Optimising the response to acute clinical deterioration: the role of observation and response charts

We sought the role of the hospital inpatient observation and response chart (ORC) in reducing adverse outcomes. We sourced articles written in English and published in PubMed. Track, trigger and response systems can be tiered and use single parameter or aggregate scoring systems, the latter being more prone to error. The documentation and detection of abnormal vital signs can be affected by choice of trigger and response and by ORC design. There is considerable variation in the design of ORC and of rapid response systems (RRS) in general, and this impairs assessment of their efficacy. A high rate of modification of pre‐determined triggers and poor sensitivity of measured outcomes further compromise systematic review. The best‐designed ORC and RRS should optimise the frequency of response team activation to minimise adverse patient outcomes without excess resource utilisation. The role and the risks of electronic data recording are under‐explored. Detecting and responding to deteriorating patients relies on accurate and clear documentation of vital signs. ORC design and staff education on ORC implementation and usage are integral to minimising ALF and optimising patient outcomes. Standardisation of the design of both the ORC and the hospital RRS are overdue.     

恩替卡韦治疗慢性HBV感染者KIR基因多态性与疗效的相关性研究

目的探讨慢性HBV感染者杀伤细胞免疫球蛋白样受体(killer immunoglobulin-like receptor,KIR)基因多态性及其与应用恩替卡韦疗效差异相关性。方法采用序列特异性引物聚合酶链反应(PCR-SSP)法,对60例应用恩替卡韦治疗的慢性HBV感染者(试验组)和60例健康对照者(对照组)的KIR基因进行基因分析,比较试验组和对照组的差异。60例患者中18例为治疗完全应答者(完全应答组),42例为非完全应答者(非完全应答组),比较2组之间差异。结果通过试验组和对照组的16种KIR基因分析,框架基因KIR2DL4、3DL2、3DL3和3DP1存在于所有个体中,其基因频率均为1.0。试验组KIR 2DS2和KIR2DS3基因型频率高于对照组(P值依次为0.038和0.035);完全应答组KIR2DS1、KIR3DS1和KIR2DL5基因型频率高于非完全应答组(P值依次为0.010、0.029和0.018)。结论 KIR2DS2、KIR2DS3可能是HBV的易感基因型,KIR2DS1、KIR3DS1、KIR2DL5可能与恩替卡韦抗HBV治疗有效应答有关。     

Predictive value of rapid virological response and early virological response on sustained virological response in HCV patients treated with pegylated interferon alpha-2a and ribavirin

BACKGROUND AND AIM: The therapeutic effect of pegylated interferon (peg-IFN)-alpha-2a combination with ribavirin on patients with chronic hepatitis C virus (HCV) infection is dependent on the rapidity of the virological response. The aim of this study was to investigate the predictive value of rapid virological response (RVR) and early virological response (EVR) on sustained virological response (SVR) in HCV patients treated with peg-IFN-alpha-2a and ribavirin. METHODS: The HCV genotypes of 105 patients with chronic hepatitis C were detected by enzyme-immunoassay. Patients received subcutaneous 180 microg peg-IFN-alpha-2a once weekly plus daily ribavirin. Patients with genotype 1 were treated for 48 weeks and patients with genotype 2 or 3 were treated for 24 weeks. HCV RNA was assessed by qualitative PCR at pretreatment, at weeks 4 and 12 during treatment, and at week 24 of follow-up. Virological response rates at different weeks were investigated, with RVR defined as serum HCV RNA undetectable after 4 weeks and EVR defined as HCV RNA either undetectable or decrease by >or=2 log(10) after 12 weeks. The effects of virological response rates at different weeks on SVR were analyzed. RESULTS: Of the 105 patients, 44 (41.9%) were genotype 1, 46 (43.8%) were genotype 2, and 15 (14.3%) were genotype 3. RVR rates (19.5%) of patients with genotype 1 were significantly lower than those (60.7%) of genotype 2 or 3 (chi(2) = 16.836, P = 0.000); and EVR rates (73.2%) of patients with genotype 1 were significantly lower than those (96.7%) of genotype 2 or 3 (chi(2) = 12.220, P = 0.000). The SVR rates (86.7%) of patients who had achieved RVR were significantly higher than those (43.9%) of patients who had not achieved RVR (chi(2) = 19.713, P = 0.000). The positive predictive value of RVR in all patients was higher than that of EVR, but there was no significant difference between RVR and EVR. The negative predictive value of RVR in all patients or with genotype 1 was significantly lower than that of EVR. In univariate analysis, HCV RNA level (P = 0.014), genotype (P = 0.001), RVR (P = 0.000) and EVR (P = 0.000) were associated with effect of treatment. However, in stepwise regression analysis, the independent factors associated with effect of antiviral therapy were RVR (OR = 6.501, P = 0.001), EVR (OR = 2.776, P = 0.003) and genotype (OR = 3.061, P = 0.024). CONCLUSIONS: The RVR and EVR rates of patients with genotype 1 were significantly lower than those of patients with genotype 2 or 3. RVR had a similar predictive value as EVR on SVR. Genotype, HCV RNA level, RVR and EVR were associated with SVR. Genotype, RVR and EVR were independent factors for predicting the effect of antiviral therapy.     

