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Background RSV causes respiratory infections that can lead to serious respiratory complications in older adults (OA). Presently, there is no approved vaccine to prevent RSV infections. RSVPreF3 OA is an investigational vaccine containing 120 µg RSVPreF3 and the AS01E adjuvant. Here we show safety results up to month (M) 6 post-vaccination with RSVPreF3 OA. Methods This phase 3 multi-country ongoing study (NCT04732871) enrolled adults ≥ 60 years of age over a period of 3 years. Participants were randomized (3:1:1) to receive RSVPreF3 OA with different vaccination schedules. All participants received a dose of RSVPreF3 OA on day 1. Solicited and unsolicited adverse events (AEs) were evaluated within 4 and 30 days post-vaccination. All serious AEs (SAEs) and potential immune mediated diseases (pIMDs) were collected up to M6 post-vaccination. SAEs and pIMDs related to vaccination, and fatal AEs are collected up to study end but reported here up to M6. Results Overall, 1653 participants received a dose of RSVPreF3 OA and 1618 completed the M6 follow-up. The mean age was 70.0 (±6.6) years and 54.6% were women. The most frequently reported solicited injection site reaction within 4 days post-vaccination was pain (996 participants; 60.5%, 95% confidence interval [CI]: 58.1–62.9). Twenty-two participants (1.3%, 95% CI: 0.8–2.0) reported grade 3 pain (Figure). The most reported solicited systemic reactions were myalgia (551 participants; 33.5%, 95% CI: 31.2–35.8) and fatigue (517 participants; 31.4%, 95% CI: 29.2–33.7). Twenty-five participants (1.5%) reported fever (no grade 3). Most solicited AEs were transient lasting ∼2 days and were of mild to moderate intensity. Overall, 212 (12.8%, 95% CI: 11.3–14.5) participants reported at least 1 unsolicited AE within 30 days post-vaccination. At least 1 SAE was reported by 65 participants (3.9%, 95% CI: 3.0–5.0). Seven participants (0.4%, 95% CI: 0.2–0.9) reported at least 1 pIMD. Of the SAEs and pIMDs reported, 1 event (Guillain-Barre syndrome) was considered by the investigator as related to vaccination. Fatal SAEs were reported for 6 participants; none related to vaccination. Conclusion One dose of investigational RSVPreF3 OA vaccine was well tolerated and had an acceptable safety profile in adults ≥ 60 years of age. Funding GlaxoSmithKline Biologicals SA. Disclosures Tino F. Schwarz, Prof. Dr. MD, Biogen, Merck-Serono, Pfizer, Alexion, Bavarian Nordic, Janssen-Cilag, AstraZeneca, Biontech, MSD: Grants|GlaxoSmithKline Biologicals SA: Honoraria John E. Ervin, MD, The Alliance for Multispecialty Research – KCM: Contractual agreement for conduct of study protocol Charles Andrews, MD, GlaxoSmithKline Biologicals SA: Institutional grant|Merck and Boehringer Ingelheim: Consulting fees outside of the submitted work Miguel Vicco, PhD MD, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Stocks/Bonds Marc Lievens, MSc, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Stocks/Bonds Céline Maréchal, PhD, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Stocks/Bonds Phoebe Nakanwagi, Master’s in Biostatistics, GlaxoSmithKline Biologicals SA: Employee Veronica Hulstrøm, PhD MD, GlaxoSmithKline Biologicals SA: Employee.

