Keynote: “Re-engineering acute care”

Introduction:Admission white blood cell (WBC) count and thrombosis in myocardial infarction (TIMI) risk score have been associated with adverse outcomes after acute myocardial infarction (AMI). This study investigated the joint effect of WBC count and TIMI risk score on predicting in-hospital outcomes in patients with AMI.Materials and Methods:WBC count and TIMI risk score were measured at the time of hospital admission in 70 patients with AMI. Echocardiogram was done on prior to discharge by a cardiologist and ejection fraction (EF) was determined according to the Simpson formula. Patients were stratified into tertiles (low and high) based on WBC count and TIMI risk score.Results:Patients with a high WBC count had a 5.0-fold increase in-hospital congestive heart failure and 2.2 increases in mortality compared with those with a low WBC count. Patients with a high TIMI risk score had a 10-fold increase in congestive heart failure presentation and mortality compared with those with a low TIMI risk score. When a combination of different strata for each variable was analyzed, a stepwise increase in mortality was seen. There were a few number of patients with a high WBC count and low TIMI risk score or with a low WBC count and high TIMI risk score. These patients had an intermediate risk, whereas those with a high WBC count and TIMI risk score had the highest risk.Conclusion:These findings suggested that a simple combination of WBC count and TIMI risk score might provide further information for predicting outcomes in patients with AMI.

A positive relation between the metabolic syndrome (MetS) and inflammatory activity has been reported. The purpose of this investigation was to study the relationships between 1) white blood cell (WBC) count and MetS, 2) WBC count and the individual components of MetS and 3) WBC count and insulin sensitivity in 75-year-old women and men from the general population. The study included 200 women and 196 men comprising 64% of the 75-year old people from the city of Västerås in Sweden. MetS was defined according to the National Cholesterol Education Program (NCEP). WBC count (10(9)/L; median and interquartile range) was 5.7 (4.9-6.8) for women and 6.3 (5.4-7.2) for men, P < .001 for gender difference. For women with and without MetS, WBC count was 6.3 (5.3-7.3) and 5.4(4.7-6.3), respectively. For men the corresponding figures were 6.7 (5.9-7.6) and 6.1 (5.4-7.1).The difference in WBC count between individuals with and without MetS was significant (P < .001 for women; P = .014 for men). All individual components of MetS (with exception of blood pressure) were more strongly associated with WBC count for women than for men. Insulin sensitivity, measured as HOMA-IR (HOmeostasis Model Assessment-Insulin Resistance) index, was significantly associated with WBC count in women but not in men. In this elderly population, individuals with MetS had a higher WBC count than those without. Women had a lower WBC count and stronger relationship between WBC count and insulin sensitivity than did men.

Weight Increase during Induction Therapy Predicts Intensive Care Unit (ICU) Transfer in Patients (Pts) with Acute Promyelocytic Leukemia (APL)

A positive association between white blood cell count and carotid atherosclerosis has been reported. Our previous study also found an inverse association between height and carotid atherosclerosis in overweight but not non-overweight men. However, no studies have reported on the association between high white blood cell (WBC) count and height accounting for body mass index (BMI) status. We conducted a hospital-based general population cross-sectional study of 3016 Japanese men aged 30-59years undergoing general health check-ups between April 2013 and March 2014. High WBC count was defined as the highest tertiles of WBC count among total subjects. Independent of classical cardiovascular risk factors, height was found to be inversely associated with high WBC count, especially for subjects with a BMI≥23kg/m2. The classical cardiovascular risk factors adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of high WBC count for an increment of one standard deviation (SD) in height (5.7cm) were 0.91 (0.83-0.99) for total subjects, 1.00 (0.86-1.15) for subjects with a BMI<23kg/m2 and 0.86 (0.77-0.96) for subjects with a BMI≥23kg/m2. Independent of classical cardiovascular risk factors, height was found to be inversely associated with high WBC count, especially for those with a BMI≥23kg/m2. Compared to high stature, short stature appears to convey an inflammatory disadvantage among Japanese men, especially those with a BMI≥23kg/m2.

