Acquired von Willebrand Syndrome in a 17-Year-Old With Essential Thrombocythemia: A Case Report With Literature Review.

Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that is often underdiagnosed. AVWS typically occurs in adults without a family history of bleeding disorders and with associated conditions such as lymphoproliferative, myeloproliferative, and cardiovascular disorders. Here, we present a case of AVWS in a young patient with essential thrombocythemia and a literature review on AVWS in the setting of essential thrombocythemia.

A Case Report and Literature Review of Skeletal Muscle Metastasis of Non-small Cell Lung Cancer.

Non-small cell lung cancer metastasis to skeletal muscle is an uncommon occurrence. Lung cancers are more likely to spread to the brain, bone, liver, and adrenals. Here, we present a rare case of non-small cell lung cancer metastasis to the skeletal muscle in a 54-year-old male. In addition, we present a literature review on skeletal metastasis of non-small cell lung cancer. The most frequent presentation of skeletal muscle metastasis is muscular pain with or without swelling. The mechanism of metastasis to muscle is not well understood; it is theorized that hematogenous spread is the most likely route. As with our patient, the presence of skeletal muscle mass is considered an aggressive disease with poor survival, usually less than one year. The treatment for muscle metastasis is often palliative in the form of radiation therapy, chemotherapy, or surgical removal of the mass.

Real-world performance of blood-based proteomic profiling in first-line immunotherapy treatment in advanced stage non-small cell lung cancer.

PURPOSE: Immune checkpoint inhibition (ICI) therapy has improved patient outcomes in advanced non-small cell lung cancer (NSCLC), but better biomarkers are needed. A clinically validated, blood-based proteomic test, or host immune classifier (HIC), was assessed for its ability to predict ICI therapy outcomes in this real-world, prospectively designed, observational study. MATERIALS AND METHODS: The prospectively designed, observational registry study INSIGHT (Clinical Effectiveness Assessment of VeriStrat® Testing and Validation of Immunotherapy Tests in NSCLC Subjects) (NCT03289780) includes 35 US sites having enrolled over 3570 NSCLC patients at any stage and line of therapy. After enrolment and prior to therapy initiation, all patients are tested and designated HIC-Hot (HIC-H) or HIC-Cold (HIC-C). A prespecified interim analysis was performed after 1-year follow-up with the first 2000 enrolled patients. We report the overall survival (OS) of patients with advanced stage (IIIB and IV) NSCLC treated in the first-line (ICI-containing therapies n=284; all first-line therapies n=877), by treatment type and in HIC-defined subgroups. RESULTS: OS for HIC-H patients was longer than OS for HIC-C patients across treatment regimens, including ICI. For patients treated with all ICI regimens, median OS was not reached (95% CI 15.4 to undefined months) for HIC-H (n=196) vs 5.0 months (95% CI 2.9 to 6.4) for HIC-C patients (n=88); HR=0.38 (95% CI 0.27 to 0.53), p<0.0001. For ICI monotherapy, OS was 16.8 vs 2.8 months (HR=0.36 (95% CI 0.22 to 0.58), p<0.0001) and for ICI with chemotherapy OS was unreached vs 6.4 months (HR=0.41 (95% CI 0.26 to 0.67), p=0.0003). HIC results were independent of programmed death ligand 1 (PD-L1). In a subgroup with PD-L1 ≥50% and performance status 0-1, HIC stratified survival significantly for ICI monotherapy but not ICI with chemotherapy. CONCLUSION: Blood-based HIC proteomic testing provides clinically meaningful information for immunotherapy treatment decision in NSCLC independent of PD-L1. The data suggest that HIC-C patients should not be treated with ICI alone regardless of their PD-L1 expression.

Risk and clinical outcomes of acute myocardial infarction and acute ischemic stroke following gram-negative bloodstream infection.

