Feasibility of Transseptal Puncture Using a Nonfluoroscopic Catheter Tracking System.

BACKGROUND: Radiation exposure in the electrophysiology lab is a major occupational hazard to the electrophysiologists. A catheter localization system (MediGuide Technology, St. Jude Medical Inc., St. Paul, MN, USA) allows the integration of electroanatomical mapping and x-ray imaging, and has been shown to be effective in reducing radiation exposure during several electrophysiological procedures. We intended to evaluate the feasibility of this catheter tracking system to guide transseptal (TS) access. METHODS: The feasibility of performing TS puncture with MediGuide (MDG) was assessed in a prospective observational study in 16 patients undergoing radiofrequency ablation for atrial fibrillation. These patients were compared to 16 matched patients undergoing similar procedures during the same time frame using conventional approach. There were no differences in mean age, gender distribution, and body mass index between the two groups. Total duration of fluoroscopic exposure during TS puncture was compared between the two groups. RESULTS: All patients underwent successful TS puncture. Fluoroscopy time for double TS puncture using the MDG system was significantly lower than the control group (0.48 ± 0.17 minutes vs. 5.9 ± 0.65 minutes; P < 0.0001). No major complications occurred during the procedures in either group. CONCLUSIONS: TS puncture can be successfully performed using MDG, and results in significant reduction in radiation exposure.

Extracorporeal life support for support of children with malignancy and respiratory or cardiac failure: The extracorporeal life support experience.

BACKGROUND: Extracorporeal life support (ECLS) is a means of respiratory and hemodynamic support for patients failing conventional therapies. Children with cancer who develop complications during therapy may require ECLS. METHODS: The extracorporeal life support organization (ELSO) registry was queried for all patients younger than 21 years with an International Classification of Diseases, Ninth Revision diagnosis of neoplasm. ELSO centers were also asked whether patients with neoplasms should be offered ECLS. RESULTS: From 1994 to 2007, 107 children met inclusion criteria: 73 with hematologic malignancies and 34 with solid tumors. The median age was 3.71 years. Patients had a total of 112 ECLS runs (five patients had two runs). Patients required ECLS primarily for pulmonary support (n = 86). Median duration of ECLS was 6.1 days. Overall, 62 of 107 patients (58%) died while on ECLS because of irreversible organ failure (n = 37), diagnosis incompatible with life (n = 11), hemorrhage (n = 6), and family request (n = 8). Forty-five of 107 patients (42%) survived ECLS. During the remaining hospitalization, eight patients died resulting in 37 of 107 surviving to hospital discharge (35%). Risk factors for death included lower Po2 before ECLS, higher oxygen index, higher positive end-expiratory pressure, and development of renal or cardiopulmonary complications (p < 0.05). No differences in outcomes were noted in patients with either hematologic malignancies or solid tumors. One hundred eighteen of 133 eligible ECLS centers responded to the questionnaire for an 89% response rate. Among those who responded, 112 of 133 would consider placing a child (95%) with a neoplasm on ECLS. CONCLUSION: Children with cancer and respiratory failure can be offered ECLS with a reasonable expectation for survival. The opinions of the ELSO center suggest that decisions to offer ECLS to a child with malignancy should be made on a case by case basis, with prognosis of the malignancy being an important factor.

Enhanced fluid management with continuous venovenous hemofiltration in pediatric respiratory failure patients receiving extracorporeal membrane oxygenation support.

