Utility of a machine-guided tool for assessing risk behaviour associated with contracting HIV in three sites in South Africa.

Introduction: Digital data collection and the associated mobile health technologies have allowed for the recent exploration of artificial intelligence as a tool for combatting the HIV epidemic. Machine learning has been found to be useful both in HIV risk prediction and as a decision support tool for guiding pre-exposure prophylaxis (PrEP) treatment. This paper reports data from two sequential studies evaluating the viability of using machine learning to predict the susceptibility of adults to HIV infection using responses from a digital survey deployed in a high burden, low-resource setting. Methods: 1036 and 593 participants were recruited across two trials. The first trial was a cross-sectional study in one location and the second trial was a cohort study across three trial sites. The data from the studies were merged, partitioned using standard techniques, and then used to train and evaluate multiple different machine learning models and select and evaluate a final model. Variable importance estimates were calculated using the PIMP and SHAP methodologies. Results: Characteristics associated with HIV were consistent across both studies. Overall, HIV positive patients had a higher median age (34 [IQR: 29-39] vs 26 [IQR 22-33], p < 0.001), and were more likely to be female (155/703 [22%] vs 107/927 [12%], p < 0.001). HIV positive participants also had more commonly gone a year or more since their last HIV test (183/262 [70%] vs 540/1368 [39%], p < 0.001) and were less likely to report consistent condom usage (113/262 [43%] vs 758/1368 [55%], p < 0.001). Patients who reported TB symptoms were more likely to be HIV positive. The trained models had accuracy values (AUROCs) ranging from 78.5% to 82.8%. A boosted tree model performed best with a sensitivity of 84% (95% CI 72-92), specificity of 71% (95% CI 67-76), and a negative predictive value of 95% (95% CI 93-96) in a hold-out dataset. Age, duration since last HIV test, and number of male sexual partners were consistently three of the four most important variables across both variable importance estimates. Conclusions: This study has highlighted the synergies present between mobile health and machine learning in HIV. It has been demonstrated that a viable ML model can be built using digital survey data from an low-middle income setting with potential utility in directing health resources.

A prime/boost vaccine platform efficiently identifies CD27 agonism and depletion of myeloid-derived suppressor cells as therapies that rationally combine with checkpoint blockade in ovarian cancer.

Cancer immunotherapies have generated remarkable clinical responses for some patients with advanced/metastatic disease, prompting exploration of rational combination therapies to bolster anti-tumor immunity in patients with limited response or those who experience tumor progression following an initial response to immunotherapy. In contrast to other tumor indications, objective response rates to single-agent PD-1/PD-L1 blockade in ovarian cancer are limited, suggesting a need to identify combinatorial approaches that lead to tumor regression in a setting where checkpoint blockade alone is ineffective. Using a pre-clinical model of aggressive intraperitoneal ovarian cancer, we have previously reported on a heterologous prime/boost cancer vaccine that elicits robust anti-tumor immunity, prolongs survival of tumor-bearing mice, and which is further improved when combined with checkpoint blockade. As tumor control in this model is CD8 + T cell dependent, we reasoned that the prime/boost vaccine platform could be used to explore additional treatment combinations intended to bolster the effects of CD8 + T cells. Using whole tumor transcriptomic data, we identified candidate therapeutic targets anticipated to rationally combine with prime/boost vaccination. In the context of a highly effective cancer vaccine, CD27 agonism or antibody-mediated depletion of granulocytic cells each modestly increased tumor control following vaccination, with anti-PD-1 therapy further improving treatment efficacy. These findings support the use of immunotherapies with well-defined mechanisms(s) of action as a valuable platform for identifying candidate combination approaches for further therapeutic testing in ovarian cancer.

Dexmedetomidine and ketamine show distinct patterns of cell degeneration and apoptosis in the developing rat neonatal brain.

