Peak WBC Count Research Articles

Markers of infection and inflammation are associated with post-thrombectomy mortality in acute stroke

ObjectiveWe explored the relationship between markers of infection and inflammation and mortality in patients with acute ischemic stroke who underwent thrombectomy. MethodsWe performed retrospective chart review of stroke patients who underwent thrombectomy at two tertiary academic centers between December 2018 and November 2020. Associations between discharge mortality, WBC count, neutrophil percentage, fever, culture data, and antibiotic treatment were analyzed using the Wilcoxon rank sum test, Student’s t-test, and Fisher’s exact test. Independent predictors of mortality were identified with multivariable analysis. Analyses were repeated excluding COVID-positive patients. ResultsOf 248 patients who underwent thrombectomy, 41 (17 %) died prior to discharge. Mortality was associated with admission WBC count (11 [8–14] vs. 9 [7–12], p = 0.0093), admission neutrophil percentage (78 % ± 11 vs. 71 % ± 14, p = 0.0003), peak WBC count (17 [13–22] vs. 12 [9–15], p < 0.0001), fever (71 % vs. 27 %, p < 0.0001), positive culture (44 % vs. 15 %, p < 0.0001), and days treated with antibiotics (3 [1–7] vs. 1 [0–4], p < 0.0001). After controlling for age, admission NIHSS and post-thrombectomy ASPECTS score, mortality was associated with admission WBC count (OR 13, CI 1.32–142, p = 0.027), neutrophil percentage (OR 1.03, CI 1.0–1.07, p = 0.045), peak WBC count (OR 301, CI 24–5008, p < 0.0001), fever (OR 24.2, CI 1.77–332, p < 0.0001), and positive cultures (OR 4.24, CI 1.87–9.62, p = 0.0006). After excluding COVID-positive patients (n = 14), peak WBC count, fever and positive culture remained independent predictors of mortality. ConclusionMarkers of infection and inflammation are associated with discharge mortality after thrombectomy. Further study is warranted to investigate the causal relationship of these markers with clinical outcome.

Complications after discharge with COVID-19 infection and risk factors associated with development of post-COVID pulmonary fibrosis

IntroductionSurvivors of COVID-19 infection may develop post-covid pulmonary fibrosis (PCF) and suffer from long term multi-system complications. The magnitude and risk factors associated with these are unknown. ObjectivesWe investigated the prevalence and risk factors associated with PCF and other complications in patients discharged after COVID-19 infection. MethodsPatients had phone assessment 6 weeks post hospital discharge after COVID-19 infection using a set protocol. Those with significant respiratory symptoms were investigated with a CTPA, Pulmonary Function Tests and echocardiogram. Prevalence of myalgia, fatigue, psychological symptoms and PCF was obtained. Risk factors associated with these were investigated. ResultsA large number of patients had persistent fatigue (45.1%), breathlessness (36.5%), myalgia (20.5%) and psychological symptoms (19.5%). PCF was seen in 9.5% of the patients and was associated with persistent breathlessness at 6 weeks and inpatient ventilation [adjusted OR 5.02(1.76–14.27) and 4.45(1.27–15.58)] respectively. It was more common in men and in patients with peak CRP >171.5 mg/L, peak WBC count ≥12 × 10 9/L, severe inpatient COVID-19 CXR changes and CT changes. Ventilation was also a risk factor for persisting fatigue and myalgia, the latter was also more common in those with severe cytokine storm and severe COVID-19 inpatient CXR changes. ConclusionsAll the patients discharged after COVID-19 should be assessed using a set protocol by a multidisciplinary team. Patients who had severe COVID-19 infection particularly those who were intubated and who have persistent breathlessness are at risk of developing PCF. They should have a CT Chest and have respiratory follow-up.

Safe and Efficient Peripheral Blood Stem Cell Collection in Patients with Sickle Cell Disease Using Plerixafor

