Risk of bleeding in patients undergoing pulmonary procedures on antiplatelet or anticoagulants: A systematic review.

As many as 25% of all patients undergoing invasive pulmonary procedures are receiving at least one antiplatelet or anticoagulant agent. For those undergoing elective procedures, the decision-making process is uncomplicated and the procedure may be postponed until the antiplatelet or anticoagulant agent may be safely held. However, many invasive pulmonary procedures are semi-elective or emergent in nature in which case a risk-benefit calculation and discussion occur between the provider and patient or surrogate decision-maker. Therefore, it is critical for providers to have an awareness of the risk of bleeding complications with different pulmonary procedures on various antiplatelet and anticoagulant agents. This systematic review summarizes the bleeding complications associated with different pulmonary procedures in patients on various antiplatelet or anticoagulant agents in the literature and reveals a paucity of high-quality evidence across a wide spectrum of pulmonary procedures and antiplatelet or anticoagulant agents. The results of this review can help inform providers of the bleeding risk in these patients to aid in the shared decision-making process and risk vs benefit discussion.

Optimal imaging protocol for measuring dynamic expiratory collapse of the central airways.

AIM: To compare measurements of expiratory collapse obtained using multidetector computed tomography (MDCT) of the central airways on routine axial and multiplanar reformatted (MPR) images. MATERIALS AND METHODS: Fifty volunteers with normal pulmonary function and no smoking history were imaged using a 64 MDCT system (40 mAs, 120 kVp, 0.625 mm collimation) with spirometric monitoring at end-inspiration and during forced expiration. Measurements of the trachea, right main (RMB) and left main bronchus (LMB) were obtained on axial and MPR images. Inspiratory and dynamic-expiratory cross-sectional area (CSA) measurements were used to calculate the mean percentage expiratory collapse (%Collapse). A paired t-test was used to assess within-subject differences and a Bland-Altman plot was used to assess agreement between the methods. RESULTS: Among 24 men and 26 women (mean age±standard deviation 50±15 years), CSA values were significantly greater on axial than MPR images (all p<0.001); however, the mean difference in %Collapse values for axial versus MPR were small: trachea ≈1% (55 ±19 versus 56±18, p=0.338); LMB identical (60±20 versus 60±17 p=0.856); and, RMB 4% (62 ±19 versus 66±19 p<0.001). On average, creation of MPR required 12 minutes of additional time per case (range=10-15 min). CONCLUSION: Differences in mean %Collapse for axial versus MPR images were small and unlikely to influence clinical management. This finding suggests that MPR may not be indicated for routine assessment of central airway collapse.

Sterilization by gamma radiation of antibiotic impregnated polymethylmethacrylate and plaster of Paris beads. A pilot study.

INTRODUCTION: Ethylene oxide is currently recommended for sterilization of antibiotic impregnated beads; however this method carries health risks to personnel and is becoming less available. OBJECTIVE: To perform a pilot study of the effect of radiation for sterilization of polymethylmethacrylate (PMMA) and plaster of Paris (POP) beads impregnated with amikacin, enrofloxacin, and ceftiofur. HYPOTHESIS: Radiation would effectively sterilize the beads without affecting the efficacy of the antibiotic. MATERIALS AND METHODS: Beads of PMMA and POP were prepared in a clean but non-sterile manner with one of the three antibiotics (amikacin, enrofloxacin, ceftiofur) or no antibiotic. Beads were then exposed to radiation for a total dose of 0 kiloGray (kGy), 10 kGy and 25 kGy. Beads were incubated on Mueller-Hinton agar plates seeded with Escherichia coli, Staphylococcus aureus or Pseudomonas aeruginosa for 24 hours or cultured in brain-heart infusion broth for 48 hours. Zones of inhibition were measured on the agar plates and statistics were performed on the diameters of the zones of inhibition using an analysis of variance. RESULTS: There were no differences in the diameters of inhibition for all levels of radiation for all PMMA beads. The same was true with POP beads with the exception of enrofloxacin which had a significantly decreased zone of inhibition with increased levels of radiation, though the clinical significance of this finding was not assessed. Only beads without antibiotics and not exposed to radiation had bacterial growth. CLINICAL SIGNIFICANCE: Radiation may be an effective method of sterilization for antibiotic impregnated beads.

