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Funding formula reform may help address unequal impacts of uncertainty from data error and privacy protections

Chronic hepatitis B virus (HBV) is a major public health concern. Transient elastrography (TE) is a reliable method in assessing hepatic fibrosis in patients with liver disease. We assess the potential clinical associations between HBsAg seroclearance and the severity of liver fibrosis.We retrospectively performed a matched analysis of 23 consecutive HBsAg seroclearance patients who underwent TE between March 2008 and August 2021 from a community practice at a 1:3 ratio based on clinic visit date. Baseline laboratory and clinical data were collected. Fisher's exact test and Chi-square test for proportions, and Wilcoxon rank-sum test for median were performed.Twenty-three cases and 69 controls were identified. Median follow up (interquartile range) for the cases and controls was 24,314 (1402) and 2332 (1587) days (p = 0.15), respectively. All patients were Asian. Median age of cases was higher than controls (64 vs 52, p 0.01, respectively). While most comorbidities were similar, diabetes and hyperlipidemia were more prevalent in cases. Baseline HBV DNA was detectable in 78% of cases and 97% of controls (p 0.01). More cases had baseline HBsAg titers below 1000 IU/mL than controls (81% vs 8.7%, p 0.01). Other baseline laboratory values were similar. Few cases had a fibrosis score greater than 1, while control had over a quarter of patients with a fibrosis score of 2 or 3.Spontaneous HBsAg seroclearance remains rare in patients with chronic HBV infection. It is associated with low baseline HBsAg, and lower level of liver fibrosis as detected by TE.

This article belongs to the Special Issue Breastmilk as a Model: Efforts to Improve Infant Formulae for Term Infants., Research on milk fat globule membrane (MFGM) is gaining traction. The interest is two-fold; on the one hand, it is a unique trilayer structure with specific secretory function. On the other hand, it is the basis for ingredients with the presence of phospho- and sphingolipids and glycoproteins, which are being used as food ingredients with valuable functionality, in particular, for use as a supplement in infant nutrition. This last application is at the center of this Review, which aims to contribute to understanding MFGM’s function in the proper development of immunity, cognition, and intestinal trophism, in addition to other potential effects such as prevention of diseases including cardiovascular disease, impaired bone turnover and inflammation, skin conditions, and infections as well as age-associated cognitive decline and muscle loss. The phospholipid composition of MFGM from bovine milk is quite like human milk and, although there are some differences due to dairy processing, these do not result in a chemical change. The MFGM ingredients, as used to improve the formulation in different clinical studies, have indeed increased the presence of phospholipids, sphingolipids, glycolipids, and glycoproteins with the resulting benefits of different outcomes (especially immune and cognitive outcomes) with no reported adverse effects. Nevertheless, the precise mechanism(s) of action of MFGM remain to be elucidated and further basic investigation is warranted., This study was carried out within the framework of the AGL2017-87884 Project (MINECO/AEI/FEDER, UE). J.F. gratefully acknowledges support from the Spanish Fulbright Program for his stay as a visiting scholar and the hospitality of Dr. Jimenez-Flores at FST (OSU, OH).

Background: Data sharing accelerates scientific progress but sharing individual-level data while preserving patient privacy presents a barrier. Methods and Results: Using pairs of deep neural networks, we generated simulated, synthetic participants that closely resemble participants of the SPRINT trial (Systolic Blood Pressure Trial). We showed that such paired networks can be trained with differential privacy, a formal privacy framework that limits the likelihood that queries of the synthetic participants’ data could identify a real a participant in the trial. Machine learning predictors built on the synthetic population generalize to the original data set. This finding suggests that the synthetic data can be shared with others, enabling them to perform hypothesis-generating analyses as though they had the original trial data. Conclusions: Deep neural networks that generate synthetic participants facilitate secondary analyses and reproducible investigation of clinical data sets by enhancing data sharing while preserving participant privacy.

Purpose Hemodynamically significant arterial inflow stenosis in dysfunctional fistulae and grafts is poorly understood. No reliable clinical methods exist to detect arterial inflow stenosis. In this study, we assessed the accuracy of a novel screening method to detect arterial inflow stenosis in dysfunctional fistulae and grafts following successful juxta-anastomotic and venous outflow intervention. Methods We prospectively evaluated all patients (N= 204) referred to our academic center for angiographic evaluation of a dysfunctional dialysis fistula/graft from May 1, 2006 to June 30, 2007. Following successful angioplasty/stenting of the venous outflow and juxta-anastomotic areas, patients were screened for arterial inflow stenosis. The screening method involved detection of 1) weak thrill, or sluggish blood flow on the post-intervention angiogram, 2) low mean arterial blood pressures in the dialysis access arm compared to the contralateral arm, and 3) inadequate blood flow at the first hemodialysis session post-intervention. If patients screened positive for any of these, they were further evaluated for arterial inflow stenosis. Results Fifteen patients (15/204) were positive for arterial inflow stenosis on screening study. Eleven of those 15 had arterial stenosis on angiography, giving our screening method a positive predictive value of 73.3%. Eight patients were successfully treated by angioplasty/stenting. Two patients successfully underwent surgical intervention. Two year patency of revascularization was 91% (10/11). Conclusions Hemodynamically significant arterial inflow stenosis occurs and can be detected by simple clinical methods. Interventions for correction of the arterial inflow stenosis are successful.

