Vaccination of patients with haematological malignancies with one or two doses of influenza vaccine: a randomised study

An open, randomised study was performed to determine whether two doses of influenza vaccine were more effective than one to elicit an immune response in 70 patients with haematological malignancies. The responses were not improved by two doses compared with one (influenza A virus serotypes H1/N1 18% vs. 22% and H3/N2 26% vs. 14%; influenza B 25% vs. 22%). The results were similar in patients with ongoing and discontinued therapy. Patients treated with monoclonal antibodies for lymphoma had very poor responses. We conclude that two doses of influenza vaccine do not improve the antibody response in patients with haematological malignancies.     

Characteristics of 10 patients with paraneoplastic rheumatologic musculoskeletal manifestations

Abstract

Objectives. To evaluate the possible correlation of malignant neoplasms and paraneoplastic rheumatologic syndromes.

Methods. We studied a series of 10 patients with paraneoplastic rheumatological syndromes collected from our Division of Rheumatic Disease between 2006 and 2012.

Results. Our series consisted of four males and six females, with a mean age of 65.5 years (range, 57–78 years). Of the 10 patients recruited, six had hematological malignancies and four had solid cancers. Malignancies were diagnosed after rheumatic symptoms were reported in all patients. Compared to solid tumors, hemopathy was diagnosed at a later time point (16.2 vs. 7.3 months). Extra-articular symptoms were associated with rheumatologic musculoskeletal manifestations in 100% of the patients. Polyarthritis was the main rheumatologic musculoskeletal manifestation (50% of the patients). The other manifestations were oligopolyarthritis and polymyalgia rheumatic-like symptoms (20% of the patients). Symmetric arthritis was present in 60% of the patients, and the remaining patients developed asymmetric arthritis. Musculoskeletal manifestations completely regressed in 66.7% of the patients after cancer therapy. When tumor relapse was observed, rheumatic symptoms did not recur in any of our patients (100%).

Conclusions. Rheumatic disorders with atypical clinical presentation in older patients, poor response to usual treatment and systemic features such as weight loss and clinical findings compatible with well-recognized paraneoplastic syndromes should alert clinicians to the possible coexistence of an occult malignancy. Especially in cases of paraneoplastic rheumatic/musculoskeletal manifestations associated with hemopathy, the primary disease is unlikely to have manifested yet, making the diagnosis difficult. Thus, caution is required.     

Management of intracranial fungal infections in patients with haematological malignancies

The incidence of, and mortality associated with, invasive fungal infections remains far higher than hoped. As a consequence of the overall increase in the incidence of such infections over time, the incidence of central nervous system (CNS) fungal infections is also increasing and, despite improvements in diagnostic techniques and the introduction of novel antifungal agents, therapy for CNS infections is still associated with discouragingly poor results. In patients with haematological malignancies, opportunistic infections with Candida or Aspergillus remain the most common infections affecting the CNS; however, opportunistic infections with less well-known fungi are becoming more common and must be considered in the differential diagnosis. New techniques for the early diagnosis of invasive fungal infections are emerging. Pharmacologic options for treating invasive fungal infections have also improved during the past few years, with new drugs becoming available that have broader antifungal spectra and better safety profiles. Other novel treatment approaches, such as combination therapy, are also being explored. Early investigations have produced encouraging results; however, large, prospective studies involving many patients are necessary to validate the widespread use of these approaches. This review analyses the existing guidelines for treatment of CNS fungal infections and the literature available on the use of new drugs to generate sets of recommendations for treatment of these life-threatening infections in patients with haematological malignancies.     

脓毒症金黄色葡萄球菌感染监测及治疗体会

目的分析常见抗菌药物敏感性及对确诊金黄色葡萄球菌感染脓毒症患者目标性治疗情况。方法收集兰州军区兰州总医院2009年1—3月送检血液标本及2010年1—3月送检的多种标本(血液、痰、支气管肺泡灌洗液等)。筛选送检的阳性标本中2次或2次以上培养出同一种金黄色葡萄球菌的脓毒症患者72例,记录用药情况,病情转归。结果 2010年1—3月共收集各种微生物标本3153份,检出阳性标本1108份,分离出细菌和真菌1557株,其中金黄色葡萄球菌106株(6.81%),耐甲氧西林金黄色葡萄球菌(MRSA)61株,占金黄色葡萄球菌的57.55%;2009年及2010年血液标本中金黄色葡萄球菌检出率分别为8.33%和10.71%。MRSA对万古霉素、利奈唑胺敏感性相当,对万古霉素耐药率为4.92%。对确诊金黄色葡萄球菌感染患者进行目标性治疗,临床疗效较好。结论金黄色葡萄球菌是脓毒症患者重要致病菌之一,耐药率较高,2010年同期检出率高于2009年,利奈唑胺是治疗耐药金黄色葡萄球菌感染的良好选择。     