Optimal transseptal puncture location for robot-assisted left atrial catheter ablation.

BACKGROUND: The preferred method of treatment for atrial fibrillation (AF) is by catheter ablation, in which a catheter is guided into the left atrium through a transseptal puncture. However, the transseptal puncture constrains the catheter, thereby limiting its manoeuvrability and increasing the difficulty in reaching various locations in the left atrium. In this paper, we address the problem of choosing the optimal transseptal puncture location for performing cardiac ablation to obtain maximum manoeuvrability of the catheter. METHODS: We have employed an optimization algorithm to maximize the global isotropy index (GII) to evaluate the optimal transseptal puncture location. As part of this algorithm, a novel kinematic model for the catheter has been developed, based on a continuum robot model. Pre-operative MR/CT images of the heart are segmented using the open source image-guided therapy software, 3D Slicer, to obtain models of the left atrium and septal wall. These models are input to the optimization algorithm to evaluate the optimal transseptal puncture location. RESULTS: The continuum robot model accurately describes the kinematics of the catheter. Simulation and experimental results for the optimal transseptal puncture location are presented in this paper. The optimization algorithm generates discrete points on the septal wall for which the dexterity of the catheter in the left atrium is maximum, corresponding to a GII of 0.4362. CONCLUSION: We have developed an optimization algorithm based on the GII to evaluate the optimal position of the transseptal puncture for left atrial cardiac ablation.

Predicting atelectasis by assessment of collateral ventilation prior to endobronchial lung volume reduction: a feasibility study.

BACKGROUND: The advent of endoscopic lung volume reduction (ELVR), especially relying on valve technology to achieve atelectasis, has aroused new interest in the assessment of collateral ventilation, which has been implicated in ELVR failures. We are reporting on the use of a catheter-based device that measures airway pressures and flows, and calculates airway resistance in vivo. OBJECTIVES: To assess the safety of this catheter-based system and the feasibility of obtaining measurements predictive of atelectasis after ELVR. METHODS: Patients undergoing ELVR were prospectively included in this double-blind cohort study. Each lobe targeted for ELVR was blocked with a catheter system (Chartis® System; Pulmonx, Inc., Redwood, Calif., USA); pressures and flows were assessed continuously. The primary endpoints were to evaluate the safety and feasibility; the secondary endpoint was to assess whether there was a relationship between the measurements and the incidence of atelectasis following ELVR. RESULTS: From June 2008 to November 2008, 25 patients were included in the study. All procedures could be performed without any complications. Due to pneumothorax in 1 case and inability to assess the catheter-based measurements in 4 cases, the final analysis included 20 patients. Atelectasis occurred in 8 out of 20 cases following implantation. In 18 patients (90%), the resistance measurements correlated with the postimplantation atelectasis visualized on a chest X-ray; in 2 patients (10%), a mismatch was detected. CONCLUSIONS: Resistance measurements were safely and successfully achieved. In 90% of the analyzable cases, the resistance measurements correlated with the occurrence of atelectasis after ELVR. The clinical impact of these findings will need to be evaluated in subsequent trials.

Use of tunnelled catheters for malignant pleural effusions in patients fit for pleurodesis.

The aim of the present study was to examine the effectiveness of tunnelled pleural catheters (TPC) in patients with malignant pleural effusions who would otherwise be candidates for pleurodesis. Patients were selected from a previously reported database of 250 TPC insertions. The study group was selected based on lung re-expansion and survival as a surrogate maker of eligibility for pleurodesis procedure, as defined by survival of > or =90 days and lung re-expansion > or =80% post-drainage on a standard chest radiograph 2 weeks post TPC placement. There were 109 procedures in 97 patients that met the entry criteria. Spontaneous pleurodesis (SP) was achieved following 70% of procedures and correlated with symptom control. The mean time to SP was 90 days. There was no need for a repeat procedure in 87% of cases overall and in 92% of patients experiencing SP. There were few complications and no procedure-related deaths. Tunnelled pleural catheters are an effective way of controlling malignant pleural effusions when used as first-line treatment in patients who appear to be candidates for pleurodesis procedures.

