The impact of vascular access type on survival in haemodialysis: time for a paradigm shift? A prospective cohort study

Introduction Although arteriovenous autologous fistula is the vascular access of choice due to better long-term outcome than central venous catheters, the use of central venous catheters is increasing. Our study aims to describe the survival and epidemiological features of a cohort of dialysis patients with a focus on the role of vascular access.Methods Our study comprises a follow-up period from 2001 to 2020 in a single center. Descriptive analysis was performed on baseline data. Moreover, we analysed predictive variables of death with univariable and multivariable logistic regressions. Predictors of survival were analysed by univariable and multivariable Cox regression.Results Our analysis includes 754 patients undergoing chronic haemodialysis. In the multivariable logistic regression, the use of tunnelled catheters resulted protective against death from any cause (Odds Ratio 0.43; p = 0.017). In the multivariable Cox analysis, being "late referral" was associated with decreased survival in the first 6 months since haemodialysis start (Hazard Ratio 3.79; p = 0.001). In the subgroup of elderly (age = 75 years) patients (n = 201/472) with a follow up of 7-60 months, multivariable logistic regression showed that tunnelled catheters at the start of haemodialysis were associated with lower mortality (Odds Ratio, 0.25; p = 0.021), whereas vascular disease was found to be the main risk factor for death (Odds Ratio, 5.11; p = 0.000). Moreover, vascular disease was confirmed as the only independent risk factor by Cox analysis (Hazard Ratio, 1.58; p = 0.017).Conclusions In our cohort, mortality was found to be more closely associated with comorbidities than with the type of vascular access. Tunnelled central venous catheters might be a viable option for haemodialysis patients

Rituximab as Maintenance Treatment for Systemic Lupus Erythematosus: A Multicenter Observational Study of 147 Patients.

OBJECTIVE: The efficacy of rituximab (RTX) in systemic lupus erythematosus (SLE) is a subject of debate. This study was undertaken to investigate the outcomes of RTX treatment in a European SLE cohort, with an emphasis on the role of RTX as a maintenance agent. METHODS: All patients with SLE who were receiving RTX as induction therapy in 4 centers were included. Patients who received a single course of RTX and those who received RTX maintenance treatment (RMT) were followed up after treatment. Disease flares during the follow-up period were defined as an increase in disease activity and the number or dose of immunosuppressive drugs. RESULTS: Of 147 patients, 27% experienced treatment failure at 6 months. In a multivariate analysis, a low number of previous immunosuppressive therapies (P = 0.034) and low C4 levels (P = 0.008) reduced the risk of treatment failure. Eighty patients received RMT over a median of 24.5 months during which 85 relapses, mainly musculoskeletal, were recorded (1.06 per patient). At the time of the last RTX course, 84% of the patients were in remission. Twenty-eight (35%) of 80 patients never experienced a flare during RMT and had low damage accrual. Active articular disease at the time of the first RTX administration was associated with a risk of flare during RMT (P = 0.011). After RMT, relapse-free survival was similar to that in patients receiving a single RTX course (P = 0.72). CONCLUSION: RMT is a potential treatment option for patients with difficult-to-treat disease. Relapses occur during RMT and are more likely in those with active articular disease at the time of the first RTX administration. Relapse risk after RMT remains high and apparently comparable to that seen after a single RTX course

Slowly progressive anti-neutrophil cytoplasmic antibody-associated renal vasculitis: clinico-pathological characterization and outcome.

BACKGROUND: Although rapidly progressive glomerulonephritis is the main renal phenotype of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), slow renal disease progression is sometimes observed. These forms have been rarely discussed; we analysed their prevalence, clinico-pathological characteristics and outcome. METHODS: We screened patients with microscopic  polyangiitis (MPA) and granulomatosis with polyangiitis followed at seven referral centres and selected those with estimated glomerular filtration rate (eGFR) reduction 25% as compared with diagnosis, while 4/34 (12%) had started RRT. CONCLUSIONS: AAV may present with slow renal disease progression; this subset is hallmarked by advanced age at diagnosis, positive MPO-ANCA, subclinical interstitial lung lesions and chronic damage at kidney biopsy. Partial renal recovery may occur following immunosuppression

The Role of Rituximab in Primary Focal Segmental Glomerular Sclerosis of the Adult

