The association between killer‐cell immunoglobulin‐like receptor (KIR) and KIR ligand genotypes and the likelihood of BK virus replication after kidney transplantation

BK virus is a common opportunistic post‐transplantation viral infection. Although some risk factors have been studied in this context, the contribution of NK cells has not been assessed in detail. In a group of kidney transplant recipients, we studied the association between (i) the likelihood of BK virus replication during the two‐year period after kidney transplantation and (ii) the genotypes of the killer cell immunoglobulin‐like receptor (KIR) repertoire and their human leukocyte antigen (HLA) ligands. Other clinical factors (such as defective organ recovery and immunosuppressive treatment) were also assessed. BK virus replication was observed in 43 of the 103 recipients (41%). Patients with BK virus replication in the plasma were more likely to display defective organ recovery in the first seven days post‐transplantation. BK virus replication was not associated with Missing KIR ligands. However, BK virus replication was more frequent in patients with responsive NK cells (i.e. when a ligand for activating KIRs was not homozygous in the recipient and present in the donor). Our results suggest that defective organ recovery and the recipient's activating KIR repertoire may be related (depending on HLA ligands present in the couple recipient / donor) to the reactivation of BK virus replication after kidney transplantation.     

Urinary metal concentrations among mothers and children in a Mexico City birth cohort study

Personal care product use is a potential source of metals exposure among children, but studies have been limited. We measured urinary concentrations of 10 metals (aluminum, arsenic [As], barium [Ba], cadmium, cobalt [Co], lead [Pb], manganese [Mn], molybdenum [Mo], nickel, and zinc [Zn]) in third trimester pregnant women (n?=?212) and their children at 8–14 years of age (n?=?250). Demographic factors (child sex, age, socioeconomic status, and maternal education), body mass index (BMI) z-score, and child personal care product use in the 24?h prior to urine collection were examined as predictors of urinary metal concentrations. Metals were detected in 80–100% of urine samples, with significant differences in maternal versus childhood levels. However, metal concentrations were not strongly correlated within or between time points. In linear regression models including all demographic characteristics, BMI z-score, and specific gravity, age was associated with higher Co (6% [95% CI: 2, 10]), while BMI z-score was associated with lower Mo (-6% [95% CI: -11, -1). In addition, significantly higher metal concentrations were observed among users of colored cosmetics (Mo: 42% [95% CI: 1, 99]), deodorant (Ba: 28% [3, 58]), hair spray/hair gel (Mn: 22% [3, 45]), and other toiletries (As: 50% [9, 108]), as well as with an increasing number of personal care products used (As: 7% [3, 11]) after adjustment for child sex, age, total number of products used, and specific gravity. However, significantly lower metal concentrations were noted for users of hair cream (As and Zn: -20% [-36, -2] and -21% [-35, -2], respectively), shampoo (Pb: -40% [-62, -7]), and other hair products (Pb: -44% [-65, -9]). We found that personal care product use may be a predictor of exposure to multiple metals among children. Further research is recommended to inform product-specific exposure source identification and related child health risk assessment efforts.     

Study of the influence of coating methods on lipid spheres manufactured on rotor fluidized bed process

Abstract

Different previous works have shown that various kinds of spheres can be manufactured by rotor granulation in a ‘single-pot process’ using a lipid base: hydrogenated castor oil. This single-pot technology is based on wet granulation where all components are placed in the powder form in the rotor bowl; then, they are continuously suspended in a fluidized air, with a tangentially sprayed liquid solution. This process allows the granulation and manufacturing of sphere during the same time. Previous experiments have studied the influence of the formulation and the manufacturing process parameters on spheres in terms of feasibility and dissolution properties. Both the spraying time and the weight of liquid sprayed were found to be the most relevant parameters that govern the final quality of the sphere. Now, in a second part of the work, a first comparison is made with two different fluid bed methods: the tangential rotor spray and the Wurster bottom spray for coating the lipid spheres previously manufactured with the rotor tangential spray. The external aspect of the coated spheres manufactured has been evaluated with an electronic microscopy analysis and a study of dissolution properties of the active ingredient has been done by USP in vitro dissolution tests.     