OBJECTIVES: This retrospective cohort study examines incidence, risk factors, and clinical outcomes of acute myocardial infarction (AMI) and acute ischemic stroke (AIS) within one year of gram-negative bloodstream infection (GN-BSI) based on predefined clinical criteria. METHODS: Hospitalized adults with GN-BSI at Prisma Health-Midlands hospitals in South Carolina, USA from 2010 through 2015 were identified. Kaplan-Meier analysis was used to determine incidence of AMI and AIS within one year after GN-BSI. Multivariate Cox proportional hazards regression models were used to examine risk factors for AMI or AIS and impact on 1-year mortality. RESULTS: Among 1292 patients with GN-BSI, 263 and 17 developed AMI and AIS within 1-year with incidences of 23.4% and 1.9%, respectively. Majority of AMI were type 2 (164; 62%); 99 patients had type 1 AMI with incidence of 8.9%. Age >65 years (hazard ratio [HR] 1.52, 95% CI: 1.17-1.99), prior coronary artery disease or stroke (HR 1.74, 95% CI: 1.34-2.25), hypertension (HR 1.55, 95% CI: 1.13-2.15), end-stage renal disease (HR 1.52, 95% CI: 1.09-2.08), and quick Pitt bacteremia score (HR 1.55 per point, 95% CI: 1.40-1.72) were predictors of AMI/AIS. Development of type 1 AMI or AIS after GN-BSI was independently associated with increased 1-year mortality (HR 1.47, 95% CI: 1.03-2.07). CONCLUSIONS: AMI and AIS occur frequently within one year of GN-BSI and have negative impact on 1-year survival. Future randomized clinical trials are needed to determine the most effective clinical interventions for prevention of AMI/AIS following BSI in high risk patients and improve survival after these events.

Nonvariceal upper GI hemorrhage after percutaneous coronary intervention for acute myocardial infarction: a national analysis over 11 months.

BACKGROUND AND AIMS: Nonvariceal upper GI hemorrhage (NVUGIH) is a feared adverse event after percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). We aimed to determine the incidence of NVUGIH after PCI for AMI and its impact on mortality, morbidity, and health care resource utilization over 11 months. METHODS: We used the Nationwide Readmission Database 2014. Inclusion criteria were (1) a principal diagnosis of ST or non-ST-elevation myocardial infarction, (2) in-hospital PCI, and (3) admission in January. Exclusion criteria were age less than 18 years and elective admission. The primary outcome was the 11-month incidence of NVUGIH. Secondary outcomes were 11-month mortality rate, prolonged mechanical ventilation, shock, upper endoscopy, length of stay, and total hospitalization costs and charges. Independent risk factors for NVUGIH were identified using multivariate logistic regression analysis. RESULTS: A total of 22,669 patients were included in the study. The mean age was 63.8 years (range, 63.4-64.1 years), and 31.7% of patients were female. The 11-month incidence of NVUGIH was 1.6%. The onset of NVUGIH was associated with an increase in the 11-month mortality rate (adjusted odds ratio, 1.94; 95% confidence interval, 1.01-3.72; P =.04). The upper endoscopy, shock, and prolonged mechanical ventilation rates were 72%, 6.2%, and 1.9%, respectively. In total, 26,532 days were associated with NVUGIH, with a total health care in-hospital economic burden of U.S.$17.6 million. Independent predictors of NVUGIH were female gender, Charlson comorbidity score, and length of stay. CONCLUSIONS: The 11-month incidence of NVUGIH among patients who undergo PCI for AMI is 1.6%. NVUGIH has a substantial impact on mortality, morbidity, and in-hospital health care resource utilization.

A Portable Wireless Communication Platform Based on a Multi-Material Fiber Sensor for Real-Time Breath Detection.

In this paper, we present a new mobile wireless communication platform for real-time monitoring of an individual's breathing rate. The platform takes the form of a wearable stretching T-shirt featuring a sensor and a detection base station. The sensor is formed by a spiral-shaped antenna made from a multi-material fiber connected to a compact transmitter. Based on the resonance frequency of the antenna at approximately 2.4 GHz, the breathing sensor relies on its Bluetooth transmitter. The contactless and non-invasive sensor is designed without compromising the user's comfort. The sensing mechanism of the system is based on the detection of the signal amplitude transmitted wirelessly by the sensor, which is found to be sensitive to strain. We demonstrate the capability of the platform to detect the breathing rates of four male volunteers who are not in movement. The breathing pattern is obtained through the received signal strength indicator (RSSI) which is filtered and analyzed with home-made algorithms in the portable system. Numerical simulations of human breath are performed to support the experimental detection, and both results are in a good agreement. Slow, fast, regular, irregular, and shallow breathing types are successfully recorded within a frequency interval of 0.16-1.2 Hz, leading to a breathing rate varying from 10 to 72 breaths per minute.

