Cytomegalovirus immune plasma in bone marrow transplant recipients

The effects of passive immunization on cytomegalovirus infection and interstitial pneumonia in marrow transplants were evaluated in a randomized, controlled trial. Twenty-four patients received cytomegalovirus immune plasma before and after transplantation, and 24 patients were controls. Although the incidence of cytomegalovirus infection was similar in the control and plasma groups, symptomatic infection (12 of 24 versus five of 24, p = 0.07) and interstitial pneumonia (11 of 24 versus five of 24, p = 0.12) occurred less frequently in the group receiving plasma. Cytomegalovirus infection occurred in 11 of 13 recipients of leukocyte transfusions and in 16 of 35 patients not given leukocyte transfusions (p = 0.02). Among patients not given leukocyte transfusions, the incidence of cytomegalovirus infection was similar in the control and plasma groups, but symptomatic infection (eight of 18 versus one of 17, p = 0.03) and interstitial pneumonia (nine of 18 versus one of 17, p = 0.01) were significantly less in the group receiving plasma. These results suggest that passive immunization modifies cytomegalovirus infection in humans and prevents interstitial pneumonia in marrow transplants especially when leukocyte transfusions are not used.     

Idiopathic CD4 Lymphocytopenia: Clinical and Immunologic Characteristics and Follow-Up of 40 Patients

Idiopathic CD4 T lymphocytopenia (ICL) is a rare and severe condition with limited available data. We conducted a French multicenter study to analyze the clinical and immunologic characteristics of a cohort of patients with ICL according to the Centers for Disease Control criteria.We recruited 40 patients (24 female) of mean age 44.2 ± 12.2 (19–70) years. Patients underwent T-lymphocyte phenotyping and lymphoproliferation assay at diagnosis, and experiments related to thymic function and interferon (IFN)-γ release by natural killer (NK) cell were performed. Mean follow-up was 6.9 ± 6.7 (0.14–24.3) years. Infectious, autoimmune, and neoplastic events were recorded, as were outcomes of interleukin 2 therapy.In all, 25 patients had opportunistic infections (12 with human papillomavirus infection), 14 had autoimmune symptoms, 5 had malignancies, and 8 had mild or no symptoms. At the time of diagnosis, the mean cell counts were as follows: mean CD4 cell count: 127/mm³ (range, 4–294); mean CD8: 236/mm³ (range, 1–1293); mean CD19: 113/mm³ (range, 3–547); and mean NK cell count: 122/mm³ (range, 5–416). Most patients had deficiency in CD8, CD19, and/or NK cells. Cytotoxic function of NK cells was normal, and patients with infections had a significantly lower NK cell count than those without (p = 0.01). Patients with autoimmune manifestations had increased CD8 T-cell count. Proliferation of thymic precursors, as assessed by T-cell rearrangement excision circles, was increased. Six patients died (15%). CD4 T-cell count <150/mm³ and NK cell count <100/mm³ were predictors of death.In conclusion, ICL is a heterogeneous disorder often associated with deficiencies in CD8, CD19, and/or NK cells. Long-term prognosis may be related to initial CD4 and NK cell deficiency.Abbreviations: AIHA = autoimmune hemolytic anemia, CDC = Centers for Disease Control, CMV = cytomegalovirus, cpm = count per minute, CVID = common variable immunodeficiency, CXCR4 = C-X-C chemokine receptor type 4, HIV = human immunodeficiency virus, HLA = human leukocyte antigen, HPV = human papillomavirus, HTLV-1/2 = human T-cell lymphotropic 1/2, ICL = idiopathic CD4 T lymphocytopenia, IFN-γ = interferon-γ, IL = interleukin, JC virus = John Cunningham virus, LPA = lymphocyte proliferation assay, NK = natural killer, P = patient, PBMC = peripheral blood mononuclear cell, Pwd = pokeweed, SI = stimulation index, sj = signal joint, TREC = T-cell rearrangement excision circle     

Where is the neck?: Alpha angle measurement revisited

Background and purpose

The alpha angle is the most used measurement to classify concavity of the femoral head-neck junction. It is not only used for treatment decisions for hip impingement, but also in cohort studies relating hip morphology and osteoarthritis. Alpha angle measurement requires identification of the femoral neck axis, the definition of which may vary between studies. The original “3-point method” uses 1 single point to construct the femoral neck axis, whereas the “anatomic method” uses multiple points and attempts to define the true anatomic neck axis. Depending on the method used, the alpha angle may or may not account for other morphological characteristics such as head-neck offset.