Pharmacokinetics and tolerance of intravenous and intramuscular recombinant alpha 2 interferon in patients with malignancies

Fifteen patients with advanced hematopoietic and other malignancies were treated with recombinant DNA produced Alpha 2 Interferon (IFN) (Schering) by intravenous (IV) and intramuscular (IM) routes at weekly intervals in escalating doses from 1 X 10(6) IU to 100 X 10(6) IU in order to determine the tolerance and pharmacokinetics. The most common side effects included fever, chills, myalgia, and arthralgia. At doses of 60 X 10(6) or above, severe but reversible hypotension was observed in five patients receiving interferon by intravenous route. Patients receiving interferon by intramuscular route had fever, chills, and myalgias but did not develop hypotension at the same dosage. Two patients with non-Hodgkin lymphoma showed objective evidence of regression. Our data suggest a biphasic pattern of elimination with terminal half-life ranging from 1.9 to 2.9 hours and peak titer of 16,000 units and under for IV interferon, and terminal half-life of 6 hours with peak titers of 600 units for intramuscular interferon. However, interpatient variability precludes a definite conclusion. Although the areas under the serum concentration vs time curves were similar, the intravenous route provided higher but unsustained levels of interferon than the intramuscular route.     

Survival of European patients diagnosed with lymphoid neoplasms in 2000-2002: results of the HAEMACARE project

Background

The European Cancer Registry-based project on hematologic malignancies (HAEMACARE), set up to improve the availability and standardization of data on hematologic malignancies in Europe, used the European Cancer Registry-based project on survival and care of cancer patients (EUROCARE-4) database to produce a new grouping of hematologic neoplasms (defined by the International Classification of Diseases for Oncology, Third Edition and the 2001/2008 World Health Organization classifications) for epidemiological and public health purposes. We analyzed survival for lymphoid neoplasms in Europe by disease group, comparing survival between different European regions by age and sex.

Design and Methods

Incident neoplasms recorded between 1995 to 2002 in 48 population-based cancer registries in 20 countries participating in EUROCARE-4 were analyzed. The period approach was used to estimate 5-year relative survival rates for patients diagnosed in 2000–2002, who did not have 5 years of follow up.

Results

The 5-year relative survival rate was 57% overall but varied markedly between the defined groups. Variation in survival within the groups was relatively limited across European regions and less than in previous years. Survival differences between men and women were small. The relative survival for patients with all lymphoid neoplasms decreased substantially after the age of 50. The proportion of ‘not otherwise specified’ diagnoses increased with advancing age.

Conclusions

This is the first study to analyze survival of patients with lymphoid neoplasms, divided into groups characterized by similar epidemiological and clinical characteristics, providing a benchmark for more detailed analyses. This Europe-wide study suggests that previously noted differences in survival between regions have tended to decrease. The survival of patients with all neoplasms decreased markedly with age, while the proportion of ‘not otherwise specified’ diagnoses increased with advancing age. Thus the quality of diagnostic work-up and care decreased with age, suggesting that older patients may not be receiving optimal treatment.     

Short-term mortality of bacteraemia in elderly patients with haematological malignancies

Bacterial infections are important complications in patients with haematological malignancies. We compared the outcome of bacteraemia among elderly and younger patients with haematological malignancies, and evaluated the impact of comorbidity on this association using population-based registries from 1992 to 2002. Among 358 patients with an incident haematological malignancy and an episode of bacteraemia, 207 (58%) were older than 60 years and 37 (10%) older than 80 years. The 7-d mortality was 10% among patients younger than 60 years, 21% among patients aged 60-79 years, and 27% for patients older than 80 years. When compared with patients younger than 60 years, the adjusted mortality rate ratios (MRRs) were 1.9 [95% confidence interval (CI): 0.9-3.8] for patients aged 60-79 years and 1.6 (95% CI: 0.6-4.2) for patients older than 80 years. The 30-d mortality was 23% among patients younger than 60 years of age, 35% among patients aged 60-79 years, and 54% among patients 80 years or older. Adjusted MRRs were 1.7 (95% CI: 1.1-2.7) and 2.3 (95% CI: 1.2-4.3), respectively. We found that increasing age was associated with increased mortality from bacteraemia in patients with haematological malignancies. An increased burden of comorbidity among the elderly did not explain this association.     