Hot biopsy forceps in the diagnosis of endobronchial lesions.

Electrocoagulation bronchoscopy biopsy forceps may prevent bleeding, but could also impair the quality of the specimens obtained. Patients with endobronchial lesions during bronchoscopy underwent six endobronchial biopsies each with a hot biopsy forceps, alternating between with electrocoagulation ("hot") and without ("cold"). Bleeding was quantified on a scale of 1-4, with 1 being no bleeding. The generator was set on "soft coagulation" mode, with power settings of 40, 60, 80 and 100 W for each group of 10 patients in a sequential fashion. Clinical pathology results were recorded before samples were reviewed by a second, blinded, pulmonary pathologist. A total of 39 patients with 40 endobronchial lesions had six biopsies performed (one patient had only four samples taken), giving a total of 238 biopsy samples. Concordance between hot and cold samples was 92.5% for the clinical pathologist and 87% for the blinded pathologist. Paired analysis suggested lower average bleeding score with the use of hot forceps. Overall bleeding rates for cold and hot biopsies, respectively, were as follows: grade 1: 30.3 and 41.2%; grade 2: 62.2 and 49.6%; grade 3: 7.6 and 9.2%; and grade 4: 0 and 0%. In conclusion, the use of hot biopsy forceps for endobronchial biopsy does not appear to have a negative impact on the pathological samples. Hot biopsy forceps showed a statistically significant reduction in bleeding score, which is unlikely to be of clinical significance.

Physician interpretation of electrocardiographic artifact that mimics ventricular tachycardia.

BACKGROUND: Patients who are misdiagnosed with ventricular tachycardia because of electrocardiographic artifact may be subjected to unnecessary procedures. The purpose of this study was to determine how often electrocardiographic artifact is misdiagnosed as ventricular tachycardia. METHODS: Physicians (n = 766) were surveyed with a case simulation that included a two-lead electrocardiographic monitor tracing of artifact simulating a wide-complex tachycardia. RESULTS: The rhythm strip was not recognized as artifact by 52 of the 55 internists (94%), 128 of the 221 cardiologists (58%), and 186 of the 490 electrophysiologists (38%). One hundred fifty-six of the 181 electrophysiologists (88%), 67 of the 126 cardiologists (53%), and 14 of the 15 internists (31%) who misdiagnosed the rhythm as ventricular tachycardia recommended an invasive procedure for further evaluation or therapy. CONCLUSIONS: This physician survey suggests that electrocardiographic artifact that mimics ventricular tachycardia may frequently result in patients being subjected to unnecessary invasive cardiac procedures. Physicians should include artifact in their differential diagnosis of wide complex tachycardias to minimize unneeded procedures.

Complete atrioventricular block after valvular heart surgery and the timing of pacemaker implantation.

The natural history of patients who developed complete atrioventricular block after valvular heart surgery was investigated to determine the optimal timing for pacemaker implantation. Patients who developed complete atrioventricular block within 24 hours after operation, which then persisted for > 48 hours, were unlikely to recover; such patients could potentially undergo earlier pacemaker implantation if otherwise ready for discharge.

A randomized trial comparing heparin initiation 6 h or 24 h after pacemaker or defibrillator implantation.

