Incidence and significance of the JAK2 V617F mutation in patients with chronic myeloproliferative disorders

BACKGROUND: The chronic myeloproliferative disorders (MPD) are clonal haemopoietic stem cell disorders.

AIMS: The incidence of JAK2 V617F mutation was sought in a population of patients with MPD.

METHODS: The JAK2 V617 mutation status was determined in 79 patients with known MPD and 59 patients with features suggestive of MPD.

RESULTS: The mutation was found in patients with polycythaemia vera, essential thrombocythaemia, idiopathic myelofibrosis and in patients with other chronic myeloproliferative disorders. Eight JAK2 V617F positive cases were identified amongst those patients with features suggestive of MPD.

CONCLUSIONS: The incidence of the JAK2 V617F mutation in MPD patients is similar to that reported by other groups. The assay confirmed and refined the diagnosis of several patients with features indicative of MPD. We suggest screening for this mutation in all patients with known and suspected MPD as identification is valuable in classification and is a potential target for signal transduction therapy.

The influence of cyclosporin alone, or cyclosporin and methotrexate, on the incidence of mixed haematopoietic chimaerism following allogeneic sibling bone marrow transplantation for severe aplastic anaemia

We previously reported a randomized trial comparing Cyclosporin-A (CsA) and short-term methotrexate versus CsA alone for graft-versus-host disease (GvHD) prophylaxis in 71 patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) from a human leucocyte antigen-identical sibling for severe aplastic anaemia (SAA). We found a better survival in the group receiving the two-drug prophylaxis regimen with no significant difference in the probability of developing GvHD between the two groups. The present study details chimaeric analysis and its influence on survival and GvHD occurrence in 45 of the original 71 patients in whom serial samples were available. Analysis was carried out in a blinded prospective manner. Seventy-two per cent achieved complete donor chimaerism (DC), 11% stable mixed chimaerism (SMC) and 17% progressive mixed chimaerism (PMC). The overall 5-year survival probability was 82% (+/-11%) with a significant survival advantage (P = 0.0009) in DC or SMC compared to those with PMC. Chronic GvHD was more frequent in DC patients, whereas no patient with SMC developed chronic GvHD. Graft failure occurred in 50% of the PMC group. This study demonstrates the relevance of chimaerism analysis in patients receiving HSCT for SAA and confirms the occurrence of mixed chimaerism in a significant proportion of recipients.

Campath-1G in vivo confers a low incidence of graft-versus-host disease associated with a high incidence of mixed chimaerism after bone marrow transplantation for severe aplastic anaemia using HLA-identical sibling donors

We have evaluated the effect of in vivo Campath-1G on engraftment and GVHD in 23 patients with severe aplastic anaemia transplanted from HLA-identical sibling donors. In 14 patients Campath 1g was given pre-transplant for up to 9 days in an attempt to overcome graft rejection (group 1). In nine patients Campath-1G was given pre-transplant, but also continued post-transplant until day +5 to reduce GVHD (group 2). There were three patients with late graft failure in group I following initial neutrophil engraftment, and four cases of grade II+ GVHD. In group II, two patients had early graft failure (no take), and there were no cases of acute GVHD out of seven evaluable patients. One patient in group I developed chronic GVHD of the liver, and two patients (one in each group) had transient localised chronic GVHD. PCR of short tandem repeats was used to evaluate chimaeric status in 13 patients. Of 11 patients with initial neutrophil engraftment, only one had 100% donor haemopoiesis at all times. The remaining patients had either transient mixed chimaerism or persistence of recipient (< 20%) cells. We conclude that in vivo Campath-1G is associated with a high incidence of mixed chimaerism which tips the balance away from GVHD but towards graft rejection.

Causes and five-year incidence of blindness and visual impairment in urban southern China:The Liwan Eye Study

PURPOSE. We determined the causes and five-year incidence of blindness and visual impairment (VI) in an adult, urban Chinese population. METHODS. Participants underwent a comprehensive eye examination at baseline in 2003 and then five years later. The World Health Organization (WHO) and United States (US) definitions were used to define incident blindness (WHO visual acuity [VA] < 20/400 in the better-seeing eye, US VA ≤ 20/200) and incident VI (WHO VA < 20/60-20/400, US VA < 20/40->20/200). RESULTS. Among 1405 baseline participants, 924 (75%) of 1232 survivors (87.7%) participated in the 5-year follow-up. The incidences of VI and blindness were 5.38% (95% confidence interval [CI] 3.99% ~ 7.07%) and 0.33% (95% CI 0.07% ~ 0.95%), respectively, based on the WHO definition, and 9.85% (95% CI 7.96% ~ 12.0%) and 1.42% (95% CI 0.76% ~ 2.41%), respectively, based on the US definition. Incidence of blindness and VI (WHO definition) increased significantly with older age (P < 0.001) and poorer baseline presenting VA in the worse-seeing eye (P < 0.001). The leading cause of best-corrected VI (WHO definition) was cataract (64.6%), whereas the main causes of presenting VI were refractive error (40.4%) and cataract (38.4%). CONCLUSIONS. The incidence of VI in urban Southern China is high. The major causes are unoperated cataract and undercorrected refractive error, reflecting the need for better surgical and refractive care, even in this urban setting. © 2013 The Association for Research in Vision and Ophthalmology, Inc.