BACKGROUND/PURPOSE: Children receiving extracorporeal membrane oxygenation (ECMO) for respiratory failure can have significant fluid overload and renal insufficiency. Addition of inline continuous venovenous hemofiltration (CVVH) could provide additional benefits in fluid management compared to use of standard medical therapies with ECMO. METHODS: Patients with pediatric respiratory failure receiving ECMO with CVVH were case-matched to similar patients receiving ECMO without CVVH to compare fluid balance, medication use, and clinical outcomes. RESULTS: Twenty-six of eighty-six patients with pediatric respiratory failure on ECMO (30%) received CVVH for >24 h (median 7.5 days on CVVH). Survival was not significantly different between patients receiving CVVH and those who did not receive CVVH (P = 0.51). For ECMO survivors receiving CVVH, overall fluid balance was less than that in non-CVVH survivors (median 25.1 ml kg(-1) day(-1); range -40.2 to 71.2 vs. 40.2, 1.1 to 134.9; P = 0.028). Time to desired caloric intake was faster in patients receiving CVVH (1 day, 1-5) than in patients who did not receive CVVH (5 days; 1-11; P < 0.001). Patients receiving CVVH-ECMO also received less furosemide (0.67 vs. 2.11 mg kg(-1) day(-1); P = 0.009). CONCLUSIONS: Use of CVVH in ECMO was associated with improved fluid balance and caloric intake and less diuretics than in case-matched ECMO controls.

New developments in the treatment of hypoactive sexual desire disorder - a focus on Flibanserin.

The objective of the authors is to highlight the historical complexities for the diagnosis and treatment of hypoactive sexual desire disorder (HSDD) with a focus on Flibanserin. A systematic review of the medical literature published in PubMed using the search terms HSDD and Flibanserin was conducted. Each author reviewed the results of the systematic review for articles to include in this study. HSDD is defined as a persistent or recurrent deficiency or absence of sexual fantasies and desire for sexual activity causing marked distress or interpersonal difficulty that is not better accounted for by another diagnosis. Until 2015, only homeopathic products and off-label use of prescription medications were medical treatment options for women with HSDD. Flibanserin, approved by the US Food and Drug Administration (FDA) in 2015, is the first to target female HSDD in premenopausal women. Flibanserin is a centrally acting nonhormonal oral medication taken once daily that affects serotonin, dopamine and norepinephrine levels, the key neurotransmitters in the biology of desire. Understanding prescribing guidelines and awareness of black box warnings is paramount for prescribers. Adherence to proper oversight will ensure Flibanserin can fulfil an unmet need for an FDA approved prescription medication for the treatment of HSDD in premenopausal women.

Outbreak of pertussis among healthcare workers in a hospital maternity unit.

In December 2015, an outbreak of pertussis was detected among staff working in the Maternity Unit of a district general hospital in Hampshire. This occurred in the background of increased pertussis activity in the community. The outbreak occurred over the Christmas holiday period causing staff shortages at a time when the departments were already overstretched. The high prevalence of upper respiratory tract infections at the time were difficult to distinguish from pertussis. This paper describes the outbreak, infection control measures implemented and the learning points.

Uteroovarian ligament torsion of the due to a paratubal cyst.

Paratubal cysts rarely undergo torsion. When they do, typically they involve the infundibulopelvic ligament and affect the ovary and fallopian tube. We present a case and discussion of torsion of the uteroovarian ligament secondary to a large paratubal cyst with preservation of the ovary and fallopian tube.

Somatic DNA alterations in endometriosis: high frequency of chromosome 17 and p53 loss in late-stage endometriosis.