AQP1 Promoter Variant and Peritoneal Dialysis Variability in ultrafiltration influences prescriptions and outcomes in patients treated with peritoneal dialysis. This study showed that a common variant in AQP1, the gene that encodes the water channel aquaporin-1, was associated with decreased ultrafiltration and an increased risk of death or technique failure among such patients.Background Variability in ultrafiltration influences prescriptions and outcomes in patients with kidney failure who are treated with peritoneal dialysis. Variants in AQP1, the gene that encodes the archetypal water channel aquaporin-1, may contribute to that variability. Methods We gathered clinical and genetic data from 1851 patients treated with peritoneal dialysis in seven cohorts to determine whether AQP1 variants were associated with peritoneal ultrafiltration and with a risk of the composite of death or technique failure (i.e., transfer to hemodialysis). We performed studies in cells, mouse models, and samples obtained from humans to characterize an AQP1 variant and investigate mitigation strategies. Results The common AQP1 promoter variant rs2075574 was associated with peritoneal ultrafiltration. Carriers of the TT genotype at rs2075574 (10 to 16% of patients) had a lower mean (+/- SD) net ultrafiltration level than carriers of the CC genotype (35 to 47% of patients), both in the discovery phase (506 +/- 237 ml vs. 626 +/- 283 ml, P=0.007) and in the validation phase (368 +/- 603 ml vs. 563 +/- 641 ml, P=0.003). After a mean follow-up of 944 days, 139 of 898 patients (15%) had died and 280 (31%) had been transferred to hemodialysis. TT carriers had a higher risk of the composite of death or technique failure than CC carriers (adjusted hazard ratio, 1.70; 95% confidence interval [CI], 1.24 to 2.33; P=0.001), as well as a higher risk of death from any cause (24% vs. 15%, P=0.03). In mechanistic studies, the rs2075574 risk variant was associated with decreases in AQP1 promoter activity, aquaporin-1 expression, and glucose-driven osmotic water transport. The use of a colloid osmotic agent mitigated the effects of the risk variant. Conclusions A common variant in AQP1 was associated with decreased ultrafiltration and an increased risk of death or technique failure among patients treated with peritoneal dialysis. (Funded by the Swiss National Science Foundation and others.)

Background This study evaluated immunogenicity and safety of the adjuvanted recombinant zoster vaccine (RZV) when the first dose was co-administered with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in adults aged ≥50 years. Methods In this open label, multi-center study (NCT02045836), participants were randomized 1:1 to receive either the first dose of RZV and PPSV23, co-administered at Day 0 and the second dose of RZV at Month 2 (Co-Ad group), or PPSV23 at Day 0, the first dose of RZV at Month 2 and second dose of RZV at Month 4 (Control group). Co-primary objectives were the RZV vaccine response rate (VRR) in the Co-Ad group and the non-inferiority of the antibody responses to RZV and PPSV23 in the Co-Ad group compared to the Control group. Reactogenicity and safety were also assessed. Results 865 participants were vaccinated (Co-Ad: 432, Control: 433). VRRs to RZV were >98% in both groups. Humoral immune responses to co-administration of RZV and PPSV23 were non-inferior to sequential administration. All three co-primary immunogenicity objectives were met. Solicited local symptoms after the first RZV dose were reported by similar percentages of participants in both groups. Solicited general symptoms were more frequently reported when the first dose of RZV and PPSV23 were co-administered. No differences were apparent between groups after the second RZV dose. Conclusions No immunologic interference was observed between RZV and PPSV23 when co-administered in adults ≥50 years. No safety concerns were raised.

Autosomal dominant polycystic kidney disease (ADPKD) is associated with a urine-concentrating defect attributed to renal cystic changes. As PKD genes are expressed in the brain, altered central release of arginine vasopressin could also play a role. In order to help determine this we measured central and nephrogenic components of osmoregulation in 10 adults and 10 children with ADPKD, all with normal renal function, and compared them to 20 age- and gender-matched controls. Overnight water deprivation caused a lower rise in urine osmolality in the patients with ADPKD than controls, reflecting an impaired release of vasopressin and a peripheral defect in the patients. The reactivity of plasma vasopressin to water deprivation, as found in controls, was blunted in the patients with the latter showing lower urine osmolality for the same range of plasma vasopressin. The maximal urine osmolality correlated negatively with total kidney volume. Defective osmoregulation was confirmed in the children with ADPKD but was unrelated to number of renal cysts or kidney size. Thus, patients with ADPKD have an early defect in osmoregulation, with a blunted release of arginine vasopressin. This reflects expression of polycystins in hypothalamic nuclei that synthesize vasopressin, and this should be considered when evaluating treatments targeting the vasopressin pathway in ADPKD.

