重症监护室免疫抑制和免疫健全脓毒症患儿28天内死亡因素的病例对照研究

目的评估伴免疫抑制相关基础疾病的儿童重症监护室脓毒症患儿入PICU 28 d内死亡及其危险因素。方法病例对照研究。回顾性收集复旦大学附属儿科医院（我院）因脓毒症/脓毒性休克收入PICU的患儿临床资料,分为免疫抑制组和免疫健全组,考察免疫抑制患儿入PICU 28 d内死亡的危险因素。结果2015年12月1日至2018年12月31日我院PICU出院诊断脓毒症连续病例385例,排除入科后24 h内死亡和PICU获得性脓毒症病例,251例PICU脓毒症/脓毒性休克患儿进入本文分析,免疫抑制组110例 (43.8%),免疫健全组141例。与免疫健全组比较,免疫抑制组以住院转入患儿（70%）为主,PICU维持治疗需求（血管活性药物、有创/无创机械通气）高、24 h PRISM评分高,不明确感染部位比例高,免疫抑制组接受ECMO治疗者全部死亡,持续肾脏代替治疗（CRRT）存活率为17.4%,入PICU第28 d病死率69.1%。免疫健全组和免疫抑制组28 d内存活和死亡患儿比较,除脓毒性休克、有创机械通气、CRRT、PRISM Ⅲ评分、乳酸>2 mmol·L-1比例、PICU住院时间、总住院时间、脱离PICU时间、24 h内放弃治疗、总放弃治疗差异有统计学意义外,应用血管活性药物在免疫抑制组入PICU 28 d内存活和死亡因素比较中差异有统计学意义。多因素COX比例风险模型分析显示,PRISM Ⅲ评分、有创机械通气、乳酸>2 mmol·L-1是免疫抑制组和免疫健全组入PICU 28 d内病死率的共同危险因素,休克是免疫抑制组入PICU 28 d内病死率的危险因素。结论重症监护室脓毒症患儿病死率较高;伴免疫抑制相关基础疾病的脓毒症患儿病死率更高;PRISMⅢ评分、48 h内有创机械通气和入院乳酸值(>2 mmol·L-1)是其预后的重要危险因素。应建立早期预警指标,对免疫抑制患儿进行早期识别,早期干预,可能改善预后。     

Effectiveness analysis of high-frequency oscillatory ventilation in pediatrics patients with acute respiratory failure in a tertiary hospital

Introduction. High frequency oscillatory ventilation (HFOV) is a rescue therapy for hypoxemic patients who deteriorate in conventional mechanical ventilation and/or for the air-leak syndrome treatment. A recent meta analysis showed that HFOV might have reduced mortality in pediatric and adult patients compared with conventional ventilation. In this context it's important to evaluate the effectiveness of this method in everyday use. Objectives. Main: To analize the effectiveness of HFOV in everyday practice in a center without extra corporeal membrane oxygenation (ECMO) capabilities. Secondary: To describe demographics and causes of severe respiratory failure of patients requiring HFOV. To assess the relationship between potential predictors and the occurrence of mortality. Population and methods. Retrospective study analyzing medical records of all patients that required HFOV in a tertiary care pediatric hospital pediatric intensive care units between march 1st 2008 and july 1st 2010. Results. Sixty-nine patients received 76 HFOV treatments. Eighty percent were diagnosed with acute lower respiratory infection or sepsis and 62.3% (n= 43) had preexisting chronic co-morbidities. The majority of HFOV treatments were because refractory hypoxemia (93.4%). Non survivors patients had worse clinical status at PICU admission, higher multiorgan failure, worse oxygenation and pulmonary condition. Conclusions. Everyday use of HFOV in a population with high incidence of chronic, oncologic and/or immunocompromised patients was associated with a survival of 33.4%. More prognostic studies are needed for a more effective selection of HFOV candidates.     

Identification of adrenal insufficiency in pediatric critical illness.