OBJECTIVE: Early exposure to common anesthetic and sedative agents causes widespread brain cell degeneration and apoptosis in the developing rat brain, associated with persistent learning deficits in rats. This study was designed to determine whether the α2 adrenergic receptor agonist, dexmedetomidine, produces brain cell degeneration and apoptosis in postnatal day-7 rats in the same brain areas when compared to ketamine. METHODS: Systemic saline, ketamine 20 mg/kg, or dexmedetomidine at 30 or 45 µg/kg were given six times to postnatal day 7 rats (n = 6/group) every 90 min. Twenty-four hours after the initial injection, brain regions were processed and analyzed for cell degeneration using the silver stain and for apoptosis using activated caspase-3 immunohistochemistry. RESULTS: Exposure to ketamine resulted in significant cellular degeneration and apoptosis in limbic brain regions, but nonsignificant changes in primary sensory brain regions. In contrast, dexmedetomidine produced significant cellular degeneration and apoptosis in primary sensory brain regions, but nonsignificant changes in limbic regions. CONCLUSIONS: These data show that ketamine and dexmedetomidine result in anatomically distinct patterns of cell degeneration and apoptosis in the brains of 7-day-old rat pups. The meaning and the clinical significance of these findings remain to be established.

Neuraxial Anesthesia in Parturients with Thrombocytopenia: A Multisite Retrospective Cohort Study.

BACKGROUND: The primary aim of this study was to estimate the risk of neuraxial hematoma associated with neuraxial anesthetic procedures in thrombocytopenic parturients. METHODS: A multicenter retrospective cohort study design was used to estimate the risk for spinal-epidural hematoma in parturients with a platelet count of <100,000/mm receiving neuraxial anesthesia and the risk of complications in thrombocytopenic parturients who receive general anesthesia. RESULTS: No cases of spinal hematoma were observed in 102 thrombocytopenic parturients receiving epidural analgesia or 71 receiving spinal anesthesia. Including data from the previous published series (total n = 499), the exact binomial 95% confidence interval for the risk of spinal-epidural hematoma was 0% to 0.6%. Given the small number of patients at each specific platelet count, the theoretical risks at individual platelet count strata are presented. Overall aggregate serious morbidity rate in women who received general anesthesia secondary to thrombocytopenia was 6.5% (95% confidence interval, 2.1%-14.5%). CONCLUSIONS: Our work supports the relative maternal safety of neuraxial anesthesia in parturients with mild thrombocytopenia and estimates the maternal complication rate associated with the avoidance of neuraxial anesthesia. Remaining uncertainties at lower platelet counts make a national "low platelet" registry critical to a more accurate assessment of the risk of epidural hematoma and would aid in standardization of anesthesia practice.

Between-Habitat Variation of Benthic Cover, Reef Fish Assemblage and Feeding Pressure on the Benthos at the Only Atoll in South Atlantic: Rocas Atoll, NE Brazil.

The Southwestern Atlantic harbors unique and relatively understudied reef systems, including the only atoll in South Atlantic: Rocas atoll. Located 230 km off the NE Brazilian coast, Rocas is formed by coralline red algae and vermetid mollusks, and is potentially one of the most "pristine" areas in Southwestern Atlantic. We provide the first comprehensive and integrative description of the fish and benthic communities inhabiting different shallow reef habitats of Rocas. We studied two contrasting tide pool habitats: open pools, which communicate with the open ocean even during low tides, thus more exposed to wave action; and closed pools, which remain isolated during low tide and are comparatively less exposed. Reef fish assemblages, benthic cover, algal turfs and fish feeding pressure on the benthos remarkably varied between open and closed pools. The planktivore Thalassoma noronhanum was the most abundant fish species in both habitats. In terms of biomass, the lemon shark Negaprion brevirostris and the omnivore Melichtys niger were dominant in open pools, while herbivorous fishes (mainly Acanthurus spp.) prevailed in closed pools. Overall benthic cover was dominated by algal turfs, composed of articulated calcareous algae in open pools and non-calcified algae in closed pools. Feeding pressure was dominated by acanthurids and was 10-fold lower in open pools than in closed pools. Besides different wave exposure conditions, such pattern could also be related to the presence of sharks in open pools, prompting herbivorous fish to feed more in closed pools. This might indirectly affect the structure of reef fish assemblages and benthic communities. The macroalgae Digenea simplex, which is uncommon in closed pools and abundant in the reef flat, was highly preferred in herbivory assays, indicating that herbivory by fishes might be shaping this distribution pattern. The variations in benthic and reef fish communities, and feeding pressure on the benthos between open and closed pools suggest that the dynamics in open pools is mostly driven by physical factors and the tolerance of organisms to harsh conditions, while in closed pools direct and indirect effects of species interactions also play an important role. Understanding the mechanisms shaping biological communities and how they scale-up to ecosystem functioning is particularly important on isolated near-pristine systems where natural processes can still be studied under limited human impact.