The foundation of endovascular procedures by nephrologists was laid in the private practice arena. Because of political issues such as training, credentialing, space and equipment expenses, and co-management concerns surrounding the performance of dialysis-access procedures, the majority of these programs provided care in an outpatient vascular access center. On the basis of the improvement of patient care demonstrated by these centers, several nephrology programs at academic medical centers have also embraced this approach. In addition to providing interventional care on an outpatient basis, academic medical centers have taken a step further to expand collaboration with other specialties with similar expertise (such as with interventional radiologists and cardiologists) to enhance patient care and research. The enthusiastic initiative, cooperative, and mutually collaborative efforts used by academic medical centers have resulted in the successful establishment of interventional nephrology programs. This article describes various models of interventional nephrology programs at academic medical centers across the United States.

Purpose Patients on clopidogrel are at increased risk of bleeding. This study was commenced to assess the incidence of bleeding in dialysis patients who underwent tunneled hemodialysis catheter procedures while on clopidogrel therapy. Methods This is a single center retrospective study of 25 (10 men, 15 women; median age 70) dialysis patients in whom clopidogrel could not be discontinued and underwent tunneled hemodialysis catheter insertion, removal or exchange between the period March 2010 to November 2011. The medical records of patients were reviewed and complications were classified according to the Society of Interventional Radiology system. Fifty-three procedures (22 insertions, 11 exchanges and 20 removals) were performed in these patients. The pre-procedural median platelet count, International Normalized Ratio and partial thromboplastin time were 195×103/dL (range 50-666), 1.1 (range 0.9-3.3) and 26.3 seconds (range 22.5-69.8) respectively. Results and Conclusions Forty-six procedures were performed in patients on clopidogrel and aspirin treatment. Five procedures were performed in patients while on clopidogrel in combination with aspirin and warfarin, and two procedures were performed with patients on clopidogrel alone. There were no documented bleeding complications from tunneled hemodialysis catheter procedures performed in patients on concurrent clopidogrel therapy in our study. Further prospective assessment with a larger cohort is necessary in order to validate these findings.

Creating a vascular access in the presence of a cardiovascular implantable electronic device (CIED) in a patient with or approaching end-stage renal disease can be challenging. In this study, we aimed to evaluate the impact of a CIED on the outcomes of vascular access creation in hemodialysis patients and determine their effects on vascular access patency. This is a single-center retrospective review of hemodialysis patients who underwent vascular access creation after CIED placement. Outcomes of vascular access creation and need for endovascular interventions were compared between patients with vascular access created ipsilateral and contralateral to the site of CIED. Comparing patients with arteriovenous (AV) access created ipsilateral to CIED placement (n=19) versus the contralateral side (n=17), the primary failure rate was 78.9% versus 35.3% (p=0.02). For AV accesses that were matured, the median primary patency durations for AV accesses created ipsilateral to the CIED was 11.2 months compared to 7.8 months for AV accesses created contralateral to the CIED (p=1.00). AV accesses created ipsilateral to a CIED have a higher primary failure rate compared with the contralateral arm and should be avoided as much as possible.

Dialysis vascular access associated coronary-subclavian steal or hypoperfusion syndrome is an uncommon but potentially life threatening condition. Awareness of this syndrome is important in the management of vascular access in hemodialysis patients. We report a case of dialysis vascular access associated coronary-subclavian steal syndrome and review the literature on its pathogenesis and therapeutic implications.

Summary Dialysis vascular access dysfunction is currently a huge clinical problem. We believe that comprehensive academic-based dialysis vascular access programs that go all the way from basic and translational science investigation to clinical research to a dedicated curriculum and opportunities in vascular access for nephrologists in training are essential for improving dialysis vascular access care. This paper reviews the fundamental concepts and requirements for us to move toward this vision.

For the development of human antibody Fc (fraction crystallizable) region-containing therapeutic protein candidates, which can be either monoclonal antibodies (mAbs) or pharmacologically active proteins/peptides fused to the Fc region of human Immunoglobulin G (IgG), reliable quantification of these proteins in animal pharmacokinetic study plasma samples is critical. LC-MS/MS has emerged as a promising assay platform for this purpose. LC-MS/MS assays used for bioanalysis of human antibody Fc region-containing therapeutic protein candidates frequently rely upon quantification of a 'signature' surrogate peptide whose sequence is unique to the protein analyte of interest. One drawback of the signature peptide approach is that a new LC-MS/MS assay must be developed for each new human Fc region-containing therapeutic protein. To address this issue, we propose an alternative 'universal surrogate peptide' approach for the quantification of human antibody Fc region-containing therapeutic protein candidates in plasma samples from all nonclinical species. A single surrogate tryptic peptide was identified in the Fc region of most human antibody Fc-containing therapeutic protein candidates. An LC-MS-MS method based upon this peptide was shown to be capable of supporting bioanalysis of a diversity of human Fc region-containing therapeutic protein candidates in plasma samples of all commonly used animal species.

