Clinical characteristics,prognostic factors,and outcomes of adult patients with hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a rare clinical syndrome characterized by the activation of the mononuclear phagocytic system. The diagnosis of HLH in adults is challenging not only because the majority of the reported data are from pediatric patients, but also because HLH occurs in many disease entities. This study reports the clinical and laboratory findings and prognostic factors of adult HLH in a large cohort managed at a single medical center from 2003 to 2014. Seventy‐three patients met the HLH‐2004 diagnostic criteria. The median age was 51 years (range, 18–82 years); 41 (56.2%) were male. Patients manifested fever, cytopenias, and elevated ferritin in >85% of cases. Likely causes of HLH were as follows: 30 (41.1%) infections, 21 (28.8%) malignancies, 5 (6.8%) attributed to autoimmune disorders, 1 (1.4%) primary immunodeficiency, 2 (2.7%) post solid organ transplantation, and 13 (17.8%) idiopathic. The median overall survival was 7.67 months. Patients with malignancy‐associated HLH had a markedly worse survival compared with patients with non–malignancy‐associated HLH (median overall survival 1.13 vs. 46.53 months, respectively; P < 0.0001). In a multivariable analysis, malignancy (hazard ratio = 12.22; 95% CI: 2.53–59.02; P = 0.002) correlated with poor survival. Ferritin >50,000 µg/L correlated with 30‐day mortality. Survival after a diagnosis of HLH is dismal, especially among those with malignancy‐associated HLH. The development of a registry for adults with HLH would improve our understanding of this syndrome, validate diagnostic criteria, and help develop effective treatment strategies. Am. J. Hematol. 90:220–224, 2015. © 2014 Wiley Periodicals, Inc.     

Elevated serum ferritin is not specific for hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a rare, potentially fatal, syndrome of excessive and ineffective activation of the immune system. The majority of the reported data on HLH is from pediatric patients and lacks specificity. This makes HLH diagnosis challenging especially in adults where HLH is triggered by many conditions and can resemble many disease entities. Elevated ferritin is one of the diagnostic criteria for HLH. We determined the conditions associated with elevated ferritin at our medical center to assess how specific ferritin is for predicting HLH. We retrospectively reviewed all ferritin results >10,000 μg/L in pediatric and adult patients. The most common condition associated with elevated ferritin was hematologic malignancy in adults (25.7%) and HLH in pediatric patients (48.9%). HLH was diagnosed in 14.2% of adults and 48.9% of children with ferritin >10,000 µg/L. Hyperferritinemia occurs in a variety of conditions and is not specific for adult or pediatric HLH. Common causes of elevated ferritin should be considered before entertaining the possibility of HLH, especially in adult patients.     

Haemophagocytic lymphohistiocytosis in adults: a multicentre case series over 7 years

Haemophagocytic lymphohistiocytosis (HLH) is a syndrome of uncontrolled immune activation that has gained increasing attention over the past decade. Although classically known as a familial disorder of children caused by mutations that affect cytotoxic T‐cell function, an acquired form of HLH in adults is now widely recognized. This is often seen in the setting of malignancy, infection or rheumatological disorders. We performed a retrospective review across 3 tertiary care centres and identified 68 adults with HLH. The average age was 53 years (range 18–77 years) and 43 were male (63%). Underlying disorders included malignancy in 33 patients (49%), infection in 22 (33%), autoimmune disease in 19 (28%) and idiopathic HLH in 15 (22%). Patients were treated with disease‐specific therapy and immunomodulatory agents. After a median follow‐up of 32·2 months, 46 patients had died (69%). The median overall survival was 4 months (95% CI: 0·0–10·2 months). Patients with malignancy had a worse prognosis compared to those without (median survival 2·8 months versus 10·7 months, P = 0·007). HLH is a devastating disorder with a high mortality. Further research is needed to improve treatment and outcomes.     