OBJECTIVE: To determine physicians' beliefs and practices regarding adrenal dysfunction in pediatric critical illness. DESIGN: Cross-sectional mail survey. SETTING: Canada. PARTICIPANTS: All members of the Canadian Pediatric Endocrine Group and all physicians identified as practicing pediatric intensive care medicine in any of 16 tertiary care teaching centers in Canada. INTERVENTIONS: Three pediatric intensive care physicians and three pediatric endocrinologists reviewed the questionnaire before administration to ensure clarity. We asked participants to report their views on the following: a) the frequency of adrenal insufficiency in pediatric critical illness; b) diagnosis/definition of adrenal insufficiency in pediatric critical illness; and c) the use of empirical glucocorticoids in fluid/vasopressor-resistant hypotension in pediatric critical illness. MEASUREMENTS AND MAIN RESULTS: Forty-six of 57 (80.7%) endocrinologists responded, with 43 participating (75.4%). Among intensivists, 59 of 70 (84.3%) responded with no refusals. Of intensivists, 81.4% believe that adrenal insufficiency occurs sometimes or often in critically ill pediatric intensive care unit patients, whereas 41.8% of endocrinologists believe adrenal insufficiency occurs never or rarely in these patients. Six definitions of adrenal insufficiency were proposed (varying cortisol level vs. peak/increment of cortisol in response to corticotropin), with no consensus on the definition of adrenal insufficiency from the endocrinologists or intensivists. Half (50.9%) of intensivists said they would sometimes or often empirically treat hypotensive pediatric patients with glucocorticoids, whereas 81.0% of endocrinologists would occasionally or never recommend glucocorticoids on this basis. CONCLUSIONS: There is no consensus among pediatric intensivists or endocrinologists as to how often adrenal insufficiency occurs in pediatric critical illness or how to diagnose this condition. Despite this lack of consensus, however, many pediatric intensivists would empirically treat hypotensive patients who they suspect may have adrenal insufficiency. Prospective studies are required to determine the definition, frequency, and appropriate treatment of adrenal insufficiency in critically ill pediatric patients.     

New antifungal drugs and the pediatric cancer patient: current status of clinical development

Invasive mycoses are important causes for treatment related morbidity and mortality in severely immunocompromised pediatric patients with hematological malignancies or hematopoietic stem cell transplantation. The past decade has witnessed a major expansion of antifungal drug research, which has resulted in the development of the novel class of echinocandin lipopeptides (anidulafungin, micafungin, caspofungin) and a new generation of antifungal triazoles with improved pharmacological properties (posaconazole, ravuconazole, voriconazole). Whereas caspofungin and voriconazole have been licensed in the European Union, the United States, Canada and several other countries throughout the world, posaconazole, ravuconazole, anidulafungin and micafungin are under regulatory review or in advanced stages of clinical development. Caspofungin and voriconazole are increasingly prescribed in pediatric patients, although pediatric dosage finding and safety evaluations have not been completed. This article reviews the clinical pharmacology of the new antifungal agents and the status of their clinical development in immunocompromised pediatric patients.     

Downfall of the current antibody correlates of influenza vaccine response in yearly vaccinated subjects: Toward qualitative rather than quantitative assays

Response to seasonal influenza vaccination is currently evaluated by antibody correlates that estimate vaccine seroconversion as well as immune protection. These correlates rely on the general dogmas surrounding seasonal influenza vaccination; that is, that vaccine‐induced antibodies would exclusively generate immunity to influenza vaccine strains and that protective immunity would wane before the next season. Here, we summarize recently reported data on immunity to seasonal influenza in healthy individuals and rediscuss results on yearly vaccinated pediatric immunocompromised patients that together highlight the need for revision of the current correlates of vaccine response to shift from quantitative to qualitative measurements.     

Resuscitation update for the pediatrician

Survival and neurologic outcome among pediatric patients in CPA have not improved measurably in the past decade, but the evolution of the pediatric Utstein guidelines has provided those involved in pediatric resuscitation a common language with which to exchange information and hopefully conduct meaningful research. The widespread use of the LMA may hold real promise for airway management of pediatric patients in the prehospital setting. Several of the developments in adult resuscitation, including ACD CPR and IAC CPR, seem auspicious for pediatric patients in cardiac arrest. At first glance, the widespread use of the AED would not be expected to alter the outcome of pediatric patients in CPA, but two studies suggest that ventricular fibrillation is more common in the pediatric population than originally believed, and thus the AED may have a significant role for this group of patients. The value of high-dose epinephrine remains controversial. All of these areas require research in the pediatric population before a judgment on their worth can be made. Research in pediatric resuscitation requires the study of larger populations, most feasibly with multicenter studies. How the "final rule" will influence this type of research remains to be seen. Finally, if investigators are to make real progress in improving the outcome of pediatric patients in CPA, they must concentrate their efforts on education of the lay public and enhancement of prehospital care.     