Pain in primary Sjögren's syndrome: the role of catastrophizing and negative illness perceptions.

OBJECTIVES: Pain is a major factor in health quality in Sjögren's syndrome (SS), but little is known about the factors that contribute to pain severity. Because pain perception has been linked to catastrophizing in other diseases, we assessed subjects with primary SS (pSS) to explore a possible link between pain, illness appraisal, and catastrophizing. METHOD: A total of 92 subjects who met American-European consensus criteria for the diagnosis of pSS completed a questionnaire that included health history, medication use, illness perceptions, pain severity, mood, fatigue, pain anxiety, and pain catastrophizing. Linear regression was used to test the effect of each variable on pain severity. Multivariate models were constructed using backwards elimination to assess the significant predictors of pain severity. RESULTS: From linear regression analysis, catastrophizing was more strongly predictive of pain severity than age, fatigue, depression, or anxiety in both seropositive and seronegative pSS patients. In the multivariate model identified using backwards selection, four variables (pain catastrophizing, fibromyalgia status, serological status, and the conviction that illness would have severe consequences) predicted 55% of the variance in pain severity. CONCLUSIONS: Pain catastrophizing was a significant predictor of pain severity in both seropositive and seronegative pSS patients. This study suggests that behavioural interventions designed to reduce pain catastrophizing and negative appraisal of illness could be of benefit in pSS patients. Research is needed to test the effect of psycho-educational therapies on key patient-reported outcomes, particularly pain, depression, and fatigue, in pSS.

The association between epidural labor analgesia and maternal fever.

The association between epidural labor analgesia and maternal fever is complex and controversial. Observational, retrospective, before-and-after, and randomized controlled trials all support the association, with the most current evidence supporting the mechanistic involvement of noninfectious inflammation. Considering the clinically significant neonatal consequences that have been previously demonstrated, and the possibility of more common subclinical fetal brain injury that animal models imply, the avoidance of maternal fever during labor is imperative. With the current popularity of epidural analgesia in labor, it is important that clinicians delineate how epidurals cause maternal fever and how to block the noninfectious inflammatory response that seems to warm a subset of women laboring with epidurals.

Oxidative stress and fatigue in systemic lupus erythematosus.

OBJECTIVE: The objective of this study is to investigate the relationship of oxidative stress to fatigue in systemic lupus erythematosus (SLE). METHODS: Patients with a confirmed diagnosis of SLE by ACR criteria and healthy controls completed validated questionnaires to assess depression and fatigue. Fatigue was measured with the Fatigue Severity Scale (FSS) and the Profile of Fatigue (Prof-F). Visual analogue scales (VAS) were also used to assess fatigue and pain. Depression was measured with the Center for Epidemiologic Studies Depression Scale (CES-D). Plasma F(2)-isoprostane was measured with gas chromatography/mass spectroscopy to assess oxidative stress. Evaluation included medical record review, physical exam and calculation of body mass index (BMI), disease activity (SLEDAI) and damage (SLICC) in the SLE patients. RESULTS: Seventy-one SLE patients with low disease activity (mean SLEDAI = 1.62 standard error (SE) 0.37, range 0-8) were compared to 51 controls. Fatigue-limiting physical activity (defined as FSS ≥ 4) was present in 56% of patients and 12% of controls. F(2)-isoprostane was higher in SLE patients with fatigue compared to not-fatigued SLE subjects (p = .0076) who were otherwise similar in ethnicity, disease activity and cardiovascular risk factors. Plasma F(2)-isoprostane was strongly correlated with FSS and Profile of Somatic Fatigue (Prof-S) (p < .0001), VAS fatigue (p = .005), CES-D (p = .008) and with BMI (p = .0001.) In a multivariate model, F(2)-isoprostane was a significant predictor of FSS after adjustment for age, BMI, pain and depression (p = .0002). CONCLUSION: Fatigue in SLE patients with low disease activity is associated with increased F(2)-isoprostane. F2-isoprostane could provide a useful biomarker to explore mitochondrial function and the regulation of oxidative pathways in patients with SLE in whom fatigue is a debilitating symptom.

Primary Sjogren's syndrome: cognitive symptoms, mood, and cognitive performance.