Toxoplasma‐induced hemophagocytic lymphohistiocytosis after haploidentical allogeneic stem cell transplantation

Hemophagocytic lymphohistiocytosis (HLH) is a disorder of immune regulation, manifested by fever, pancytopenia, hyperferritiniemia, hypertriglyceridemia, and extensive hemophagocytosis involving the bone marrow and spleen. HLH can occur in adults with an underlying hematopoietic malignancy, or with systemic infections. HLH following hematopoietic stem cell transplantation (HSCT) is unusual, and the diagnosis may be challenging particularly because the diagnostic criteria in the HLH‐2004 guidelines overlap with common post‐transplant complications such as engraftment syndrome, graft‐vs‐host disease, and infections. HLH is commonly triggered by viral, bacterial and, less commonly, parasitic infections. Following HSCT, patients with latent Toxoplasma infection may develop systemic disease secondary to reactivation, and rarely this may lead to a HLH physiology, with a very high mortality rate. Herein we describe the successful management of disseminated toxoplasmosis associated with life‐threatening HLH using tocilizumab and antimicrobial therapy.     

Hemophagocytic Lymphohistiocytosis in Intensive Care Unit: A 71-Case Strobe-Compliant Retrospective Study

Hemophagocytic lymphohistiocytosis (HLH) is a critical condition that may lead to organ failure and early death. The aim of this retrospective observational study was to describe a cohort of HLH patients admitted to intensive care unit (ICU) and investigate the risk factors of early death.A positive HLH diagnosis was defined by an HScore ≥169. Univariate and multivariate analyses were carried out to investigate hospital and 28-day mortality risk factors. Between January 2002 and July 2014, 71 HLH cases were seen at our institution.The overall 28-day mortality (start at ICU admission) and hospital mortality were 38% and 68%, respectively. The factors associated with increased 28-day mortality were the sequential organ failure assessment score at ICU admission (P < .001) and advance in age (P = 0.03). The factors associated with increased hospital mortality were a high sequential organ failure assessment score at ICU admission (P < 0.01), advance in age (P = 0.04), and the presence of lymphoma-related HLH or HLH of unknown origin (P < 0.01).Organ failure overtops the classical early-death risk factors in adult ICU-admitted HLH patients. This failure and the subsequent early death may be prevented by timely specific cytotoxic therapies and the control of the underlying disease.     

X-linked lymphoproliferative disease due to SAP/SH2D1A deficiency: a multicenter study on the manifestations, management and outcome of the disease

X-linked lymphoproliferative disease (XLP1) is a rare immunodeficiency characterized by severe immune dysregulation and caused by mutations in the SH2D1A/SAP gene. Clinical manifestations are varied and include hemophagocytic lymphohistiocytosis (HLH), lymphoma and dysgammaglobulinemia, often triggered by Epstein-Barr virus infection. Historical data published before improved treatment regimens shows very poor outcome. We describe a large cohort of 91 genetically defined XLP1 patients collected from centers worldwide and report characteristics and outcome data for 43 patients receiving hematopoietic stem cell transplant (HSCT) and 48 untransplanted patients. The advent of better treatment strategies for HLH and malignancy has greatly reduced mortality for these patients, but HLH still remains the most severe feature of XLP1. Survival after allogeneic HSCT is 81.4% with good immune reconstitution in the large majority of patients and little evidence of posttransplant lymphoproliferative disease. However, survival falls to 50% in patients with HLH as a feature of disease. Untransplanted patients have an overall survival of 62.5% with the majority on immunoglobulin replacement therapy, but the outcome for those untransplanted after HLH is extremely poor (18.8%). HSCT should be undertaken in all patients with HLH, because outcome without transplant is extremely poor. The outcome of HSCT for other manifestations of XLP1 is very good, and if HSCT is not undertaken immediately, patients must be monitored closely for evidence of disease progression.     