The development of interventional nephrology has undoubtedly led to an improvement in patient care at many facilities across the United States. However, these services have traditionally been offered by interventional nephrologists in the private practice arena. While interventional nephrology was born in the private practice setting, several academic medical centers across the United States have now developed interventional nephrology programs. University Medical Centers (UMCs) that offer interventional nephrology face challenges, such as smaller dialysis populations, limited financial resources, and real or perceived political "turf" issues." Despite these hurdles, several UMCs have successfully established interventional nephrology as an intricate part of a larger nephrology program. This has largely been accomplished by consolidating available resources and collaborating with other specialties irrespective of the size of the dialysis population. The collaboration with other specialties also offers an opportunity to perform advanced procedures, such as application of excimer laser and endovascular ultrasound. As more UMCs establish interventional nephrology programs, opportunities for developing standardized training centers will improve, resulting in better quality and availability of nephrology-related procedures, and providing an impetus for research activities.

Summary Background and objectives The safety of percutaneous endovascular declotting procedures for thrombosed hemodialysis fistulae/grafts is well described in the general population; however, its safety in the presence of a patent foramen ovale (PFO) is not known. The objective of this study is to assess the incidence of symptomatic paradoxical embolic events associated with declotting procedure of thrombosed arteriovenous (AV) graft or fistula in patients with documented PFO. Design, setting, participants, & measurements This was a retrospective study in a hospital-based, academic practice. It included 23 patients (10 men; mean age, 65) with PFO and thrombosed hemodialysis graft/fistula who underwent a standardized declotting procedure with 2 mg of Alteplase and balloon thrombectomy. Twenty patients (87%) had AV grafts, and three (13%) had AV fistulae. The PFO shunt was right to left in two (9%), left to right in eight (34%), and bidirectional in ten (44%). The shunt direction was not specified in three patients (13%). The technical success of the declotting procedure and the frequency of clinically manifested paradoxical embolic events in this patient population were calculated. Results Fifty declotting procedures were performed on 23 patients with a technical success rate of 96% (48 of 50, 96%). No symptomatic paradoxical embolic events were found in any of the 23 patients with PFO. Conclusions Symptomatic paradoxical embolic events after percutaneous endovascular declotting procedures of thrombosed AV grafts and fistulae in patients with documented PFO are rare. This procedure appears to be safe in patients with a PFO.

While hemodialysis access ligation has been used to manage pacemaker (PM) and implantable cardioverter-defibrillator (ICD) lead-induced central venous stenosis (CVS), percutaneous transluminal balloon angioplasty (PTA) has also been employed to manage this complication. The advantages of PTA include minimal invasiveness and preservation of arteriovenous access for hemodialysis therapy. In this multi-center study we report the patency rates for PTA to manage lead-induced CVS. Consecutive PM/ICD chronic hemodialysis patients with an arteriovenous access referred for signs and symptoms of CVS due to lead-induced CVS were included in this analysis. PTA was performed using the standard technique. Technical and clinical success was examined. Technical success was defined as the ability to successfully perform the procedure. Clinical success was defined as the ability to achieve amelioration of the signs and symptoms of CVS. Both primary and secondary patency rates were also analyzed. Twenty-eight consecutive patients underwent PTA procedure. Technical success was 95%. Postprocedure clinical success was achieved in 100% of the cases where the procedure was successful. The primary patency rates were 18% and 9% at 6 and 12 months, respectively. The secondary patency rates were 95%, 86%, and 73% at 6, 12, and 24 months, respectively. On average, 2.1 procedures/year were required to maintain secondary patency. There were no procedure-related complications. This study finds PTA to be a viable option in the management of PM/ICD lead-induced CVS. Additional studies with appropriate design and sample size are required to conclusively establish the role of PTA in the management of this problem.

Laser-evoked potentials are widely used to investigate nociceptive pathways. The newly developed contact heat stimulator for evoking brain response has the advantages of obtaining reliable scalp potentials and absence of cutaneous lesions. This study aimed to identify the most appropriate stimulation site with consistent cortical responses, and to correlate several parameters of the contact heat evoked potentials (CHEPs) with age, gender, and body height in normal subjects. CHEPs were recorded at Cz with a contact heat stimulator (Medoc, Israel) in 35 normal controls. The subjects were asked to keep eyes open and remain alert. The baseline temperature was 32 degrees C, and stimulation peak heat intensity of 51 degrees C was applied to five body sites: bilateral forearm, right dorsum hand, right peroneal area, and right dorsum foot. Reproducible CHEPs were recorded more frequently when stimulated at volar forearm (62.5%) than at the lower limbs (around 40%). The first negative peak latency (N1) was 370.1 +/- 20.3 ms, first positive peak latency (P1) was 502.4 +/- 33.0 ms, and peak to peak amplitude was 10.2 +/- 4.9 microV with stimulation of the forearm. Perceived pain intensity was not correlated with the presence or amplitude of CHEPs. No gender or inter-side differences were observed for N1 latency and N1-P1 amplitude. Also, no correlation was noted between N1 and age or body height. These results support future clinical access of CHEPs as a diagnostic tool.