Enumeration of blood cells is an integral metric for evaluating patient health and can be used to screen for a wide range of diseases and conditions. Conventional methods rely on large, expensive, and complicated instrumentation that requires trained technicians and is not amenable to point-of-care analysis. This work demonstrates the use of a multiplexed, bead-based assay for both rapid white blood cell (WBC) count screening and accurate, multiplexed WBC counts for point-of-care analysis. Blood samples were lysed and diluted before being incubated with silica-coated magnetic particles under chaotropic conditions, a rotating magnetic field, and a source of agitation. The resulting bead aggregation was imaged and correlated to a known WBC count. After establishing standard curves, the WBC count for 18 whole blood samples were determined by this method and compared to values obtained conventionally. When the optimal dilution factor for lysis of whole blood samples was established, 17 of 18 samples (94.4%) were correctly screened and categorized as having high, typical, or low WBC count, while 14 of 18 samples were within 16% of the reported clinical values. The developed system provides analysis of 13 samples in <3 min with a total analysis time of approximately 10 min (including incubation and dilution) and represents comparable throughput to conventional instrumentation, while providing point-of-care capability with reduced size (14 × 21 × 14 cm) and simplicity. This work demonstrates the potential for a multiplexed, bead-based assay to be used as a rapid, point-of-care screening method for WBC counting from whole blood samples.

The use of "care bundles" in the prevention of ventilator-associated pneumonia (VAP) and other intensive care unit (ICU) complications have been increasingly used in critical care practice. However, the effective implementation of these strategies represents a challenge in a busy Level I trauma ICU. We devised a daily "Quality Rounds Checklist" (QRC) tool for use in the ICU to increase compliance with these prophylactic measures and identify areas for improvement in quality of care. A prospective before-after design was used to examine the effectiveness of the QRC tool in promoting compliance with 16 prophylactic measures for VAP, deep venous thrombosis or pulmonary embolism, central line infection and other ICU complications. Compliance was assessed for 1 month before institution of the QRC. On daily analysis, the QRC was then applied by the ICU fellow to assess compliance. Any deficiencies were actively corrected in real time. Compliance was assessed by a multidisciplinary team for the next 3 months and compared with the pre-QRC compliance rates. Implementation of the QRC tool facilitated improvement of all measures not already at >95% compliance. Compliance with VAP prevention measures of head of bed elevation >30 degrees (35.2% vs. 84.5%), sedation holiday (78.0% vs. 86.0%), and prophylaxis for both peptic ulcer disease (76.2% vs. 92.3%) and deep venous thrombosis (91.4% vs. 92.8%) were all increased. A decrease in central line duration >72 hours (62.4% vs. 52.8%) and ventilator duration >72 hours (74.0% vs. 61.7%) was also noted. Additionally, a decrease in mean monthly rates per 1,000 device days of VAP (16.3 vs. 8.9), central line infection (11.3 vs. 5.8) and self-extubation (7.8 vs. 2.2) was demonstrated. Introducing a daily QRC tool facilitated improved compliance rates for 16 clinically significant prophylactic measures in a busy Level I trauma ICU. The daily use of this tool, requiring just a few minutes per patient to complete, results in a sustainable improvement in patient outcomes.

BackgroundA low cerebrospinal fluid (CSF) white-blood cell count (WBC) has been identified as an independent risk factor for adverse outcome in adults with bacterial meningitis. Whereas a low CSF WBC indicates the presence of sepsis with early meningitis in patients with meningococcal infections, the relation between CSF WBC and outcome in patients with pneumococcal meningitis is not understood.MethodsWe examined the relation between CSF WBC, bacteraemia and sepsis in a prospective cohort study that included 352 episodes of pneumococcal meningitis, confirmed by CSF culture, occurring in patients aged >16 years.ResultsCSF WBC was recorded in 320 of 352 episodes (91%). Median CSF WBC was 2530 per mm3 (interquartile range 531–6983 per mm3) and 104 patients (33%) had a CSF WBC <1000/mm3. Patients with a CSF WBC <1000/mm3 were more likely to have an unfavourable outcome (defined as a Glasgow Outcome Scale score of 1–4) than those with a higher WBC (74 of 104 [71%] vs. 87 of 216 [43%]; P < 0.001). CSF WBC was significantly associated with blood WBC (Spearman's test 0.29), CSF protein level (0.20), thrombocyte count (0.21), erythrocyte sedimentation rate (-0.15), and C-reactive protein levels (-0.18). Patients with a CSF WBC <1000/mm3 more often had a positive blood culture (72 of 84 [86%] vs. 138 of 196 [70%]; P = 0.01) and more often developed systemic complications (cardiorespiratory failure, sepsis) than those with a higher WBC (53 of 104 [51%] vs. 69 of 216 [32%]; P = 0.001). In a multivariate analysis, advanced age (Odds ratio per 10-year increments 1.22, 95%CI 1.02–1.45), a positive blood culture (Odds ratio 2.46, 95%CI 1.17–5.14), and a low thrombocyte count on admission (Odds ratio per 100,000/mm3 increments 0.67, 95% CI 0.47–0.97) were associated with a CSF WBC <1000/mm3.ConclusionA low CSF WBC in adults with pneumococcal meningitis is related to the presence of signs of sepsis and systemic complications. Invasive pneumococcal infections should possibly be regarded as a continuum from meningitis to sepsis.