Resume La frequentation des services d’urgences pediatriques par des nouveau-nes suit la problematique croissante de l’utilisation des services d’urgences. But Analyser les caracteristiques epidemiologiques d’une cohorte de nouveau-nes consultant dans un service d’urgences pediatriques. Patients et methodes Etude prospective entre aout 2008 et avril 2009 incluant tout enfant d’âge inferieur ou egal a 28 j admis au service d’urgences pediatriques. Chez le nouveau-ne : l’âge, le sexe, le terme, le type d’allaitement, les horaires d’admission, le mode et le motif de recours, les antecedents neonatals, la duree de sejour et le devenir ont ete analyses. Pour les enfants admis d’aout a octobre 2008, les retours sur les 6 mois suivants ont ete etudies. Concernant les meres, l’âge, la parite, le mode de vie, la profession, l’accouchement et la duree du sejour en maternite ont ete analyses. Resultats Analyse descriptive : 538 enfants ont ete inclus, leur moyenne d’âge etait egale a 17 j, le sex-ratio a 1,1. Les recours etaient domines par des motifs medicaux (90 %) et 47 % ont ete hospitalises. Les meres etaient âgees de 30 ans en moyenne, 53 % etaient primipares et elles avaient sejourne en maternite 5 j en moyenne. Analyse comparative : les nouveau-nes etaient plus souvent adresses, plus souvent hospitalises, consultaient plus souvent la nuit et la gravite de leur etat repondait a la loi du tout ou rien. Le risque de recours aux urgences etait plus eleve si la mere etait jeune, primipare, seule ou sans emploi, habitait pres de l’hopital et si l’enfant âge de moins de 15 j. Conclusion Initialement rattachee a un raccourcissement des sejours en maternite, l’augmentation de la frequentation des services d’urgences pediatriques par des nouveau-nes est multifactorielle, liee a leur vulnerabilite, a leurs antecedents, a leur environnement familial et a des facteurs sociologiques.

Adder bites and their progression to severe envenomations are more frequent in children than in adults. AIM: To describe the clinical, biological, and therapeutic characteristics of children bitten by adders and to identify risk factors associated with severe envenomations corresponding to grades II and III of the Audebert et al. classification (Toxicon 1992). MATERIAL AND METHODS: A retrospective study was conducted between 2001 and 2009 in the pediatric emergency department of a tertiary children's hospital. The data collected were: age and sex of children; day and time of admission; day, time, and circumstances of the accident; snake identification; bite location; envenomation severity based on the Audebert et al. classification; presence of fang marks; prehospital care; use of specific immunotherapy (Viperfav(®)), associated treatments; length of stay; orientation, progression, and any complications. RESULTS: Fifty-eight children were included (43 boys, 15 girls). The mean age was 7.8±4.1 years (range, 1.8-15 years). Bites occurred more often between 12:00 pm and 6:00 pm (62%), and were most often located in the lower extremities (77%). The classification of envenomation was: 83% low grade (grade 0, absence of envenomation, fang marks present; grade I, minor envenomation) and 17% high grade (grades II and III, moderate and severe envenomations). All high-grade envenomations received specific immunotherapy (Viperfav(®) F(ab')(2) fragments against Vipera aspis, Vipera berus, and Vipera ammodytes). The mean time from bite to Viperfav(®) injection was 23±11h (range, 8-36h). Being bitten on the upper extremities (p Language: fr

Although renal transplantation improves survival, cardiovascular morbidity and mortality remain significantly elevated compared with nonrenal populations. The negative impact of traditional, uremia-related, and transplantation-related risk factors in this process remains, however, largely unexplored. Surrogate markers such as aortic stiffness and central wave reflections may lead to more accurate cardiovascular risk stratification, but outcome data in renal transplant recipients are scarce. We aimed to establish the prognostic significance of these markers for fatal and nonfatal cardiovascular events in renal transplant recipients. Carotid-femoral pulse wave velocity, central augmentation pressure, and central augmentation index were measured in a cohort of 512 renal transplant recipients using the SphygmoCor system. After a mean follow-up of 5 years, 20 fatal and 75 nonfatal cardiovascular events were recorded. Using receiver operating characteristic curves, the area under the curve for predicting cardiovascular events was 0.718 (95% CI 0.659–0.776) for pulse wave velocity, 0.670 (95% CI 0.604–0.736) for central augmentation pressure, and 0.595 (95% CI 0.529–0.660) for central augmentation index. When we accounted for age, gender, and C-reactive protein in Cox-regression analysis, pulse wave velocity (hazard ratio: 1.349 per 1 SD increase; 95% CI 1.104–1.649; P =0.003) and central augmentation pressure (hazard ratio: 1.487 per 1 SD increase; 95% CI 1.219–1.814; P