Background: Hematopoietic stem cell (HSC) gene therapy is potentially curative for sickle cell disease (SCD) provided that a sufficient quantity of long-term engrafting CD34+ HSCs can be safely collected and infused. In patients with SCD, peripheral blood (PB) mobilization with granulocyte colony stimulating factor is contraindicated, and steady-state bone marrow (BM) harvesting is associated with suboptimal HSC quality and yield. Hence, agents that promote safe and effective peripheral HSC mobilization in SCD are required. Methods: This phase I multicenter study investigated the safety and efficacy of plerixafor mobilization (240 µg/kg) followed by apheresis, processing, and HSC enrichment in 15 adult subjects with SCD (NCT03226691). Hydroxyurea treatment was stopped at least two weeks prior to mobilization and all participants who were not receiving long-term transfusion therapy received prophylactic red blood cell exchange prior to plerixafor administration to achieve a target sickle Hb (HbS) &lt;30%. The primary endpoint was efficient collection of PB HSCs (target 2.0x106 CD34+ cells/kg, minimum 1.5x106) after plerixafor mobilization without serious adverse events (SAEs). Collection products were assessed for total WBC, CD34+, CD3+, and CD19+ composition by flow cytometry. Spearman's correlation test was used to assess the relationship between baseline CD34/µL, total CD34+ cells/kg collected, and total blood volume processed. Findings: Fifteen participants with SCD (HbSS n=13, HbSC n=1, HbSβ+ n=1) who met inclusion criteria were enrolled at St. Jude Research Children's Hospital (n=3) or NIH (n=12) between July 2017 and February 2019. All participants except one successfully met the minimum target CD34+ cells/kg yield with 2 or fewer mobilization and apheresis procedures, with almost half the participants (n=7) achieving ≥5.0x106 CD34+ cells/kg. The total WBC count increased by an average of 3.2-fold over baseline (range 1.7-5.0) to an average peak WBC count of 26.5x103/µL (range 14.1-47.4), with counts returning to baseline within 1-2 days. Median total WBC, CD34+, CD19+, and CD3+ cells/kg in the final apheresis product after one (n=12) or two (n=3) collection procedures were 0.9 x109 WBC/kg (range 0.4-1.7), 4.5x106 CD34+ cells/kg (range 0.9-12.0), 3.4x108 CD19+ cells/kg (range 0.5-4.9), and 3.6x108 CD3+ cells/kg (range 1.7-7.3), respectively. There was a strong positive correlation between baseline CD34/µL and total CD34+ cells/kg (rs = 0.7776, 95% CI 0.446-0.9215, p = 0.001). Participants with the lowest pre-apheresis CD34 cell count generally underwent higher blood volume processing (rs = - 0.1443, 95% CI -0.6075 to 0.3921, p = 0.59) in an effort to achieve target yields. However, higher blood volume processing did not translate to higher total CD34+ cells/kg collection yields (rs = - 0.2104, 95% CI -0.6488 to 0.3328, p = 0.43). A median of 97% of positively selected CD34+ cells were CD34high (range 73.6-99.4%) compared to 1.3% CD34low (range 0.09-24.4%) phenotype suggesting enrichment for long-term engrafting HSCs. Seven grade III AEs (two non-pain and five pain related) and one grade IV AE (non-pain - hemolysis) occurred and each resolved with symptomatic treatment. Plerixafor mobilization was overall safe and in most cases generated CD34+ cell yields that were sufficient for both genetic modification and back-up allogeneic transplantation (median cell yield 4.2x106 CD34+ cells/kg). Interpretation: This first multi-institutional phase I study suggests the efficiency and safety of plerixafor mobilization and apheresis collection in 15 adult subjects with SCD. The primary endpoint to obtain a target of 2.0x106 CD34+ cells/kg from the PB was exceeded without SAEs. Importantly, immunophenotyping data suggest that for individuals with SCD, the plerixafor mobilized cell product is more enriched for long-term engrafting HSCs compared to CD34+ cells isolated from BM. Given the risks of general anesthesia and the low quality and yield of CD34+ cells harvested from the BM of individuals with SCD, plerixafor mobilization represents a safe and potentially superior alternative for HSC isolation. Disclosures Hankins: Novartis: Research Funding; ASPHO: Honoraria; NHLBI: Research Funding; LYNKS Foundation: Research Funding; NHLBI: Honoraria; National Committee for Quality Assurance: Consultancy; Global Blood Therapeutics: Research Funding; Bluebird Bio: Consultancy. Sharma:Vertex Pharmaceuticals: Other: Study PI; Doris Duke Foundation: Research Funding. Weiss:GlaxoSmithKline: Consultancy; Rubius INC: Consultancy; Esperian: Consultancy; Beam Therapeutics: Consultancy; Cellarity INC: Consultancy.

The Significance of Leukocytosis in Malignancies: A Novel Paradigm Between Leukocytosis, G-CSF, Myeloid-Derived Suppressor Cells and Prognosis