Heart transplantation in ischemic heart disease when recipients are older than 55 years and donors older than 50

The purpose of this article is to analyze patients affected with ischemic cardiomyopathy, older than 55 years, who have undergone heart transplantation. We conducted a retrospective analysis comparing clinical course and outcome in patients whose donor age was > or = 50 years (Group A) with patients who had younger donor heart (Group B). Group A was composed of 25 patients, 55 to 68 years old (27.4% of the patients), 20 males and 5 females; Group B was composed of 68 patients, 55 to 66 years old, 65 males and 3 females. Mean donor age in Group A was 54.7 years old (range 51-61), while in Group B it was 29.5 years old (range 9-49). Operative mortality was 16% (4 cases) and 12% in Group B (8 cases) p = ns. Total mortality in Group A was 24%, or 6 cases: 2 graft failures, 1 infection, 1 neoplasm, 1 multiorgan failure, 1 ischemic heart disease; in Group B it was 27%, or 18 cases: 2 cerebrovascular accidents, 4 graft failures, 3 infections, 5 neoplasms, 3 multiorgan failures, 1 acute rejection, p = ns. Coronarography was performed in 51 patients, 14 in Group A (10 cases normal, 3 with irregularities, and 1 case with a critical stenosis of the circumflex artery; 37 in Group B (32 cases were normal, 3 had irregularities and 2 had critical stenosis in a coronary artery). In conclusion, we emphasize that extending donor age in recipients older than 55 years of age does not determine a higher risk and mortality.     

National Patterns of Heart Failure Hospitalizations and Mortality by Sex and Age

BackgroundEarlier work has demonstrated significant sex and age disparities in ischemic heart disease. However, it remains unclear if an age or sex gap exists for heart failure (HF) patients.Methods and ResultsUsing data from the 2007–2008 Healthcare Cost and Utilization Project, we constructed hierarchic regression models to examine sex differences and age-sex interactions in HF hospitalizations and in-hospital mortality. Among 430,665 HF discharges, 51% were women and 0.3%, 27%, and 73% were aged <25, 25–64, and >64 years respectively. There were significant sex differences among HF risk factors, with a higher prevalence of coronary disease among men. Men had higher hospitalization rates for HF and in-hospital mortality across virtually all ages. The relationship between age and HF mortality appeared U-shaped; mortality rates for ages <25, 25–64, and >64 years were 2.9%, 1.4%, and 3.8%, respectively. No age-sex interaction was found for in-hospital mortality for adults >25 years old.ConclusionsUsing a large nationally representative administrative dataset we found age and sex disparities in HF outcomes. In general, men fared worse than women regardless of age. Furthermore, we found a U-shaped relationship between age and in-hospital mortality during an HF hospitalization, such that young adults have similar mortality rates to older adults. Additional studies are warranted to elucidate the patient-specific and treatment characteristics that result in these patterns.     

Malignancy‐associated haemophagocytic lymphohistiocytosis in children and adolescents

Haemophagocytic lymphohistiocytosis (HLH) in the context of malignancy is mainly considered a challenge of adult haematology. While this association is also observed in children, little is known regarding inciting factors, appropriate treatment and prognosis. We retrospectively analysed 29 paediatric and adolescent patients for presenting features, type of neoplasm or preceding chemotherapy, treatment and outcome. Haemophagocytic lymphohistiocytosis was considered triggered by the malignancy (M‐HLH) in 21 patients, most of whom had T‐ (n = 12) or B‐cell neoplasms (n = 7), with Epstein–Barr virus as a co‐trigger in five patients. In eight patients, HLH occurred during chemotherapy (Ch‐HLH) for malignancy, mainly acute leukaemias (n = 7); an infectious trigger was found in seven. In M‐ and Ch‐HLH, median overall survival was 1·2 and 0·9 years, and the 6 month survival rates were 67% and 63%, respectively. Seven of 11 deceased M‐HLH patients exhibited active malignancy and HLH at the time of death, while only two out of five deceased Ch‐HLH patients had evidence of active HLH. To overcome HLH, malignancy‐ and HLH‐directed treatments were administered in the M‐HLH cohort; however, it was not possible to determine superiority of one approach over the other. For Ch‐HLH, treatment ranged from postponement of chemotherapy to the use of etoposide‐containing regimens.     