An Open-Label, Randomized, Controlled Phase II Study of Paclitaxel-Carboplatin Chemotherapy With Necitumumab Versus Paclitaxel-Carboplatin Alone in First-Line Treatment of Patients With Stage IV Squamous Non-Small-Cell Lung Cancer.

BACKGROUND: The combination of necitumumab with gemcitabine-cisplatin significantly improved overall survival (OS) in patients with stage IV squamous non-small-cell lung cancer (NSCLC), in the phase III SQUamous NSCLC treatment with the Inhibitor of EGF REceptor (SQUIRE) trial. Paclitaxel-carboplatin was selected as an alternative standard of care in the current phase II study. PATIENTS AND METHODS: Patients were randomized (stratified according to Eastern Cooperative Oncology Group performance status and sex) 2:1 to ≤ six 3-week cycles (Q3W) of paclitaxel and carboplatin with or without necitumumab. Chemotherapy was paclitaxel 200 mg/m2 on day 1 Q3W and carboplatin area under the curve 6 on day 1 Q3W. Necitumumab 800 mg, on days 1 and 8, was continued until disease progression or intolerable toxicity occurred. The primary end point was objective response rate (ORR) on the basis of Response Evaluation Criteria In Solid Tumors version 1.1. RESULTS: One hundred sixty-seven patients were randomized to the necitumumab-containing arm (n = 110) or the chemotherapy-only arm (n = 57). The combination of necitumumab with chemotherapy resulted in an ORR of 48.9% versus 40.0%. Median progression-free survival and OS were 5.4 versus 5.6 months (hazard ratio [HR], 1.0) and 13.2 versus 11.2 months (HR, 0.83; P = .379) in each treatment arm, respectively. Disease control rate was 87.2% versus 84.0%. Grade ≥ 3 adverse events typically associated with epidermal growth factor receptor (EGFR) monoclonal antibodies showing a > 2% increase were hypomagnesemia (5.7% vs. 0) and rash (2.8% vs. 0). Any Grade thromboembolic events occurred in < 4% of patients in either arm. CONCLUSION: The results of our study support previously reported results that the combination of necitumumab with chemotherapy improves survival in patients with advanced squamous NSCLC and shows a safety profile consistent with that of EGFR monoclonal antibodies.

A phase 1/2 trial of ublituximab, a novel anti-CD20 monoclonal antibody, in patients with B-cell non-Hodgkin lymphoma or chronic lymphocytic leukaemia previously exposed to rituximab.

This phase 1/2 study evaluated the safety, pharmacokinetic behavior and anti-tumour activity of ublituximab, a unique type I, chimeric, glycoengineered anti-CD20 monoclonal antibody, in rituximab-relapsed or -refractory patients with B-cell non-Hodgkin lymphoma (B-NHL) or chronic lymphocytic leukaemia (CLL). Induction therapy (doses of 450-1200 mg) consisted of 4 weekly infusions in cycle 1 for NHL and 3 weekly infusions in cycles 1 and 2 for CLL. Patients received ublituximab maintenance monthly during cycles 3-5, then once every 3 months for up to 2 years. Enrolled patients with B-NHL (n = 27) and CLL (n = 8) had a median of 3 prior therapies. No dose-limiting toxicities or unexpected adverse events (AEs) occurred. The most common AEs were infusion-related reactions (40%; grade 3/4, 0%); fatigue (37%; grade 3/4, 3%); pyrexia (29%; grade 3/4, 0%); and diarrhoea (26%; grade 3/4, 0%). Common haematological AEs were neutropenia (14%; grade 3/4, 14%) and anaemia (11%; grade 3/4, 6%). The overall response rate for evaluable patients (n = 31) was 45% (13% complete responses, 32% partial responses). Median duration of response and progression-free survival were 9·2 months and 7·7 months, respectively. Ublituximab was well-tolerated and efficacious in a heterogeneous and highly rituximab-pre-treated patient population.