OBJECTIVE: To investigate the relationships between self-reported cognitive abilities, psychological symptoms and neuropsychological outcomes in PSS. METHODS: Patients with Primary Sjogren's syndrome (PSS) and healthy controls completed a comprehensive neuropsychometric battery and questionnaires: the Centers for Epidemiological Scale-Depression, the Profile of Fatigue-mental domain (Prof-M) for cognitive symptoms, Fatigue Severity Scale, and the Short-Form McGill Pain Questionnaire. RESULTS: Female patients with PSS (N = 39) were similar to controls (N = 17) in estimated premorbid intellectual function, age and education. Depression (P = 0.002), cognitive symptoms (P = 0.001), fatigue (P = 0.000003), and pain (P = 0.024) scores were greater in the patient group. Patients with PSS demonstrated inferior performance relative to controls in psychomotor processing (P = 0.027) and verbal reasoning (P = 0.007). Patients with PSS with and without depression had similar performance on multiple tests, but depressed patients had significantly lower scores for executive function (P = 0.041). Cognitive symptoms correlated with verbal memory (P = 0.048), whereas pain correlated with executive function measures (Stroop, P = 0.017) and working memory (Trails B, P = 0.036). In the regression model, depression and verbal memory were independent predictors that accounted for 61% of the variance in cognitive symptoms. CONCLUSION: The Prof-M is a simple self-report measure which could be useful in screening PSS subjects who may benefit from detailed psychometric evaluation. Our results are consistent with the hypothesis that depression and verbal memory impairment are overlapping but independent aspects of neural involvement in PSS. While pain and depression are significant confounders of cognitive function in PSS, this study suggests that impaired verbal reasoning ability in PSS is not attributable to pain or depression.

Molecular epidemiology and risk factors for colonization by vancomycin-resistant Enterococcus in patients with hematologic malignancies.

OBJECTIVE: To study the molecular epidemiology of vancomycin-resistant Enterococcus (VRE) colonization and to identify modifiable risk factors among patients with hematologic malignancies. SETTING: A hematology-oncology unit with high prevalence of VRE colonization. PARTICIPANTS: Patients with hematologic malignancies and hematopoietic stem cell transplantation recipients admitted to the hospital. METHODS: Patients underwent weekly surveillance by means of perianal swabs for VRE colonization and, if colonized, were placed in contact isolation. We studied the molecular epidemiology in fecal and blood isolates by pulsed-field gel electrophoresis over a 1-year period. We performed a retrospective case-control study over a 3-year period. Cases were defined as patients colonized by VRE, and controls were defined as patients negative for VRE colonization. Case patients and control patients were matched by admitting service and length of observation time. RESULTS: Molecular genotyping demonstrated the primarily polyclonal nature of VRE isolates. Colonization occurred at a median of 14 days. Colonized patients were characterized by longer hospital admissions. Previous use of ceftazidime was associated with VRE colonization (P < .001), while use of intravenous vancomycin and antibiotics with anaerobic activity did not emerge as a risk factor. There was no association with neutropenia or presence of colonic mucosal disruption, and severity of illness was similar in both groups. CONCLUSION: Molecular studies showed that in the majority of VRE-colonized patients the strains were unique, arguing that VRE acquisition was sporadic rather than resulting from a common source of transmission. Patient-specific factors, including prior antibiotic exposure, rather than breaches in infection control likely predict for risk of fecal VRE colonization.

Natalizumab (Tysabri).

Natalizumab is a humanized IgG4κ monoclonal antibody that is a selective adhesion molecule inhibitor, which prevents adhesion of leukocytes to endothelial cells. It is the first monoclonal antibody approved by the FDA for the treatment of relapsing-remitting MS. This article will review the mechanism of action and clinical role of this agent.

Critical action procedures testing: a novel method for test-enhanced learning.