PROBLEM: Genetic predisposition to endometriosis is well established, but the gene(s) involved largely remain unknown. Although endometriosis is considered a benign disease, it displays several features similar to malignancy: altered morphology, disregulated growth, invasion. We hypothesize endometriosis arises as result of somatic DNA alterations occurring in a multi-step process, analogous to origin of neoplasia. Since chromosome 17 and TP53 tumor suppressor gene (TSG) alterations occur frequently in premalignant and malignant tissues, including endometrial and ovarian epithelial carcinomas, we sought to determine if similar somatic changes occur in late stage endometriosis. METHOD OF STUDY: To determine the frequencies of monosomy for chromosome 17, as well as for perturbations of p53 and other loci on 17, two different approaches were used. Fluorescent in situ hybridization (FISH) analysis was used to detect monosomy for the 17 centromere and for the p53 locus. For FISH, archival tissue (n=6) and fresh endometriotic touch preparations were prepared from women (n=8) undergoing extirpation of advanced stage endometriosis. Direct-labeled probes specific for p53 (17p13.1) and for the chromosome 17 alpha-satellite centromere region (1711.1-q11.1) were used to compare single glandular and stromal cells from endometriosis and normal tissue. DNA analysis of polymorphic DNA loci were used to detect loss of heterozygosity (LoH) for other loci on 17. We assessed matched endometriotic and normal DNA (peripheral blood) from women with severe/late stage disease (n=15), studying these dinucleotide markers: HGH (located on 17q22-24), D17S250 (17q11.2-q12) and CHRNB1 (17p13.1). RESULTS: Loss of the chromosome 17 centromere (monosomy) was shown by FISH in some cells from all 14 endometriosis specimens, although in no case did every cell show monosomy 17. In 12 of 14 specimens, significant proportions of cells not only were monosomic for the chromosome 17-centromere (8 to 42% of cells) but also showed loss of p53 locus. In the two remaining cases, p53 loss alone was observed in 8 and 14%. LoH for other alleles on chromosome 17 was observed less often, namely only 3 of 15 specimens for HGH, 1 of 15 for D17S250, and 0 of 15 for CHRNB1. CONCLUSIONS: Our study indicates that perturbations of chromosome 17 in general and the p53 locus in particular occur frequently in severe/late stage endometriosis. That not all cells show loss of whole chromosome 17 or the p53 locus suggests somatic mutation, perhaps occurring late in the pathogenesis of endometriosis. Clonal evolution of endometriosis must depend not only on somatic mutations for p53 but also on other oncogenes or TSG. Alternatively, the clone could begin with a germline or somatic mutation involving a nonneoplastic process, followed by one or more somatic mutations involving an oncogene or TSG like p53. Additional candidate genes clearly must be evaluated in order to determine the precise role chromosome 17 and p53 alterations play in endometriosis; however, additional genes seem unlikely to involve region connoted by HGH, D17S250 or CHRNB1.

Pregnancies following use of metformin for ovulation induction in patients with polycystic ovary syndrome.

OBJECTIVE: To assess pregnancy outcome in anovulatory infertility patients diagnosed with polycystic ovary syndrome (PCOS) who were treated with metformin. DESIGN: Case series. SETTING: Outpatient. PATIENT(S): Anovulatory patients (n = 48) with a diagnosis of PCOS based on clinical, diagnostic, and laboratory evaluations were enrolled in the study over a 15-month period. INTERVENTION(S): Metformin was started at 500 mg b.i.d. for 6 weeks and then increased to 500 mg t.i.d. if no ovulation occurred. Clomiphene citrate (CC; 50 mg) was added if no ovulatory response occurred after 6 weeks. MAIN OUTCOME MEASURE(S): Resumption of menses, presumptive ovulation, and pregnancy. RESULT(S): Nineteen of 48 (40%) patients resumed spontaneous menses following treatment and showed presumptive evidence of ovulation with metformin alone; 15/48 (31%) required CC (50 mg) in conjunction with metformin therapy, and 10 of these 15 (67%) had evidence of ovulation; 20/48 (42%) conceived with a median time to conception of 3 months, and 7 of these 20 (35%) had spontaneous abortions (SAB); 19/48 (40%) had gastrointestinal-related side effects, and 5 of 48 patients (10%) had to decrease the dosage of metformin. Only 1 patient discontinued therapy. CONCLUSION(S): Metformin alone in patients with PCOS results in a substantial number of pregnancies, with 69% (20/29) of those who ovulated conceiving in less than 6 months.

Characterizing ectopic pregnancies that rupture despite treatment with methotrexate.

OBJECTIVE: To identify risk factors for tubal rupture among ectopic pregnancies treated with methotrexate (MTX). DESIGN: Retrospective case-control analysis. SETTING: An urban medical center. PATIENT(S): Eighty-one women diagnosed with an ectopic gestation treated with MTX: 19 patients experienced subsequent tubal rupture, and 62 patients experienced ectopic resolution. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Predictive variables including serial human chorionic gonadotropin (hCG) values. RESULT(S): The hCG incremental rate before as well as after MTX administration was positively associated with tubal rupture. HCG values prior to ectopic diagnosis that increased at least 66% over 48 hours and rising hCG values after treatment with methotrexate were independent predictors of tubal rupture. A disproportionate number (47%) of ectopic pregnancies that ruptured were located in the tubal isthmus. CONCLUSION(S): The hCG incremental rate both before and after MTX represents an independent risk factor for subsequent tubal rupture. Concentrations of hCG before ectopic diagnosis that increased at least 66% over 48 hours, or persistently rising hCG concentrations after treatment with MTX, may lower the threshold for surgical intervention. Implantation site may represent an unidentifiable risk factor for tubal rupture.

