Varicella Zoster Virus CNS disease in hematopoietic cell transplantation: A single center experience

Background: Varciella Zoster Virus (VZV) can lead to serious complications in Hematopoietic Cell Transplant (HCT) recipients. Central nervous system (CNS) VZV can be one of the most devastating infections in transplant recipients, yet little is known about this rare disease. Objectives: To describe CNS VZV in the post-transplant period and to define potential risk factors in the HCT population. Methods: We reviewed the course of all patients who received a first HCT at the Fred Hutchinson Cancer Center (FHCRC) in Seattle, WA from 1/1996 through 12/2007. Data were collected retrospectively using the Long-Term Follow-Up database, which includes on-site examinations, outside records, laboratory tests, and yearly questionnaires. Patients were classified as CNS VZV if they had laboratory confirmation of VZV in the cerebrospinal fluid (CSF), or had zoster with associated clinical and laboratory findings consistent with CNS disease. Results: A total of six patients developed VZV CNS disease during the evaluation period (table 1). Diagnosis was confirmed in 3/6 by detection of VZV in CSF by PCR. All other patients had a clinical diagnosis based on the presence of CNS symptoms, zoster, lymphocytic pleiocytosis, and response to IV acyclovir. Patients who developed CNS disease had a mean age of 42 years (range 34-51) at time of transplant. CNS disease developed at a mean of 9 months posttransplantation (range 0.5-24 months), and severity varied, ranging from meningitis (3/6) to encephalitis/myelitis (3/6). All had active graft-versus host disease (GHVD) and all were being treated with immunosuppressive therapy at time of diagnosis. Fever and headache were the most common symptoms, but patients who developed focal CNS findings or seizures (3/6) had a more complicated clinical course. While most patients presented with classic VZV/zoster skin lesions, 2/6 patients had no dermatologic findings associated with their presentation. Four (66%) of patients who developed VZV CNS disease died, two related to VZV complications despite aggressive antiviral therapy. Conclusions: In this cohort of HCT patients, VZV CNS disease was a rare complication. Mortality due to CNS VZV is high, particularly in patients who develop focal neurologic findings or seizures. Even in the absence of skin lesions, VZV CNS disease should be considered in patients who develop fevers and neurologic symptoms.

Appropriateness of early management of newly diagnosed Crohn's disease in a European population-based cohort.

OBJECTIVE: The European Panel on the Appropriateness of Crohn's disease Therapy (EPACT) has developed appropriateness criteria. We have applied these criteria retrospectively to the population-based inception cohort of Crohn's disease (CD) patients of the European Collaborative Study Group on Inflammatory Bowel Disease (EC-IBD). MATERIAL AND METHODS: A total of 426 diagnosed CD patients from 13 European centers were enrolled at the time of diagnosis (first flare, naive patients). We used the EPACT definitions to identify 247 patients with active luminal CD. We then assessed the appropriateness of the initial drug prescription according to the EPACT criteria. RESULTS: Among the cohort patients 163 suffered from mild-to-moderate CD and 84 from severe CD. Among the mild-to-moderate disease group, 96 patients (59%) received an appropriate treatment, whereas for 66 patients (40%) the treatment was uncertain and in one case (1%) inappropriate. Among the severe disease group, 86% were treated medically and 14% required surgery. 59 (70%) were appropriately treated, whereas for one patient (1%) the procedure was considered uncertain and for 24 patients (29%) inappropriate. CONCLUSION: Initial treatment was appropriate in the majority of cases for non-complicated luminal CD. Inappropriate or uncertain treatment was given in a significant minority of patients, with an increased potential risk of adverse events.

Pneumopathie interstitielle granulomato-lymphocytaire dans l'immunodéficience commune variable [Granulomatous lymphocytic interstitial lung disease in common variable immunodeficiency].

Common variable immunodeficiency (CVID) is the most frequent primary immune deficiency. Recurrent infections are classical consequences of CVID, but their impact has been largely reduced by immunoglobulin replacement. CVID is also associated with various inflammatory and autoimmune manifestations resulting from abnormal cellular immunity. The lungs are especially affected by a recently described entity called granulomatous lymphocytic interstitial lung disease (GLILD). GLILD currently constitutes an important cause of morbidity and mortality in these patients. It is distinct from bronchiectasis secondary to recurrent infections, and presents similarities but also striking differences with sarcoidosis.