An 8-year-old boy developed anorexia, fatigue, and fever. Laboratory examination revealed a high white blood cell (WBC) count of 145×10/μL with 97.5% abnormal promyelocytic cells that contained Auer bodies. Faggot cells were seen. He was diagnosed with acute promyelocytic leukemia. Later, a chromosome analysis showed 46,XY,t(15;17)(q22;q12). Promyelocytic Leukemia-retinoic acid receptor α-fused gene and chimeric mRNA were confirmed by fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction, respectively. He was complicated with disseminated intravascular coagulation (DIC) and his fibrin and fibrinogen degradation product at the onset was 37.6 μg/mL. Human recombinant thrombomodulin (rTM) was started for DIC. After dexamethasone was administered at a dose of 8 mg/m to prevent all-trans retinoic acid syndrome on day 1, all-trans retinoic acid was started at a dose of 45 mg/m on day 4. Cytarabine (100 mg/m/d) and daunorubicin (45 mg/m/d) were started on day 9. The WBC count gradually increased to 270×10/μL on day 8, and then decreased beginning on day 9. DIC improved after the initiation of chemotherapy and only minor petechia was noted. DIC did not become worse even after rTM was stopped on day 8. The risk of DIC and bleeding is high in the early stage of treatment for acute promyelocytic leukemia, especially in patients with a high WBC count. In our patient, rTM may have prevented fatal DIC and made it possible to safely administer induction chemotherapy.

Stroke-associated pneumonia (SAP) often occurs after ischemic stroke. A deterioration in SAP manifests itself in a decreased partial pressure oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, indicating gas exchange dysfunction. We aimed to investigate independent predictors and outcomes of SAP with low PaO2/FiO2 ratio among patients with acute large vessel occlusion (ALVO) undergoing endovascular therapy. We retrospectively analyzed the prospective data of consecutive adult post-interventional patients with ALVO admitted to neuro-intensive care units in Wuhan No. 1 Hospital from December 2020 to December 2022. Patients developing SAP without coronavirus disease 2019 were included in this study and divided into two subgroups: PaO2/FiO2 ratio > 240 and ≤ 240. The primary outcome was favorable neuro-function at 90 days (modified Rankin Scale score of 0-2). Secondary outcomes included hospitalization days, occurrence of symptomatic intracerebral hemorrhage, and 90-day mortality. The independent risk factors and prognosis for SAP with PaO2/FiO2 ratio ≤ 240 were identified by logistic regression analyses. A total of 159 subjects developing SAP were included in this study: 53 with PaO2/FiO2 ratio > 240 and 106 with ratio ≤ 240. Compared to subjects with PaO2/FiO2 ratio > 240, those with PaO2/FiO2 ratio ≤ 240 had older ages, higher baseline National Institutes of Health Stroke Scales scores, larger proportions of baseline Glasgow Coma Scale (GCS) score of 3-8 and grade of kobuta water swallow test ≥ 3, higher white blood cell (WBC) counts (all p values <0.05). The independent predictors for SAP with PaO2/FiO2 ratio ≤ 240 included ages (adjusted odds ratio [OR], 1.043; 95% confidential interval [CI], 1.011-1.077; p = 0.009), baseline GCS scores of 3-8 (adjusted OR, 2.802; 95% CI, 1.214-6.465; p = 0.016), and ln-transformed WBC counts after SAP diagnosis (adjusted OR, 3.977; 95% CI, 1.226-12.896; p = 0.021). SAP with PaO2/FiO2 ratio ≤ 240 was robustly associated with longer hospitalization days (adjusted OR, 1.074; 95% CI, 1.01-1.143; p = 0.024). SAP with PaO2/FiO2 ratio ≤ 240 is shown in significant relevance to the prolonged in-hospital stays among post-interventional patients. Older ages, baseline GCS scores of 3-8, and higher WBC counts after SAP diagnosis can independently predict the occurrence of SAP with a lower PaO2/FiO2 ratio. Further validation studies are needed.

