Comparing predictive performance of pulmonary embolism risk stratification tools for acute clinical deterioration.

Objectives: Existing pulmonary embolism (PE) risk scores were developed to predict death within weeks, but not more proximate adverse events. We determined the ability of 3 PE risk stratification tools (simplified pulmonary embolism severity index [sPESI], 2019 European Society of Cardiology guidelines [ESC], and PE short-term clinical outcomes risk estimation [PE-SCORE]) to predict 5-day clinical deterioration after emergency department (ED) diagnosis of PE. Methods: We analyzed data from six EDs on ED patients with confirmed PE. Clinical deterioration was defined as death, respiratory failure, cardiac arrest, new dysrhythmia, sustained hypotension requiring vasopressors or volume resuscitation, or escalated intervention within 5 days of PE diagnosis. We determined sensitivity and specificity of sPESI, ESC, and PE-SCORE for predicting clinical deterioration. Results: Of 1569 patients, 24.5% had clinical deterioration within 5 days. sPESI, ESC, and PE-SCORE classifications were low-risk in 558 (35.6%), 167 (10.6%), and 309 (19.6%), respectively. Sensitivities of sPESI, ESC, and PE-SCORE for clinical deterioration were 81.8 (78, 85.7), 98.7 (97.6, 99.8), and 96.1 (94.2, 98), respectively. Specificities of sPESI, ESC, and PE-SCORE for clinical deterioration were 41.2 (38.4, 44), 13.7 (11.7, 15.6), and 24.8 (22.4, 27.3). Areas under the curve were 61.5 (59.1, 63.9), 56.2 (55.1, 57.3), and 60.5 (58.9, 62.0). Negative predictive values were 87.5 (84.7, 90.2), 97 (94.4, 99.6), and 95.1 (92.7, 97.5). Conclusions: ESC and PE-SCORE were better than sPESI for detecting clinical deterioration within 5 days after PE diagnosis.

Quality of life 1 month after acute pulmonary embolism in emergency department patients.

OBJECTIVE: The Pulmonary Embolism Quality-of-Life (PEmb-QoL) questionnaire assesses quality of life (QoL) after pulmonary embolism (PE). We aimed to determine whether any clinical or pathophysiologic features of PE were associated with worse PEmb-QoL scores 1 month after PE. METHODS: In this prospective multicenter registry, we conducted PEmb-QoL questionnaires. We determined differences in QoL domain scores for four primary variables: clinical deterioration (death, cardiac arrest, respiratory failure, hypotension requiring fluid bolus, catecholamine support, or new dysrhythmia), right ventricular dysfunction (RVD), PE risk stratification, and subsequent rehospitalization. For overall QoL score, we fit a multivariable regression model that included these four primary variables as independent variables. RESULTS: Of 788 PE patients participating in QoL assessments, 156 (19.8%) had a clinical deterioration event, 236 (30.7%) had RVD of which 38 (16.1%) had escalated interventions. For those without and with clinical deterioration, social limitations had mean (±SD) scores of 2.07 (±1.27) and 2.36 (±1.47), respectively (p = 0.027). For intensity of complaints, mean (±SD) scores for patients without RVD (4.32 ± 2.69) were significantly higher than for those with RVD with or without reperfusion interventions (3.82 ± 1.81 and 3.83 ± 2.11, respectively; p = 0.043). There were no domain score differences between PE risk stratification groups. All domain scores were worse for patients with rehospitalization versus without. By multivariable analysis, worse total PEmb-QoL scores with effect sizes were subsequent rehospitalization 11.29 (6.68-15.89), chronic obstructive pulmonary disease (COPD) 8.17 (3.91-12.43), and longer index hospital length of stay 0.06 (0.03-0.08). CONCLUSIONS: Acute clinical deterioration, RVD, and PE severity were not predictors of QoL at 1 month post-PE. Independent predictors of worsened QoL were rehospitalization, COPD, and index hospital length of stay.

Electrocardiographic findings associated with early clinical deterioration in acute pulmonary embolism.