Virologic and biochemical responses to clevudine in patients with chronic HBV infection‐ associated cirrhosis: data at week 48

Summary. Clevudine shows high rates of virologic and biochemical responses in patients with chronic hepatitis B. However, the efficacy and safety of clevudine in patients with cirrhosis are unknown. The aims of this study were to evaluate the safety and to assess the virologic and the biochemical responses to clevudine in patients with cirrhosis with chronic hepatitis B virus (HBV) infection. We reviewed data from treatment‐naïve patients with chronic hepatitis B with and without cirrhosis who started clevudine between April 2007 and March 2008 (n = 52, hepatitis B without cirrhosis n = 21 and chronic hepatitis B with cirrhosis n = 31) at Korea University Ansan/Guro Hospital. All of the patients were treated for more than 48 weeks. The mean age was older in the patients with cirrhosis. Baseline HBV DNA levels were 6.9 and 7.78 log copies/mL (P = 0.042), and alanine aminotransferase (ALT) levels were 104.9 and 147.4 IU/L (P = 0.204), for those with and without cirrhosis, respectively. Virologic response (HBV DNA <1000 copies/mL) (87.1%vs 71.4%, P = 0.24) and biochemical response (83.9%vs 80.9%, P = 0.99) at week 48 were not significantly different between the two groups. Early virologic response at week 12 was even higher in the patients with cirrhosis (61.3%vs 28.6%, P = 0.026). Neither ALT flare nor newly onset hepatic decompensation was found in the patients with cirrhosis, whereas ALT flare was transiently observed in 14.3% of the chronic hepatitis group. In conclusion, although clevudine may produce a transient elevation of ALT during the early treatment period, such findings were not observed in patients with cirrhosis and the virologic and biochemical responses of the groups were comparable.     

Role of endogenous biological response modifiers in pathogenesis of infectious diseases

Biologic response modifiers (BRMs) interact with the host immune system and modify the immune response. BRMs can be therapeutically used to restore, augment, or dampen the host immune response. Although they have been used for decades, their clinical applications have been expanded in the past decade for diagnosis and treatment of many diseases including cancers, immunologic disorders, and infections. This article discusses endogenous biological response modifiers (ie, naturally occurring immunomodulators as a part of the host immune system), which play vital roles as regulators of both innate and adaptive immune responses.     

Metabolic and functional results after laparoscopic colorectal surgery: a randomized,controlled trial

PURPOSE: This study was designed to compare metabolic and functional results after laparoscopic and open colorectal resection. METHODS: Seventy-nine patients were randomly assigned to laparoscopic (n = 40) or open (n = 39) colorectal resection. Before and after operation, the following parameters were determined: respiratory function (spirography and blood gas); serum level of cortisol, lactate, and C-reactive protein; total lymphocyte count; and CD4 and CD8 lymphocyte subsets. Intraoperative core temperature was measured by a bladder probe. Postoperative pain and analgesic consumption were also monitored. RESULTS: Mild operative hypothermia, a trend to postoperative reduction of total lymphocyte count, and significant impairment of respiratory function early after surgery were found in both groups. Laparoscopy showed a higher CD4/CD8 ratio (P = 0.01) on postoperative Day 1 and a faster return of C-reactive protein to preoperative values (P = 0.01) than in the open colorectal resection group. Morphine consumption in the first 48 hours after surgery was lower in the laparoscopic than in the open group (P = 0.02). CONCLUSIONS: Laparoscopy was associated with a less pronounced immunosuppression and inflammatory response and a lower consumption of analgesic drugs than open surgery. Moreover, our data did not show any additional detrimental effect of laparoscopy on either operative core temperature or early postoperative respiratory function.     