重症监护室免疫抑制和免疫健全脓毒症患儿28天内死亡因素的病例对照研究

目的评估伴免疫抑制相关基础疾病的儿童重症监护室脓毒症患儿入PICU 28 d内死亡及其危险因素。方法病例对照研究。回顾性收集复旦大学附属儿科医院（我院）因脓毒症/脓毒性休克收入PICU的患儿临床资料，分为免疫抑制组和免疫健全组，考察免疫抑制患儿入PICU 28 d内死亡的危险因素。结果2015年12月1日至2018年12月31日我院PICU出院诊断脓毒症连续病例385例，排除入科后24 h内死亡和PICU获得性脓毒症病例，251例PICU脓毒症/脓毒性休克患儿进入本文分析，免疫抑制组110例 (43.8%)，免疫健全组141例。与免疫健全组比较，免疫抑制组以住院转入患儿（70%）为主，PICU维持治疗需求（血管活性药物、有创/无创机械通气）高、24 h PRISM评分高，不明确感染部位比例高，免疫抑制组接受ECMO治疗者全部死亡，持续肾脏代替治疗（CRRT）存活率为17.4%，入PICU第28 d病死率69.1%。免疫健全组和免疫抑制组28 d内存活和死亡患儿比较，除脓毒性休克、有创机械通气、CRRT、PRISM Ⅲ评分、乳酸>2 mmol·L-1比例、PICU住院时间、总住院时间、脱离PICU时间、24 h内放弃治疗、总放弃治疗差异有统计学意义外，应用血管活性药物在免疫抑制组入PICU 28 d内存活和死亡因素比较中差异有统计学意义。多因素COX比例风险模型分析显示，PRISM Ⅲ评分、有创机械通气、乳酸>2 mmol·L-1是免疫抑制组和免疫健全组入PICU 28 d内病死率的共同危险因素，休克是免疫抑制组入PICU 28 d内病死率的危险因素。结论重症监护室脓毒症患儿病死率较高；伴免疫抑制相关基础疾病的脓毒症患儿病死率更高；PRISMⅢ评分、48 h内有创机械通气和入院乳酸值(>2 mmol·L-1)是其预后的重要危险因素。应建立早期预警指标，对免疫抑制患儿进行早期识别，早期干预，可能改善预后。     

Fiberoptic bronchoscopy and bronchoalveolar lavage for the evaluation of pulmonary disease in children with primary immunodeficiency and cancer

BACKGROUND: Patients with childhood cancer or primary immunodeficiencies (PID) are at high risk for developing pulmonary infections and non-infectious complications. The broad differential diagnoses and the critical condition of these patients often drive physicians to start broad-spectrum antibiotic therapy before a definite diagnostic procedure is performed. A definite diagnosis may be achieved in these situations by fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL). PATIENTS AND METHODS: The records of 58 PIDs and cancer (immunocompromised group) pediatric patients who underwent 62 fiberoptic bronchoscopies between 2000 and 2004 were retrospectively reviewed and compared to 158 non-cancer patients who underwent 182 fiberoptic bronchoscopies during the same period. RESULTS: The overall diagnostic rate achieved by macroscopic inspection of purulent secretions or hemorrhage, abnormal cell count, and infectious agent isolation in the immunocompromised patients was 84%. A definite organism was recovered in 53.2% of the patients. Probable infection defined as purulent secretions or abnormal cell count without infectious agent isolation was diagnosed in another 21% of the patients. The rate of complications was 30.6%. In the control group, the overall diagnostic rate was 76.9% (n.s) and an infectious agent was demonstrated in 12.1% (P < 0.001). Probable infection was diagnosed in 24.2% (n.s) while the rate of complications was lower (15%) (P < 0.01). CONCLUSIONS: Rapid and accurate diagnoses were achieved in most procedures performed on immunocompromised patients. Although the rate of complications was higher in the immunocompromised group, they were usually very mild with no mortality. Based on these results, broncoalveolar lavage should be considered as an initial diagnostic tool in pediatric immunocompromised patients with pulmonary complications.     