Poldip2 controls vascular smooth muscle cell migration by regulating focal adhesion turnover and force polarization.

Polymerase-δ-interacting protein 2 (Poldip2) interacts with NADPH oxidase 4 (Nox4) and regulates migration; however, the precise underlying mechanisms are unclear. Here, we investigated the role of Poldip2 in focal adhesion turnover, as well as traction force generation and polarization. Poldip2 overexpression (AdPoldip2) in vascular smooth muscle cells (VSMCs) impairs PDGF-induced migration and induces a characteristic phenotype of long cytoplasmic extensions. AdPoldip2 also prevents the decrease in spreading and increased aspect ratio observed in response to PDGF and slightly impairs cell contraction. Moreover, AdPoldip2 blocks focal adhesion dissolution and sustains H2O2 levels in focal adhesions, whereas Poldip2 knockdown (siPoldip2) significantly decreases the number of focal adhesions. RhoA activity is unchanged when focal adhesion dissolution is stimulated in control cells but increases in AdPoldip2-treated cells. Inhibition of RhoA blocks Poldip2-mediated attenuation of focal adhesion dissolution, and overexpression of RhoA or focal adhesion kinase (FAK) reverses the loss of focal adhesions induced by siPoldip2, indicating that RhoA and FAK mediate the effect of Poldip2 on focal adhesions. Nox4 silencing prevents focal adhesion stabilization by AdPoldip2 and induces a phenotype similar to siPoldip2, suggesting a role for Nox4 in Poldip2-induced focal adhesion stability. As a consequence of impaired focal adhesion turnover, PDGF-treated AdPoldip2 cells are unable to reduce and polarize traction forces, a necessary first step in migration. These results implicate Poldip2 in VSMC migration via regulation of focal adhesion turnover and traction force generation in a Nox4/RhoA/FAK-dependent manner.

Mortality rate in patients with diastolic dysfunction and normal systolic function.

BACKGROUND: Diastolic dysfunction (DD) is known to be associated with increased mortality rate in the presence of impaired systolic function. However, few prognostic data exist regarding the effect of DD in patients with normal systolic function. METHODS: We reviewed clinical records and echocardiographic findings of consecutive patients who underwent an outpatient echocardiogram that revealed normal systolic function (ejection fraction, ≥55%) from January 1, 1996, through December 31, 2005. Diastolic function was graded using echocardiographic Doppler variables designated as normal, mild (grade I, ie, impaired relaxation pattern), moderate (grade II, ie, pseudonormal pattern), or severe (grade III, ie, restrictive filling pattern) dysfunction. Propensity analysis was performed to compare outcomes among the groups. RESULTS: A total of 36 261 patients were identified (mean [SD] age, 58.3 [15.4] years; 54.4% female) with a mean (SD) follow-up time of 6.2 (2.3) years. In 65.2% of the cohort, DD was present, with mild DD being the most prevalent type of dysfunction. A total of 5789 deaths occurred during the follow-up period. The unadjusted survival rate was worse according to the presence and degree of DD (P <.001). However, after propensity matching, only moderate and severe DD were associated with an increased mortality risk (hazard ratio, 1.58; 95% confidence interval, 1.20-2.08; and hazard ratio, 1.84; 1.29-2.62, respectively; P <.001 for each). CONCLUSIONS: In this single-center study of patients with normal ejection fraction who presented for outpatient echocardiography, the presence of moderate or severe DD was an independent predictor of mortality. Mild DD, although prevalent, did not affect survival rate.

Adjunctive treatment with ticagrelor, but not clopidogrel, added to tPA enables sustained coronary artery recanalisation with recovery of myocardium perfusion in a canine coronary thrombosis model.