Methods

We compared 2 methods of alpha angle measurement (termed “anatomic” and “3-point”) in 59 cadaver femora and 83 cross-table lateral radiographs of asymptomatic subjects. Results were compared using Bland-Altman plots.

Results

Discrepancies of up to 13 degrees were seen between the methods. The 3-point method had an “equalizing effect” by disregarding femoral head position relative to the neck: in femora with high alpha angle, it resulted in lower values than anatomic measurement, and vice versa in femora with low alpha angles. Using the anatomic method, we derived a reference interval for the alpha angle in normal hips in the general population of 30–66 degrees.

Interpretation

We recommend the anatomic method because it also reflects the position of the femoral head on the neck. Consensus and standardization of technique of alpha angle measurement is warranted, not only for planar measurements but also for CT or MRI-based measurements.Hip morphology variants may influence the development of osteoarthritis (OA) (Ganz et al. 2008). Femoral morphology variants may be best characterized by concavity, a compound measure determined by the sphericity and offset of the femoral head (determined from relative neck width and femoral head position on the neck). The most used concavity measure is the alpha angle, described initially by Nötzli et al. (2002) to diagnose cam deformity and increasingly used in cohort studies examining the risk of OA development (Johnston et al. 2008, Nicholls et al. 2011, Agricola et al. 2013). Nötzli et al. (2002) measured the alpha angle between 2 lines drawn between 3 points (“3-point method”). One line is called the femoral neck axis based on a single point at the center of the narrowest part of the femoral neck (Figure 1), but it is important to recognize that this line will only correspond to the anatomic femoral neck axis if the femoral head is positioned centrally on the neck.Open in a separate windowFigure 1.3-point and anatomic method compared in high alpha angle (A) and low alpha angle (B). 3-point method (A.1 and B.1) uses the midpoint of the femoral neck at its narrowest point. The anatomic method (B.2 and B.2) defines the femoral neck axis by connecting the centers of 3 circles projected over the neck contour. The axis is translated to the center of the femoral head if necessary, to measure the alpha angle. In this example, alpha angle A.1 = 64˚, A.2 = 73˚. Angle B.1 and B.2 are both 30˚, while the femoral head is positioned central on the femoral neck.However, in many human femora the position of the femoral head on the neck may not be central, but shifted or tilted posteriorly (Murray and Duncan 1971, Hogervorst et al. 2009). In such femora, use of a femoral neck axis line connecting the center of the femoral head and neck will decrease the alpha angle (Figure 1). Use of the anatomic center line (the “anatomic method”) rather than a single point for the femoral neck axis (the “3-point method”) probably more accurately represents femoral head-neck morphology, as it may also account for femoral head translation as measured by the anterior offset ratio (Eijer et al. 2001, Pollard et al. 2010). Furthermore, the increasing number of cohort studies using the alpha angle mandates consensus on measurement technique.Measurements in 155 cross-table radiographs

Outcomes beyond hospital discharge in infants and children with viral meningitis: A systematic review

Viruses are the commonest cause of childhood meningitis, but outcomes beyond hospital discharge are poorly described. We undertook a systematic literature review of long‐term outcomes following paediatric viral meningitis. A search was carried out using MEDLINE, Embase, and Cochrane Review for studies from 1 January 1990 to 31 December 2018. Studies were included where specific outcome measures were available beyond hospital discharge for children <16 years old with viral meningitis. In total, 3588 papers were identified of which 14 were eligible for inclusion. Four studies reported outcomes in children with nonenterovirus 71 meningitis. A US study of 16 cases demonstrated subtle language difficulties at 3‐year follow‐up in infants in contrast to an Australian study, which revealed no impairment in language. A Fijian study showed that two out of eight cases had sensorineural hearing loss compared with none in a UK cohort of 668 infants. Three studies evaluated outcomes of enterovirus 71 meningitis in China and Taiwan, two showed cases recovered without sequelae, while one demonstrated an increased risk of attention deficit hyperactivity disorder. Two studies including 141 cases of human parechovirus revealed no evidence of neurodevelopmental sequelae. Conversely, an Australian study demonstrated neurodevelopmental sequelae in 11 out of 77 infants with parechovirus meningitis. Most studies identified in this review demonstrated a high proportion of good clinical outcomes following viral meningitis. However, the data are limited, so robustly conducted neurodevelopmental studies are warranted to inform the evidence‐based management of viral meningitis beyond hospital discharge.