Clinical analysis of macrophage activation syndrome in pediatric patients with autoimmune diseases

Macrophage activation syndrome (MAS) belongs to secondary hemophagocytic lymphohistiocytosis (HLH) syndrome. It is usually associated with rheumatic diseases. We retrospectively reviewed our hospital's medical records of 102 HLH/MAS patients from the past 20 years. Demographics, clinical data, treatment, and outcomes were analyzed. Among 102 patients, eight patients with underlying juvenile systemic lupus erythematous (two patients), mixed connective tissue disease (one patient), primary anti-phospholipid syndrome (one patient), and systemic type juvenile rheumatoid arthritis (sJRA; four patients) with 13 episodes of MAS were studied. Clinical manifestations of MAS included fever (100 %), hepatosplenomegaly (77 %), lymphadenopathy (38 %), skin rash (62 %), and neurological involvement (31 %). Laboratory features included leukopenia (54 %), anemia (46 %), thrombocytopenia (77 %), jaundice (27 %), hypofibrinogenemia (40 %), decreased erythrocyte sedimentation rate (67 %), and elevated liver enzymes (77 %), lactate dehydrogenase (100 %), ferritin (88 %), triglycerides (91 %), C-reactive protein (85 %), plasma D-dimer (50 %), and hemophagocytosis in bone marrow (83 %). The Epstein-Barr virus and adenovirus infection triggered MAS in two patients with sJRA. Methylprednisolone pulse therapy was effective in two out of three patients, and high-dose intravenous immunoglobulin (IVIG) was effective in two out of six patients. Patients with sJRA responded well to corticosteroids and cyclosporine. Complications included opportunistic infection with Pneumocystis jiroveci, multiple organ failure, and intensive care unit myopathy. The mortality rate was one out of eight (12.5 %). Our results showed that MAS could be fatal and complicate various pediatric autoimmune diseases. It generally has a good response to corticosteroids and IVIG. Prompt recognition and timely treatment can result in good outcomes.     

Plasmapheresis therapy in an elderly patient with rapidly progressive Henoch-Schönlein purpura with disseminated organ involvement

Henoch-Schönlein purpura (HSP) frequently occurs in children below the age of 15 years and is rare with increasing age. Prognosis and therapy largely depend on the clinical presentation. The disease may be preceded by an upper respiratory tract infection, and drugs have also been implicated in the pathogenesis of the disease. Most children recover from the illness, whereas 40% of adults have persistent hematuria and 10% develop chronic renal failure. Recent studies strongly suggest that adults with HSP should be monitored for prolonged periods and treated aggressively. Here, we present a case of a patient with HSP who developed multiorgan failure requiring assistance in breathing and dialysis, and also sustained gastrointestinal bleeding despite aggressive immunosuppressive therapy. In analogy to published data in children with severe HSP, the patient was treated by plasma exchange in combination with low dose oral cyclophosphamide, while high dose steroids were reduced over time. The patient could be discharged 70 days after admission. One year after discharge, the patient is doing well without any signs of activity of HSP and completely unremarkable renal function. The maintenance daily dose of steroids is 7.5 mg.     

Bacteremia caused by Aeromonas species [corrected] complex in the Caribbean Islands of Martinique and Guadeloupe

Aeromonas species are Gram-negative bacilli of the water environment whose survival appears facilitated by warm climates. There have been no reports on Aeromonas species in the [corrected] Caribbean to date. Our aim was to describe clinical and bacteriological features in patients presenting with such bacteremia in Martinique and Guadeloupe. During a 14-year period, we retrospectively identified 37 patients. The mean age was 55 years and in 89% of cases underlying disease such as digestive diseases, cutaneous wounds, and malignancy were identified. One case was related to severe strongyloidiasis and one with snake bite. Polymicrobial bacteremia was identified in 38%, essentially with Enterobacteriaceae. All Aeromonas isolates were resistant to amoxicillin but extended-spectrum beta-lactam and fluoroquinolone were active against more than 95%. During hospitalization 10 patients died (27%). Older age, occurrence of multiorgan failure, and impaired renal function were associated with in-hospital mortality.     