口服伊曲康唑治疗危重患者白色念珠菌肺部感染临床疗效观察

目的评估伊曲康唑口服制剂治疗重症监护病房(ICU)中危重患者白色念珠菌肺部感染的临床疗效。方法将2005年11月至2007年5月天津市第一中心医院ICU住院患者中痰培养为白色念珠菌者71例分为2组:伊曲康唑口服组36例,予伊曲康唑口服液200mg口服,每12h1次,疗程14d;氟康唑静脉制剂组35例,氟康唑静脉制剂首剂400mg静脉滴注,以后200mg静脉滴注,每日1次,疗程14d。结果伊曲康唑口服组完成总疗程者31例,真菌清除率64.52%(20/31),平均清除时间(10.12±2.57)d,有效率58.06%(18/31),痊愈率19.35%(6/31)。氟康唑静脉制剂组完成总疗程者29例,真菌清除率65.52%(19/29),平均清除时间(8.87±1.95)d,有效率62.07%(18/29),痊愈率17.24%(5/29)。伊曲康唑口服组与氟康唑静脉制剂组不良反应发生情况比较,差异无显著性意义,肝功能异常发生率分别为25.81%(8/31)和24.14%(7/29),经治疗无效停药者分别为3.23%(1/31)和6.90%(2/29)。结论伊曲康唑口服制剂治疗ICU白色念珠菌肺部感染疗效确切,且用药方便、安全、副反应低。     

Clinical significance of Aspergillus fungaemia in patients with haematological malignancies and invasive aspergillosis

The clinical significance of Aspergillus fungaemia in the setting of a deep-seated aspergillosis has not been clearly established. Among 107 microbiologically documented Aspergillus infections in patients with haematological diseases observed over a 17-year period, blood cultures grew Aspergillus species from 10 cases. Aspergillus fungaemia was documented in 9 out of 89 (10.1%) patients with pulmonary aspergillosis at a median of 5 d from the onset of clinical signs of infection, and in one patient with central venous catheter focal infection. Five (50%) patients died as a result of fungal infection a median of 12 d (range 4--48) from the documentation of Aspergillus fungaemia. A comparison between cases of invasive aspergillosis with or without fungaemia showed that fungaemic patients were similar to those without positive blood cultures regarding clinical presentation, risk factors, clinical course and outcome. The diagnostic role of Aspergillus fungaemia in the setting of a deep-seated infection is limited because blood cultures become positive when a microbiological or clinical diagnosis of aspergillosis has already been performed. Aspergillus fungaemia does not necessarily seem to be correlated with a disseminated infection or a poorer prognosis.     

Candida krusei– a serious complication in patients with hematological malignancies: successful treatment with caspofungin

Abstract: Candida krusei infections are serious complications in neutropenic patients with hematological malignancies. We report the successful treatment of C. krusei infection with caspofungin in 3 allogeneic hematopoietic stem cell transplant recipients and 1 patient with induction chemotherapy for acute myeloid leukemia.     

纤维支气管镜技术在ICU重症肺炎患者临床运用分析

目的分析研究纤维支气管镜技术在ICU重症肺炎患者中的临床应用。方法选择我院ICU收治的120例重症肺炎患者为研究对象,将其随机分成治疗组和对照组各60例,治疗组采用纤支镜治疗,对照组采用常规的抗感染和机械通气等支持治疗,比较两组患者的疗效。结果治疗组与对照组的总有效率分别为86.67%和66.67%,两组之间具有显著差异,P0.05。结论使用纤支镜对患者进行吸痰以及灌洗治疗,可有效改善重症肺炎症状,并缩短患者的住院时间,安全性好,值得在临床推广应用。     

ICU老年危重患者深部真菌感染的高危因素分析及防治

目的探讨重症监护病房（ICU）老年危重患者的深部真菌感染的高危因素及防治策略。方法回顾性分析52例老年危重患者深部真菌感染的临床资料。结果52例分离出病原菌78株，分离的部位以下呼吸道为主，其次为泌尿系统，血液和深静脉导管。所有患者都具有多种高危因素，包括接受侵入性操作，应用广谱抗生素，ICU住院时间长，静脉营养，糖尿病，恶性肿瘤，激素应用等。本组患者死亡率为40／52（76．9％），深部真菌感染相关死亡率为28／52（53．9％）。结论深部真菌感染已成为ICU老年危重患者死亡的重要原因，应予高度重视，及时抗真菌治疗，可以明显减少病死率。     