OBJECTIVES: The purpose of this randomized study was to evaluate the prevalence of pocket hematomas in patients treated with heparin 6 h or 24 h after pacemaker or defibrillator implantation. BACKGROUND: The risks of pocket hematoma and need for evacuation after device implantation have not been defined in patients who require anticoagulation. METHODS: Forty-nine consecutive patients with an indication for anticoagulation with heparin after implantable defibrillator or pacemaker implantation were randomized to receive intravenous heparin either 6 h (n = 26) or 24 h (n = 23) postoperatively. Both groups also received warfarin on a daily basis starting the evening of surgery. Twenty-eight patients who received postoperative warfarin alone and 115 patients who did not receive anticoagulation were followed up in a study registry. RESULTS: A pocket hematoma developed in 6 of 26 patients (22%) who were treated with intravenous heparin 6 h postoperatively, as compared with 4 of 23 patients (17%) who were treated with intravenous heparin 24 h postoperatively (p = 0.7). In total, a pocket hematoma developed in 10 of 49 patients (20%) treated with heparin, 1 of 28 patients (4%) treated with warfarin alone and 2 of 115 (2%) patients who received no anticoagulation (p < 0.001). CONCLUSIONS: Intravenous heparin initiation 6 h or 24 h after pacemaker or defibrillator implantation is associated with a 20% prevalence of pocket hematoma formation. Warfarin therapy or no anticoagulation is associated with only a 2% to 4% risk of pocket hematoma formation.

Radiofrequency catheter ablation of inappropriate sinus tachycardia guided by activation mapping.

OBJECTIVE: The purpose of this study was to evaluate the value of activation mapping for radiofrequency modification of the sinus node and the long-term success rate of the procedure in a series of patients with inappropriate sinus tachycardia. BACKGROUND: The results of radiofrequency ablation of inappropriate sinus tachycardia have been reported in only a small number of patients. METHODS: The subjects of this study were 29 consecutive drug-refractory patients who underwent catheter ablation of inappropriate sinus tachycardia. Target sites were selected by activation mapping during sinus tachycardia. RESULTS: The ablation procedure was successful acutely in reducing the baseline sinus rate to <90/min and the sinus rate during isoproterenol infusion by >20% in 22 of 29 patients (76%). In 13 of 22 patients (59%) with a successful acute outcome, successive applications of radiofrequency energy at the site of earliest endocardial activation resulted in a cranial-caudal migration of earliest endocardial activation from the high lateral right atrium, along with a step-wise reduction in heart rate. In the other nine patients (41%) with a successful acute outcome, the reduction in sinus rate occurred abruptly, unaccompanied by migration of the site of earliest activation. Symptoms due to inappropriate sinus tachycardia recurred at a mean of 4.4+/-; 3 months after the ablation procedure in 6 of 22 patients (27%). After additional procedures in three patients, symptoms of inappropriate sinus tachycardia ultimately were successfully eliminated over the long-term in 19 of 29 patients (66%). CONCLUSIONS: In conclusion, radiofrequency ablation is at best only modestly effective for managing patients with inappropriate sinus tachycardia. The two different responses of heart rate to radiofrequency ablation may reflect differences in the number and/or multicentricity of subsidiary sites of impulse generation within the sinus node and/or atrium in patients with inappropriate sinus tachycardia.

TGF-beta 1 induces the cyclin-dependent kinase inhibitor p27Kip1 mRNA and protein in murine B cells.

TGF-beta1 inhibits the cell cycle progression of many types of cells by arresting them in the G1 phase. This cell cycle arrest has been attributed to the regulatory effects of TGF-beta1 on both the levels and the activities of the G1 cyclins and their kinase partners. The activities of these kinases are negatively regulated by a number of proteins, such as p15INK4b, p21WAF1/Cip1, and p27Kip1, that physically associate with cyclins, cyclin-dependent kinases (Cdk), or cyclin-Cdk complexes. In epithelial cell lines, TGF-beta1 was previously shown to inhibit cell cycle progression through down-regulation of Cdk4 and/or up-regulation of p15INK4b and/or p21WAF1/Cip1. However, TGF-beta1 had little or no effect on the p27Kip1 mRNA and protein levels. In this report, we show that, in contrast to observations in epithelial cell lines, TGF-beta1 increased the p27Kip1 mRNA and protein levels in the murine B cell lines CH31 and WEHI231. This TGF-beta1-mediated induction of p27Kip1 also resulted in an increased association of p27Kip1 with Cdk2 and a decreased Cdk2 kinase activity. In contrast to epithelial cells, however, TGF-beta1 had little or no effect on the Cdk4 and p21WAF1/Cip1 protein levels in these B cells. Finally, although several studies suggested a direct role of p53 in TGF-beta1-mediated cell cycle arrest in epithelial cells, TGF-beta1 inhibited cell cycle progression in CH31 even in the absence of wild-type p53. Taken together, these results suggest that TGF-beta1 induces G1 arrest in B cells primarily through a p53-independent up-regulation of p27Kip1 protein.