Haemophagocytic lymphohistiocytosis: experience at two U.K. centres

Summary Haemophagocytic lymphohistiocytosis (HLH) is a rare disorder of inappropriate macrophage activation. Both familial and sporadic forms, which may be infection-associated, are recognized. Between 1985 and 1991 we treated 23 cases of HLH (12 male, 11 female). There were eight familial cases, defined by a previously affected sibling and/or history of consanguinity, age 3 d to 15 months at presentation. The age of the remaining 15 cases varied from 1 month to 9.5 years. A potential viral trigger was identified in four cases (EBV, two; parvovirus B19, one; echovirus II, one) including one familial case. Six of eight (75%) patients who received supportive care alone, including all four familial cases, died within 6 months of presentation. Both long-term survivors in this group presented at an older age (7.5 and 8 years) and had proven or suspected virus-associated HLH. 15 patients were treated with etoposide (150–250 mg/m² days 1–3 every 21 d) and methylprednisolone; 10 patients received intrathecal methotrexate in addition. In nine (60%) of these cases a complete (six) or partial (three) response was achieved, though one child suffered a fatal 'tumour lysis' syndrome. Overall mortality in the treated group was 66.6%, being highest (75%) in patients under 2 years at presentation compared to 33% in those over 2 years. Two of three familial and one of five sporadic cases relapsed and died 3 d to 20 months from diagnosis. Only one familial case survives at follow-up of 11 months. Of the five remaining survivors, two received allogeneic bone marrow transplantation (one matched related, one haploidentical) and are alive at 11 and 29 months. Three cases aged 2.5, 7.5 and 9.5 years remain in remission at 11, 20 and 25 months respectively. The high mortality of HLH supports a role for allogeneic BMT in selected cases, particularly those with a familial basis or under 2 years at presentation.     

Coagulation Disorders and Bleedings in Critically Ill Patients With Hemophagocytic Lymphohistiocytosis

Reactive hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition related to a cytokine storm leading to multiorgan dysfunction. A better understanding of coagulation disorders, frequently reported in HLH patients, may improve outcomes.Critically ill HLH patients managed in a multidisciplinary national reference center were retrospectively included. Relationships between coagulation disorders, severe bleedings, and outcomes were assessed.One hundred and seventeen patients fulfilled the HLH 2004 criteria. The most common HLH etiology was hematologic conditions (73%), followed by infectious diseases (20%), systemic rheumatic diseases (5%), and undetermined HLH etiology (3%). All patients exerted thrombocytopenia. Coagulation disorders were diagnosed in 79 (68%) patients (61 had hypofibrinogenemia < 1.5 g/L, 51 had prothrombin time [PT] < 50%). The worst median value throughout ICU stay was 52% (38–65) for PT with a factor V level of 35% (27–43), 1.59 (1.30–2.09) for the activated partial thromboplastin time (APTT) ratio, and 2.33 g/L (1.13–3.86) for the fibrinogen level. Disseminated intravascular coagulation (DIC) was found in 50% of patients. Coagulation disorders were more frequent in immunocompromised patients, those with histological/cytological feature of hemophagocytosis, those with the highest ferritin concentrations, and in patients with HLH not related to infection. These patients were more prone to receive mechanical ventilation, vasopressors, or renal replacement therapy. Twenty-six (22%) patients presented severe bleeding complications, including 5 patients dying from hemorrhagic shock. Strikingly, the only coagulation parameter significantly associated with severe bleeding was low fibrinogen with a cutoff value of 2 g/L (P = 0.03). Overall, 33 (28%) patients died in the ICU and hospital mortality was 44%. Coagulation disorders were associated with higher mortality, especially fibrinogen < 2 g/L (P = 0.04) and PT value (P = 0.03). The occurrence of bleeding complications was not associated with higher risk of hospital death. Risk factors associated with mortality by multivariate analysis were fibrinogen level < 2 g/L (OR 2.42 [1.08–5.41]), SOFA score > 6 (OR 3.04 [1.32–6.98]), and age > 46 years (OR 2.26 [1.02–5.04]).Up to two-third of critically ill HLH patients present with coagulation disorders. Hypofibrinogenemia or DIC was found in half of the patients and low PT in 40%. These patients require more life support and have a higher mortality rate. Fibrinogen <2 g/L is associated with the occurrence of severe bleeding and mortality.     