In clinical practice, leukocytosis is often overlooked after infectious and hematologic disease are ruled out, particularly in patients with solid tumors. This is unfortunate, as the mechanisms that mediate paraneoplastic leukocytosis may play a significant role in the underlying pathophysiology of cancer progression and prognosis. The relatively new discovery of neutrophilic and monocytic myeloid-derived suppressor cells (MDSCs) and their role in mediating tumor metastasis has particularly shed light into this process [Annu Rev Med, 66:97-110 (2015)].Here, we present the case of a 58-year old gentleman with non-small cell lung cancer complicated by brain metastasis, status post resection who presented with sepsis and acute kidney injury (AKI) requiring ICU care for worsening AKI, hypoxic respiratory failure and leukocytosis. His peak WBC count, absolute neutrophilia and monocytosis were: 178.1, 172.7 and 4.2k/µL, respectively. His peripheral blood smear revealed mature neutrophils with left-shift and no blast forms. The underlying etiology of his leukocytosis was initially attributed to steroids administration and infection (Figure 1). His leukocytosis progressed, however, despite improvement in his sepsis and tapering of his steroids. Thus, we suspected either an evolving hematologic neoplasm or exogenous secretion of G-CSF by his tumor. Nonetheless, given his worsening clinical status, we initiated empiric hydroxyurea and leukapheresis. His FISH and PCR for BCR-ABL were negative in addition to the absence of leukemia-associated mutations and gene fusions and a normal phenotype by flow cytometry. However, we detected the highest documented level of G-CSF secreted by any tumor in the literature at 41,108.6pg/mL (normal <39.1pg/mL), confirming that the etiology of his marked leukocytosis was indeed exogenous secretion of G-CSF by his cancer.On evaluation of this patient's clinical history, his malignancy and white count were stable until day 388 of his diagnosis when he developed new onset leukocytosis and neutrophilia associated with disease progression and metastasis. Furthermore, he died within 23 days of developing peak leukocytosis, neutrophilia and monocytosis and the discovery of his profoundly elevated G-CSF level. The association between the onset of his leukocytosis with the discovery of his disease progression and metastasis suggest that G-CSF secretion and leukocytosis may have been linked to his poor prognosis.We performed an extensive literature review and found that neutrophilic and monocytic MDSCs may provide a potential explanation for this phenomenon. We believe that leukocytosis in the setting of solid neoplasms may be driven by increased G-CSF secretion by tumors or tumor microenvironments. Additionally, G-CSF secretion fosters the expansion of neutrophilic and monocytic MDSCs, which play a significant role in tumor progression and metastasis and may contribute to poor prognosis [PNAS 106(16): 6742-7 (2009), PNAS 107(50): 21248-55 (2010)]. Consequently, we believe that the significance of leukocytosis in patients with solid tumors should not be overlooked and that there may exist a novel, untapped paradigm between paraneoplastic G-CSF secretion, leukocytosis, neutrophilic and monocytic MDSCs and prognosis. DisclosuresMauro:Novartis: Consultancy, Research Funding; Pfizer: Consultancy; Takeda: Consultancy; Bristol-Myers Squibb: Consultancy.

Abstract 13514: Serial Quantitative Assessment of Thrombogenicity in LVAD Recipients: A Case for Personalized Antithrombotic Therapy

Introduction: Bleeding and thrombotic complication affect between 25-40% of left ventricular assist device (LVAD) recipients. Measures of thrombogenicity such as maximum platelet-fibrin clot strength (MAKH), endogenous thrombin potential (ETP) and platelet reactivity may indicate thrombotic and bleeding risk in patients on LVAD support and may vary after LVAD implantation. Methods: We prospectively assessed thrombogenicity using the novel point-of-care (TEG-6S) with PlateletMapping and the calibrated automated thrombogram (CAT) in 31 patients before and serially after LVAD implantation (HeartWare HVAD, n = 17; Heartmate II, n = 14). All LVAD patients were on aspirin 325mg/daily and warfarin (INR 2.0 to 2.5) therapy. Standard hematologic and hemolysis laboratories were compared. Results: Markers of thrombogenicity were highly variable post-LVAD. Overall, in the acute phase, MAKH, and maximum ADP-, and arachidonic acid (AA)-induced clot strength increased (p &lt; 0.05, Table) and returned to near baseline by ≥3 months. Despite target INR values at ≥ 3 months (2.0±0.3) and antiplatelet therapy, the R-time (7.1±1.8min) remained within the normal range. Hypercoagulable patients (MAKH≥69mm) had higher endogenous thrombin potential, peak thrombin generation, WBC count, and LDH (p≤0.05). Conclusions: A state of heightened thrombogenicity indicated by high MAKH and high platelet reactivity are present in the acute phase after LVAD implantation and in selected patient during the chronic phase despite therapy with warfarin/aspirin. These findings suggest that intensification of antithrombotic therapy in a personalized fashion based on sensitive thrombogenicity testing, rather than INR should be investigated to mitigate adverse events.

Homoharringtonine in newly diagnosed acute promyelocytic leukemia treatment: a prospective, randomized controlled trial

目的比较高三尖杉酯碱（HHT）±柔红霉素（DNR）联合全反式维甲酸（ATRA）和以DNR为基础的方案治疗初诊中低危急性早幼粒细胞白血病（APL）患者的疗效及耐受性。方法采用前瞻性随机对照研究方法，将96例初诊中低危APL患者随机分配至HHT组、DNR组和HHT+DNR组，比较三组患者的完全缓解（CR）率、总生存（OS）及无事件生存（EFS）情况。结果HHT组31例，DNR组33例，HHT+DNR组32例，三组患者一般资料具有可比性。三组治疗方案诱导治疗CR率均为100%，无早期死亡患者。三组诱导治疗期间WBC达峰值的中位时间分别为9(1~27）、7(1~27）和4(1~23）d，HHT+DNR组短于HHT组（P=0.008）和DNR组（P=0.240）。三组治疗方案在维甲酸综合征的发生率，达CR的中位时间，WBC峰值及血小板、红细胞、血浆输注量方面的差异均无统计学意义（P值均>0.05）。所有患者均在巩固治疗阶段达分子生物学完全缓解（CMR），三组患者达CMR的时间差异无统计学意义（P>0.05）。HHT组、DNR组及HHT+DNR组的3年OS率分别为95.0%、100.0%、91.0%；3年EFS率分别为93.0%、90.0%、85.0%，差异均无统计学意义（P值分别为0.595和0.382）。三组患者不良事件发生率比较差异无统计学意义（P>0.05）。结论以HHT联合ATRA为基础的诱导、巩固治疗方案可以有效治疗初诊APL，疗效与以蒽环类药物为基础的方案类似，可以作为APL的治疗选择之一。