OBJECTIVES: We sought to determine associations of early electrocardiogram (ECG) patterns with clinical deterioration (CD) within 5 days and with RV abnormality (abnlRV) by echocardiography in pulmonary embolism (PE). METHODS: In this prospective, multicenter study of newly confirmed PE patients, early echocardiography and initial ECG were examined. Initial ECG patterns included lead-specific ST-segment elevation (STE) or depression (STD), T-wave inversion (TWI), supraventricular tachycardia (SVT), sinus tachycardia, and right bundle branch block as complete (cRBBB) or incomplete (iRBBB). We defined CD as respiratory failure, hypotension, dysrhythmia, cardiac arrest, escalated PE intervention, or death within 5 days. We calculated odds ratios (ORs) for CD and abnlRV with univariate and full multivariate models in the presence of other variables. RESULTS: Of 1676 patients, 1629 (97.2%) had both ECG and GDE; 415/1676 (24.7%) had CD, and 529/1629 (32.4%) had abnlRV. AbnlRV had an OR for CD of 4.25 (3.35, 5.38). By univariable analysis, the absence of abnormal ECG patterns had OR for CD and abnlRV of 0.34 (0.26, 0.44; p < 0.001) and 0.24 (0.18, 0.31; p < 0.001), respectively. By multivariable analyses, one ECG pattern had a significant OR for CD: SVT 2.87 (1.66, 5.00). Significant ORS for abnlRV were: TWI V2-4 4.0 (2.64, 6.12), iRBBB 2.63 (1.59, 4.38), STE aVR 2.42 (1.58, 3.74), S1-Q3-T3 2.42 (1.70, 3.47), and sinus tachycardia 1.68 (1.14, 2.49). CONCLUSIONS: SVT was an independent predictor of CD. TWI V2-4 , iRBBB, STE aVR, sinus tachycardia, and S1-Q3-T3 were independent predictors of abnlRV. Finding one or more of these ECG patterns may increase considerations for performance of echocardiography to look for RV abnormalities and, if present, inform concerns for early clinical deterioration.

Can right ventricular assessments improve triaging of low risk pulmonary embolism?

OBJECTIVES: Identifying right ventricle (RV) abnormalities is important to stratifying pulmonary embolism (PE) severity. Disposition decisions are influenced by concerns about early deterioration. Triaging strategies, like the Simplified Pulmonary Embolism Severity Index (sPESI), do not include RV assessments as predictors or early deterioration as outcome(s). We aimed to (1) determine if RV assessment variables add prognostic accuracy for 5-day clinical deterioration in patients classified low risk by sPESI, and (2) determine the prognostic importance of RV assessments compared to other variables and to each other. METHODS: We identified low risk sPESI patients (sPESI = 0) from a prospective PE registry. From a large field of candidate variables, we developed, and compared prognostic accuracy of, full and reduced random forest models (with and without RV assessment variables, respectively) on a validation database. We reported variable importance plots from full random forest and provided odds ratios for statistical inference of importance from multivariable logistic regression. Outcomes were death, cardiac arrest, hypotension, dysrhythmia, or respiratory failure within 5 days of PE. RESULTS: Of 1736 patients, 610 (35.1%) were low risk by sPESI and 72 (11.8%) experienced early deterioration. Of the 610, RV abnormality was present in 157 (25.7%) by CT, 121 (19.8%) by echocardiography, 132 (21.6%) by natriuretic peptide, and 107 (17.5%) by troponin. For deterioration, the receiver operating characteristics for full and reduced random forest prognostic models were 0.80 (0.77-0.82) and 0.71 (0.68-0.73), respectively. RV assessments were the top four in the variable importance plot for the random forest model. Echocardiography and CT significantly increased predicted probability of 5-day clinical deterioration by the multivariable logistic regression. CONCLUSIONS: A PE triaging strategy with RV imaging assessments had superior prognostic performance at classifying low risk for 5-day clinical deterioration versus one without.

Evaluation of Glial and Neuronal Blood Biomarkers Compared With Clinical Decision Rules in Assessing the Need for Computed Tomography in Patients With Mild Traumatic Brain Injury.