Reperfusion therapy for myocardial infarction is limited by significant re-occlusion rates and less-than-optimal myocardial tissue perfusion. It was the objective of this study to assess and compare the effect of ticagrelor, the first reversibly binding oral P2Y12 receptor antagonist, with that of clopidogrel, in conjunction with thrombolytic therapy, on platelet aggregation, thrombus formation, and myocardial perfusion in a canine model. Thrombus formation was induced by electrolytic injury and blood flow was measured with a Doppler ultrasonic flowmeter. All animals received tissue plasminogen activator (tPA) (1 mg/kg over 20 min); 10 animals received clopidogrel (10 mg/kg IV bolus over 5 min), 10 animals received ticagrelor initiated with a 1-min bolus (75 microg/kg/min), followed by continuous infusion (10 microg/kg/min) for 2 h, and 10 animals received IV saline. Re-occlusion rate and cyclic flow variation decreased with ticagrelor compared to saline groups (p<0.05). Adenosine phosphate (ADP)-induced platelet aggregation decreased with ticagrelor (1.9% +/- 2.67) and clopidogrel (1.11% +/- 2.0) vs. saline (26.3% +/- 23.5, p<0.05) at the end of adjunctive therapy. Bleeding time increased in the clopidogrel compared to the ticagrelor group (p=0.01). Infarct size was reduced with ticagrelor compared to the clopidogrel and saline groups (p<0.05). Blood flow remained significantly below baseline values at 20 min after tPA administration in the saline and clopidogrel groups but not in the ticagrelor group. In conclusion, in a dog coronary thrombosis model, ticagrelor blocks ADP-induced platelet activation and aggregation; prevents platelet-mediated thrombosis; prolongs reperfusion time and reduces re-occlusion and cyclic flow variation; and significantly decreases infarct size and rapidly restores myocardial tissue perfusion.

Critical role for leukocyte hypoxia inducible factor-1alpha expression in post-myocardial infarction left ventricular remodeling.

RATIONALE: Hypoxia inducible factor (HIF)-1alpha is a transcription factor stabilized by hypoxia. It regulates cytokines involved in the inflammatory response after ischemia and affects white blood cell (WBCs) function. The effect of HIF-1alpha on WBC function and inflammation following myocardial infarction (MI) is unknown. OBJECTIVE: We assessed peritoneal and myocardial inflammation in the setting of low WBC HIF-1alpha expression through bone marrow transplantation of hematopoietic stem cells transfected with scramble or HIF-1alpha small interfering (si)RNA. METHODS AND RESULTS: Rosa hematopoietic stem cells (lin(-), cKit(+)) were transfected with a green fluorescent protein (GFP) reporter lentivirus encoding a siRNA to HIF-1alpha or scramble. Irradiated 6- to 8-week-old C57/BL6J mice received 50 000 GFP(+) HIF-1alpha or scramble siRNA-transfected hematopoietic stem cells. Peritonitis or myocardial infarction via left anterior descending coronary artery ligation was induced 6 weeks after bone marrow transplantation. In the peritonitis model, HIF-1alpha siRNA group exhibited a significant decrease in neutrophil and monocyte entry to the peritoneum compared to scramble mice. Similarly neutrophil infiltration into the infarct zone was decreased in the HIF-1alpha siRNA group. No difference of myocardial infarct size was observed between groups. Interestingly, the ejection fraction were similar in both groups at baseline and 3 days post-MI but increased significantly in the HIF-1alpha siRNA group compared to control beginning 7 days after MI. Gene array studies demonstrated that downregulation of WBC HIF-1alpha was associated with decreased WBC CCR1, -2, and -4 expression. Chemotaxis assay results confirmed that decreased monocyte migration induced by downregulation of HIF-1alpha was partially reversed by overexpression of CCR2. CONCLUSIONS: Downregulation of leukocyte HIF-1alpha expression resulted in decreased recruitment of WBC to the sites of inflammation and improvement in cardiac function following MI. Downregulation of HIF-1alpha suppressed WBC cytokine receptors CCR1, -2, and -4, which are necessary for WBC mobilization and recruitment to inflammatory cytokines following MI. The effects of downregulation of leukocyte HIF-1alpha on WBC migration are attributable, at least in part, to the decreased CCR2 expression. These results demonstrate that WBC infiltration into the newly injured myocardium plays a significant role in left ventricular remodeling, but not infarct size.