Hematopoietic growth factors for graft failure after bone marrow transplantation: a randomized trial of granulocyte-macrophage colony- stimulating factor (GM-CSF) versus sequential GM-CSF plus granulocyte- CSF

Delay in hematologic recovery after bone marrow transplantation (BMT) can extend and amplify the risks of infection and hemorrhage, compromise patients' survival, and increase the duration and cost of hospitalization. Because current studies suggest that granulocyte- macrophage (GM) colony-stimulating factor (CSF) may potentiate the sensitivity of hematopoietic progenitor cells to G-CSF, we performed a prospective, randomized trial comparing GM-CSF (250 micrograms/m2/d x 14 days) versus sequential GM-CSF x 7 days followed by G-CSF (5 micrograms/kg/d x 7 days) as treatment for primary or secondary graft failure after BMT. Eligibility criteria included failure to achieve a white blood cell (WBC) count > or = 100/microL by day +21 or > or = 300/microL by day +28, no absolute neutrophil count (ANC) > or = 200/microL by day +28, or secondary sustained neutropenia after initial engraftment. Forty-seven patients were enrolled: 23 received GM-CSF (10 unrelated, 8 related allogeneic, and 5 autologous), and 24 received GM- CSF followed by G-CSF (12 unrelated, 7 related allogeneic, and 5 autologous). For patients receiving GM-CSF alone, neutrophil recovery (ANC > or = 500/microL) occurred between 2 and 61 days (median, 8 days) after therapy, while those receiving GM-CSF+G-CSF recovered at a similar rate of 1 to 36 days (median, 6 days; P = .39). Recovery to red blood cell (RBC) transfusion independence was slow, occurring 6 to 250 days (median, 35 days) after enrollment with no significant difference between the two treatment groups (GM-CSF: median, 30 days; GM-CSF+G- CSF; median, 42 days; P = .24). Similarly, platelet transfusion independence was delayed until 4 to 249 days (median, 32 days) after enrollment, with no difference between the two treatment groups (GM- CSF: median, 28 days; GM-CSF+G-CSF: median, 42 days; P = .38). Recovery times were not different between patients with unrelated donors and those with related donors or autologous transplant recipients. Survival at 100 days after enrollment was superior after treatment with GM-CSF alone. Only 1 of 23 patients treated with GM-CSF died versus 7 of 24 treated with GM-CSF+G-CSF who died 16 to 84 days (median, 38 days) after enrollment, yielding Kaplan-Meier 100-day survival estimates of 96% +/- 8% for GM-CSF versus 71% +/- 18% for GM-CSF+G-CSF (P = .026). These data suggest that sequential growth factor therapy with GM-CSF followed by G-CSF offers no advantage over GM-CSF alone in accelerating trilineage hematopoiesis or preventing lethal complications in patients with poor graft function after BMT.(ABSTRACT TRUNCATED AT 400 WORDS)     

Hepatitis-B-associated glomerulonephritis: pathology, pathogenesis, and clinical course