Introduction: Primary focal segmental glomerular sclerosis (FSGS) is a rare, likely immune-mediated disease. Rituximab (RTX) may play a role in management, although data in adults are scanty. Methods: We collected cases of RTX-treated primary FSGS within the Italian Society of Nephrology Immunopathology Working Group and explored response rate (24-hour proteinuria <3.5 g and <50% compared with baseline, stable estimated glomerular filtration rate). Results: A total of 31 patients were followed for at least 12 months; further follow-up (median 17 months, interquartile range [IQR] 15–33.5) was available for 11. At first RTX administration, median creatinine and 24- hour proteinuria were 1.17 mg/dl (IQR 0.83–1.62) and 5.2 g (IQR 3.3–8.81), respectively. Response rate at 3, 6, and 12 months was 39%, 52%, and 42%, respectively. In the first 12 months, creatinine level remained stable whereas proteinuria and serum albumin level improved, with an increase in the proportion of patients tapering other immunosuppressants. There were 6 patients who were retreated with RTX within 12 months, either for proteinuria increase or refractory disease; only the 2 responders to the first RTX course experienced a further response. At univariate analysis, 6-month response was more frequent in steroid-dependent patients (odds ratio [OR] 7.7 [95% CI 1.16–52.17]) and those with proteinuria <5 g/24 h (OR 8.25 [1.45–46.86]). During long-term follow-up, 4 of 5 responders at 12 months maintained a sustained response, either without further immuno- suppression (2 of 4) or with pre-emptive RTX (2 of 4); 1 relapsed and responded to RTX retreatment. Conclusion: RTX may be an option in primary FSGS, especially in steroid-dependent patients, with 24- hour proteinuria <5 g and previously responders to RTX. Optimal long-term management for re- sponders is unclear, with some patients experiencing sustained remission and others requiring RTX retreatment, either preemptive or after rising proteinuria

Quantifying Sources of Variability in Infancy Research Using the Infant-Directed-Speech Preference

Psychological scientists have become increasingly concerned with issues related to methodology and replicability, and infancy researchers in particular face specific challenges related to replicability: For example, high-powered studies are difficult to conduct, testing conditions vary across labs, and different labs have access to different infant populations. Addressing these concerns, we report on a large-scale, multisite study aimed at (a) assessing the overall replicability of a single theoretically important phenomenon and (b) examining methodological, cultural, and developmental moderators. We focus on infants’ preference for infant-directed speech (IDS) over adult-directed speech (ADS). Stimuli of mothers speaking to their infants and to an adult in North American English were created using seminaturalistic laboratory-based audio recordings. Infants’ relative preference for IDS and ADS was assessed across 67 laboratories in North America, Europe, Australia, and Asia using the three common methods for measuring infants’ discrimination (head-turn preference, central fixation, and eye tracking). The overall meta-analytic effect size (Cohen’s d) was 0.35, 95% confidence interval = [0.29, 0.42], which was reliably above zero but smaller than the meta-analytic mean computed from previous literature (0.67). The IDS preference was significantly stronger in older children, in those children for whom the stimuli matched their native language and dialect, and in data from labs using the head-turn preference procedure. Together, these findings replicate the IDS preference but suggest that its magnitude is modulated by development, native-language experience, and testing procedure

The dynamic range of the upgraded surface-detector stations of AugerPrime

The detection of ultra-high-energy cosmic rays by means of giant detector arrays is often limited by the saturation of the recorded signals near the impact point of the shower core at the ground, where the particle density dramatically increases. The saturation affects in particular the highest energy events, worsening the systematic uncertainties in the reconstruction of the shower characteristics. The upgrade of the Pierre Auger Observatory, called AugerPrime, includes the installation of an 1-inch Small PhotoMultiplier Tube (SPMT) inside each water-Cherenkov station (WCD) of the surface detector array. The SPMT allows an unambiguous measurement of signals down to about 250m from the shower core, thus reducing the number of events featuring a saturated station to a negligible level. In addition, a 3.8m2 plastic scintillator (Scintillator Surface Detector, SSD) is installed on top of each WCD. The SSD is designed to match the WCD (with SPMT) dynamic range, providing a complementary measurement of the shower components up to the highest energies. In this work, the design and performances of the upgraded AugerPrime surface-detector stations in the extended dynamic range are described, highlighting the accuracy of the measurements. A first analysis employing the unsaturated signals in the event reconstruction is also presented