Exploitation of stem cell homing for gene delivery.

Stem cells have been the focus of numerous investigations to treat diseases as far ranging as diabetes, chronic heart failure and multiple sclerosis over the past decade. The process of stem-cell-based repair of acute injury involves homing and engrafting of the stem cell of interest to the site of injury followed by either differentiation of the stem cell to indigenous end-organ cells or liberation of paracrine factors that lead to preservation and/or optimization of organ function. Recognition of the ability of stem cells to home to sites of acute injury suggests that, if appropriately defined and harnessed, stem cell homing could serve as a means of local drug delivery through the infusion of genetically engineering stem cells that secrete gene products of interest. The authors have recently demonstrated the use of this approach in preclinical studies of acute myocardial function. In addition, the use of engineered cells that home to appropriate niches have been used to correct genetic deficiency states (i.e., severe combined immunodeficiency, diabetes mellitus) in patients with otherwise chronic debilitating diseases. This review focuses on exploiting stem cell homing for gene transfer and on the state of the art and the challenges that face the field.

Trends in epidemiology and management of breast cancer in developing Arab countries: a literature and registry analysis.

BACKGROUND: Registries and research on breast cancer in Arabic and developing countries are limited. METHODS: We searched PubMed, Medline, WHO and IAEA publications, national, regional, hospital tumor registries and abstracts. We reviewed and analyzed available data on epidemiological trends and management of breast cancer in Arab countries, and compared it to current international standards of early detection, surgery and radiation therapy. RESULTS: Breast cancer constitutes 13-35% of all female cancers. Almost half of patients are below 50 and median age is 49-52 years as compared to 63 in industrialized nations. A recent rise of Age-Standardized Incidence Rates (ASR) is noted. Advanced disease remains very common in Egypt, Tunisia, Saudi Arabia, Syria, Palestinians and others. Mastectomy is still performed in more than 80% of women with breast cancer. There are only 84 radiation therapy centers, 256 radiation oncologists and 473 radiation technologists in all Arab countries, as compared with 1875, 3068 and 5155, respectively, in the USA, which has an equivalent population of about 300 million. Population-based screening is rarely practiced. Results from recent campaigns and studies show a positive impact of clinical breast examination leading to more early diagnosis and breast-conserving surgery. CONCLUSIONS: Breast cancer is the most common cancer among women in Arab countries with a young age of around 50 years at presentation. Locally advanced disease is very common and total mastectomy is the most commonly performed surgery. Awareness campaigns and value of clinical breast examination were validated in the Cairo Breast Cancer Screening Trial. More radiation centers and early detection would optimize care and reduce the currently high rate of total mastectomies. Population-based screening in those countries with affluent resources and accessible care should be implemented.

Effects of young age at presentation on survival in breast cancer.