Intravitreal chemotherapy for vitreous disease in retinoblastoma revisited: from prohibition to conditional indications.

BACKGROUND: Tumour control of vitreous seeds remains challenging owing to their resistance to radiation and systemic chemotherapy. OBJECTIVE: To describe the short-term efficacy of intravitreal melphalan for vitreous disease in retinoblastoma using a new injection technique and dose. METHODS: This study is a retrospective non-comparative review of 23 consecutive heavily pretreated patients (23 eyes) with active vitreous seeding and eligible for intravitreous chemotherapy (IViC). They received a total of 122 intravitreal injections of melphalan (20-30 μg) given every 7-10 days. The ocular status was objectively monitored under anaesthesia with fundus photography. RESULTS: All patients are alive without evidence of extraocular spread (95% CI 82.19% to 100%). Concomitant treatments, including other chemotherapeutic modalities, were used until complete sterilisation of the retinal seeding source and subretinal seeds. Globe retention was achieved in 87% (20/23) of cases. All retained eyes were in complete remission after a median follow-up period of 22 months (range 9-31 months). The Kaplan-Meier estimate of ocular survival rates at 2 years was 84.14% (95% CI 62.48% to 95.28%). A localised peripheral salt-and-pepper retinopathy was noted in 10 eyes (43%) at the site of injection. CONCLUSIONS: This study reports the first clinically documented case series of patients with retinoblastoma treated with IViC. Despite a possible confounding effect of concomitant chemotherapy prescription using other routes of administration in four of the successfully treated eyes (20%), IViC achieved an unprecedented success rate of tumour control in the presence of vitreous seeding. Of note, none of the treated eyes required external beam irradiation to control the vitreous seeding. Further studies are required to assess IViC retinal toxicity and to better delineate its role in the management of retinoblastoma.

Umbilical venous concentrations of estradiol in infants with early-onset neonatal sepsis and chorioamnionitis.

Objective: Fetuses are exposed to high concentrations of estradiol due to placental production. Experimental data suggest that estradiol is an important modulator of the immune response. However, the role of estradiol in the pathogenesis of early-onset neonatal sepsis (EOS) is unknown. The purpose of this pilot study was to determine estradiol levels in umbilical venous blood of newborns with EOS or chorioamnionitis exposure. Methods: Estradiol concentrations were measured by enzyme immunoassay in 37 newborns with EOS, 37 newborns with chorioamnionitis and 37 controls matched for gestational age and gender. Results: Estradiol levels correlated with gestational age, birth weight, gender and mode of delivery (p < 0.05). Multivariate analysis revealed higher estradiol levels in the EOS than in the chorioamnionitis group (odds ratio 8.43, 95% CI 1.63-43.45, p = 0.01) with the highest levels in patients with proven bacteraemia (p = 0.02). No difference was found between the EOS and the control group. Exploratory analysis showed an association between lower estradiol levels and a longer duration of mechanical ventilation (n = 28, p = 0.02). Conclusions: Umbilical venous estradiol levels were similar in EOS compared to controls. Further investigation is needed to evaluate whether high estradiol levels in infants with chorioamnionitis increases the risk of developing EOS.

Markers of atherosclerosis and inflammation for prediction of coronary heart disease in older adults.

Although both inflammatory and atherosclerosis markers have been associated with coronary heart disease (CHD) risk, data directly comparing their predictive value are limited. The authors compared the value of 2 atherosclerosis markers (ankle-arm index (AAI) and aortic pulse wave velocity (aPWV)) and 3 inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)) in predicting CHD events. Among 2,191 adults aged 70-79 years at baseline (1997-1998) from the Health, Aging, and Body Composition Study cohort, the authors examined adjudicated incident myocardial infarction or CHD death ("hard" events) and "hard" events plus hospitalization for angina or coronary revascularization (total CHD events). During 8 years of follow-up between 1997-1998 and June 2007, 351 participants developed total CHD events (197 "hard" events). IL-6 (highest quartile vs. lowest: hazard ratio = 1.82, 95% confidence interval: 1.33, 2.49; P-trend < 0.001) and AAI (AAI </= 0.9 vs. AAI 1.01-1.30: hazard ratio = 1.57, 95% confidence interval: 1.14, 2.18) predicted CHD events above traditional risk factors and modestly improved global measures of predictive accuracy. CRP, TNF-alpha, and aPWV had weaker associations. IL-6 and AAI accurately reclassified 6.6% and 3.3% of participants, respectively (P's </= 0.05). Results were similar for "hard" CHD, with higher reclassification rates for AAI. IL-6 and AAI are associated with future CHD events beyond traditional risk factors and modestly improve risk prediction in older adults.