BACKGROUND AND OBJECTIVES: The actuarial risk at 5 years for clinical recurrence of Henoch-Schonlein purpura nephritis (HSPN) and graft loss caused by recurrence of -HSPN after renal transplantation was reported in 1994 to be as high as 35% and 11%, respectively. The aim of this study is to re-evaluate, in a large cohort of patients with a long-term follow-up, whether these rates have changed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients from six transplant centers in Belgium and France with strict diagnostic criteria of HSPN and a potential post transplant follow-up of ≥3 years were included. RESULTS: Forty-three patients were included. Patient survival is excellent: 98%, 95%, and 95% at 5, 10, and 15 years, respectively. Overall graft survival rates were 84%, 66%, and 56% at 5, 10, and 15 years, respectively. Clinical recurrence in a first kidney transplant occurred in five patients. Three patients lost their first graft due to HSPN recurrence 19 to 96 months after transplantation, two of whom had systemic signs of the illness. Actuarial risk for clinical recurrence in a first graft is 2.5% and 11.5% at 5 and 10 years, respectively. Actuarial risk for graft loss caused by recurrence in a first graft is 2.5% and 7.5% at 5 and 10 years, respectively. Severity of the disease at presentation and type of immunosuppression after transplantation did not affect recurrence. CONCLUSIONS: We found that recurrence rates of HSPN after transplantation are lower than previously reported. The actuarial risk of graft loss from recurrence in a first graft is 7.5% at 10 years.

AIM: Analysis of domestic low-voltage (220-240V) electrical injury in children admitted to a pediatric emergency department to illustrate the low risk of initial or delayed risk of arrhythmia. MATERIAL AND METHODS: Retrospective study between 2001 and 2008 analyzing all children aged less than 15 years admitted for a low-voltage electrical injury. The data collected were age, sex, time and circumstances of the accident, time and day of admission, transport modalities, presence of risk factors for arrhythmia (transthoracic current, wet skin, tetany, loss of consciousness or neurological symptoms, and initial EKG abnormalities), injuries, EKG, muscular and/or cardiac enzyme values, progression and complications. For statistical analysis, data were entered in Microsoft Excel tables. Analysis was done with StatView5.1 (SAS Institute((R))) and Epi Info 6.04fr (VF, ENSP epiconcept((R))). In the descriptive analysis, the data are presented as mean values with SD, median and range. RESULTS: Forty-eight children were included. The mean annual number of admissions was equal to 6 (range, 3-12). The mean age was 6.2+/-4.3 years (median, 4.6 years). There was a male predominance: the overall sex ratio was 1.5, i.e., 3 before the age of 2 and 2.6 before the age of 10. The electrical injury occurred after contact with a wire or a connected cord or after the introduction of a metallic object in a wall socket. Ten children had risk factors of arrhythmia (mainly wet skin or thoracic pain). Twenty-nine children suffered from burns to the extremities (digits and hands, 70 %). At admission, 45 children had an EKG performed. The initial EKG was considered abnormal in 8 cases showing: sinusal tachycardia (n=4), incomplete right bundle branch block (n=4), and V(1) negative T waves (n=1). The EKG normalized within the first 12h. Hospitalization for cardiac monitoring was required for 18 children. No delayed arrhythmia occurred. In a mean time of 3.5h after the accident, a troponin dosage was given to 15 children and was normal in all cases. One child developed rhabdomyolysis and evolved without needing dialysis. CONCLUSION: After a low-voltage electrical injury, initial arrhythmia is not frequent, with often a nonspecific and transitory EKG expression; delayed arrhythmia is very rare. Children presenting to the emergency department after such an electrical accident, who are asymptomatic, without any risk factors for arrhythmia (wet skin, tetany, vertical pathway of the current, preexistent cardiological conditions, loss of consciousness) and with a normal initial EKG do not require cardiac monitoring. Language: fr

Severe cases of pediatric tramadol intoxication are rarely reported. We report on serotonin syndrome after tramadol intoxication. An 8-month-old girl developed extreme agitation after accidentally ingesting a tablet of her father's medication (Monocrixo LP (Thérabel Lucien Pharma, Levallois Perret, France), 200 mg tramadol). Unable to sleep, she was admitted the next morning to our Pediatric Emergency Department after an episode of epistaxis. Vital signs were significant for sinus tachycardia and a neurologic examination revealed intermediately reactive pupils, agitation alternating with drowsiness with a Glasgow Coma Scale of 10, and increased lower-limb reflexes. Within 24 hours, she developed hyperthermia and high blood pressure. She did not experience seizures. Neurologic and cardiovascular effects resolved on day 2. Tramadol serum plasma levels confirmed the intoxication (680 μg/L). She was discharged on day 5 with no sequelae. Serotonin syndrome was described in adults when tramadol was associated with selective serotonin-reuptake inhibitors in contexts of therapy or intoxication. Our patient developed moderate serotonin syndrome. The clinical presentation was unusual compared with previous pediatric cases of tramadol intoxication, in which opioid effects and seizures were usually predominant. This case illustrates that serotonin syndrome can occur in children intoxicated with tramadol.