Importance: In 2018, the combination of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase (UCH-L1) levels became the first US Food and Drug Administration-approved blood test to detect intracranial lesions after mild to moderate traumatic brain injury (MTBI). How this blood test compares with validated clinical decision rules remains unknown. Objectives: To compare the performance of GFAP and UCH-L1 levels vs 3 validated clinical decision rules for detecting traumatic intracranial lesions on computed tomography (CT) in patients with MTBI and to evaluate combining biomarkers with clinical decision rules. Design, Setting, and Participants: This prospective cohort study from a level I trauma center enrolled adults with suspected MTBI presenting within 4 hours of injury. The clinical decision rules included the Canadian CT Head Rule (CCHR), New Orleans Criteria (NOC), and National Emergency X-Radiography Utilization Study II (NEXUS II) criteria. Emergency physicians prospectively completed data forms for each clinical decision rule before the patients' CT scans. Blood samples for measuring GFAP and UCH-L1 levels were drawn, but laboratory personnel were blinded to clinical results. Of 2274 potential patients screened, 697 met eligibility criteria, 320 declined to participate, and 377 were enrolled. Data were collected from March 16, 2010, to March 5, 2014, and analyzed on August 11, 2021. Main Outcomes and Measures: The presence of acute traumatic intracranial lesions on head CT scan (positive CT finding). Results: Among enrolled patients, 349 (93%) had a CT scan performed and were included in the analysis. The mean (SD) age was 40 (16) years; 230 patients (66%) were men, 314 (90%) had a Glasgow Coma Scale score of 15, and 23 (7%) had positive CT findings. For the CCHR, sensitivity was 100% (95% CI, 82%-100%), specificity was 33% (95% CI, 28%-39%), and negative predictive value (NPV) was 100% (95% CI, 96%-100%). For the NOC, sensitivity was 100% (95% CI, 82%-100%), specificity was 16% (95% CI, 12%-20%), and NPV was 100% (95% CI, 91%-100%). For NEXUS II, sensitivity was 83% (95% CI, 60%-94%), specificity was 52% (95% CI, 47%-58%), and NPV was 98% (95% CI, 94%-99%). For GFAP and UCH-L1 levels combined with cutoffs at 67 and 189 pg/mL, respectively, sensitivity was 100% (95% CI, 82%-100%), specificity was 25% (95% CI, 20%-30%), and NPV was 100%; with cutoffs at 30 and 327 pg/mL, respectively, sensitivity was 91% (95% CI, 70%-98%), specificity was 20% (95% CI, 16%-24%), and NPV was 97%. The area under the receiver operating characteristic curve (AUROC) for GFAP alone was 0.83; for GFAP plus NEXUS II, 0.83; for GFAP plus NOC, 0.85; and for GFAP plus CCHR, 0.88. The AUROC for UCH-L1 alone was 0.72; for UCH-L1 plus NEXUS II, 0.77; for UCH-L1 plus NOC, 0.77; and for UCH-L1 plus CCHR, 0.79. The GFAP biomarker alone (without UCH-L1) contributed the most improvement to the clinical decision rules. Conclusions and Relevance: In this cohort study, the CCHR, the NOC, and GFAP plus UCH-L1 biomarkers had equally high sensitivities, and the CCHR had the highest specificity. However, using different cutoff values reduced both sensitivity and specificity of GFAP plus UCH-L1. Use of GFAP significantly improved the performance of the clinical decision rules, independently of UCH-L1. Together, the CCHR and GFAP had the highest diagnostic performance.

Development and validation of a prognostic tool: Pulmonary embolism short-term clinical outcomes risk estimation (PE-SCORE).