Risk of cardiovascular disease in a traditional African population with a high infectious load: a population-based study.

BACKGROUND: To test the inflammatory origin of cardiovascular disease, as opposed to its origin in western lifestyle. Population-based assessment of the prevalences of cardiovascular risk factors and cardiovascular disease in an inflammation-prone African population, including electrocardiography and ankle-arm index measurement. Comparison with known prevalences in American and European societies. METHODOLOGY/PRINCIPAL FINDINGS: Traditional population in rural Ghana, characterised by adverse environmental conditions and a high infectious load. Population-based sample of 924 individuals aged 50 years and older. Median values for cardiovascular risk factors, including waist circumference, BMI, blood pressure, and markers of glucose and lipid metabolism and inflammation. Prevalence of myocardial infarction detected by electrocardiography and prevalence of peripheral arterial disease detected by ankle-arm index. When compared to western societies, we found the Ghanaians to have more proinflammatory profiles and less cardiovascular risk factors, including obesity, dysglycaemia, dyslipidaemia, and hypertension. Prevalences of cardiovascular disease were also lower. Definite myocardial infarction was present in 1.2% (95%CI: 0.6 to 2.4%). Peripheral arterial disease was present in 2.8% (95%CI: 1.9 to 4.1%). CONCLUSIONS/SIGNIFICANCE: Taken together, our data indicate that for the pathogenesis of cardiovascular disease inflammatory processes alone do not suffice and additional factors, probably lifestyle-related, are mandatory.

Meningococcal disease in a kidney transplant recipient with mannose-binding lectin (MBL) deficiency

Background: There is an increasing amount of data associating MBL deficiency with a higher susceptibility to meningococca[ disease. In addition, meningococca[ disease has been reported in patients with various immunosuppressive conditions. However, to our knowledge, only three cases of meningococca[ disease have been reported in solid organ recipients (SOT). Methods & Results: A 32 year-old male patient underwent cadaveric kidney transplantation for endstage renal disease of unknown origin. On day 71 post-transplantation he developed fever (39.6°C), shaking chilis, and tachycardia without hypotension. At this time, immunosuppression consisted of tacro[imus, prednisone 10mg daily and mycopheno[ ate mofeti[ 2 g daily. Physical examination on admission was normal, except for two small petechia[ lesions on the forearm. No meningeal signs were present. Three sets of blood cultures grew Neisseria meningitidis group C susceptible to ceftriaxone (MIC=0.003mg/[). Antibiotic therapy consisted in intravenous ceftriaxone 2 g per day for a total duration of 7 days. Serum immunog[obu[in levels, C3, C4 and CHS0 were normal However, using a method to screen for the functional activity of a[[ three pathways of complement (Wies[ab, Lund, Sweden), no activation via the MBL pathway could be detected (0%). A subsequent quantification of MBL pathway components revealed normal levels of MASP 2 but undetectab[e amounts of MBL (below 10 ng/m[, normal range: >500 ng/m[). Conclusion: Since the exact incidence and the possible relationship between meningococca[ disease and organ transplantation is not we[[ understood, we strongly encourage transplantation centers to report additional cases. The potential clinical usefu[ ness of screening SOT candidates for MBL deficiency in relation to infectious complications after transplantation remains to be determined.

Introducing a first AIDS vaccine in Switzerland: a Policy Delphi analysis.