Severe hypomagnesemia has been reported with use of proton-pump inhibitors (PPIs). We assessed the effect, if any, of PPI use on serum magnesium level in a cross-sectional analysis of a large published cohort of renal transplant recipients (RTRs). Between February 2004 and February 2006, 512 consecutive prevalent RTRs were enrolled at two university hospitals in Belgium (Brussels and Ghent). Serum creatinine was 1.5 ± 0.7 mg/dl, and estimated glomerular filtration rate (eGFR) 53 ± 19 ml/min/1.73 m(2). Mean (and median) magnesium level was 1.91 ± 0.23 mg/dl. PPIs were prescribed in 20 % (n = 101) of cases. At multivariable analysis, PPI use was not an independent predictor of serum magnesium level or hypomagnesemia. The independent predictors of a lower serum magnesium level were the use of tacrolimus, cyclosporin and sirolimus, the absence of use of mycophenolate mofetil, lower levels of parathyroid hormone and higher eGFR. This study is the first to analyze the potential impact of PPIs on magnesium level in a large, representative cohort of RTR patients. Our results suggest that PPIs may be used without particular fear of favoring hypomagnesemia-related side effects in RTRs, an important finding in a population at high risk of hypomagnesemia.

During thymus development, the TCR β locus rearranges before the TCR α locus. Pairing of productively rearranged TCR β-chains with an invariant pTα chain leads to the formation of a pre-TCR and subsequent expansion of immature pre-T cells. Essentially nothing is known about the TCR Vβ repertoire in pre-T cells before or after the expression of a pre-TCR. Using intracellular staining, we show here that the TCR Vβ repertoire is significantly biased at the earliest developmental stage in which VDJβ rearrangement has occurred. Moreover (and in contrast to the VH repertoire in immature B cells), Vβ repertoire biases in immature T cells do not reflect proximity of Vβ gene segments to the DJβ cluster, nor do they depend upon preferential Vβ pairing with the pTα chain. We conclude that V gene repertoires in developing T and B cells are controlled by partially distinct mechanisms.

Disseminated varicella zoster virus (VZV) infection, whether due to primary infection or reactivation, may be life threatening in renal transplant recipients. The aims of this study were to assess the outcome of disseminated VZV infection in renal transplant recipients and to determine potential risk factors for mortality.A search of the English literature from 1985 to 2011 using PUBMED was performed. Reports involving renal transplant recipients younger than 16 years of age were excluded.A total of 56 adult patients presenting with a disseminated cutaneous or visceral VZV infection was included. Seventy percent of cases occurred within 5 years after transplantation, and 89% within 10 years. Visceral complications including disseminated intravascular coagulation occurred in two thirds of patients. Mortality decreased significantly from 47% in the era before 1995 to 17% after 1995 (P = .04). Risk factors for mortality included visceral involvement, use of azathioprine as immunosuppressant, and longer time between transplantation and VZV infection. VZV seropositivity did not influence fatal outcome.Disseminated VZV infection can be life threatening in renal transplant recipients with a global mortality rate of 30%. This rate seems to have decreased since 1995. Seropositive VZV patients with disseminated infection are not protected from fatal outcome.