Prone Positioning in Cardiac Surgery: For Many, But Not for Everyone

Prone positioning is a therapeutic maneuver to improve arterial oxygenation in patients with acute lung injury that is not implemented in most centers performing adult cardiac surgery. The aim of this study was to review our experience with prone positioning to assess the effects of this maneuver in patients with postoperative acute respiratory failure. From 2010-2014, 127 adult patients with postoperative acute respiratory failure were treated with prone positioning in addition to specific therapy. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors associated with in-hospital mortality. In-hospital mortality was 22.8% (n = 29). No significant differences were observed in preoperative risk factors between patients who survived (S) and those who died (D), except for age (62.7 ± 11.2 vs 70.2 ± 11.3; P = 0.007-at multivariate analysis P = 0.03, odds ratio [OR] = 1.1/year). Preproning values of PaO2/FiO2 were significantly different between groups (D vs S: 115 ± 46 vs 150 ± 56; P = 0.006), but only preproning FiO2 remained highly significant at multivariate analysis (D vs S: 0.82 ± 0.18 vs 0.67 ± 0.16; P = 0.001, OR = 1.07; with FiO2 > 0.75 vs < 75, OR = 19.6). D showed a higher improvement of PaO2/FiO2 immediately after prone positioning (207 ± 100 vs 219 ± 90, P = 0.56; within-group analysis between preproning and 1 hour after proning: S-P = 0.49, D-P = 0.019; at 12 hours: 286 ± 123 vs 240 ± 120, P = 0.06; within-group analysis between 1 hour and 12 hours after proning: S-P = 0.15; D-P = 0.17; between groups-P = 0.05). D had higher peak WBC count (26 ± 9.8 vs 17.7 ± 5.9×103/mL; P = 0.0001) and a higher rate of low output syndrome (15 vs 9 patients-51.7% vs 9.2%; P = 0.0001). At multivariate analysis, white blood cell count: P = 0.005, OR = 1.11/103 white blood cell; low output syndrome: P = 0.0002, OR = 20.5. In conclusion, our results show that prone positioning, if performed early, is a safe and effective adjunct measure for patients with postoperative acute hypoxemic respiratory failure of noncardiogenic origin.

Time to Appropriate Antibiotic Therapy Is an Independent Determinant of Postinfection ICU and Hospital Lengths of Stay in Patients With Sepsis*

To assess the timing of appropriate antibiotic therapy as a determinant of postinfection hospital and ICU lengths of stay in patients with sepsis. Single-center retrospective cohort study (January 2008-December 2012). One thousand two hundred fifty-bed academic hospital. One thousand fifty-eight consecutive blood culture positive patients. We retrospectively identified adult patients with severe sepsis or septic shock. Timing of appropriate antibiotic therapy was determined from blood culture collection time to the administration of the first dose of antibiotic therapy with documented in vitro susceptibility against the identified pathogen. We constructed generalized linear models to examine the determinants of attributable lengths of stay. The median (interquartile range) time from blood culture collection to the administration of appropriate antibiotic therapy was 6.7 hours (0.0-23.3 hr). Linear regression analysis adjusting for severity of illness and comorbid conditions identified time to appropriate antibiotic therapy to be an independent determinant of postinfection ICU length of stay (0.095-d increase per hr of time to deliver appropriate antibiotic therapy; 95% CI, 0.057-0.132 d; p < 0.001) and postinfection hospital length of stay (0.134-d increase per hr of time to deliver appropriate antibiotic therapy; 95% CI, 0.074-0.194 d; p < 0.001). Other independent determinants associated with increasing ICU length of stay and hospital length of stay were mechanical ventilation (both ICU and hospital lengths of stay) and incremental peak WBC counts (hospital length of stay only). Incremental changes in severity of illness assessed by Acute Physiology and Chronic Health Evaluation II scores and comorbidity burden assessed by the Charlson comorbidity score were independently associated with decreases in ICU length of stay and hospital length of stay. We identified time to appropriate antibiotic therapy in patients with sepsis to be an independent determinant of postinfection ICU and hospital lengths of stay. Clinicians should implement local strategies aimed at timely delivery of appropriate antibiotic therapy to improve outcomes and reduce length of stay.