OBJECTIVE: Develop and validate a prognostic model for clinical deterioration or death within days of pulmonary embolism (PE) diagnosis using point-of-care criteria. METHODS: We used prospective registry data from six emergency departments. The primary composite outcome was death or deterioration (respiratory failure, cardiac arrest, new dysrhythmia, sustained hypotension, and rescue reperfusion intervention) within 5 days. Candidate predictors included laboratory and imaging right ventricle (RV) assessments. The prognostic model was developed from 935 PE patients. Univariable analysis of 138 candidate variables was followed by penalized and standard logistic regression on 26 retained variables, and then tested with a validation database (N = 801). RESULTS: Logistic regression yielded a nine-variable model, then simplified to a nine-point tool (PE-SCORE): one point each for abnormal RV by echocardiography, abnormal RV by computed tomography, systolic blood pressure < 100 mmHg, dysrhythmia, suspected/confirmed systemic infection, syncope, medico-social admission reason, abnormal heart rate, and two points for creatinine greater than 2.0 mg/dL. In the development database, 22.4% had the primary outcome. Prognostic accuracy of logistic regression model versus PE-SCORE model: 0.83 (0.80, 0.86) vs. 0.78 (0.75, 0.82) using area under the curve (AUC) and 0.61 (0.57, 0.64) vs. 0.50 (0.39, 0.60) using precision-recall curve (AUCpr). In the validation database, 26.6% had the primary outcome. PE-SCORE had AUC 0.77 (0.73, 0.81) and AUCpr 0.63 (0.43, 0.81). As points increased, outcome proportions increased: a score of zero had 2% outcome, whereas scores of six and above had ≥ 69.6% outcomes. In the validation dataset, PE-SCORE zero had 8% outcome [no deaths], whereas all patients with PE-SCORE of six and above had the primary outcome. CONCLUSIONS: PE-SCORE model identifies PE patients at low- and high-risk for deterioration and may help guide decisions about early outpatient management versus need for hospital-based monitoring.

Defining an Ultrasound-guided Regional Anesthesia Curriculum for Emergency Medicine.

OBJECTIVES: Ultrasound-guided regional anesthesia (UGRA) can be a powerful tool in the treatment of painful conditions commonly encountered in emergency medicine (EM) practice. UGRA can benefit patients while avoiding the risks of procedural sedation and opioid-based systemic analgesia. Despite these advantages, many EM trainees do not receive focused education in UGRA and there is no published curriculum specifically for EM physicians. The objective of this study was to identify the components of a UGRA curriculum for EM physicians. METHODS: A list of potential curriculum elements was developed through an extensive literature review. An expert panel was convened that included 13 ultrasound faculty members from 12 institutions and from a variety of practice environments and diverse geographical regions. The panel voted on curriculum elements through two rounds of a modified Delphi process. RESULTS: The panelists voted on 178 total elements, 110 background knowledge elements, and 68 individual UGRA techniques. A high level of agreement was achieved for 65 background knowledge elements from the categories: benefits to providers and patients, indications, contraindications, risks, ultrasound skills, procedural skills, sterile technique, local anesthetics, and educational resources. Ten UGRA techniques achieved consensus: interscalene brachial plexus, supraclavicular brachial plexus, radial nerve, median nerve, ulnar nerve, serratus anterior plane, fascia iliaca, femoral nerve, popliteal sciatic nerve, and posterior tibial nerve blocks. CONCLUSIONS: The defined curriculum represents ultrasound expert opinion on a curriculum for training practicing EM physicians. This curriculum can be used to guide the development and implementation of more robust UGRA education for both residents and independent providers.

Central Venous Catheterization: Are We Using Ultrasound Guidance?