This preliminary exploration was limited by a number of factors. The format of the study has necessarily induced some form of selection bias of the panelists, because of the complexity of some questions, and the time required to complete the questionnaires. Several issues have not been addressed. One example could be the response to HIV infection occurring in a vaccinee. The study also did not address the difficulties related to the licensing of the vaccine. Indeed, the proposed scenario assumed that the vaccine had been registered as a starting point for the analysis. Finally, it has not been possible to conduct a sensitivity analysis, in order to evaluate how the responses would have been modified if some important characteristics of the vaccine had been modified.Very diverse evaluations were given in response to questions related with attitudes and perception of AIDS and AIDS vaccine. The possibility that vaccine availability or usage can be associated with an increased frequency in risky behaviors was spontaneously mentioned by half of the panelists. The estimation of the proportion of persons at highest risk who would choose to use this vaccine also indicated a high degree of uncertainty. This study offers important lessons. According to a broad and diverse panel of individuals, an incompletely effective AIDS vaccine would result in an additional level of complexity for the AIDS prevention strategy, rather than a simplification. The use of such a vaccine would have to be coupled with counselling. This implies a sustained emphasis on the recommendations which have been central to the STOP AIDS campaigns until now. In addition, consensual issues, as well as other issues more likely to be controversial have been identified. This should greatly help focusing the work of any committee designated to develop and implement a vaccination policy if an AIDS vaccine became available. Finally, our experience with the Policy Delphi indicates that this mode of structured communication could be usefully applied to other public health issues presenting a high visibility as well as a complex relationship with public perception.

Traitements des facteurs de risque cardiovasculaire et dépistage de la maladie coronarienne dans le diabète de type 2 [Treatments for cardiovascular risk factors and screening for coronary artery disease in type 2 diabetes mellitus]

The recent ACCORD and DIAD studies revealed results which could modify treatments and the screening of diabetes vascular complications. Indeed, ACCORD shows no benefit on the prevention of diabetes vascular complications by aggressive treatment of hypertension or the combined treatment of the dyslipidemia. The intensive treatment of the blood glucose, if associated with severe hypoglycemias, increases mortality. DIAD revealed 20% of silent myocardial ischaemia in diabetic patients but no beneficial effect on the cardiovascular mortality. A careful reading of these studies in the light of long term studies such as UKPDS and STENO reveals that these negative results are generated by a too short follow-up and too aggressive objectives. The long term studies reveal that more realistic objectives remain beneficial.

Ruling out coronary heart disease in primary care patients with chest pain: a clinical prediction score.

ABSTRACT: BACKGROUND: Chest pain raises concern for the possibility of coronary heart disease. Scoring methods have been developed to identify coronary heart disease in emergency settings, but not in primary care. METHODS: Data were collected from a multicenter Swiss clinical cohort study including 672 consecutive patients with chest pain, who had visited one of 59 family practitioners' offices. Using delayed diagnosis we derived a prediction rule to rule out coronary heart disease by means of a logistic regression model. Known cardiovascular risk factors, pain characteristics, and physical signs associated with coronary heart disease were explored to develop a clinical score. Patients diagnosed with angina or acute myocardial infarction within the year following their initial visit comprised the coronary heart disease group. RESULTS: The coronary heart disease score was derived from eight variables: age, gender, duration of chest pain from 1 to 60 minutes, substernal chest pain location, pain increases with exertion, absence of tenderness point at palpation, cardiovascular risks factors, and personal history of cardiovascular disease. Area under the receiver operating characteristics curve was of 0.95 with a 95% confidence interval of 0.92; 0.97. From this score, 413 patients were considered as low risk for values of percentile 5 of the coronary heart disease patients. Internal validity was confirmed by bootstrapping. External validation using data from a German cohort (Marburg, n = 774) revealed a receiver operating characteristics curve of 0.75 (95% confidence interval, 0.72; 0.81) with a sensitivity of 85.6% and a specificity of 47.2%. CONCLUSIONS: This score, based only on history and physical examination, is a complementary tool for ruling out coronary heart disease in primary care patients complaining of chest pain.

La thrombose veineuse profonde chez l'adolescent [Venous thromboembolic disease in adolescents]

Deep vein thrombosis in children and adolescents is a quite rare event. Risk factors most often associated with DVT in this particular population are: central vein catheters, neoplasia, vascular malformations and oral contraception. Diagnosis and management of DVT in adolescents does not differ greatly from that of adults. Compression ultrasound is the initial exam of choice. Hospitalization is often not necessary and treatment can be started by using low molecular weight heparin followed by oral anti-vitamin K antagonists. Thrombophilia screening is not routinely recommended and should be reserved for those patients for whom results would change therapeutical management.