Hematopoietic Progenitor Cell Mobilization In Response To G-CSF Is More Robust In Healthy African American Compared To Caucasian Donors

▪Hematopoietic progenitor cells (HPCs) collected by apheresis of G-CSF-stimulated donors have surpassed bone marrow as the predominant graft source for hematopoietic stem cell transplantation in adults. Among healthy allogeneic donors, demographic characteristics (age, sex, and BMI) and baseline hematologic parameters have been shown to affect HPC mobilization, leading to significant variability in peak levels of CD34 cell egress into the blood and in quantity of CD34 cells harvested by apheresis. Racial differences in G-CSF-mediated HPC mobilization are less well characterized. Benign physiologic neutropenia is common among healthy African Americans (AAs), and may be due to decreased stem cell reserve, fewer G-CSF receptors, or Duffy (null) blood group antigen-mediated decrease in leukocyte trafficking into the circulation. However, preliminary studies have shown relatively robust CD34+ cell mobilization among non-Caucasians given G-CSF (Vasu et al., Blood 2006).We retrospectively analyzed 1,096 consecutive healthy allogeneic related and unrelated first-time donors who self-characterized their race as AA or Caucasian. They underwent G-CSF (filgrastim, Neupogen, Amgen) stimulated HPC collection by leukapheresis from April 1999 to May 2013. G-CSF dose ranged from 10-16 mcg/kg, given daily for 5 days. An unstimulated leukapheresis procedure for lymphocyte collection was performed in the 7 days preceding G-CSF in 336 subjects. Apheresis procedures were performed on the CS-3000 Plus or COBE Spectra device. Baseline lab data included CBC, serologic blood group antigen typing, and Hb electrophoresis in AA donors. CD34+ cell counts were performed on peripheral blood immediately pre-apheresis (2 hours after the 5th dose of G-CSF) and on the apheresis product. Values are given as mean ± SD.All AA (n=215) and Caucasian donors (n=881) with complete data sets were included. Sex ratio was similar among the groups (45 vs 52% male; p=0.09). AAs were younger (39 vs 43 yrs, p=0.001) and had greater weight (86 vs 81 kg, p=0.001) and BMI (30 vs 27; p<0.0001) than Caucasians. G-CSF dose/kg was similar in the 2 groups, but total daily dose of G-CSF was greater in AAs than Caucasians (920 vs 850 mcg, p<0.0001). After adjusting for age, sex, height, weight, and total daily G-CSF dose, peak CD34+ cell mobilization immediately pre-apheresis was higher among AAs than Caucasians (123 ± 87 vs 75 ± 47 cells/uL; p<0.0001) (Figure). When laboratory parameters such as baseline WBC, MNC, and platelet counts were included in the stepwise regression model, AA race remained a significant predictor of higher peak CD34 cell counts. At higher G-CSF doses (16 mcg/kg/d), the difference in mobilization responses between the 2 groups was less apparent (peak CD34 counts 123 vs 93 cells/uL, AA (n=33) vs Caucasian (n=73), p=0.07) than at lower doses (10 mcg/kg/d), where peak CD34 counts were 123 vs 74 cells/uL, AA (n=182) vs Caucasian (n=808), p<0.0001. AAs had lower baseline ANC (3.4 vs 4.0 x 103 cells/uL, p<0.001) than Caucasians, but demonstrated significantly higher peak WBC and MNC counts after G-CSF. In AA donors with known HbS status, presence of sickle cell trait had no effect on CD34 mobilization (peak CD34 counts 123 ± 91 vs 107 ± 72 cells/uL, HbAS (n=41) vs HbAA (n=84), p=0.34). Similarly, in AA donors with known Duffy phenotype, Duffy expression did not affect CD34 mobilization (peak CD34 counts 114 ± 81 vs 134 ± 85 cells/uL, Fya-b- (n=49) vs Fya+ &/Fyb+ (n=20), p=0.4). Lymph-apheresis prior to starting G-CSF was associated with significantly improved CD34+ cell mobilization; however the effect did not differ by race. CD34 apheresis yield was also greater in AAs than Caucasians (51 ± 35 vs 32 ± 21 x 106 cells per liter processed, p <0.0001), consistent with higher pre-apheresis counts.African Americans demonstrated significantly more robust CD34 mobilization responses to G-CSF than Caucasians. The effect was independent of age, BMI, HbS and other variables, and occurred despite physiologically lower neutrophil counts among AAs. A ceiling effect in response to increased doses of G-CSF (>10 mcg/kg) was seen in AAs but not in Caucasians, suggesting that dose titration based on race might be used to optimize HPC yields. Further evaluation of race-associated genetic polymorphisms in relation to G-CSF pharmacokinetics may help improve G-CSF dosing strategies. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Pegfilgrastim in dose-dense, sequential adjuvant chemotherapy for patients with breast cancer (BC)