Impact of nonfluoroscopic MediGuide™ tracking system on radiation exposure in radiofrequency ablation procedures (LESS-RADS registry)-an initial experience.

BACKGROUND: Radiation exposure in the electrophysiology (EP) lab is a major concern to most electrophysiologists. A new technology, MediGuide™ nonfluoroscopic catheter tracking system, has been used for the first time in the USA recently. We intended to evaluate the efficacy of this novel catheter tracking system in reducing radiation exposure. METHODS: We performed a prospective observational study by comparing the radiation exposure with MediGuide™ system to that of conventional mapping systems. The first 45 EP procedures performed with the MediGuide™ system were compared to 45 matched patients undergoing similar procedures during the same time frame using conventional mapping systems (CARTO and NavX) and fluoroscopy. We collected and compared baseline characteristics, procedural variables including fluoroscopic exposure between both groups. RESULTS: Forty-five patients underwent EP procedures using the MediGuide™ technology. They were matched with an equal number of patients with conventional mapping systems. Of the 45 patients included in the study, 33 underwent right atrial flutter ablations, 5 underwent atrioventricular nodal reentrant tachycardia ablations, 4 underwent ablation of Wolf-Parkinson-White syndrome, and 3 underwent EP studies with no ablation. There were no differences in mean age, gender distribution, and body mass index between the groups. Procedure duration in the MediGuide™ group was significantly lower than the duration in the conventional group (103 vs. 142 min, p = 0.03). The fluoroscopic time was significantly less during the procedures performed with the MediGuide™ technology when compared to the control group (8 vs. 21 min, p < 0.001). No major complications occurred during the procedures in either group. CONCLUSION: MediGuide™, a new nonfluoroscopic catheter tracking system, is associated with more than a 50 % reduction in fluoroscopic time when compared to conventional mapping systems.

Atrial Flutter Ablation Using MediGuideTM Non-fluoroscopic Catheter Tracking System: A Novel Technology to Reduce Radiation Exposure.

We describe the first case of cardiac arrhythmia ablation with the novel MediGuideTM non-fluoroscopic catheter tracking system in North America. This new technology uses electromagnetic field to track sensor integrated intracardiac electrophysiology catheters which are projected on pre-recorded fluoroscopy cine loops. This new technology permits catheter tracking in virtual biplane fluoroscopy and enhances spatial resolution of conventional 3D mapping systems while drastically reducing radiation exposure.

Epidemiology of antimicrobial resistance among gram-negative organisms recovered from patients in a multistate network of long-term care facilities.

We identified 1,805 gram-negative organisms in cultures of urine samples obtained over a 10-month period from residents of 63 long-term care facilities. The prevalence of fluoroquinolone resistance in Escherichia coli was 51% (446 of 874 isolates), whereas the prevalences of ceftazidime and imipenem resistance in Klebsiella species were 26% and 6% (84 and 19 of 323 isolates), respectively. The prevalence of resistance varied significantly by facility type, size, and geographic location.

Oocyte-specific G-protein-coupled receptor 3 (GPR3): no perturbations found in 82 women with premature ovarian failure (first report).

The oocyte-specific G-protein-coupled receptor 3 (GPR3) gene is essential in maintaining meiotic arrest in mouse oocytes. Disruption of GPR3 results in early depletion of oocytes and thus premature ovarian aging. To determine if mutations of the GPR3 gene were present in 82 predominantly North American caucasian women with premature ovarian failure (POF), we used denaturing high-performance liquid chromatography and DNA sequencing to detect sequence variants. None of the 82 POF samples showed perturbations of significance. We conclude that perturbations in GPR3 are not a common explanation for POF in this population.