OBJECTIVES: To assess the self-reported frequency of use of ultrasound guidance for central venous catheterization by emergency medicine (EM) residents, describe residents' perceptions regarding the use of ultrasound guidance, and identify barriers to the use of ultrasound guidance. METHODS: A longitudinal cross-sectional study was conducted at 5 academic institutions. A questionnaire on the use of ultrasound guidance for central venous catheterization was initially administered to EM residents in 2007. The same questionnaire was distributed again in the 5 EM residency programs in 2013. RESULTS: In 2007 and 2013, 147 and 131 residents completed questionnaires, respectively. A significant increase in the use of ultrasound guidance for central venous catheterization was reported in 2013 compared to 2007 (P< .001). In 2007, 53% (95% confidence interval, 44%-61%) of residents reported that they were initially trained in central venous catheterization using ultrasound guidance compared to 96% (95% confidence interval, 92%-99%) in 2013 (P < .0001). In 2007, more residents thought that faculty were insufficiently adopting ultrasound (42% versus 9%), and there was a lack of ultrasound teaching during residency training (14% versus 5%) compared to 2013. CONCLUSIONS: The use of self-reported ultrasound guidance for central venous catheterization significantly increased from 2007 to 2013 at academic institutions. Most residents were aware of the benefits of using ultrasound guidance. Although faculty adoption of ultrasound for central venous catheterization remains a barrier, it has decreased.

Do emergency ultrasound fellowship programs impact emergency medicine residents' ultrasound education?

OBJECTIVES: Recent years have seen a rapid proliferation of emergency ultrasound (EUS) programs in the United States. To date, there is no evidence supporting that EUS fellowships enhance residents' ultrasound (US) educational experiences. The purpose of this study was to determine the impact of EUS fellowships on emergency medicine (EM) residents' US education. METHODS: We conducted a cross-sectional study at 9 academic medical centers. A questionnaire on US education and bedside US use was pilot tested and given to EM residents. The primary outcomes included the number of US examinations performed, scope of bedside US applications, barriers to residents' US education, and US use in the emergency department. The secondary outcomes were factors that would impact residents' US education. The outcomes were compared between residency programs with and without EUS fellowships. RESULTS: A total of 244 EM residents participated in this study. Thirty percent (95% confidence interval, 24%-35%) reported they had performed more than 150 scans. Residents in programs with EUS fellowships reported performing more scans than those in programs without fellowships (P = .04). Significant differences were noted in most applications of bedside US between residency programs with and without fellowships (P < .05). There were also significant differences in the barriers to US education between residency programs with and without fellowships (P < .05). CONCLUSIONS: Emergency US fellowship programs had a positive impact on residents' US educational experiences. Emergency medicine residents performed more scans overall and also used bedside US for more advanced applications in programs with EUS fellowships.

Outcomes of renal transplantation in older high risk recipients: is there an age effect?

BACKGROUND: The purpose of this study was to evaluate long-term outcomes in high risk renal transplant recipients over 60 years of age compared with those younger than 60 years of age. MATERIALS AND METHODS: We analyzed outcomes in 131 consecutive renal transplant recipients at our institution between November 2001 and December 2007. Primary outcomes included incidence of delayed graft function (DGF), acute rejection, graft survival, patient survival, and incidence of infections and neoplasms. RESULTS: Older recipients (Over 60 group, n = 45) received more organs from extended criteria donors (ECD) or donation after cardiac death donors (DCD) compared with younger recipients (Under 60 group, n = 86), 42% versus 17% respectively, P = 0.001. Multivariate analyses revealed that African American ethnicity and DCD donation had the greatest impact on the incidence of DGF in both groups; P < 0.05. Patient survival and graft survival beyond 1 y were similar between the two groups. CONCLUSION: Our data suggest that long-term transplant outcomes in older, high risk renal transplant recipients are similar to those of younger, high risk recipients. Older recipients' age and high-risk characteristics, such as African American ethnicity and increased sensitization, should not be a contraindication to renal transplantation in the elderly.

Targeting alloantibody production with bortezomib: does it make more sense?

BACKGROUND: The effectiveness of current therapies for humoral rejection and decreasing antibody production directed against human leukocyte antigens (HLA) remains controversial. Standard regimens are unable to abrogate alloantibody production long term, most likely due to a lack of a direct effect on inhibiting and depleting mature plasma cells. Bortezomib (BZ) may be more effective at removing long-lived plasma cells compared to standard regimens that modulate alloantibody production by different mechanisms. METHODS: We report a kidney transplant recipient with several episodes of mixed antibody mediated and cellular rejection treated with numerous therapies including BZ. Monitoring included serial measurements of donor specific antibodies (DSA) by Luminex assay and repeated allograft biopsies. RESULTS: One cycle of BZ was able to reverse humoral rejection and graft dysfunction. DSA levels to multiple donor HLA antigens which were not affected by previous therapies were reduced to undetectable levels post BZ. Abrogation of DSA was only transient. Despite continued stable renal function post-BZ, the patient had a reemergence of DSA, and evidence of humoral rejection detected by allograft biopsy. CONCLUSIONS: Despite the promise of BZ as a therapy for humoral rejection, current data on how it should be used and its efficacy long-term remains limited.