10708 Background: Large randomized trials in the US and Europe have recently shown, that increased dose density of adjuvant chemotherapy leads to a relevant and significant prolongation of disease-free and overall survival in breast cancer. Dose density refers to the administration of drugs with a shortened intertreatment interval. G-CSF support is an essential requirement for increasing dose intensity. We explored the feasibility of pegylated filgrastim (Neulasta) in this setting. Methods: Patients (pts) up to the age of 60 with a confirmed histology of breast cancer and lymph node involvement were recruited into the study. A dose-dense chemotherapy, consisting of 3 x 4 sequential single drug cycles of epirubicin 90 mg/m2, paclitaxel 175 mg/m2, and cyclophosphamide 600 mg/m2 was planned on a two-weekly schedule (similar to Citron et al., J Clin Oncol, 21 (2003): 1431–1439). Pegfilgrastim was to be administered on day 2 of each cycle, 24 h after chemotherapy application. Results: Seventeen pts with a mean age of 49 years were enrolled into this feasibility study. 76% of pts had pN2–3 stage, 65% G2 and 35% G3 tumors, 71%/47% a positive estrogen/progesterone receptor status, respectively. All but one pt were HER2-negative. The full number of 12 cytotoxic courses could be administered in all but one patient due to an anaphylactic reaction against paclitaxel. A total of nine weeks of treatment delay was recorded in 6 of the remaining 16 patients (38%), resulting in an overall mean relative dose intensity of 95.9% (range 80– 100%). Pegfilgrastim was given during 85% of the 198 courses. Febrile or grade 4 neutropenia were not recorded, grade 3 neutropenia in one cycle (6%) without G-CSF support. Antibiotic treatment was necessary in only 18% of pts. Median peak WBC count during the complete treatment course was 28,150/μl, no values above 100,000/μl were recorded. Bone pain was reported in 4 patients (24%) and occurred in a total of 6 cycles (3%). Conclusions: Pegfilgrastim can be used safely and seems to achieve the required supportive efficiency in a dose dense sequential chemotherapy schedule for locally advanced BC. [Table: see text]

Low-dose warfarin does not decrease the rate of thrombosis in patients with cervix and vulvo-vaginal cancer treated with chemotherapy, radiation, and erythropoeitin

Objectives. We had previously reported an association between the use of recombinant human erythropoietin (rHuEPO) and thrombosis in patients with cervix and vulvo-vaginal cancer treated with chemotherapy and radiation. We hypothesized that low-dose warfarin would be effective prevention for thromboembolic events in this setting. Methods. A retrospective analysis of patients with cervical or vulvo-vaginal carcinoma receiving chemoradiation and rHuEpo was performed. Thirty-two patients received rHuEpo alone, and 24 received warfarin (1–2 mg) and rHuEpo. The primary endpoint was objectively proven symptomatic venous thrombosis. Results. There was no difference in the baseline characteristics (e.g. age, stage, body mass index, mean and peak hemoglobin, WBC and platelet counts, and number of transfusions) between these two groups. The rate of thrombosis also was not statistically different ( P = 0.62). Nine of 24 patients had a symptomatic deep vein thrombosis (DVT) while receiving warfarin compared to 10 of 32 patients not on warfarin. There was no difference between the two groups in the percentage of patients with upper extremity DVT ( P = 0.83) or lower extremity DVT ( P = 0.64). Conclusion. Daily low-dose warfarin did not alter the incidence of symptomatic DVT in patients with cervical or vulvo-vaginal cancer who received rHuEpo in conjunction with chemoradiation.

Incidence of symptomatic venous thrombosis in cervical and vulvo-vaginal carcinoma treated with concurrent chemoradiation, erythropoietin, and coumadin

8101 Background: We had previously reported an increase in the incidence of symptomatic deep vein thrombosis (DVT) in 144 cervical and vulvo-vaginal cancer patients receiving recombinant human erythropoietin (rHuEpo) compared to patients not receiving rHuEpo in conjunction with chemoradiation therapy (Cancer 2003; 98: 1514-20). From April 2002, we instituted a policy of prophylactic low dose coumadin in an attempt to prevent DVT in this cohort receiving rHuEpo. Methods: A retrospective analysis of 56 consecutive patients with cervical or vulvo-vaginal carcinoma (FIGO Stage IB-IVA) who received chemoradiation and rHuEpo from 2001 to 2003 were performed. Subjects were divided into two groups: 32 subjects received rHuEpo alone, 24 subjects received daily coumadin (1–2 mg) in addition to rHuEpo. Primary endpoint was symptomatic DVT proven by duplex ultrasound. Results: There was no difference in baseline characteristics (e.g. age, stage, body mass index, mean and peak hemoglobin, WBC and platelet counts recorded at the time of peak hemoglobin, and number of transfusions) between these two cohorts (p ≥ 0.06, Wilcoxon rank sum test). 9 out of 24 patients (37.5%) had a symptomatic DVT while receiving coumadin compared to 10 out of 32 patients (31.3%) not on any anticoagulation. The incidence of thrombosis was not different between the two groups studied (p=0.62, Chi-square test; OR=1.32, 95% CI=(0.43,4.02)). Out of the 9 patients who had a DVT while receiving coumadin, 7 developed upper extremity (UE) DVT while 3 had lower extremity (LE) DVT (1 patient had both UE and LE thromboses). For the 10 patients who were not on coumadin and developed thromboses, 9 were UE DVT and 2 were LE DVT (1 patient had both UE and LE DVT). There was no difference between the two groups in the percentage of patients with UE DVT (p=0.83, Chi-square test; OR=1.14, 95% CI=(0.35,3.74)) or LE DVT (p=0.64, Fisher's test; OR=2.2, 95% CI=(0.33,14.79)). Conclusions: Daily low dose coumadin did not alter the incidence of symptomatic DVT in patients with cervical or vulvo-vaginal cancer who received rHuEpo in conjunction with chemoradiation therapy. No significant financial relationships to disclose.