CONTEXT: Human error is a leading cause of adverse events in anaesthesia. Residents' knowledge of how to respond to rare, yet potentially life-threatening events has been shown to deteriorate over time and thus cost-effective educational interventions are indicated. Previous research has shown that test-enhanced learning has the potential to strengthen both clinical knowledge and performance. We hypothesised that critical action procedures (CAPs) tests, similar to those employed by high-performance aircraft pilots, would help improve resident knowledge about how to respond to rare and potentially catastrophic events encountered during the perioperative period. METHODS: Knowledge assessments were administered to 29 first-year anaesthesiology residents over the course of 9 months. Five-minute closed-book tests were administered with fill-in-the-blank questions regarding the American Society of Anesthesiologists' difficult airway guideline, advanced cardiac life support protocols, an institutional airway fire protocol and drug dosing for malignant hyperthermia. Inter-group comparisons were evaluated using the Kruskal-Wallis test. The difference between the pre-test and final test scores for each subsection was determined with the Mann-Whitney U-test for independent samples. RESULTS: Composite subtest scores, when compared with baseline pre-test scores and subsequent scores, and when adjusted for attrition, significantly improved over the course of 9 months (20.5% versus 80%; P < or = 0.001). Likert-based survey data indicated a positive report for attainment of knowledge. CONCLUSIONS: In this longitudinal observational study of first-year anaesthesiology residents, CAPs testing helped improve knowledge about critical events. Although the study was limited by its small number of subjects, a significant attrition rate and the lack of a control group, it demonstrates a cost-effective educational intervention that improved resident knowledge. This intervention may enable residents to transfer learned skills from theoretical testing situations to real-life scenarios. We propose the use and further study of CAPs testing as a cost-effective modality to augment both simulated and actual experiential learning.

Late infectious complications after cord blood stem cell transplantation.

The slower engraftment kinetics and impaired immune reconstitution of cord blood stem cell transplant recipients increase the risk of infectious complications. We retrospectively reviewed patients who underwent cord blood stem cell transplantation at Roswell Park Cancer Institute for hematological malignancies and who survived beyond day 100 for late infectious events. Among 15 patients who were included in the study, there were 18 episodes of bacteremia, 5 cases of bacterial pneumonia, 9 viral, 4 fungal, and 1 nontuberculous mycobacterial infection. Overall mortality was 60%, with infections contributing in 44% of cases. In conclusion, survival beyond day 100 following cord bloodstem cell transplantation is associated with a considerable risk of infections in our single center experience.

Add-on cases in the endoscopy unit: Factors that affect volume.

BACKGROUND: Although most procedures in the endoscopy clinic are elective, emergency add-on cases in hospital-based endoscopy clinics are common, frequently consuming a great deal of time and resources relative to elective endoscopy procedures. OBJECTIVE: To determine which specific factors correlate with the high volume of add-on emergency cases in a tertiary care, hospital-based endoscopy unit. METHODS: A retrospective chart review of all gastrointestinal add-on, and electively booked cases of esophagastroduodenoscopy (EGD), colonoscopy(C) and flexible sigmoidoscopy(FS)procedures from September 2006 to May 2007, was conducted. The day of the week, month, type of procedure and physician were recorded. Emergency add-on procedures performed during the weekends were not assessed. These cases were then compared with elective cases during a similar time frame to determine differences in the aspects of add-on cases versus those that were elective. RESULTS: Seven hundred twenty-one add-on cases were reviewed (mean patient age 57.4 years; 46% women) and compared with 736 elective cases (mean age 56 years; 49% women; P not significant). Of the add-on cases, 377 (52%) were EGD, 216 C (30%) and 105 (15%) were FS, with 23 combined procedures (3.2%) versus 202 (27%) EGD, 442 (60%) C and 74 (10%) FS in the elective group. Add-on cases were more likely to be EGDs than elective cases (OR 2.7; 95% CI 1.8 to 4.3; P<0.0001) and less likely to be Cs (OR 0.24; 95% CI 0.15 to 0.38; P<0.0001). There were significantly more add-on cases on Mondays (OR 1.7; 95% CI 1.0 to 2.28; P>0.03). Conversely, there were significantly fewer procedures added on Fridays (OR 0.31; 95% CI 0.16 to 0.57; P=0.0001). There were statistically fewer add-on cases in September compared with the other months that were evaluated (OR 0.31; 95% CI 0.11 to 0.78; P=0.0006). CONCLUSION: With the present system of performing only emergency cases on the weekend, Monday tends to have more add-on cases. Consistent with the fact that upper gastrointestinal bleeding is the most common emergency condition, EGD is more common in add-on cases than with elective cases. Although speculative, the reasons for Friday having fewer add-on cases may be the result of a change of physician on call that day; consequently, most cases may be performed earlier in the week. For unknown reasons, fewer cases tend to be added on in September than in the other months evaluated. These data demonstrate that even in the same institution with similar patients, variability in the number of add-on cases likely is a result of many additional factors governing add-on cases, which require appropriate resource planning to ensure adequate allocation of services to ensure ideal patient care.

