib and bevacizumab was well-tolerated but had limited activity in unselected patients with previously treated MBC. Biomarkers are needed to identify those MBC patients likely to respond to anti-EGFR/HER1 plus anti-VEGF therapy.

BACKGROUND: Pleomorphic liposarcoma (PLS) is a rare high-grade sarcoma that has lipoblastic differentiation. In this study, the authors evaluated PLS natural history, patient outcomes, and commonly deregulated protein biomarkers. METHODS: Medical records from patients (n = 155) who had PLS from 1993 to 2010 were reviewed. Univariate and multivariate analyses were conducted to identify independent prognosticators. A PLS tissue microarray (TMA) (n = 56 patient specimens) was constructed for immunohistochemical analysis of molecular markers, and p53 gene sequencing (exons 5-9) was conducted. RESULTS: The average patient age was 57 years, and the patients presented with primary disease (n = 102), recurrent disease (n = 16), and metastatic disease (n = 37). Lower extremity was the most common disease site (40%), and the average tumor size was 11 cm. Complete follow-up data were available for 83 patients, and their median follow-up was 22.6 months. The 5-year disease-specific survival rate was 53%; and recurrent disease, unresectability, and microscopic positive margins were identified as predictors of a poor prognosis. Systemic relapse (the strongest poor prognostic determinant) developed in 35% of patients with localized PLS. Immunohistochemical analysis revealed increased expression of peroxisome proliferator-activated receptor gamma (an adipogenic marker), B-cell leukemia 2 and survivin (survival factors), vascular endothelial growth factor (an angiogenic factor), matrix metalloproteinase 2, and other biomarkers. Frequent loss of retinoblastoma protein expression and high p53 mutation rates (approximately 60%) were observed. CONCLUSIONS: PLS is an aggressive, metastasizing sarcoma. Identifying ubiquitous molecular events underlying PLS progression is crucial for progress in patient management and outcomes.

BACKGROUND: Vitamin D deficiency may contribute to impaired glucose metabolism. There are sparse data regarding vitamin D and the development of gestational diabetes (GDM). The objective of this study was to assess if first-trimester vitamin D deficiency is more prevalent in women later diagnosed with GDM compared with women with uncomplicated pregnancies. METHODS: We conducted a nested case-control study of pregnant women who had previously given blood for routine genetic multiple marker screening and subsequently delivered at a tertiary hospital between November 2004 and July 2009. From an overall cohort of 4225 women, 60 cases of GDM were matched by race/ethnicity with 120 women delivering at term (≥37 weeks) with uncomplicated pregnancies. Banked maternal serum was used to measure maternal 25-hydroxyvitamin D [25(OH)D]. RESULTS: The prevalence of first-trimester maternal vitamin D deficiency (defined as 25(OH)D < 50 nmol/L) was comparable among women with GDM compared with controls (5/60 vs 8/120, p = 0.90). The median 25(OH)D level for all subjects was 89 nmol/L (interquartile range, 73-106 nmol/L). Seventy three percent (117/160) of the cohort had 25(OH)D levels ≥75 nmol/L. CONCLUSIONS: In a cohort of pregnant women with mostly sufficient levels of serum 25(OH)D, vitamin D deficiency was not associated with GDM. Further studies are warranted with larger cohorts, especially in populations with lower levels of vitamin D.