Pleuro-pulmonary ultrasound in the diagnosis and follow-up of lung infections in children with cancer: a pilot study

PurposeFebrile neutropenia and lung infections are common and potential fatal complications of pediatric cancer patients during chemotherapy. Lung ultrasound (LUS) has a good accuracy in the diagnosis of pneumonia in childhood, but there is no data concerning its use in the diagnosis and follow-up of pulmonary infection in children with cancer. The goal of this pilot study is to verify the feasibility of lung ultrasonography for the diagnosis and follow up of pneumonia in children and adolescents with cancer.Material and methodsThis is a prospective observational case–control monocentric study conducted in the Pediatric Hematology and Oncology Department of University Hospital of Catania in patients aged < 18 years with cancer. Attending Physician used ultrasonography to detect pneumonia in cancer children with fever. As control group, cancer patients with no infection suspicion were also tested. LUS results were compared to chest X-ray (CXR) and/or chest CT scan, when these imaging techniques were performed, according to clinical indication.ResultsThirty-eight patients were studied. All underwent LUS, 16 underwent CXR, 3 chest CT. Statistical analysis showed LUS specificity of 93% (95% CI 84–100%), and sensitivity of 100%; CXR, instead, showed a specificity of 83% (95% CI 62–100%) and a sensitivity of 50% (95% CI 1–99%).ConclusionThis study shows for the first time that LUS allows physicians to diagnose pneumonia in children and young adults with cancer, with high specificity and sensitivity.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40477-021-00650-3.     

Catheter-related bloodstream infection by Microbacterium paraoxydans in a pediatric patient with B-cell precursor acute lymphocytic leukemia: A case report and review of literature on Microbacterium bacteremia

Microbacterium species are coryneform gram-positive rods that are widely distributed in the environment and have been recently recognized as rare pathogens in humans. However, information about the epidemiologic and clinical characteristics of Microbacterium species is scarce. We herein reported an 11-year-old girl with acute leukemia who was found to have catheter-related bloodstream infection in her neutropenic phase. Gram-positive bacilli repeatedly grew on the blood cultures and were later confirmed by 16S rRNA analysis as Microbacterium paraoxydans. A literature review found available clinical courses in 21 cases (7 pediatric cases) of Microbacterium spp. bacteremia. Our case and those in literature suggested that Microbacterium spp. bacteremia often occurs in patients with indwelling central venous catheters; the literature review further suggested that removal of central venous catheters is required in most cases and that 16S rRNA sequence was useful in identifying in detail the species of Microbacterium.     

Recent advances in understanding the pathogenesis and management of reticular dysgenesis

Reticular Dysgenesis is a rare immunodeficiency which is clinically characterized by the combination of Severe Combined Immunodeficiency (SCID) with agranulocytosis and sensorineural deafness. Mutations in the gene encoding adenylate kinase 2 (AK2) were identified to cause this phenotype. In this review, we will demonstrate important clinical differences between reticular dysgenesis and other SCID entities and summarize recent concepts in the understanding of the pathophysiology of the disease and the management strategies for this difficult condition.     

Impact of chemotherapy-induced neutropenia on quality of life: a prospective pilot investigation

Purpose In this exploratory, prospective study evaluated quality of life (QoL) changes in patients with diverse cancers during the first cycle of myelosuppressive chemotherapy.Patients and methods Of 80 patients enrolled, 71 were observed during one of five chemotherapy regimens: docetaxel; CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone); carboplatin-paclitaxel; carboplatin-docetaxel; and carboplatin-gemcitabine. Complete blood counts were taken weekly. QoL and symptom burden measures were administered at baseline and throughout the cycle, and included SF-36, Cancer Care Monitor (CCM), Hospital Anxiety and Depression Scale (HADS), and Psychosocial Adjustment to Illness Scale (PAIS). Using generalized estimating equations, we modeled the change in each measure from baseline to the end of each week using the following covariates: baseline QoL measure, baseline SF-36 Physical and Mental Health Summary scores, sex, age, cycle week, grade 4 neutropenia any time in the past 7 days (yes/no), and the interaction of the latter two covariates.Results Of the 71 patients observed, 33 developed grade 4 neutropenia during the first 2 weeks. Changes from baseline in SF-36 Bodily Pain, HADS Anxiety, and PAIS Social Environment scores were significantly less favorable (P<0.05) when patients experienced grade 4 neutropenia any time in the past 7 days compared to when they did not (grade 0–3). A similar, but non-significant, trend was also observed for 12 other QoL measures.Conclusion QoL may be adversely affected up to 7 days after patients experience grade 4 (versus grade 0–3) neutropenia. Such findings need to be examined further in studies with adequate statistical power to test a priori hypotheses regarding specific QoL measures.Support for this work was provided by Amgen Inc.Portions of the research were previously presented at: Mayo Clinic Assessing Clinical Significance for QoL Measures in Oncology Research, State-of-the-Science, March 2002, Rochester, MN; the 27th Meeting of the European Society of Medical Oncology, October 2002, Nice, France; and the American Society of Hematology, December 2002, Philadelphia, PA.     