Association Between Serum C-Reactive Protein Elevation and Left Ventricular Thrombus Formation After First Anterior Myocardial Infarction

Most left ventricular (LV) thrombi that occur after acute myocardial infarction (AMI) are formed within 2 weeks, when inflammatory cells have infiltrated into the necrotic myocardium. Inflammatory changes on the endocardial surface may induce platelet deposition and fibrin net formation through interaction with proinflammatory cytokines. We sought to determine the significance of the inflammatory response reflected by serum C-reactive protein (CRP) elevation in LV thrombus formation after AMI. We examined 160 patients with first anterior AMI. Peak serum creatine kinase (CK) and CRP levels were determined by serial measurements. Echocardiography was performed 10 to 14 days after the onset. We assessed the association between the elevation of serum CRP levels and LV thrombus formation after AMI. LV thrombus was observed in 13 patients (8%). There was no difference in age, sex, coronary risk factors, preinfarction angina, use of revascularization therapy and anticoagulant therapy, platelet count, and fibrinogen level on hospital admission between the two groups. The mean (+/- SD) peak serum CRP level was markedly increased in patients with LV thrombus compared to those without (18.0 +/- 12.6 vs 9.4 +/- 8.1 mg/dL; p = 0.001), despite their having similar peak CK levels. Multivariate analysis showed that a peak CRP level of > or =20 mg/dL was an independent predictor of thrombus formation (relative risk, 4.82; p = 0.037) among variables including older age (> or =60 years old), peak CK level (> or =3,000 IU/L), and peak WBC count (> or =12,000 cells/ microL). A greater elevation of serum CRP level was associated with a higher incidence of LV thrombus after AMI, suggesting an important role of the inflammatory response in mural thrombus formation.

Short-term prognostic value of CRP in the patients with acute coronary syndrome

Background and Objectives:Acute coronary syndrome occurs most commonly in the setting of atherosclerotic coronary artery disease, but there is little information concerning the mechanism responsible for the transition from stable to unstable coronary atherosclerotic plaque. Hypothetically, several microorganism (Chlamydia pneumonia, Cytomegalovirus and Helicobacter pylori) and their inflammatory reaction have been suggested as a causative motive in progression of acute coronary syndrome. Although it is unclear whether the serum level of CRP as an inflammatory parameter is concerned with previous inflammatory change or myocardial necrosis, CRP appears to be predictive of higher risk for cardiac event in the patients with acute coronary syndrome. Our objective was to evaluate whether the inflammatory parameters (CRP, ESR and WBC count) are useful in predicting the short-term cardiac risk within 30 days. Materials and Method:One hundred and ten patients with acute coronary syndrome were enrolled from April 1998 through August 1998. Blood samples were collected at 1st hour, 24th hour, 48th hour and 7th day and tested for CRP, ESR, WBC count and CK-MB level. Values of 323 normal were used as control. All patients were followed up for 30 days and assessed for the presence of cardiac complications. Results:Peak CRP value of the patients with acute myocardial infarction (3.4±3.85 mg/dL, n= 62) was higher than that of the patients with unstable angina (0.7±0.93 mg/dL, n=48, p 2 mg/dL, n=30), the cardiac complication rate was higher than the low-CRP group (≤2 mg/dL, n=80)(43.3% vs 2.5%, p<0.05). Peak CRP value was correlated with age (r=0.191, p=0.045), pulse rate (r=0.186, p=0.008), left ventricular ejection fraction (r=-0.384, p<0. 001), peak ESR (r=0.383, p<0.001) and peak WBC count (r=0.307, p=0.001), but not with peak CK-MB level. Conclusion:Elevated CRP level in patients with acute coronary syndrome seems to be a valuable 논문접수일:1999년 8월 16일 심사완료일:2000년 12월 19일 교신저자:채성철, 700-721 대구광역시 중구 삼덕동 2가 50번지 경북대학교병원 순환기내과 전화:(053) 420-5527·전송:(053) 426-2046 E-mail:scchae@knu.ac.kr