Ultrasound can accurately guide gastrostomy tube replacement and confirm proper tube placement at the bedside.

BACKGROUND: Malfunctioning or dislodged gastrostomy tubes (G-tubes) often require urgent replacement and reinsertion in the Emergency Department (ED). Few data exist regarding the best technique for bedside catheter replacement and verification, and individual operator preferences vary. Although a few reports have described the use of ultrasound guidance during the initial percutaneous insertion, no data are available concerning its role during subsequent G-tube replacements. OBJECTIVE: We sought to investigate the utility of bedside ultrasonography during G-tube replacements in the ED. METHODS: This was a prospective pilot study conducted at a Level 1 Trauma Center with an annual census of 90,000 patients. Seven adults and three children with malfunctioning G-tubes were enrolled. Three tubes were cracked and leaking, and seven tubes had been dislodged. Under ultrasound, a new G-tube was inserted through the previously fashioned tract. After insertion, color Doppler was applied over the catheter tip to enhance visualization during gentle tube oscillation. RESULTS: Ultrasound successfully visualized G-tube replacement in all 10 patients. Application of color Doppler over the G-tube tip during catheter oscillation enhanced placement confirmation. Sonographic findings were corroborated with gastric content aspiration, contrast-enhanced radiographs, and successful use of the new G-tubes. No false tracts were identified during ultrasound-guided insertion, post-procedure sonographic confirmation, or subsequent radiographs. CONCLUSION: The improper replacement of a G-tube can lead to devastating consequences. Verifying appropriate placement through aspirate evaluation can be misleading, and post-procedure radiographs increase radiation exposure and ED wait times. Bedside ultrasonography can be used to guide catheter insertion while providing a safe and quick adjunct to confirm proper G-tube placement.

Risk of thrombogenicity among nonionic radiocontrast agents.

Several contrast agents have been approved in the United States for radiographic imaging purposes. Most of the older ionic, high-osmolar contrast agents are no longer used because of their side effect profile. Therefore, newer nonionic, low or iso-osmolar contrast agents have been widely accepted as an alternative due to their improved tolerability and safety. We investigated the thrombogenicity of the 6 different nonionic radiocontrast media in terms of their platelet reactivity and noted some minor differences among them. In the 50% contrast concentration group, all of the nonionic contrast agents inhibited aggregation, whereas in the 10% contrast concentration group, all agents showed similar aggregation curves in comparison to the normal control. At 50% contrast concentration, the inhibitory effect of aggregation appeared to be related to the inhibition of calcium mobilization, which may be one of the mechanistic effects.

A randomized controlled trial of ultrasound-assisted lumbar puncture.

OBJECTIVE: Evidence showing the systematic utility of ultrasound imaging during lumbar puncture (LP) in the emergency department is lacking. Our hypothesis was that ultrasound-assisted LP would increase the success rate and ease of performing LP with a greater benefit in obese patients. METHODS: This was an Institutional Review Board-approved, randomized, prospective, double-blind study conducted at the emergency department of a teaching institution. Patients undergoing LP from January to December 2004 were eligible for enrollment. Patients were randomized to undergo LP using palpation landmarks (PLs) or ultrasound landmarks (ULs). Data collected included age, body mass index, number of attempts, ease of performance and patient comfort on a 10-cm Visual Analog Scale, procedure time, success, and traumatic LP. Statistical analysis of data included relative risk (RR), the Mann-Whitney U test, and the Student t test. RESULTS: A total of 46 patients were enrolled, 22 randomized to PLs and 24 to ULs. There were no differences between the groups in mean age or body mass index. Six of 22 attempts failed with PLs versus 1 of 24 with ULs (RR, 1.32; 95% confidence interval, 1.01-1.72). In 12 obese patients, 4 of 7 PL attempts failed versus 0 of 5 UL attempts (RR, 2.33; 95% confidence interval, 0.99-5.49). The ease of the procedure was better with ULs versus PLs. There were no statistical differences in the number of attempts, traumatic LPs, patient comfort, or procedure length. CONCLUSIONS: The use of ultrasound for LP significantly reduced the number of failures in all patients and improved the ease of the procedure in obese patients.