Front Line Treatment of Elderly Patients with Acute Promyelocytic Leukemia: Long-Term Results of the German AML Cooperative Group

Dear Editor, Extracorporeal membrane oxygenation (ECMO) has a significant impact on intensive care unit (ICU) patient costs. Human resources are a major cost driver for ECMO in severe acute respiratory distress syndrome (ARDS) [1]. However, recent developments in ECMO technology has allowed safe patient management by a single caregiver [2–4]. In the present report, we analyze the direct ICU costs of patients with influenza A (H1N1)-related ARDS supported with miniaturized ECMO systems and managed by a single caregiver. We performed an observational study of all patients (n = 10) with H1N1-associated ARDS treated with ECMO in Hospital S. Joao (Porto, Portugal), between November 2009 and April 2011. The clinical data and ECMO treatment details of this ICU patient cohort have been described in a previous report [5]. Patients were admitted in medical ICUs and managed by a single caregiver using miniaturized ECMO circuits (Rotaflow Centrifugal Pump plus Quadrox PLS and CARDIOHELP; Maquet Cardiopulmonary AG). In our single caregiver model, the ICU nurse primarily managed the ECMO patient under the coordination of 24/7 inhouse ICU physicians, with the backup of an on-call ECMO specialist. Our multidisciplinary ECMO specialist team (ICU physicians, ICU nurses, and cardiovascular perfusionists) is responsible for managing equipment and supplies, circuit preparation, patient transportation, troubleshooting, daily rounds, education, and service administration. Per patient ICU direct costs were analyzed retrospectively from clinical records and hospital databases using both top-down and bottom-up approaches. Bottom-up analysis was performed for all drugs, transfusion requirements, laboratory and imagiology exams. Regarding disposable items, bottom-up analysis was possible for ECMO-specific disposables and for renal replacement therapies. Costs with human resources were assessed using the top-down approach. Specific ECMO costs were also individualized for each ICU episode: (1) disposables devices; (2) laboratory tests; (3) transfusion requirements; and (4) drugs. The Ethics Committee of the Hospital S. Joao approved this study and waived the need for patients’ informed consent. Variables are reported as median and interquartile ranges, if not otherwise indicated. The cost drivers of H1N1-related ARDS patients treated with miniaturized ECMO are presented in Table 1. ECMO support corresponded to 63.6 (62.5–88.5) % of the ICU length of stay (LOS). The ICU LOS positively correlated (r = 0.97; p \ 0.001) with ICU patient costs [42,721 (33,358–56,801) €], but not with specific ECMO costs [r = 0.17; p = 0.63; 7,516 (5,599–7,736) €]. ECMO-specific costs represented 17.6 (13.1–18.1) % of the total ICU direct costs, mostly ECMO disposable devices [94.8 (87.1–96.1) %]. Daily ICU costs with antibiotics, sedation, analgesia and neuromuscular blockade, fluids and nutrition, vasoactive drugs, anticoagulation medications, and other unspecific drugs were higher during the period of ECMO support compared with the period without ECMO support. In conclusion, the use of miniaturized ECMO had a small impact on direct ICU costs in our cohort of H1N1-related severe ARDS patients managed by a single caregiver and did not correlate with the ICU LOS. Knowledge of the incremental costs associated with miniaturized ECMO will contribute to the clarification of its cost-effectiveness in severe ARDS.

Increased Frequency of Expression of Elevated Dihydrofolate Reductase in T-Cell Versus B-Precursor Acute Lymphoblastic Leukemia in Children

MIS1-6 - First-Line Chemotherapy Plus Cetuximab in Patients Grouped According to Prognostic Risk Factors: Analysis of the Crystal and OPUS Studies

BackgroundSystemic lupus erythematosus (SLE) patients are at an increased risk for infection. It is known that some SLE patients develop severe acute illnesses and require admission to the intensive care...