The Clinical Host Response to Microbial Infection in Medical Patients With Fever

Predictors among demographic, clinical, and laboratory variables for a microbial (nonviral/nonchlamydial) infection in hospitalized medical patients with new onset of fever (temperature > or =38.0 degrees C axillary or > or =38.3 degrees C rectal) were analyzed and compared with the criteria for the systemic inflammatory response syndrome (SIRS), including an abnormal body temperature and WBC count, tachypnea and tachycardia, and sepsis, defined as SIRS and the presence of a clinical infection. A prospective cohort study. Department of internal medicine at a university hospital. In 300 hospitalized medical patients with new onset of fever, demographic, clinical, and laboratory variables were obtained during the first 2 days after inclusion, and peak and nadir values, when appropriate, were taken. Microbiologic results for 7 days were collected. Clinical information was used to decide on the presence of a clinical infection. One hundred thirty-three of 300 patients (44%) had a microbial infection: 26% suffered from local microbial infection only, 9% from bacteremia only, and 9% had bloodstream plus local microbial infections. Patients with a microbial infection had a higher World Health Organization performance score at home (p<0.05), higher peak body temperature (p<0.001), higher nadir and peak WBC counts (p<0.05), lower nadir platelet count (p<0.01), higher peak alanine and aspartate aminotransferases (p<0.01), and lower nadir albumin (p<0.001) levels in blood during the first 2 days after inclusion than those without infection. Using multivariate techniques, predictors for microbial infection or bacteremia alone, independent of age, sex, underlying disease, and clinical infection, were peak temperature, peak WBC count, and nadir platelet count and albumin level. In contrast, conventional SIRS/sepsis definitions and criteria predicted microbial infection less well, mainly because tachypnea and tachycardia were of no predictive value. In febrile medical patients, microbial infection can be predicted with use of easily obtained clinical and laboratory variables, including peak temperature, peak WBC count, and nadir platelet count and albumin level within the first 2 days. The new model predicted microbial infection better than conventional SIRS/sepsis criteria. This may help to improve the clinical recognition of the systemic host response to microbial infection and to refine SIRS/sepsis definitions.

Role of granulocyte colony stimulating factor (G‐CSF) in reversing neutropenia in renal allograft recipients

Neutropenia in solid organ transplant recipients may be caused by immunosuppressive therapy, antimicrobial therapy, as well as bacterial and viral infections. Filgrastim, a human granulocyte colony stimulating factor (G‐CSF) is used for the reversal of neutropenia. Although its influence is principally restricted to neutrophil progenitors, the safety of G‐CSF in terms of percipitating or aggravating allograft rejection and its efficacy in reversing neutropenia in kidney and combined kidney and pancreas transplant patients has not been studied or reported. In this study we retrospectively analyzed the use of G‐CSF between March 1992 and May 1994 at the University of Cincinnati Medical Center, in patients who received either a kidney or a combined kidney and pancreas transplant. A total of 25 patients developed 35 episodes of neutropenia and received an average of 2.9 doses of G‐CSF per episode. The mean WBC nadir was 2.6×103/cu mm with an average peak WBC count of 15.5×103/cu mm following treatment (p=&lt;0.00001). The average number of days to peak WBC after initiation of treatment was 4.6 days. The mean pre‐treatment serum creatinine level was 2.3 mg/dl and the peak serum creatinine in the week following tratment remained the same. We conclude that G‐CSF is an effective treatment in reversing neutropenia in renal transplant recipients and does not precipitate or aggravate allograft rejection.

Preventive Antibiotic Usage in Traumatic Thoracic Injuries Requiring Closed Tube Thoracostomy

To evaluate the safety and effectiveness of antibiotics in reducing the infectious complications following closed tube thoracostomy for isolated chest trauma. Double-blind, randomized clinical trial. Medical school affiliated large urban teaching hospital and trauma center. One hundred nineteen of 159 patients over 18 years old presenting to the emergency department requiring closed tube thoracostomy for isolated chest injuries (113 penetrating, 6 blunt). Patients received either placebo or 1 g cefonicid daily intravenously started at chest tube insertion and stopped within 24 h of removal. The development of wound infections, pneumonia (CDC criteria), or empyema; the incidence of adverse events; length of hospitalization. One nonspecific infection was seen in the cefonicid group (1.6 percent) and six respiratory tract infections (10.7 percent) in the placebo group (three empyema, one empyema with pneumonia, two pneumonia) (p = 0.0505; p = 0.0094 [excluding nonspecific infection]). No significant differences with antibiotic use were seen in the duration of chest tube use (p = 0.766), peak WBC counts (p = 0.108), lower peak temperatures (p = 0.063), or length of hospitalization (p = 0.165). Patients who developed infectious complications averaged approximately 8 days longer hospitalization than those without (p < 0.0001). This study showed that patients receiving antibiotics had a significantly reduced rate of infection than did patients administered placebo. No significant adverse events were seen in either group.