Impending cardiac tamponade: a case report highlighting the value of bedside echocardiography.

Cardiac tamponade is a life-threatening process that must be diagnosed and treated in a timely fashion. As blood fills the pericardial sac, right ventricular filling is impeded and cardiac output is diminished, ultimately leading to cardiovascular collapse. Fortunately, emergency ultrasonography has improved the way we manage these patients today. In this report, we discuss a patient with hypotension and tachycardia who was found to have a massive loculated posterior pericardial effusion with impending cardiac tamponade. The diagnosis and appropriate treatment of this patient were rapidly ascertained with the use of bedside echocardiography. We review the literature on emergency ultrasonography, and consider the numerous instances in which emergency echocardiography can be life-saving.

p53, Bcl-2 and C-Myc expressions in colorectal carcinoma associated with schistosomiasis in Egypt.

BACKGROUND AND AIMS: Oncogenes and tumor suppressor genes expression are well described in bladder cancer associated with schistosomiasis especially in Egypt. Scarce studies were directed to colorectal cancer (CRC) associated with Schistosoma mansoni (S. mansoni). Apoptosis (programmed cell death) and the genes regulating this process (e.g., Bcl-2) have recently become a focus of interest in the study of cancer development and progression. In the present study, we aimed to investigate the expression pattern of p53, Bcl-2 and C-Myc in CRC tissues obtained from Egyptian colorectal cancer patients divided in two different groups, one associated with Schistosoma mansoni (CRC-Sm) and the other without Schistosoma mansoni (CRC-NSm). METHODS: Seventy-five CRC tumors containing 36 draining lymph node metastatic tumors were immunohistochemically stained using specific monoclonal antibodies for p53, Bcl-2 and C-Myc, in addition the apoptotic activity of these tumors were analyzed. RESULTS AND CONCLUSIONS: Regardless of the S. mansoni infection, the obtained results showed that the apoptotic activity was more evident in p53 diffuse positive tumors (P = 0.021). There was a significant correlation between p53 diffuse positive staining and Bcl-2 positive immunostaining (P = 0.011). Signet ring cell carcinoma and mucinous adenocarcinoma exhibited both intense C-Myc expression than non-mucinous carcinoma (P = 0.001). When adjusting for S. mansoni infection, 58.3% of CRC-Sm cases were Bcl-2 positive compared to only (33.3%) of CRC-NSm (P = 0.046). Apoptotic activity was more evident in the latter group than of CRC-Sm tumors (P = 0.009). p53 and C-Myc expressions were found insignificantly different in CRC-Sm compared with CRC-NSm (P > 0.05). These observations suggest that the genotoxic agents produced endogenously through the course of schistosomiasis mansoni may play a role in CRC-Sm pathogenesis through the dysregulation of apoptosis by alteration the expression pattern of Bcl-2 protein differently from CRC-NSm suggesting a different biological behavior.

Cardiac transplantation across a positive prospective lymphocyte cross-match in sensitized recipients.