Legionella bozemanii pulmonary abscess in a pediatric allogeneic stem cell transplant recipient

Legionella spp. infections are often considered in the differential diagnosis of pneumonia in adults. This case report describes a pediatric stem cell transplant recipient presenting with cavitary pulmonary disease secondary to Legionella bozemanii infection. Also highlighted with this atypical clinical presentation are challenges in diagnosing legionellosis and concerns of increased vulnerability for such infections when severely immunocompromised patients are changed to nontrimethoprim-sulfamethoxazole Pneumocystis jiroveci pneumonia prophylaxis.     

Voriconazole treatment of presumptive disseminated Aspergillus infection in a child with acute leukemia

Invasive fungal infection continues to pose a significant threat to immunocompromised patients. The authors describe a pediatric patient receiving chemotherapy for acute undifferentiated leukemia who developed presumptive Aspergillus species infection disseminated to lung, liver, spleen, and bone. The authors report the successful treatment of this infection with the addition of voriconazole, a triazole antimycotic, to treatment with amphotericin and surgical debridement, in the setting of ongoing intensive chemotherapy.     

Bronchoalveolar lavage for diagnosis of pneumonia in the immunocompromised child

Seven children with immunocompromised states were referred to the pediatric bronchoscopy service for evaluation of pneumonia. Flexible fiberoptic bronchoscopy accompanied with bronchoalveolar lavage was performed in all seven of these children. A definitive diagnosis was made for six of these seven patients. The diagnosis included Pneumocystis carinii in three, Candida albicans in two, and cytomegalovirus in one. There were no complications associated with the procedure. Flexible fiberoptic bronchoscopy with bronchoalveolar lavage should be considered early in the evaluation of the immunocompromised child with pneumonia.     

Diagnostic and treatment challenges for the pediatric hematologist oncologist in endemic areas for coccidioidomycosis

Coccidioidomycosis is a mycosis endemic to certain areas in the Southwest, mostly Arizona and California, Mexico, and parts of Central and South America. Disseminated coccidioidomycosis is much more common in immunocompromised hosts; therefore, it is frequently encountered by pediatric oncologists in endemic areas. Special attention is needed to diagnose, effectively treat the infection, and appropriately adjust chemotherapy treatment plans to minimize immunosuppression. We describe the presentation and course of 6 patients with coccidioidomycosis who were seen by the pediatric hematology-oncology service at the University of Arizona during the last 3 years. Coccidioidomycosis is a relatively common infection encountered by pediatric oncologists in the southwestern states and should be considered in the differential diagnosis of patients living or visiting these areas.     

Clinical utility of bronchoalveolar lavage in pediatric cancer patients

BACKGROUND: Pulmonary disease in the pediatric cancer patient continues to pose a difficult clinical dilemma. Bronchoalveolar lavage (BAL) is commonly utilized for the diagnosis of pulmonary complications in the immunocompromised child. PROCEDURE: We retrospectively reviewed 53 BAL procedures performed in pediatric cancer patients with pulmonary disease between 1988 and 1998 to determine the diagnostic and clinical utility of BAL. Patients who had undergone prior myeloablative therapy were excluded from analysis. RESULTS: The majority of patients (83%) had an underlying diagnosis of acute leukemia or lymphoma. BAL yielded a specific diagnosis in 16 patients (30%), including 15 infections and 1 malignant infiltration. Medical management was altered in an additional 14 patients (26%) as a consequence of a negative BAL result. Severe but transient complications associated with the BAL procedure occurred in four patients (8%). Minor complications following the BAL occurred in 21 patients (40%) and included transiently increased oxygen requirement and anesthesia-related gastrointestinal complaints. The mortality from lung disease in this patient population was 7.5%. CONCLUSIONS: Both positive and negative BAL results contribute to the management of pediatric cancer patients with pulmonary disease. The low incidence of significant complications associated with BAL and the high mortality rate in this patient population support the choice of BAL as an initial diagnostic test in pediatric cancer patients with pulmonary disease.     

Cat-scratch disease relapse in a kidney transplant recipient

Cat-scratch disease, an infectious illness infrequently reported in kidney transplant patients, is caused by the organism Bartonella henselae and is transmitted through contact with cats or kittens. It is a self-limited disorder in the general pediatric population. Here we present a case of unsuspected cat-scratch disease in a pediatric kidney transplant patient who presented with fever and lymphadenopathy. Eight months after treatment with a short course of azithromycin, the patient developed a recurrence of cat-scratch disease. We emphasize that the evaluation of a young immunocompromised kidney transplant patient presenting with fever and lymphadenopathy should include unusual infections such as cat-scratch disease. We review the diagnosis and treatment of this uncommon infection in the organ transplant population.     