BACKGROUND: Young age remains a controversial issue as a prognostic factor in breast cancer. Debate includes patients from different parts of the world. Almost 50% of patients with breast cancer seen at the American University of Beirut Medical Center (AUBMC) are below age 50. METHODS: We reviewed 1320 patients seen at AUBMC between 1990 and 2001. We divided them in three age groups: Below 35, 35-50, and above 50. Data and survival were analyzed using Chi-square, Cox regression analysis, and Kaplan Meier. RESULTS: Mean age at presentation was 50.8 years. 107 patients were below age 35, 526 between 35-50 and 687 patients above age 50. Disease stages were as follows: stage I: 14.4%, stage II: 59.9%, stage III: 20% and stage IV: 5.7%. Hormone receptors were positive in 71.8% of patients below 35, in 67.6% of patients 35-50 and in 78.3% of patients above 50. Grade of tumor was higher as age at presentation was lower. More young patients received anthracycline-based adjuvant chemotherapy. Of hormone receptor-positive patients, 83.8% of those below age 35 years, 87.76% of those aged 35-50 years, and 91.2% of those aged above 50 years received adjuvant tamoxifen. The mean follow up time was 3.7 +/- 2.9 years. Time to death was the only variable analyzed for survival analysis. Excluding stage IV patients, tumor size, lymph node, tumor grade and negative hormone receptors were inversely proportional to survival. Higher percentage of young patients at presentation developed metastasis (32.4% of patients below 35, as compared to 22.9% of patients 35-50 and 22.8% of patients above 50) and had a worse survival. Young age had a negative impact on survival of patients with positive axillary lymph nodes, and survival of patients with positive hormonal receptors, but not on survival of patients with negative lymph nodes, or patients with negative hormonal receptors. CONCLUSION: Young age at presentation conferred a worse prognosis in spite of a higher than expected positive hormone receptor status, more anthracycline-based adjuvant chemotherapy and equivalent adjuvant tamoxifen hormonal therapy in younger patients. This negative impact on survival was seen in patients with positive lymph nodes and those with positive hormonal receptors.

Effect of environment and research participant characteristics on data quality.

The purpose of this study, a component of a randomized clinical trial, was to assess the influence of the emergency department environment and participant characteristics on the accuracy of self-reported health care utilization. Interviews of 612 seniors aged 65 to 93 were conducted in two emergency departments. The research assistant, upon completion of each interview, rated characteristics of the emergency department and compared participants' self-reports of emergency department use and hospitalization during the previous 4 weeks with data from hospital records: 3.6% overreported and 2.2% underreported visits to the emergency department. Regarding hospitalizations, 2.6% overreported and 1.2% underreported. Discrepancies were associated with male gender, cognitive deficits, and risk status. Inconsistencies were not related to any of the environmental variables. These findings suggest that seniors without cognitive decline report reliable data even in a potentially challenging environment.

Thrombotic thrombocytopenic purpura: 24 years of experience at the American University of Beirut Medical Center.

Thrombotic thrombocytopenic purpura (TTP) is a hematological syndrome defined by the presence of thrombocytopenia and microangiopathic hemolytic anemia without a clinically apparent etiology. Patients may also suffer from fever in addition to neurological and renal impairment. Treatment should be initiated as soon as possible, otherwise this rare disease can be fatal. The main treatment options include therapeutic plasma exchange, fresh frozen plasma infusion, and adjuvant agents such as steroids and antiplatelet drugs. A search of patient records was carried out at the American University of Beirut Medical Center looking for patients who developed TTP over a 24-year period extending from 1980 to 2003. Relevant information was collected and analyzed. A total of 47 records were found. All presented with anemia and thrombocytopenia, 83% had neurological symptoms, 61.7% had fever and 34% had renal impairment. All patients were treated with a multimodality regimen including therapeutic plasma exchange, FFP infusion, steroids, antiplatelet agents, vincristine and others. 38 (81%) cases achieved complete remission. Out of these, 12 (31.6%) relapsed and responded to treatment. Patients who did not receive plasma exchange were more likely to relapse (P = 0.032). A second relapse was observed in 6 cases. The overall mortality rate from TTP over 24 years was 21.3%. TTP remains a fatal disease. A high index of suspicion should, therefore, always be present. Treatment options should be further developed and patients should directly be referred to tertiary care centers.

Cisplatin plus vinorelbine (PVn) as a salvage regimen for refractory breast cancer.

Breast cancer is regarded as a systemic disease even when tumors are completely resected. In patients with advanced breast cancer the overall prognosis is poor, but the disease is not uniformly fatal. Vinorelbine has proved to be effective when given as a single agent in this setting. Since it has a moderate to severe myelotoxic effect, a combination of vinorelbine with cisplatin, which is a weak myelotoxic drug, is ideal for the treatment of patients with advanced disease. In this paper, we report on a patient with advanced breast cancer who attained complete response of 14 months duration to a cisplatin/vinorelbine combination after progression during treatment with paclitaxel and doxorubicin.