BACKGROUND: Although there is an increasing body of evidence for a deleterious effect of mismatched donor HLA antigens on the outcome of human cardiac transplantation, the role of anti-HLA lymphocytotoxic antibodies remains controversial. Thus, their appearance after cardiac transplantation has been associated with poor outcome by some groups; whereas others have reported them to be of no clinical significance. Furthermore, their presence prior to cardiac transplantation has also been the subject of similarly conflicting reports. The deleterious effect of such pre-existing antibodies has been predicted by a positive lymphocyte cross-match (LCM), which, for most patients awaiting renal transplantation and in many requiring a cardiac allograft, leads to cancellation of the operation. The reason for undertaking the current study was to test the hypothesis that the constraints which a positive LCM result impose in preventing renal transplantation may not apply to orthotopic heart transplantation (OHT). PATIENTS AND METHODS: Four sensitized patients underwent OHT across a positive prospective LCM. Three were females, and one of those females also underwent cadaveric renal transplantation at the time of OHT. All four patients received aggressive early post-transplant immunosuppressive therapy, which included plasmapheresis, intravenous immunoglobulin (IVIg), antiproliferative agents (cyclophosphamide, basiliximab) and cytokine down-regulators (calcineurin inhibitors, muromonab-CD3) and anticell antibodies (OKT3, ATG). They also received standard immunosuppressive therapy which included corticosteroids. Complement-dependent cytotoxicity (CDC) was used for the identification of anti-HLA lymphocytotoxic antibodies. Reactivity of the latter against more than 10% of a panel of well-characterized T cells was considered sensitization, and required LCM to be performed prospectively, which test was also performed using the CDC technique. RESULTS: Three of the patients exhibited evidence suggestive of acute or hyperacute rejection in endomyocardial biopsy specimens by postoperative day (POD) 7. Two of the three patients with rejection also exhibited haemodynamic instability (elevated filling pressures and reduced cardiac index) on POD 1, which improved with inotropic support. One patient sustained a cardiac arrest on POD 7, and was successfully resuscitated without sequelae. All patients are now doing well, postoperatively (follow-up: 17-57 months) post-transplant. Two patients have normal left ventricular function and one patient has mild left ventricular dysfunction. Two have no further evidence of sensitization (PRA < 10%). CONCLUSIONS: Although the number of patients in this study is small, the long-term successful outcome of OHT following positive prospective cross-matches suggests that such a test result, in contrast to the restraints it imposes on renal transplantation, may not be a contra-indication to transplantation of the human heart. If OHT proceeds after the LCM is reported positive, aggressive immunotherapy should not only be initiated early, but should also be targeted at humoral-vascular rejection in particular.

p53 expression and DNA ploidy pattern in Egyptian colorectal carcinoma.

BACKGROUND/AIMS: p53 gene mutation occurs in about 50-60% of colorectal carcinoma cases. This mostly occurs as a late event in the adenoma-carcinoma sequence. These late stages are associated with more aneuploidy compared to adenomas and early carcinomas. However there is a controversy regarding the relation between p53 overexpression and DNA index. This study was designed to investigate the relationship between p53 status and DNA ploidy pattern. METHODOLOGY: Nuclear DNA content of paraffin-embedded material from 83 colectomy specimens for colorectal carcinoma was measured by flow cytometry. Also, p53 was detected by immunohistochemistry in 73 out of the 83 tumor cases using a monoclonal antibody that detects both wild and mutant p53 proteins (Biogenex 1801). RESULTS: Aneuploidy was identified in 37 cases (46.25%). Tumors with rectal location were significantly more aneuploid in comparison to other sites (P = 0.009), p53 staining showed three patterns: diffuse staining (29 cases), focal (13 cases), and negative (31 cases). Diffuse p53 staining was associated with aneuploidy (P = 0.04). The majority of DNA indices fell within the range 1.1-2.2 (32 out of 37). Twenty-one of these had DNA index = 1.1-1.8 (aneuploidy short of tetraploidy) significantly associated with diffuse p53 staining compared with peritetraploid cases (DNA index 1.8-2.2) (P = 0.034). CONCLUSIONS: p53 immunohistochemistry demonstrates two distinct patterns in colorectal carcinoma. Diffuse p53 staining, which is associated with aneuploidy short of tetraploidy (DNA index 1.1-1.8), a finding which is different from previously published work. Focal p53 staining pattern, in contrast, is related to high G2M and more abnormal tetraploid peaks but less aneuploidy.