Economic aspects of empiric antibiotic therapy for febrile neutropenia in children with cancer

Several antibiotic regimens have been proposed worldwide for empiric treatment of febrile neutropenia in children with cancer, but none of them shows clear advantages in terms of clinical efficacy. Therefore, other parameters, including drug acquisition costs, should be considered in the selection of treatment. Children receive a "fraction" of a standard daily dose, and this fraction is generally calculated on the basis of body weight; therefore, the cost of each day of therapy is determined by the packages available for each single drug. We calculated the acquisition costs of various drugs proposed for the empiric treatment of febrile neutropenia in children with cancer, and then we estimated the daily cost of therapy referred to different patient weights. In general, the combination regimen with ceftriaxone plus aminoglycoside turned out to be less expensive than other regimens (including monotherapy with third-generation cephalosporins or carbapenems).     

TCIRG1‐Associated Congenital Neutropenia

Severe congenital neutropenia (SCN) is a rare hematopoietic disorder, with estimated incidence of 1 in 200,000 individuals of European descent, many cases of which are inherited in an autosomal dominant pattern. Despite the fact that several causal genes have been identified, the genetic basis for >30% of cases remains unknown. We report a five‐generation family segregating a novel single nucleotide variant (SNV) in TCIRG1. There is perfect cosegregation of the SNV with congenital neutropenia in this family; all 11 affected, but none of the unaffected, individuals carry this novel SNV. Western blot analysis show reduced levels of TCIRG1 protein in affected individuals, compared to healthy controls. Two unrelated patients with SCN, identified by independent investigators, are heterozygous for different, rare, highly conserved, coding variants in TCIRG1.     

Clinical characteristics and outcomes of clostridial bacteraemia in cancer patients

Clostridial bacteraemia is usually associated with substantial morbidity and mortality in cancer patients. However, clinical characteristics and risk factors for early mortality in this population are poorly described. We retrospectively studied cancer patients with clostridial bacteraemia treated between January 1996 and December 2011. We compared clinical manifestations between patients with solid tumour and haematological malignancy and assessed risk factors for 7-day mortality. In all, 164 cancer patients developed clostridial bacteraemia during the study period—85 (52%) with solid tumour and 79 (48%) with haematological malignancy. Common isolates were Clostridium perfringens (27%), Clostridium septicum (19%) and Clostridium tertium (14%). Solid tumour malignancy patients were more likely to have a focal gastrointestinal source for bacteraemia and were more likely to undergo subsequent surgery. Haematological malignancy patients were more often neutropenic and more often had no focal source of bacteraemia. Seven-day mortality was 20% (33/164) and did not vary based on malignancy type. The adjusted odds ratio of dying within 7 days of clostridial bacteraemia among patients with hypotension (40/164) was 7.2 (95% CI, 2.9–18.1) and in patients with acute haemolysis (7/164) was 10.5 (95% CI, 1.3–85.2). Clostridial species also impacted mortality; no patient with C. tertium bacteraemia died within 7 days. In conclusion, clinical manifestations of clostridial bacteraemia differed between patients with solid tumour and haematological malignancy, but 7-day mortality was similar. Patients with hypotension and haemolysis at time of bacteraemia were at increased risk for early death.     

Analysis of 136 febrile neutropenic episodes in children with cancer: evaluation of treatment effectiveness and cost

In this study, 136 febrile neutropenic episodes were overviewed retrospectively. Factors affecting treatment success and cost were analyzed. Twenty percent of the episodes were microbiologically documented and 51% of the bacterial isolates were gram negatives. The most commonly used empirical therapies in febrile episodes were the combination of two drugs (58.0%), monotherapy (14.8%), and antibiotics plus fluconazole (20.6%). In lymphoproliferative tumors duration of fever and discharge from the hospital were longer. Administration of the hematopoietic growth factors shortened neither the duration of neutropenia nor fever and hospitalization. Treatment costs were higher in lymphoproliferative tumors, in bacteremia, and in episodes where glycopeptides, antifungal drugs, and hematopoietic growth factors were used. In conclusion, duration of neutropenia was a significant independent predictive factor for duration of fever. In the lymphoproliferative tumors, duration of fever was longer and cost of treatment was more than in the solid tumors.     

Serum levels of mannose-binding lectin and the risk of fever in neutropenia pediatric cancer patients

BACKGROUND: Fever in neutropenia (FN) is a frequent complication in pediatric oncology. Deficiency of mannose-binding lectin (MBL), an important component of innate immunity, is common due to genetic polymorphisms, but its impact on infections in oncologic patients is controversial. This study investigated whether MBL serum levels at cancer diagnosis are associated with the development of FN in pediatric cancer patients. PROCEDURE: Serum MBL was measured using ELISA. Frequency, duration, and cause of FN were assessed retrospectively. Association with MBL level was analyzed using uni- and multivariate Poisson regression taking into account both intensity and duration of chemotherapy. RESULTS: In 94 children, with a cumulative follow-up time of 81.7 years, 177 FN episodes were recorded. Patients with both very low MBL levels (<100 microg/L; risk ratio (RR), 1.93; 95% CI, 1.14-3.28; P = 0.014) and normal MBL levels (>or=1,000 microg/L; RR, P = 0.011) had significantly more frequent FN episodes than patients with low MBL levels (100-999 microg/L). Patients with very low MBL levels had significantly more episodes of FN with severe bacterial infection (bacteremia or pneumonia; RR, 4.49; 1.69 = 11.8; P = 0.003), while those with normal MBL levels had more FN episodes with no microbial etiology identified (RR, 1.85; 1.14 = 3.03; P = 0.014). CONCLUSIONS: Very low MBL levels are associated with more frequent FN episodes, mainly due to severe bacterial infections. The surprising finding that children with normal MBL levels had more frequent FN episodes than those with low MBL levels needs testing in prospective studies.