Metabolic and haemodynamic responses to adrenaline in normal dogs

Summary The metabolic and haemodynamic effects of adrenaline were investigated in 6 intact anaesthetized dogs, which were subjected to an infusion of adrenaline. The dose given was similar to the endogenous production rate of adrenaline in experimental myocardial infarction. Adrenaline infusion (0.8, 1.17 or 1.05g · kg^–1. min^–1) over two hours led to a variable rise in blood level of this amine, regardless of the rate of infusion. Dogs with high blood adrenaline (over 3.5 ng·ml^–1) exhibited haemodynamic deterioration, i.e a rise in peripheral vascular resistance together with a fall in cardiac output and external cardiac work. Dogs with low blood adrenaline showed little change in peripheral vascular resistance, a rise in cardiac output and external cardiac work. The myocardial consumption of each of the substrates lactate, pyruvate, glucose and FFA was measured, and its equivalent oxygen consumption expressed as a percentage of the total myocardial oxygen consumption. No relationship was found between myocardial utilisation of individual substrates and the type of haemodynamic response. Thus in intact dogs exposed to adrenaline excess, similar to that found in acute myocardial infarction, the different types of haemodynamic response cannot be attributed to the type of substrate utilization by the myocardium, but to different rates of clearance of adrenaline. Low clearance rates lead to high blood adrenaline levels and an unfavourable response of the cardiovascular system.

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Zusammenfassung An 6 narkotisierten Hunden wurden die metabolischen und hämodynamischen Auswirkungen einer Adrenalin-Infusion untersucht. Die Dosierung stimmte weitgehend mit der endogenen Produktionsrate von Adrenalin bei experimentellem Herzinfarkt überein. Eine Adrenalin-Infusion (0,8; 1,17 oder 1,05 g/kg) über 2 Stunden führte zu einem variablen Anstieg des Blutspiegels von Adrenalin. Hunde mit einem hohen Blutspiegel (über 3,5 g · kg^–1 · min^–1) zeigten hämodynamische Störungen, d. h. einen Anstieg des peripheren Widerstandes, verbunden mit einem Abfall des Herzminutenvolumens und der äußeren Herzarbeit. Hunde mit niedrigem Blutspiegel zeigten nur geringe Änderungen des peripheren Widerstandes sowie einen Anstieg des Herzminutenvolumens und der äußeren Herzarbeit. Der myokardiale Verbrauch der Substrate Laktat, Pyruvat, Glucose und freie Fettsäuren wurde gemessen und der äquivalente Sauerstoffverbrauch als Prozentsatz des gesamten myokardialen Sauerstoffverbrauchs ausgedrückt. Es wurde keine Beziehung zwischen myokardialer Utilisation der einzelnen Substrate und der Art der hämodynamischen Reaktion gefunden. Ähnlich wie beim akuten Myokardinfarkt können auch bei Hunden unter starkem Adrenalineinfluß die verschiedenen hämodynamischen Reaktionstypen nicht auf die Art der Substratutilisation im Myokard bezogen werden, sondern auf unterschiedliche Geschwindigkeiten der Adrenalin-Elimination. Niedrige Eliminationsgeschwindigkeit führt zu hohen Adrenalinblutspiegeln und ungünstigen Reaktionen des kardiovaskulären Systems.

     

心肺运动试验中窦房结变时效应频率应答特性的初步探讨

采用最大症状限制性心肺运动试验的方法，依据运动过程中心率与机体作功和体内代谢强度的变化关系研究４０名正常人运动中窦房结变时效应的频率应答特性，探讨心率储备和影响最大心率的主要因素。结果显示：心率与作功呈直线相关（Ｙ＝７５＋０．４１Ｘ，ｒ＝０．９８６３，Ｐ＜０．００１）。运动中心率与代谢当量亦呈直线相关（Ｙ＝５２．３＋１１．０１Ｘ，ｒ＝０．９１５２，Ｐ＜０．００１）。影响最大心率的主要因素是氧耗量、二氧化碳量和每分通气量。运动过程中心率与运动负荷和代谢的线性关系反映了窦房结频率应答的特性，即代谢性频率应答。窦房结的这种特性可能是单传感器频率应答性起搏器不能完全符合生理需要的基本原因。     

巨噬细胞与结核分枝杆菌的免疫反应的研究进展

巨噬细胞是结核分枝杆菌在机体内的主要宿主细胞.细胞介导的免疫反应是机体抗结核分枝杆菌的主要免疫保护机制,巨噬细胞可通过吞噬、溶酶体融合,提呈结核分枝杆菌抗原,产生多种细胞因子、反应氧中间产物和反应氮中间产物,以及细胞凋亡等多种途径来杀灭结核分枝杆菌;同时,结核分枝杆菌也可采取各种方式来逃逸巨噬细胞的免疫作用.本文就巨噬细胞与结核分枝杆菌的免疫反应的研究进展作一综述.     