Five-year incidence and postoperative visual outcome of cataract surgery in urban southern China:The liwan eye study

Purpose. To determine the 5-year incidence and visual outcome of cataract surgery in an adult urban Chinese population. Methods. A comprehensive eye examination was performed at baseline and 5 years later on subjects participating in a population-based study. Incident cataract surgery was defined as having undergone surgery in either eye during the 5-year period. Postoperative visual impairment (PVI) was defined as visual acuity (VA) <6/18 based on both presenting VA (PVA) and best corrected VA (BCVA) in the operated eye. Results. Among the 1405 baseline participants, 75% (924) of survivors were seen at the 5-year follow-up visit. Forty-four returning participants (62 eyes) had undergone incident cataract surgery, an incidence of 4.84% (95% confidence interval [CI] - [3.53, 6.44]). Detailed medical and surgical records were available for 54/62 (87.1%) eyes, and of these, 5/ 54 (24.1%) had an immediate preoperative visual acuity <6/ 120. All recorded surgeries were performed at tertiary-level hospitals with phacoemulsification and foldable intraocular lens implantation. Those undergoing cataract surgery were more educated (P < 0.05) and had poorer baseline PVA in the worse-seeing eye (P < 0.001) than 54 persons with baseline PVA <6/18 due to cataract who had not had surgery. Among the 62 operated eyes, 22.6% (14/62) had PVI based on PVA and 9.6% (6/62) based on BCVA. Conclusions. Despite somewhat lower incidence, outcomes of cataract surgery in urban southern China are comparable with developed countries and better than for rural China. In urban China, emphasis should be on improving access to surgery. (Invest Ophthalmol Vis Sci. 2012;53:7936-7942) © 2012 The Association for Research in Vision and Ophthalmology, Inc.

Supra-treatment threshold neonatal jaundice: Incidence in HIV-exposed compared to non-exposed neonates at Queen Elizabeth Central Hospital in Blantyre, Malawi

INTRODUCTION: Jaundice is the yellowish pigmentation of the skin, sclera, and mucous membranes resulting from bilirubin deposition. Children born to mothers with HIV are more likely to be born premature, with low birth weight, and to become septic-all risk factors for neonatal jaundice. Further, there has been a change in the prevention of mother-to-child transmission (PMTCT) of HIV guidelines from single-dose nevirapine to a six-week course, all of which theoretically put HIV-exposed newborns at greater risk of developing neonatal jaundice.

AIM: We carried out a study to determine the incidence of severe and clinical neonatal jaundice in HIV-exposed neonates admitted to the Chatinkha Nursery (CN) neonatal unit at Queen Elizabeth Central Hospital (QECH) in Blantyre.

METHODS: Over a period of four weeks, the incidence among non-exposed neonates was also determined for comparison between the two groups of infants. Clinical jaundice was defined as transcutaneous bilirubin levels greater than 5 mg/dL and severe jaundice as bilirubin levels above the age-specific treatment threshold according the QECH guidelines. Case notes of babies admitted were retrieved and information on birth date, gestational age, birth weight, HIV status of mother, type of feeding, mode of delivery, VDRL status of mother, serum bilirubin, duration of stay in CN, and outcome were extracted.

RESULTS: Of the 149 neonates who were recruited, 17 (11.4%) were HIV-exposed. One (5.88%) of the 17 HIV-exposed and 19 (14.4%) of 132 HIV-non-exposed infants developed severe jaundice requiring therapeutic intervention (p = 0.378). Eight (47%) of the HIV-exposed and 107 (81%) of the non-exposed neonates had clinical jaundice of bilirubin levels greater than 5 mg/dL (p < 0.001).

CONCLUSIONS: The study showed a significant difference in the incidence of clinical jaundice between the HIV-exposed and HIV-non-exposed neonates. Contrary to our hypothesis, however, the incidence was greater in HIV-non-exposed than in HIV-exposed infants.

A Role for Behavior in the Relationships Between Depression and Hostility and Cardiovascular Disease Incidence, Mortality, and All-Cause Mortality: the Prime Study

BACKGROUND: Behavioral factors are important in disease incidence and mortality and may explain associations between mortality and various psychological traits.

PURPOSE: These analyses investigated the impact of behavioral factors on the associations between depression, hostility and cardiovascular disease(CVD) incidence, CVD mortality, and all-cause mortality.

METHODS: Data from the PRIME Study (N = 6953 men) were analyzed using Cox proportional hazards models, following adjustment for demographic and biological CVD risk factors, and other psychological traits, including social support.