Hepatitis-B-associated glomerulonephritis (HBGN) is a distinct entity occurring frequently in hepatitis-B-prevalent areas of the world. The disease affects both adults and children who are chronic hepatitis-B-virus (HBV) carriers with or without a history of overt liver disease. The diagnosis is established by serologic evidence of HBV antigens/antibodies, presence of an immune complex glomerulonephritis, immunohistochemical localization of 1 or more HBV antigens, and pertinent clinical history, when available. In this study we present clinicopathologic and follow-up findings in 12 patients (7 children, 5 adults) with hepatitis-B-associated glomerulonephritis. Twelve patients provided 15 renal biopsies and 1 specimen of kidney tissue, obtained at autopsy; these were examined by light microscopy, electron microscopy, and immunohistochemical methods. Membranous glomerulonephritis (MGN) with or without mesangial proliferation was noted in 7 biopsies, mesangiocapillary (membranoproliferative) glomerulonephritis (MCGN) in 5 biopsies, and proliferative glomerulonephritis with or without membranous changes in 2 biopsies. Tubulointerstitial changes were minimal except in 3 adults, in whom they were attributable to arterionephrosclerosis. Ultrastructural findings included the presence of considerable amounts of focal or diffuse granular electron-dense deposits in the glomeruli, in the subepithelial, subendothelial, and mesangial locations, occasionally destroying or replacing the lamina densa of the basement membrane. Variable mesangial proliferation was also observed, with interposition, with focal irregular reduplication of the basement membranes and rare clusters of spherical particles, probably representing viral particles in the deposits. In addition, granular deposits along tubular basement membranes were seen in 1 case. The glomerular deposits stained for 2 or more immunoglobulins, the predominant one being IgG, and variably also for complement components (C3, C4 and C1q). Hepatitis B viral antigens (HBsAg, HBcAg, HBeAg) were demonstrated using acid elution techniques in the deposits in all biopsies where frozen tissue was available, singly or in a variety of combinations and intensities. There were deposits of IgG, C3, C1q, and HBsAg along the tubular basement membranes in 1 case. Follow-up biopsies in 2 cases, 2 and 5 years apart, showed a transformation from a diffuse MGN to MCGN with segmental membranous features. Follow-up biopsy after 3 years in the third patient, who went into clinical remission, revealed partially resolving glomerular lesions. Renal lesions secondary to chronic liver disease, parasitic diseases, certain tropical nephropathies, and lupus nephritis are some of the diseases that may morphologically resemble HBGN. Recognition and differentiation of HBGN from other entities may have significant prognostic and therapeutic implications.(ABSTRACT TRUNCATED AT 400 WORDS)     

Current Zika virus epidemiology and recent epidemics

The Zika virus (ZIKV) is a mosquito-borne flavivirus (Aedes), similar to other arboviruses, first identified in Uganda in 1947. Few human cases were reported until 2007, when a Zika outbreak occurred in Yap, Micronesia, even though ZIKV activity had been reported in Africa and in Asia through virological surveillance and entomological studies. French Polynesia has recorded a large outbreak since October 2013. A great number of cases and some with neurological and autoimmune complications have been reported in a context of concurrent circulation of dengue viruses. The clinical presentation is a “dengue-like syndrome”. Until the epidemic in French Polynesia, no severe ZIKV disease had been described so far. The diagnosis is confirmed by viral genome detection by genomic amplification (RT- PCR) and viral isolation. These two large outbreaks occurred in a previously unaffected area in less than a decade. They should raise awareness as to the potential for ZIKV to spread especially since this emergent disease is not well known and that some questions remain on potential reservoirs and transmission modes as well as on clinical presentations and complications. ZIKV has the potential to spread to new areas where the Aedes mosquito vector is present and could be a risk for Southern Europe. Strategies for the prevention and control of ZIKV disease should include the use of insect repellent and mosquito vector eradication.     

Prescription,Compliance, and Burden Associated with Salt-Restricted Diets in Heart Failure Patients: Results from the French National OFICSel Observatory

(1) Background: There is much debate about the use of salt-restricted diet for managing heart failure (HF). Dietary guidelines are inconsistent and lack evidence. (2) Method: The OFICSel observatory collected data about adults hospitalised for HF. The data, collected using study-specific surveys, were used to describe HF management, including diets, from the cardiologists’ and patients’ perspectives. Cardiologists provided the patients’ clinical, biological, echocardiography, and treatment data, while the patients provided dietary, medical history, sociodemographic, morphometric, quality of life, and burden data (burden scale in restricted diets (BIRD) questionnaire). The differences between the diet recommended by the cardiologist, understood by the patient, and the estimated salt intake (by the patient) and diet burden were assessed. (3) Results: Between March and June 2017, 300 cardiologists enrolled 2822 patients. Most patients (90%) were recommended diets with <6 g of salt/day. Mean daily salt consumption was 4.7 g (standard deviation (SD): 2.4). Only 33% of patients complied with their recommended diet, 34% over-complied, and 19% under-complied (14% unknown). Dietary restrictions in HF patients were associated with increased burden (mean BIRD score of 8.1/48 [SD: 8.8]). (4) Conclusion: Healthcare professionals do not always follow dietary recommendations, and their patients do not always understand and comply with diets recommended. Restrictive diets in HF patients are associated with increased burden. An evidence-based approach to developing and recommending HF-specific diets is required.