Bcl-6 and lymphoproliferative disorders.

We report a series of 37 cases of lymphoproliferative disorders with 3q27 structural chromosomal abnormalities. Breakpoints at 3q27, the site of the bcl-6 gene, appear in a broad range of B cell lymphoma histologies but are most frequently detected in follicular lymphomas lacking a t(14;18) and diffuse large cell lymphomas. The majority of 3q27 rearrangements result from translocations involving the immunoglobulin heavy or light chain genes, however, involvement of other partner chromosomes is also observed. Molecular rearrangement of bcl-6 is demonstrable in a subset of cases. Bcl-6 is a recently identified gene encoding a zinc-finger protein. It is normally expressed in germinal center B cells where it is believed to have a developmental or differentiation function. Transcriptional deregulation of bcl-6 through translocations, submicroscopic molecular rearrangements or point mutations may be responsible for this gene's putative lymphomagenic potential.

Expression of Bcl-x in T cells.

The thymus is a major site of apoptosis where programmed cell death is involved in the deletion of self-reactive T cells. We have investigated the role of bcl-x in T cells by defining the expression of its two isoforms, bcl-x and bcl-xs, in a series of human thymocyte cell lines and in human T lymphocytes using the ribonuclease protection assay. Bcl-x1 was the predominant isoform expressed in T cell lines and in T lymphocytes, where expression was further enhanced by PMA/ionomycin. This broad expression supports a central role for bcl-x in thymocyte development perhaps through post-transcriptional regulation.

TPA-induced arrest of erythroid differentiation is coupled with downregulation of GATA-1 and upregulation of GATA-2 in an erythroid cell line SAM-1.

GATA-1 protein is thought to be a positive regulator of erythroid differentiation. However, ectopic expression of a conditional GATA-2/estrogen receptor chimera was shown to inhibit erythroid differentiation in a hormone-dependent manner, suggesting the negative regulation of erythroid differentiation by GATA-2 protein. Accordingly, we reasoned that the quantitative balance of GATA-1 and GATA-2 protein might affect erythroid differentiation. In this report, we performed specific and quantitative measurements of GATA-1 and GATA-2 protein in a new erythroid cell line, SAM-1, after treatment with 12-O-tetradecanoylphorbol 13-acetate (TPA). On the basis of these measurements, we show that TPA-induced arrest of erythroid differentiation is coupled with the upregulation of GATA-2 protein, as well as the downregulation of GATA-1 protein. Our results suggest that it is the precise quantitative balance of GATA-1 and GATA-2 protein that regulates erythroid differentiation.

Cancer risk among workers in biomedical research.