Functional variants in the IL6 gene, in particular the -174G/C polymorphism (rs1800795), affect the mortality risk in dialysis patients. Peritoneal dialysis (PD) patients harbouring the C allele of the -174G/C polymorphism of IL6 showed faster peritoneal transport. The aim of this study was to investigate this IL6 variant as risk factor for mortality and technique failure in a large cohort of Caucasian PD patients.A Dutch multicentre cohort of 398 incident PD patients (NECOSAD) was analysed. Survival analysis was performed for death and technique failure with a maximum follow-up of 5 years. A combined PD cohort from Amsterdam (Academic Medical Center, N = 71) and Brussels (Université catholique de Louvain Medical School, N = 102) was used for independent replication.In NECOSAD, 105 patients died on dialysis [incidence rate 10.3/100 person-years (py)], and 138 patients experienced technique failure (16.2/100 py), with peritonitis as important cause. Patients with the C/C genotype had a 71% increased mortality risk compared to patients with the G/G genotype (95% confidence interval 0.98-2.98); this effect was mainly a long-term effect: a 2.7-fold increased mortality risk was found in patients having survived 2 years since the start on dialysis, and a 1.7-fold increased risk for the combined end point (mortality or technique failure). In the combined replication cohort, no increased risks were found in patients with the C/C genotype.The C/C genotype of the -174G/C polymorphism was associated with an increased mortality risk in 398 Dutch incident PD patients. The existence of substantial differences between the two academic replication cohorts and the discovery cohort from NECOSAD and the limited power of these cohorts prevented an independent replication of the NECOSAD findings.

BACKGROUND: Limited data is available on the risk of hepatitis B virus (HBV) reactivation in patients with resolved infection undergoing kidney transplantation. It is generally thought that this risk is negligible. OBJECTIVES: To evaluate the incidence of HBV reactivation in such patients, and the potential risk factors for reactivation. STUDY DESIGN: Retrospective cohort study including 93 patients transplanted with a kidney between 1995 and 2007 who had evidence of resolved HBV infection (HBsAg negative, anti-HBc positive, anti-HBs positive or negative, and normal liver enzymes). HBV reactivation was defined as HBsAg reversion with HBV DNA>2000 IU/mL. RESULTS: Six patients experienced HBsAg reversion followed by HBV reactivation, 3 within the first post-transplant year. Immunosuppression regimen was similar in patients with and without reactivation. Among patients with reactivation only one was positive for anti-HBs antibodies at time of transplantation; these were progressively lost before reactivation. The odds ratio for reactivation in patients without anti-HBs antibodies at transplantation compared to those with anti-HBs antibodies was 26 (95% CI [2.8-240.5], p=0.0012). In patients with anti-HBs antibody titer above 100 IU/L, no reactivation was observed. CONCLUSIONS: Reactivation rate of resolved hepatitis B is not negligible in patients without anti-HBs antibodies at transplantation. We suggest monitoring of liver tests and HBV serology including HBsAg and anti-HBs antibodies after transplantation as well as vaccination pre- and post-transplantation in all patients, including those with resolved hepatitis B, aiming at maintaining anti-HBs antibody level above 100 IU/L.

Viper bites and subsequent evolution to severe envenomations are more frequent in children.The aims of this study were to describe the clinical, biological, and therapeutic characteristics of children bitten by vipers in France and to identify risk factors associated with severe envenomations.A retrospective study was conducted between 2001 and 2009 in the pediatric emergency department of a tertiary-level children hospital. Collected data were age and sex of children; day and time of admission; day, time, and circumstances of the accident; snake identification; bite location; envenomation severity; presence of fang marks; prehospital care; use of specific immunotherapy and associated treatments; length of stay; and hospital course.Fifty-eight children were included (43 boys, 15 girls). The mean age was 7.8 ± 4.1 years. Bites were most often located on the lower extremities (77%). The classification of envenomation was: 83% low grade (absence or minor envenomation) and 17% high-grade (moderate to severe envenomations). All high-grade envenomations received specific immunotherapy (Viperfav). Being bitten on an upper extremity (P0.001), during the afternoon (P = 0.025), feeling violent pain (P = 0.037), and high initial glucose level (P = 0.016) were associated with a significant risk of high-grade envenomation. In the multivariate analysis, 3 factors remained significant: upper-extremity location (relative risk [RR], 60.5 [3.5-1040]; P = 0.005), immediate violent pain (RR, 21.5 [1.3-364.5]; P = 0.03), and female sex (RR, 17.5 [0.9-320.3]; P = 0.053).A certain number of criteria seem related to more significant risk of progression to high-grade envenomation. Bites to the upper extremities should be carefully observed because of the risk of evolution to a high-grade envenomation.