Tricuspid regurgitation velocity and other biomarkers of mortality in children,adolescents and young adults with sickle cell disease in the United States: The PUSH study

In the US, mortality in sickle cell disease (SCD) increases after age 18-20 years. Biomarkers of mortality risk can identify patients who need intensive follow-up and early or novel interventions. We prospectively enrolled 510 SCD patients aged 3-20 years into an observational study in 2006-2010 and followed 497 patients for a median of 88 months (range 1-105). We hypothesized that elevated pulmonary artery systolic pressure as reflected in tricuspid regurgitation velocity (TRV) would be associated with mortality. Estimated survival to 18 years was 99% and to 25 years, 94%. Causes of death were known in seven of 10 patients: stroke in four (hemorrhagic two, infarctive one, unspecified one), multiorgan failure one, parvovirus B19 infection one, sudden death one. Baseline TRV ≥2.7 m/second (>2 SD above the mean in age-matched and gender-matched non-SCD controls) was observed in 20.0% of patients who died vs 4.6% of those who survived (P = .012 by the log rank test for equality of survival). The baseline variable most strongly associated with an elevated TRV was a high hemolytic rate. Additional biomarkers associated with mortality were ferritin ≥2000 μg/L (observed in 60% of patients who died vs 7.8% of survivors, P < .001), forced expiratory volume in 1 minute to forced vital capacity ratio (FEV1/FVC) <0.80 (71.4% of patients who died vs 18.8% of survivors, P < .001), and neutrophil count ≥10x10⁹/L (30.0% of patients who died vs 7.9% of survivors, P = .018). In SCD children, adolescents and young adults, steady-state elevations of TRV, ferritin and neutrophils and a low FEV1/FVC ratio may be biomarkers associated with increased risk of death.     

Fatal adenovirus serotype 21 infection associated with hemophagocytic lymphohistiocytosis and multiorgan failure

Recent reports describe an increase in the incidence of fatal adenovirus infections. Several severe cases have been linked to adenovirus serotype 21. The exact etiology for this unexpectedly high mortality remains unknown. We report the case of a patient with severe adenovirus serotype 21 pneumonia resulting in hemophagocytic lymphohistiocytosis (HLH) with acute respiratory distress syndrome and rapidly progressive multiorgan dysfunction syndrome (MODS). HLH describes a cytokine storm due to uncontrolled accumulation of activated T-lymphocytes and activated histiocytes. This results in organ infiltration with these cells, and subsequent hemophagocytosis of erythrocytes, leukocytes and platelets. In its most severe form, HLH leads to a sepsis-like picture and MODS. The association between adenovirus 21 and HLH may at least in part explain the recently observed increase in incidence of fatal adenoviral infections. We suggest that HLH should be considered in cases of severe adenoviral infection. If HLH is present, aggressive treatment is warranted.     

Hemophagocytic lymphohistiocytosis: Recent progress in the pathogenesis,diagnosis and treatment

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome that develops as a primary (familial/hereditary) or secondary (non-familial/hereditary) disease characterized in the majority of the cases by hereditary or acquired impaired cytotoxic T-cell (CTL) and natural killer responses. The molecular mechanisms underlying impaired immune homeostasis have been clarified, particularly for primary diseases. Familial HLH (familial hemophagocytic lymphohistiocytosis type 2-5, Chediak-Higashi syndrome, Griscelli syndrome type 2, Hermansky-Pudlak syndrome type 2) develops due to a defect in lytic granule exocytosis, impairment of (signaling lymphocytic activation molecule)-associated protein, which plays a key role in CTL activity [e.g., X-linked lymphoproliferative syndrome (XLP) 1], or impairment of X-linked inhibitor of apoptosis, a potent regulator of lymphocyte homeostasis (e.g., XLP2). The development of primary HLH is often triggered by infections, but not in all. Secondary HLH develops in association with infection, autoimmune diseases/rheumatological conditions and malignancy. The molecular mechanisms involved in secondary HLH cases remain unknown and the pathophysiology is not the same as primary HLH. For either primary or secondary HLH cases, immunosuppressive therapy should be given to control the hypercytokinemia with steroids, cyclosporine A, or intravenous immune globulin, and if primary HLH is diagnosed, immunochemotherapy with a regimen containing etoposide or anti-thymocyte globulin should be started. Thereafter, allogeneic hematopoietic stem-cell transplantation is recommended for primary HLH or secondary refractory disease (especially EBV-HLH).     