Expression of immune genes in skin of channel catfish immunized with live theronts of Ichthyophthirius multifiliis

The objective of this study was to evaluate differential expression of innate and adaptive immune genes, including immunoglobulin, immune cell receptor, cytokine, inflammatory protein , toll‐like receptors (TLR) and recombination‐activating gene (RAG) in skin from channel catfish, Ictalurus punctatus after immunization with live theronts of Ichthyophthirius multifiliis (Ich) by intraperitoneal injection. The immunized catfish showed significantly higher survival rate (95%) than those of mock‐immunized control fish (0% survival) after the theront challenge. The gene expression of innate immune system, such as cytokines (IL‐1β type a, IL‐1β type b, IFN‐γ, TGF1‐β and TNF‐α) and inflammatory proteins (NF‐kB and iNOS 2), showed significant upregulation at day 1 (D1) post‐immunization. Expression of TLR genes exhibited a rapid increase from hour 4 (h4) to D10 post‐immunization. Genes of the adaptive response, such as the cell receptor MHC I, CD8⁺, CD4⁺ and TCR‐α, showed upregulation at D1, D6 and D10. The TCR‐β expression increased rapidly at h4 and remained upregulated until D10. Immunoglobulin IgM upregulation was detected from h4 until D2 while IgD expression was increased from D1 until D10. Rapid upregulation of innate and adaptive immune genes in skin of catfish following live theront vaccination was demonstrated in this study ultimately resulting in significant protection against Ich infection.     

How soon can a virological sustained response be determined after withdrawal of interferon therapy in chronic hepatitis C?

Hepatitis C virus (HCV)-RNA status and alanine aminotransferase (ALT) levels determined shortly after interferon (IFN) therapy in patients with chronic hepatitis C do not predict long-term response. To determine the virological sustained response after the completion of IFN therapy, HCV-RNA was measured at the end of treatment and at 3-4 months and 12 months after the completion of therapy in 537 patients with chronic hepatitis C. In 347 patients, HCV-RNA was not detected by polymerase chain reaction (PCR) at the completion of therapy and 175 of these patients (50%) were still PCR negative 12 months later. In contrast, of the 180 patients who were HCV-RNA negative at 3-4 months after completion of therapy, 99% remained negative at 12 months. Normal ALT levels were found in 80, 93 and 95% of patients who were negative for HCV-RNA either at the end of treatment or at 3-4 months and 12 months after the completion of therapy, respectively. Of patients who were HCV-RNA positive, 30, 15 and 20% were found to have normal ALT levels at the same respective time points. To determine a sustained virological response shortly after the completion of therapy, serum HCV-RNA was serially examined in 66 patients negative for HCV-RNA at the end of therapy. Of 31 patients who relapsed, HCV-RNA reappeared in 33, 80, 97 and 100% of patients by 1, 2, 4 and 8 weeks after the completion of therapy. In conclusion, a sustained virological response could be determined with 97 and 99% certainty at 4 weeks and at 3-4 months after the completion of therapy, respectively.     

巨噬细胞与结核分枝杆菌的免疫反应的研究进展

巨噬细胞是结核分枝杆菌在机体内的主要宿主细胞.细胞介导的免疫反应是机体抗结核分枝杆菌的主要免疫保护机制,巨噬细胞可通过吞噬、溶酶体融合,提呈结核分枝杆菌抗原,产生多种细胞因子、反应氧中间产物和反应氮中间产物,以及细胞凋亡等多种途径来杀灭结核分枝杆菌;同时,结核分枝杆菌也可采取各种方式来逃逸巨噬细胞的免疫作用.本文就巨噬细胞与结核分枝杆菌的免疫反应的研究进展作一综述.     