OBJECTIVE: This epidemiologic study was undertaken after a cluster of five cases of rare forms of cancer (bone sarcoma, non-Hodgkin's lymphoma) had been observed among biomedical research workers at the Pasteur Institute in Paris to ascertain whether their disease was connected with exposure during this research. METHODS: A mortality study included 3765 people who worked at the Pasteur Institute between 1971 and 1986 and were followed until the end of 1987. Within this cohort a nested case-referent study included 23 cases of cancer [non-Hodgkin's lymphoma (6), multiple myeloma (1), leukemia (3), pancreatic cancer (7), bone cancer (3), brain tumor (3)], and four referents per case, matched for gender and year of birth. RESULTS: Total mortality from cancer was less than expected, the standardized mortality ratio (SMR) being 72 for the men and 82 for the women. Among the women the proportion of pancreatic cancer cases was larger than expected [SMR 490, 95% confidence interval (95% CI) 158-1144], as was the number of brain cancer cases (SMR 239, 95% CI 48-696). Among the men, mortality from bone cancer was greater than expected (SMR 553, 95% CI 62-2006). In the nested case-referent study, more cases than referents had worked in the areas of molecular biology [odds ratio (OR) 7.1, 95% CI 1.5-33] and microbial genetics (OR 6.7, 95% CI 1.3-35). These cases especially included non-Hodgkin's lymphoma and bone cancer. Associated with this finding was the fact that more cases had used certain chemicals, including ethidium bromide, acrylamide, methylnitronitrosoguanidine and ethylmethanesulfonate, and radioactive compounds (essentially 32phosphorus). CONCLUSIONS: As the products used are potent genotoxicants, the present findings suggest that work in biomedical research might well involve an increased risk of certain types of cancer; this conclusion should be balanced by the fact that two of the five index cases were included in the mortality study and four in the nested case-referent study.

Deposition of transforming growth factor-beta in the marrow in myelofibrosis, and the intracellular localization and secretion of TGF-beta by leukemic cells.

The marrows of 10 patients with hematologic malignancies were examined by immunohistochemistry using anti TGF-beta antibody, CC(1-30), which detects secreted TGF-beta, and compared with four normal marrows. TGF-beta was not demonstrated in marrows with a normal level of reticulin fibrosis; however, TGF-beta was observed within collagen in marrows having collagen fibrosis or increased reticulin fibrosis. The extent of TGF-beta deposition paralleled the severity of fibrosis (P < .0001), and occurred even with normal or reduced numbers of megakaryocytes. Using another TGF-beta antibody, LC(1-30), which detects intracellular TGF-beta, TGF-beta was detected by immunofluorescence in discrete sites in the cytoplasm of immature and mature myeloid and large granular lymphocytic leukemia cells. These sites colocalized with areas detected by an anti-granule antibody (D545) suggesting that TGF-beta was stored in granules. However, neither the TGF-beta mRNA content nor the degree of TGF-beta secretion by these leukemic cells correlated with the extent of TGF-beta deposition in the marrow. Thus, TGF-beta deposition in marrow may contribute to myelofibrosis, but the source of this cytokine in the absence of megakaryocytes requires further study.

Polymerase chain reaction versus Southern blot hybridization. Detection of immunoglobulin heavy-chain gene rearrangements.

To determine efficiently the clonality of B-cell lymphoproliferative disorders, we modified an immunoglobulin heavy-chain (IGH) gene rearrangement polymerase chain reaction (PCR) assay that requires only a single primer germline variable (VH) and joining (JH) pair and does not involve nested priming, blot hybridization, radioactivity, or sequencing of the amplified PCR product. This simple PCR technique enabled detection of IGH gene rearrangements in as little as 10 pg (one cell equivalent) of DNA or when the clonal-to-polyclonal B-cell ratio was experimentally set at 1:1000. We detected IGH gene rearrangements in 83.5% (71 of 85) of clonal B-cell processes, a sensitivity approaching that of more cumbersome multiple primer and nested primer assays. Moreover, this technique is equally effective with fixed tissues, either B5 or formalin, and can be performed on minute samples, histologic sections, fine-needle aspirates, or cerebrospinal fluids. When compared with conventional Southern blot analysis using a genomic JH probe, the PCR assay demonstrated IGH gene rearrangements in 82% (37 of 45) of B-cell processes positive by Southern blot. No false-positive results were observed in 29 negative control tissues. We now use IGH gene PCR routinely in our laboratory for the detection of clonal B-cells in virtually any tissue sample as an aid in early diagnosis, staging, and monitoring, and the Southern blot procedure is reserved for only a minority of diagnostic cases. for only a minority of diagnostic cases.