Growth differentiating factor-9 mutations may be associated with premature ovarian failure.

OBJECTIVE: To determine whether perturbations of the growth differentiating factor-9 (GDF9) gene are associated with premature ovarian failure (POF). DESIGN: Mutational analysis of the GDF9 gene in 61 women with POF. SETTING: Academic institution. PATIENT(S): Sixty-one women with POF; 60 control women. INTERVENTION(S): Peripheral blood sampling, genomic DNA extraction, mutational screening, and DNA sequencing. MAIN OUTCOME MEASURE(S): Genetic perturbations in GDF9 that are associated with POF. RESULT(S): A single missense mutation, substitution of a cytosine residue with thymidine in exon 1 of GDF9, was found in a white woman in whom POF developed at age 22. This mutation occurred in a highly conserved proprotein region and resulted in replacement of a nonpolar amino acid (proline) with a polar amino acid (serine) at position 103. Neither 60 control women nor 60 other women with POF demonstrated this genetic perturbation. Exon 2 showed only previously recognized single nucleotide polymorphisms. CONCLUSION(S): GDF9 mutations may be one explanation for POF, albeit uncommon.

Gadolinium radiologic contrast is a useful alternative for hysterosalpingography in patients with iodine allergy.

OBJECTIVE: To report the successful use of gadolinium radiologic contrast for hysterosalpingography. DESIGN: Case report. SETTING: Outpatient care in a private practice setting. PATIENT(S): One female patient entering and finishing study. INTERVENTION(S): Hysterosalpingogram. MAIN OUTCOME MEASURE(S): Interpretability of radiological imaging. RESULT(S): Visualization of a normal uterine cavity and fallopian tubes with bilateral patency was confirmed during the procedure. Radiologic films were created that document the results. The best visualization of the internal pelvic anatomy was noted during the actual procedure. There was a lighter image noted on the films taken from the use of gadolinium rather than the traditional iodinated contrast. CONCLUSION(S): Gadolinium is a safe and useful alternative to iodinated contrast for hysterosalpingography in patients with iodine allergy.

Extracorporeal life support for posttraumatic acute respiratory distress syndrome at a children's medical center.

BACKGROUND: Primary traumatic injury was considered previously a contraindication for institution of extracorporeal life support because of high risk for persistent or new bleeding. Published experience in adults suggests that extracorporeal membrane oxygenation (ECMO) can successfully support trauma victims with pulmonary failure. The authors reviewed their experience with the use of ECMO in pediatric and adult trauma patients with acute respiratory distress syndrome (ARDS) at a children's medical center. METHODS: ECMO Center records from 1991 through 2001 (76 children, 8 adults) were reviewed to identify all patients with a primary or secondary ICD-9 diagnostic code of posttraumatic ARDS in addition to documented trauma. RESULTS: Five children and 3 adults with traumatic injury and ARDS received ECMO support. Seven patients were injured in motor vehicle collisions; one patient suffered a gunshot wound to the chest. Patient ages ranged from 21 months to 29 years (pediatric median, 4 years; range, 21 months to 18 years). Four patients had pre-ECMO laparotomies, including 3 who required splenectomy. Four patients had liver lacerations, 3 had pulmonary contusions, and 1 had a renal contusion. Median ventilation before ECMO was 6 days (range, 2 to 10). Seven of 8 patients were placed on venovenous (VV) ECMO. Seven patients had significant bleeding on ECMO. Patients were treated with blood product replacement, epsilon-aminocaproic acid (EACA), and aprotinin infusions. Surgical intervention was not required for bleeding. Six patients received hemofiltration. Median time on ECMO was 653 hours (range, 190 to 921 hours). Six of 8 patients overall survived (75%). Four of 5 pediatric patients survived. CONCLUSIONS: Children and adults with severe posttraumatic ARDS can be treated successfully on VV extracorporeal support. Hemorrhage occurs frequently but is manageable.