Objective To report the treatment of the first maternal patient infected with novel avian Influenza A (H5N6) virus in the world, and to investigate the clinical features and treatment of the maternal patient. Methods On December 28th, 2015, a maternal patient infected with H5N6 virus was admitted to the First Municipal Hospital of Zhaoqing City. The clinical features and treatments of this patient were analyzed. Results ① A 40-year-old female in 35-week gestation was admitted with the complaint of fever and cough for 6 days with the following characteristics: fever 6 days ago after getting a cold, mainly in the afternoon and night, the maximum body temperature was 39 ℃, with chills, shiver, single cough, short of breath after walking 50 meters which could be relieved after having a rest, but no expectoration, sore throat, nasal obstruction, rhinorrhea, chest tightness, chest pain, paroxysmal nocturnal dyspnea. The body temperature could be decreased after taking antibiotic and antipyretic which was prescribed by the doctor in the local hospital, and was repeatedly administrated. ② She had been to the local live poultry market before the onset of fever. ③ Auxiliary examination: on admission, the patient's blood test showed that the white blood cell count was normal (7.94×109/L), the neutrophil was normal (7.42×109/L), but the lymphocyte was low (0.44×109/L); it was shown by the arterial blood gas analysis that pH was 7.441, the oxygen partial pressure was 68.7 mmHg (1 mmHg = 0.133 kPa), and the carbon dioxide partial pressure was 23.9 mmHg. Infiltration was found in the lung by chest X-ray on the 2nd day, specifically, with double lung texture thickening, fuzzy, visible patchy fuzzy shadow, and double lung portal shadow. On the 3rd day, the throat swab specimen and sputum for virus nucleic acid detection of H7N9-RNA was negative, the H1N1-RNA was negative, but the avian influenza virus (AIV)-RNA was positive. The throat swab specimens and sputum for virus nucleic acid detection were performed by Disease Prevention Control Center of Zhaoqing City on the 4th day and by Disease Prevention Control Center of Guangdong Province on the 5th day, which showed positive H5N6-RNA, but her child's nasal swab specimens for AIV-RNA was negative on the 3rd day of birth. On the 5th day, blood influenza A virus antibody IgM was negative. ④ Treatment: a medium flow oxygen inhalation by nasal cannula was given after admission. On the 2nd day, the breath of the patient raised to 40 breaths/min, and the pulse oxygen saturation (SpO2) fell to 0.80, in order to avoid the fetal death because of hypoxemia, the patient was send for cesarean section, and invasive ventilation was given with 1.00 fraction of inspired oxygen (FiO2) in the intensive care unit (ICU) after the cesarean section, and the extracorporeal membrane oxygenation (ECMO) was given since the 4th day. 150 mg oseltamivir was given bid on the 4th day for 2 times a day, and it was changed to peramivir 600 mg everyday (qd) on the 6th day for 6 days, and oseltamivir 150 mg was given bid again on the 9th day for 14 days. ⑤ Outcome: the throat appeared red, and the tonsils were swollen, breath sounds on both sides was weak, but no rale or rhonchi was found at admission. But from the 2nd day fine rales were detectable in both sides of chest. The temperature was normal except on the 1st day (the maximum body temperature was 38.2 ℃), the 4th day (the maximum body temperature was 38 ℃), and the 10th day (the maximum body temperature was 37.5 ℃). The viral nucleic acid test of the throat swab specimen and sputum showed that the H5N6-RNA turned negative on the 9th day, the 10th day and the 11th day for 3 days. Pleural effusion was rapidly increased after the admission as shown by chest X-ray films, bilateral partial ground-glass opacities were observed in the low lung, and extended to all the lung fields on the 5th day, the bilateral lung infiltrations were absorbed slowly, and showed bilateral reticular opacities as the image of pulmonary fibrosis at last. The computed tomography scan of the chest showed bilateral irregular reticular opacities and basal discoid atelectasis on the 31st day. The color Doppler ultrasonography showed the systolic pressure of the pulmonary artery was about 78 mmHg on the 39th day. On the 49th day, norepinephrine was given for the hypotension, the serum creatinine (SCr) was 73.9 μmol/L; the SCr raised to 160.2 μmol/L on the 50th day, the urine output fell to less than 30 mL/h for 27 hours. Although the active antiviral, mechanical ventilation, ECMO and other therapies were prescribed, the patient eventually died due to multiple organ failure (MOF) on the 50th day. Conclusions The reported patient course was short, with an acute onset, with fever and cough as the chief complaint, and acute respiratory distress syndrome (ARDS) and MOF developed quickly. Her baby was born through cesarean delivery on the 2nd day after admission, and had not infected with H5N6 avian influenza. The clinical manifestations and the treatment strategy need to be further explored. Key words: H5N6 avian influenza A; Maternal; Anti-viral drug; Acute respiratory distress syndrome; Extracorporeal membrane oxygenation