BACKGROUND AND OBJECTIVES: Vascular calcifications predict cardiovascular disease, the major cause of death in renal transplant recipients (RTRs). We studied the determinants of fetuin-A, a potent circulating calcification inhibitor encoded by the AHSG gene, and tested its association with vascular calcifications and long-term survival and cardiovascular events (CVEs) in RTRs. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Two hundred seventy-seven prevalent RTRs from a single center were included. CVEs and deaths were prospectively recorded during a 5-year follow-up. RESULTS: Independent determinants of lower serum fetuin-A levels were lower plasma cholesterol, the AHSG rs4918 G allele, and history of smoking. Low serum fetuin-A level was a determinant of aortic calcifications (assessed using spiral CT). Low fetuin-A levels (≤0.47 g/L, first quintile) were independently associated with CVEs and deaths (hazard ratio=1.83; 95% confidence interval, 1.07 to 3.04). The association was confirmed for all-cause mortality, and the major adverse cardiovascular endpoints were analyzed separately. Patients with low fetuin-A and high high-sensitivity C-reactive protein (>4.36 mg/L, fourth quintile) levels had a 3.5-fold increased risk of all-cause mortality and CVEs. In the presence of inflammation, CVE-free survival was influenced by common variants in the AHSG gene. CONCLUSIONS: These data show that low fetuin-A levels are independently associated with aortic calcifications and a higher risk of CVEs and mortality. They support fetuin-A as a circulating biomarker able to identify RTRs at risk for vascular calcifications and CVEs.

BACKGROUND: Vascular calcification independently predicts cardiovascular disease, the major cause of death in kidney transplant recipients (KTRs). Longitudinal studies of vascular calcification in KTRs are few and small and have short follow-up. We assessed the evolution of coronary artery (CAC) and thoracic aorta calcification and their determinants in a cohort of prevalent KTRs. STUDY DESIGN: Longitudinal. SETTING & PARTICIPANTS: The Agatston score of coronary arteries and thoracic aorta was measured by 16-slice spiral computed tomography in 281 KTRs. PREDICTORS: Demographic, clinical, and biochemical parameters were recorded simultaneously. OUTCOMES & MEASUREMENTS: The Agatston score was measured again 3.5 or more years later. RESULTS: Repeated analyzable computed tomographic scans were available for 197 (70%) KTRs after 4.40 ± 0.28 years; they were not available for the rest of patients because of death (n = 40), atrial fibrillation (n = 1), other arrhythmias (n = 4), refusal (n = 35), or technical problems precluding confident calcium scoring (n = 4). CAC and aorta calcification scores increased significantly (by a median of 11% and 4% per year, respectively) during follow-up. By multivariable linear regression, higher baseline CAC score, history of cardiovascular event, use of a statin, and lower 25-hydroxyvitamin D(3) level were independent determinants of CAC progression. Independent determinants of aorta calcification progression were higher baseline aorta calcification score, higher pulse pressure, use of a statin, older age, higher serum phosphate level, use of aspirin, and male sex. Significant regression of CAC or aorta calcification was not observed in this cohort. LIMITATIONS: Cohort of prevalent KTRs with potential survival bias; few patients with diabetes and nonwhites, limiting the generalizability of results. CONCLUSION: In contrast to previous small short-term studies, we show that vascular calcification progression is substantial within 4 years in prevalent KTRs and is associated with several traditional and nontraditional cardiovascular risk factors, some of which are modifiable.

BACKGROUND: The 2009 pandemic of influenza A (H1N1) prompted an urgent worldwide vaccination campaign, especially of high-risk subjects, such as maintenance haemodialysis (HD) patients. Still the immunogenicity of the pandemic A (H1N1) vaccine in HD patients is unknown. METHODS: We prospectively studied the immunogenicity of a monovalent adjuvanted influenza A/California/2009 (H1N1) vaccine (Pandemrix, GSK Biologicals, Rixensart, Belgium) in HD patients and controls. Antibody level was measured using a seroneutralization assay before (D(0)) and 30 days after (D(30)) a single 3.75 μg vaccine dose. Specimens were tested in quadruplicates. Geometric mean (GM) antibody titers were determined in each subject at D(0) and D(30). Seroconversion was defined as an increase in GM titers by a factor 4 or more. RESULTS: Fifty-three adult HD patients [aged 71 ± 10, 58.5% males, on HD for a median of 38 (3 - 146) months] and 32 control subjects (aged 47.3 ± 14, 31.3% males) were analyzed. Baseline GM titers were similar in HD patients and controls [7.9 (6.6 - 9.6) vs 10 (6 - 17); p = 0.69]. Seroconversion was observed in 30 (93.8%) controls and 34 (64.2%) HD patients (p = 0.002). In addition, GM titers at D(30) were significantly higher in controls than in HD patients [373 (217 - 640) vs 75.5 (42.5 - 134); p = 0.001]. HD patients were significantly older than controls (p < 0.001) and more likely to be males (p = 0.02). However, by multivariate analysis, HD status [OR 0.13 (0.02-0.78), p = 0.03], but neither age [OR 0.99 (0.96 - 1.03); p = 0.7] nor male gender [OR 1.31 (0.45 - 3.85); p = 0.63] was independently associated with seroconversion. The vaccine was generally well tolerated by HD patients. CONCLUSIONS: Only 64% of chronic HD patients developed seroconversion after a single dose of adjuvanted influenza A (H1N1) vaccine, a much lower rate than in controls (94%). These results underscore the substantial immunodeficiency associated with End-Stage Renal Disease. The persistence of protective antibodies as well as the effect of a booster dose remain to be investigated in HD patients.