RESULTS: Following initial adjustment, both depression and hostility were significantly associated with both mortality outcomes (smallest SHR = 1.24, p < 0.001). Following adjustment for behavioral factors, all relationships were attenuated both when accounting for and not accounting for other psychological variables. Associations with all-cause mortality remained significant (smallest SHR = 1.14, p = 0.04). Of the behaviors included, the most significant contribution to outcomes was found for smoking, but a role was also found for fruit and vegetable intakes and high alcohol consumption.

CONCLUSIONS: These findings demonstrate well-known associations between depression, hostility, and mortality and suggest the potential importance of behaviors in explaining these relationships.

The effect of statins on intraocular pressure and on the incidence and progression of glaucoma: A Systematic Review and Meta-analysis

Purpose: We conducted a systematic review and meta-analysis of observational studies to evaluate the effect of oral statins on intraocular pressure (IOP) and the incidence and progression of glaucoma. Methods: This was a systematic review of the literature and meta-analysis. Searches of PubMed/Medline and Embase were conducted to include all types of studies. Gray literature abstracts were also considered for inclusion. Last search date was February 2016. Risk of bias was assessed using the Newcastle-Ottawa scale independently by two reviewers. Odds ratios (OR) or hazard ratios (HR) and 95% confidence intervals (CI) were extracted from each study. Pooled ORs for incidence of glaucoma were calculated using a random-effects model. Results: We identified seven cohort studies, three case–control studies, and one cross-sectional study with a total number of 583,615 participants. No randomized controlled trials were retrieved. Pooled ORs demonstrated a statistically significant association between short-term statin use (≤2 years) and reduced incidence of glaucoma (OR 0.96, 95%CI 0.94, 0.99). Pooled ORs of long-term statin use (>2 years) did not demonstrate statistically significant reduction in incidence of glaucoma (OR 0.70, 95%CI 0.46, 1.06). There was inconsistent evidence for the protective effect of statins against the progression of glaucoma, although there was no standard definition for progression across studies. There was no significant difference in IOP associated with statin use. Conclusions: Short-term statin use is associated with a reduced incidence of glaucoma. The effect of statins on glaucoma progression and IOP is uncertain.

Prevalence and Incidence of Black Band Disease of Scleractinian Corals in the Kepulauan Seribu Region of Indonesia

Black band disease (BBD) is the oldest recognised disease associated with scleractinian corals. However, despite this, few BBD surveys have been conducted in the Indonesian archipelago, one of the world’s hot spots for coral diversity. In this study, we show that BBD was recorded in the reefs of Kepulauan Seribu, Indonesia, at the time of surveying. The disease was found to mainly infect corals of the genus Montipora. In some instances, upwards of 177 colonies (31.64%) were found to be infected at specific sites. Prevalence of the disease ranged from 0.31% to 31.64% of Montipora sp. colonies throughout the archipelago. Although BBD was found at all sites, lower frequencies were
associated with sites closest to the mainland (17.99 km), as well as those that were furthest away (63.65 km). Despite there being no linear relationship between distance from major population centers and BBD incidence, high incidences of this disease were associated with sites characterized by higher
levels of light intensity. Furthermore, surveys revealed that outbreaks peaked during the transitional period between the dry and rainy seasons. Therefore, we suggest that future surveys for disease prevalence in this region of Indonesia should focus on these transitory periods.

Incidence and clinicobiologic characteristics of leukemic B-cell chronic lymphoproliferative disorders with more than one B-cell clone.

Leukemic B-chronic lymphoproliferative disorders (B-CLPDs) are generally believed to derive from a monoclonal B cell; biclonality has only occasionally been reported. In this study, we have explored the incidence of B-CLPD cases with 2 or more B-cell clones and established both the phenotypic differences between the coexisting clones and the clinicobiologic features of these patients. In total, 53 B-CLPD cases with 2 or more B-cell clones were studied. Presence of 2 or more B-cell clones was suspected by immunophenotype and confirmed by molecular/genetic techniques in leukemic samples (n = 42) and purified B-cell subpopulations (n = 10). Overall, 4.8% of 477 consecutive B-CLPDs had 2 or more B-cell clones, their incidence being especially higher among hairy cell leukemia (3 of 13), large cell lymphoma (2 of 10), and atypical chronic lymphocytic leukemia (CLL) (4 of 29). In most cases the 2 B-cell subsets displayed either different surface immunoglobulin (sIg) light chain (n = 37 of 53) or different levels of the same sIg (n = 9 of 53), usually associated with other phenotypic differences. Compared with monoclonal cases, B-CLL patients with 2 or more clones had lower white blood cell (WBC) and lymphocyte counts, more frequently displayed splenomegaly, and required early treatment. Among these, the cases in which a CLL clone coexisted with a non-CLL clone were older and more often displayed B symptoms, a monoclonal component, and diffuse infiltration of bone marrow and required early treatment more frequently than cases with monoclonal CLL or 2 CLL clones.