Peripheral blood gene expression profiling in Sjögren's syndrome.

Sjögren's syndrome (SS) is a common chronic autoimmune disease characterized by lymphocytic infiltration of exocrine glands. The affected cases commonly present with oral and ocular dryness, which is thought to be the result of inflammatory cell-mediated gland dysfunction. To identify important molecular pathways involved in SS, we used high-density microarrays to define global gene expression profiles in the peripheral blood. We first analyzed 21 SS cases and 23 controls, and identified a prominent pattern of overexpressed genes that are inducible by interferons (IFNs). These results were confirmed by evaluation of a second independent data set of 17 SS cases and 22 controls. Additional inflammatory and immune-related pathways with altered expression patterns in SS cases included B- and T-cell receptor, insulin-like growth factor-1, granulocyte macrophage-colony stimulating factor, peroxisome proliferator-activated receptor-alpha/retinoid X receptor-alpha and PI3/AKT signaling. Exploration of these data for relationships to clinical features of disease showed that expression levels for most interferon-inducible genes were positively correlated with titers of anti-Ro/SSA (P<0.001) and anti-La/SSB (P<0.001) autoantibodies. Diagnostic and therapeutic approaches targeting interferon-signaling pathway may prove most effective in the subset of SS cases that produce anti-Ro/SSA and anti-La/SSB autoantibodies. Our results strongly support innate and adaptive immune processes in the pathogenesis of SS, and provide numerous candidate disease markers for further study.

Chronic granulomatous disease.

Chronic granulomatous disease is an inherited disorder of the NADPH oxidase characterized by severe bacterial and fungal infections and disordered inflammation. We propose that NADPH oxidase has a key role in regulating acute neutrophilic and T cell responses, which in turn restrains fungal growth and calibrates the inflammatory response to minimize injury and allergy. In this model, superoxide-induced activation of indoleamine 2,3-dioxygenase (IDO) is a central mechanism by which the optimal balance of antifungal host defense and immune tolerance occurs. This model is based on studies in mice and requires correlation in humans.

Two cases of hepatic zygomycosis in allogeneic stem cell transplant recipients and review of literature.

Gastrointestinal zygomycosis is a rare condition with a high mortality rate. We present 2 fatal cases of hepatic zygomycosis following allogeneic hematopoietic stem cell transplantation and review the literature.

Successful treatment of disseminated fusariosis with posaconazole during neutropenia and subsequent allogeneic hematopoietic stem cell transplantation.

We report the case of a 16-year-old girl with acute myelogenous leukemia with disseminated fusariosis, who responded to salvage posaconazole therapy. She subsequently received additional cytotoxic chemotherapy and allogeneic hematopoietic stem cell transplantation with posaconazole continued as secondary prophylaxis. Despite intensive immunosuppressive therapy for graft-versus-host disease, no recrudescence of infection occurred.

Leflunomide failure to control recurrent cytomegalovirus infection in the setting of renal failure after allogeneic stem cell transplantation.

Cytomegalovirus (CMV) reactivation is common in the allogeneic stem cell transplant setting but the incidence of CMV organ disease and mortality has been dramatically reduced by prophylactic or preemptive antiviral therapy. We report the case of a CMV-seropositive 46-year-old man with non-Hodgkin's lymphoma who underwent an unrelated allogeneic stem cell transplant from a CMV-seronegative HLA-matched unrelated donor. CMV encephalitis and colitis developed that was refractory to single-agent therapy. The CMV isolate demonstrated genotypic resistance to both ganciclovir and foscarnet. CMV disease was controlled by prolonged combination ganciclovir and cidofovir therapy, but severe renal dysfunction developed. Leflunomide was selected as a last resort to avoid the nephrotoxicity of cidofovir. CMV antigenemia rapidly increased following leflunomide administration, necessitating discontinuing this agent and resuming prior antiviral therapy. The pharmacokinetics of leflunomide in the setting of renal insufficiency is presented. Options for salvage therapy in refractory CMV disease in allogeneic stem cell transplant recipients are briefly reviewed.