Differential Effects of Facial Nerve Transection on Heat Shock Protein 70 Expression in the Developing and Adult Hamster Facial Nucleus

In this study, the effects of axotomy on heat shock protein 70 (hsp70) protein levels were analyzed by immunoblotting with a hsp70 antibody that recognized constitutive and inducible forms of the protein. The right facial nerve of postnatal day 4 (neonate) or 100 (adult) hamsters was transected at its exit from the stylomastoid foramen, with the left nerve serving as internal control. Postoperative survival times were 2, 6, 12, and 24 h, with 3 animals per time point. Tissue punches containing individual facial nuclear groups were collected and homogenized. Approximately 10 g of total protein was loaded onto paired gels and electrophoretically separated. Immunoblots of one gel from each pair were prepared, with the other gel stained in 0.2% Coomassie blue and used for verification of equality of lane loading. The results indicate that hsp70 protein levels increase in the adult, but decrease in the neonate, after axotomy. It is concluded that a stress response to cellular damage is an initial component of the classically described axon reaction and that hsp70 plays a role in mediating motoneuron survival after peripheral nerve transection.     

Modulation of anti-idiotypic immune response by immunization with the autologous M-component protein in multiple myeloma patients

Multiple myeloma is characterized by a proliferation of clonal B lymphocytes and plasma cells. The idiotypic structure of clonal immunoglobulin (Ig) expressed on the tumour B-cell surface can be regarded as a tumour-specific antigen and, as such, a potential target for anti-idiotypic T and B cells in an immune regulation of the tumour-cell clone. Active immunization using the autologous monoclonal Ig as a 'vaccine' was shown to induce tumour-specific immunity in murine B-cell tumours and in human B-cell lymphoma. With the aim to induce or amplify an anti-idiotypic response in multiple myeloma, five stage I–III patients were repeatedly immunized with the autologous monoclonal IgG. Induction of idiotype-specific cellular immunity was analysed in vitro by an enzyme-linked immunospot assay (interferon-γ and interleukin-4 secreting cells). B cells secreting anti-idiotypic IgM antibodies were also analysed. An anti-idiotypic T-cell response was amplified 1.9–5-fold in three of the five patients during immunization. The number of B cells secreting anti-idiotypic antibodies also increased in these three patients. In two of the patients induction of idiotype-specific immunity was associated with a gradual decrease of blood CD19⁺ B cells. The induced T-cell response was eliminated during repeated immunization. Further studies are warranted to optimize the immunization schedule in order to achieve a long-lasting T-cell immunity against idiotypic determinants on the tumour clone. A role for immunity in controlling the tumour clone remains to be established.     

Guidelines for clinical protocols for chronic lymphocytic leukemia: recommendations of the National Cancer Institute-sponsored working group

The National Cancer Institute (NCI)-sponsored Chronic Lymphocytic Leukemia (CLL) Working Group was convened to develop a set of standardized eligibility, response, and toxicity criteria for clinical trials. We recognized the previous efforts in 1967 (published again in 1973 as the report of the Chronic Leukemia-Myeloma Task Force [1] and 1978 of Cancer and Leukemia Group B (CALGB) [2]). We have used these reports for guidance during the current effort. Several noteworthy developments in the past few years have made it necessary to modify the previous guidelines. First, the diagnostic criteria for CLL and its clinical staging have been developed and well defined. Second, although staging systems facilitated entry of comparable and relatively homogeneous groups of patients in clinical trials, the definitions of response (CR) and partial response (PR) were not uniformly adopted from the previous guidelines in the clinical trials (Tables IA, IB); therefore, comparisons of results obtained in different studies became difficult. Third, there has been an improvement in our understanding of the immunology and biology of CLL. Finally, we are witnessing the emergence of several chemotherapy agents that promise impressive activity in CLL (e.g., 2'-deoxycoformycin [3], fludarabine monophosphate [4, 5]), and thereby offer the potential for improving survival time in this disease. To best identify regimens worthy of continued pursuit in large comparative trials, standardized guidelines for evaluation are essential. A number of laboratory investigations are also presented for which scientific interest is high yet relevance remains to be determined; thus, they are presented as companion studies to the clinical trials. This mechanism allows for flexibility in the testing of these questions and for additional ideas in the future without requiring modification of an entire treatment protocol. The following guidelines were developed to be used as a form of standardization for clinical trials, incorporating current technologies, yet remaining relevant to the general hematology/oncology community. Based on the membership of the Working Group, it is expected that these guidelines will serve as the criteria for most clinical trials in the near future.