Arterial stiffness is a strong predictor of outcome. Hypomagnesaemia, by its association with arterial hypertension, endothelial dysfunction, dyslipidaemia and inflammation, might affect vascular stiffness. As hypomagnesaemia is common in renal transplant recipients (RTR), we examined its potential association with arterial stiffness.Cross-sectional analysis. Evaluation of vascular stiffness in 512 RTR from two university centres at a median of 72 months post-transplantation. Determination of carotid-femoral pulse wave velocity (PWV) (SphygmoCor). A multiple linear regression analysis was used to investigate the independent relationship between magnesium serum level and PWV with the following covariates: age, diabetes, smoking status, body mass index, blood pressure, heart rate (HR), C-reactive protein (CRP), high-density lipoprotein cholesterol, parathyroid hormone and use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, diuretics, calcium channel blockers, statins and calcineurin inhibitors next to their drug levels.Lower serum magnesium was independently associated with PWV (P = 0.018) in addition to age, CRP, HR, diabetes and mean arterial pressure (model R(2) = 0.45; P0.001). The relationship between magnesium and PWV was attenuated (P = 0.054) after adjustment for the use of sirolimus, which was associated with higher magnesium levels (P0.001) and lower PWV (P = 0.013). In patients55 years (median age), however (low), magnesium remained an independent predictor of PWV (P = 0.024) after accounting for the same covariates.Serum magnesium is an independent predictor of arterial stiffness in RTR, especially in patients55 years.

Using genome-wide association, we identify common variants at 2p12-p13, 6q26, 17q23 and 19q13 associated with serum creatinine, a marker of kidney function (P = 10−10 to 10−15). Of these, rs10206899 (near NAT8, 2p12-p13) and rs4805834 (near SLC7A9, 19q13) were also associated with chronic kidney disease (P = 5.0 × 10−5 and P = 3.6 × 10−4, respectively). Our findings provide insight into metabolic, solute and drug-transport pathways underlying susceptibility to chronic kidney disease. Refereed/Peer-reviewed

Background: Saddleback caterpillar sting has been very rarely reported in European countries. We report a French case of a stung toddler. Case: A 2-year-old girl was brought to the pediatric emergency department after being stung by a caterpillar in a furniture store. The emergency department physical examination revealed an inflammatory edema of the stung finger, normal vital signs, and no fever. Three hours after presentation, she was discharged with local ointment prescription. The caterpillar brought in by the parents was unusual compared to common French caterpillar species. The regional poison center was unable to identify it. With the help of the Interact, we succeeded in its identification as a saddleback caterpillar. Tracing its transatlantic importation was the most difficult. Conclusions: Saddleback caterpillars can be imported to France and carried across the Atlantic Ocean on house or garden plants especially Areca trees. French garden store owners should be informed about this risk and should check and treat host plants (especially Areca trees) at the arrival time.

A 2-year-old boy who ingested 0.8-1.5 g of amantadine developed status epilepticus. One hour later, the child presented with agitation, diaphoresis, and vomiting. He was admitted to the pediatric emergency department 2 hours later. Generalized seizures evolved to status epilepticus, with alternating generalized tonic-clonic and partial seizures, over a period of 7 hours. Other initial clinical signs were sinusal tachycardia and reactive bilateral mydriasis. All symptoms resolved within 20 hours, with a good recovery; the child was released from the hospital on day 3.

Keywords: Point Mutation Reference LNDC-ARTICLE-2001-002doi:10.1007/s004150170211View record in PubMed Record created on 2010-01-08, modified on 2017-05-12