Cryptosporidiosis in children with acute lymphoblastic leukemia on maintenance chemotherapy

Cryptosporidium is recognized as a cause of diarrhea associated with a high mortality in immunocompromised patients. We report on 2 pediatric cases of cryptosporidiosis during maintenance chemotherapy of acute lymphoblastic leukemia. The patients presented severe diarrheas, 1 of them was complicated by a cholangitis. Withdrawal of immunosuppressive treatments and adjunction of an adequate antiparasitic treatment cured the Cryptosporidium infection in both cases.     

Knowledge,attitudes, and practice styles of North American pediatric gastroenterologists: Helicobacter pylori infection

OBJECTIVE: Most Helicobacter pylori infections are acquired during childhood. The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) recently published practice guidelines for managing pediatric H. pylori infection. Before this publication, the authors conducted a survey to assess pediatric gastroenterologists' knowledge and practices regarding H. pylori. METHODS: One hundred nine of 514 NASPGHAN members completed an Internet-based questionnaire on H. pylori infection. RESULTS: Eighty-two percent of respondents performed outpatient testing for H. pylori. Of these, only 31% restricted testing to children aged >5 years. Most recommended testing for H. pylori in guideline-recommended conditions; some would not treat infected patients. Ninety-seven percent would test for H. pylori in a child with new duodenal ulcer (DU), 79% in a child with a history of DU, and 91% in a child with new gastric ulcer. However, only 86%, 60%, and 91%, respectively, would treat H. pylori infection in those conditions. A proton pump inhibitor (PPI)-based triple regimen was the first-choice therapy for 78% of respondents. Correct estimates of rates of resistance to amoxicillin, clarithromycin, metronidazole, and tetracycline were 10%, 17%, 43%, and 12%, respectively. Eighty-six percent believed there was insufficient research on H. pylori in children. CONCLUSIONS: North American pediatric gastroenterologists seem well informed about H. pylori infection in children despite the lack of published guidelines at the time of survey. Knowledge about antibiotic resistance rates was deficient. Most offered some outpatient testing for H. pylori and would test children with ulcer disease. However, some would not treat patients based on a positive result.     

Bacterial meningitis from Rothia mucilaginosa in patients with malignancy or undergoing hematopoietic stem cell transplantation

Opportunistic infections contribute to morbidity and mortality of patients undergoing hematopoietic stem cell transplantation and treatment for malignancies. Rothia mucilaginosa, a gram-positive bacterium, is responsible for rare, but often fatal meningitis in severely immunocompromised patients. We describe two cases of meningitis from discrete strains of R. mucilaginosa on our pediatric bone marrow transplant unit, summarize the published cases of R. mucilaginosa meningitis in oncology and stem cell transplant patients, and provide updated recommendations regarding the use of antibiotic therapy in this patient population.     

Importance of prevention of infectious complications in pediatric hematologic-oncologic patients

The control of severe infectious complications by preventive strategies, early diagnosis of infections and empiric broad-spectrum antibiotic therapy contributed to a marked improvement of survival in children with cancer over the last 20 years. This article overviews of the importance of prevention of infectious complications in immunocompromised pediatric patients with hematologic or oncologic diseases. The particular challenge of this age group with respect to the acquisition and the spread of pathogens, the spectrum of causative microorganisms and the principal issues of anti-infectious prophylaxis are considered.     

Oral ribavirin for paramyxovirus infection after alemtuzumab‐containing reduced‐intensity conditioning HCT regimen

Aerosolized ribavirin has been used in pediatric immunocompromised patients to treat acute respiratory viral infections, but oral ribavirin may be a less expensive alternative that allows for outpatient therapy. Oral ribavirin has compared favorably to aerosolized ribavirin in adult studies, but data on safety are lacking in pediatric populations. Four cases are described in which oral ribavirin was used to treat viral respiratory infections in recipients of allogeneic hematopoietic stem cell transplants at a Children's Hospital, demonstrating safety and feasibility.