Impact of hepatitis C virus infection on all‐cause and liver‐related mortality in a large community‐based cohort of inner city residents

Summary. The aim of this study was to measure the impact of hepatitis C virus (HCV) infection on mortality in a cohort of inner city residents. The Community Health and Safety Evaluation is a community‐based study of inner city residents followed retrospectively and prospectively through linkages with provincial virology and mortality databases. We identified participants having received HCV antibody testing, evaluated cause‐specific mortality rates and factors associated with all‐cause and liver‐related mortality using Cox Proportional Hazards models. Overall, 2332 participants received HCV antibody testing (recent non‐injection drug use – 81%). The prevalence of HCV and HIV was 64% (1495 of 2332) and 21% (485 of 2332), respectively. Between January 2003 and December 2007, there were 180 deaths (192 per 10 000 person‐years; 95% CI: 165, 222), with 21% HIV‐related, 20% drug‐related and 7% liver‐related. Mortality was associated with age >50 [adjusted hazard ratio (AHR) 2.80 vs <40 years (referent group); 95% CI 1.93, 4.07, P < 0.001] and HIV infection (AHR 3.81; 95% CI 2.72, 5.34, P < 0.001), but not positive HCV antibody status (AHR 1.19; 95% CI 0.83, 1.72, P = 0.35). Liver‐related mortality was associated with age >50 [AHR 18.49 vs <40 years (referent group); 95% CI 2.27, 150.41, P < 0.001] and positive HCV antibody status (AHR 7.69; 95% CI 0.99, 59.98, P = 0.052). This study demonstrates a high rate of mortality in this population, particularly those with HIV. HCV‐infected inner city residents >50 years of age were at significant risk of liver‐related mortality. Continued surveillance of this population infected with HCV in the 1970s and 1980s is important.     

Weight loss and reduced body mass index: a critical issue in children with multiorgan chronic graft-versus-host disease

Weight loss and malnutrition are major problems in patients with chronic graft-versus-host disease (GVHD). In adults, low body mass index (BMI) is a predictor for mortality; however, weight loss and BMI have not been studied in pediatric chronic GVHD. A retrospective study on 18 children with extensive chronic GVHD was completed. Median age at SCT was 12.3 (range 0.6-23) years; age at chronic GVHD diagnosis was 12.5 (1-23) years. Patients with multiorgan involvement had a mean maximal decrease in BMI of 20.9% and most dropped below 10th percentile in expected weight-for-age. This change in BMI not only indicates a significant decrease in weight but often a plateau in stature. In contrast, patients with one organ system involved had a mean maximal decrease in BMI of 5% and did not fall below 10th percentile. All patients with multiorgan involvement required salvage therapy beyond steroids and CSA. Three patients died due to complications of chronic GVHD. Weight loss and malnutrition (as reflected by a decrease in BMI) are clinically significant issues in children with multisystem chronic GVHD. Weight loss is likely another systemic manifestation of the disease and may contribute, along with other factors such as increased immunosuppression and infection, to increased mortality in this group.     

Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy.

We conducted a case study of human immunodeficiency virus (HIV)-negative patients with cryptococcosis at 15 United States medical centers from 1990 through 1996 to understand the demographics, therapeutic approach, and factors associated with poor prognosis in this population. Of 306 patients with cryptococcosis, there were 109 with pulmonary involvement, 157 with central nervous system (CNS) involvement, and 40 with involvement at other sites. Seventy-nine percent had a significant underlying condition. Patients with pulmonary disease were usually treated initially with fluconazole (63%); patients with CNS disease generally received amphotericin B (92%). Fluconazole was administered to approximately two-thirds of patients with CNS disease for consolidation therapy. Therapy was successful for 74% of patients. Significant predictors of mortality in multivariate analysis included age > or =60 years, hematologic malignancy, and organ failure. Overall mortality was 30%, and mortality attributable to cryptococcosis was 12%. Cryptococcosis continues to be an important infection in HIV-negative patients and is associated with substantial overall and cause-specific mortality.