Diagnostic yield of bronchoscopy with bronchoalveolar lavage in febrile patients with hematologic malignancies and pulmonary infiltrates

Infectious complications are a major cause of morbidity and mortality in immunosuppressed patients. Febrile patients with hematologic malignancies and pulmonary infiltrates have high mortality rates, especially if mechanical ventilation is required. The diagnostic value of fiberoptic bronchoscopy (FOB) with bronchoalveolar lavage (BAL) in these patients is controversial. We retrospectively analyzed the microbiological results of BAL samples obtained during 249 FOB examinations from 199 febrile patients with hematologic malignancies and pulmonary infiltrates (underlying diseases: acute leukemia 103 patients, lymphoma 84 patients, other malignancies 12 patients). Two hundred forty-six examinations could be evaluated. Seventy-three out of 246 BAL samples were sterile; 55 samples showed microbiological findings classified as contamination or colonization. One hundred eighteen samples showed positive microbiological results of bacteria and/or fungi classified as causative pathogens. Thereof, in 70 samples, only bacterial pathogens were detectable (Gram-positive, 35; Gram-negative, 30; mixed Gram-positive and Gram-negative, 5). Thirteen samples showed both fungi and bacterial pathogens. In 33 samples, only fungi were detectable, thereof, in 15 samples Aspergillus species, in 16 samples Candida species, and in 2 both. In two samples, a viral pathogen could be detected. Three nonlethal complications (bleeding, arrhythmia) occurred that required early termination of FOB. In 94 (38.2%) patient episodes, antibiotic treatment was modified as a result of microbiological findings in BAL samples. Our results show that FOB with BAL is a valuable diagnostic tool with low complication rates in high-risk febrile patients with hematologic malignancies and pulmonary infiltrates, contributing crucial results for the individual case, and also improving epidemiologic knowledge.     

ICU嗜麦芽窄食单胞菌肺部感染的诱因及耐药性分析

目的分析重症监护病房（ICU）嗜麦芽窄食单胞菌（SMA）肺部感染的诱因及敏感情况。方法分析52例ICU嗜麦芽窄食单胞菌肺部感染患者的病例资料。结果 SMA肺部感染的主要诱因为人工气道建立、广谱抗生素≥14 d、侵入性操作、机械通气和皮质激素应用等;ICU内肺部感染的SMA呈多重耐药性,其中亚胺培南耐药性最高（96.2%）,替卡西林/克拉维酸敏感性最高（73.1%）。结论应严格根据药敏结果选择敏感抗生素,加强无菌操作规程,避免医源性传播,慎重使用免疫抑制剂,增强患者免疫力,从而降低SMA肺部感染的发病率。     

Early hospital discharge with oral antimicrobial therapy in patients with hematologic malignancies and low-risk febrile neutropenia

Although consensus exists relating criteria for the identification of low-risk patients with febrile neutropenia, no clear indication on how to manage these patients has been so far provided particularly in outpatients affected by hematologic malignancies. The feasibility and safety of early discharge was prospectively evaluated in 100 outpatients with hematologic malignancies and febrile neutropenia. A strategy considering the risk-index of the Multinational Association of Supportive Care in Cancer (MASCC) was applied. High-risk patients were entirely managed at hospital. Low-risk patients were early discharged if they were afebrile since 48 h and not on supportive therapy requiring hospitalization. Out of 90 low-risk episodes, in 69 instances (76.7%), patients were discharged after a median of 4 days and continued home therapy with oral cefixime (78%) or other antibiotics. Only five outpatients (7.2%) had fever recurrence. Twenty-one low-risk patients were not early discharged due to worsening conditions (three deaths), need of multiple daily dose therapy, or discharge refuse. No clinical characteristic was able to predict the eligibility for early discharge. The MASCC risk-index is a useful aid in the identification of high-risk febrile neutropenia needing whole in-hospital treatment. As for low-risk patients, hospitalization at least in the first days of fever is required. Cefixime could be included among the oral antibacterial drugs to be used in the outpatient treatment of adult patients with febrile neutropenia.