Fistula, Arteriovenous

We screened a total of 1736 individuals identified as incident dialysis patients by dialysis staff of which, 943 (54.3%) met eligibility criteria. Those with either a pacemaker (n = 89) or an automatic implanatable cardioverter defibrillator (n = 70) at time of screening were ineligible to participate in the study in addition to other reasons such as nursing home residents, inability to consent, history of recent cancer and history of peritoneal dialysis or transplantation. A total of 574 participants (61% of 943) were consented into the study with 402 completing the baseline cardiac evaluation. The median follow-up time was 1.78 years (range 0–5.43) with 52 participants who underwent kidney transplantation, 25 who transferred to peritoneal dialysis, and 106 who died as of July 31, 2014.
The PACE study population is predominantly younger and comprised of a larger proportion of African Americans than described in the national Comprehensive Dialysis Study (CDS) or the USRDS (Table 4) [1 ,85 (link)]. In Table 5, the baseline demographic and clinical characteristics are shown for the study population enrolled. The baseline characteristics of the cardiac measures, laboratory tests and medications are also provided for those who have completed the initial study visit with the detailed cardiac evaluation.Table 4

PACE study population and comparison to incident US dialysis cohorts

Dialysis study	PACE	CDS*	USRDS*
Time period	2009-2012	2005-2007	2008
Incident population, n	574	1646	110,175
African American	66%	28%	28.8%
Mean age, yrs	56	60	62.8
Younger age <65 years	73%	61.8%	52.8%
Diabetes	53%	52.6%	44.9%
Mean BMI, kg/m2	29.3	29.8	28.4
Male	54%	55.1%	57.6%
Nutritional assessment, n	402	361	None
Follow-up	Annual in-person clinical evaluations semi-annual phone interviews	Passive	Passive
Cardiac evaluation	Signal averaged ECG	None	None
	Echocardiogram
	Cardiac CT calcium and angiography
	Pulse wave velocity
	Ankle brachial index
Hospitalizations/Mortality	Adjudicated	Passive	Passive
Baseline specimen collection	402	269	None
Follow-up specimen collection	Yes	None	None

*CDS-Comprehensive Dialysis Study 1646 completed phone interview; USRDS- United States Renal Data Systems.

Table 5

Baseline demographic and clinical characteristics of all enrolled PACE participants (n = 574) and completed cardiovascular study visit (n = 402)

Characteristics	All PACE participants	Completed cardiovascular visit*
Demographic
Male, n (%)	319 (56)	233 (59)
African-American, n (%)	397 (69)	288 (72)
Age in years, mean ± SD	56 (13.5)	55 (13.2)
Education, % graduated high school	62	248 (63)
Employment, % employed	12	47 (12)
Marital status, % married	31	29
Dialysis characteristics
Three times a week dialysis, n (%)	566 (98.6)	397 (98.8)
Three to four hour dialysis session, n (%)	505 (88.0)	353 (87.8)
Polyflux membrane, n (%)	446 (77.7)	306 (86.4)
Arteriovenous fistula access, n (%)	163 (28.7)	122 (30.3)
Self reported
Smoking, % ever smoker	59	60
Body mass index kg/m2, mean ± SD	29.4 (7.9)	29.3 (7.8)
CVD, % diagnosed	44	45
CHF, % diagnosed	23	25
Diabetes, % diagnosed	54	55
Cardiovascular study visit
Systolic blood pressure mmHg, mean ± SD	n/a	137 (25)
Diastolic blood pressure mmHg, mean ± SD	n/a	75 (15)
Waist to hip ratio	n/a	0.95 (0.08)
Frailty, % diagnosed	n/a	40
Average literacy, mean	n/a	Grade 8
Cognitively impaired, % diagnosed	n/a	14
Depression, % diagnosed	n/a	17
Medications use
Betablocker, %	n/a	58
ACEI/ARB, %	n/a	44
Calcium channel blocker, %	n/a	60
Statins, %	n/a	52
Intradialytic labs
Ionized calcium mean ± SD. mmol/L	n/a	1.15 (0.07)
Magnesium mean ± SD, mg/dL	n/a	1.76 (0.24)

*Cardiovascular study visits were conducted at the Institute for Clinical and Translational Research and the Cardiology Research Laboratory.

The intervention is based on the psychological theory of flow, which posits the existence of a ‘flow state’, a state of optimal experience that results from complete absorption in a task. In order to induce a flow state, the task must present a challenge to the individual that they can overcome through the development of their skills [65 , 66 (link)]. Qualitative literature has suggested arts-in-medicine programmes, person-centred arts programmes that are delivered within hospitals, can induce the hallmark experiences of a flow state in patients who participate, such as an altered perception of time and reduction in rumination and anxiety [43 (link), 45 (link), 67 ]. Therefore, the intervention has been modelled on these programmes, with additional structure put in place to allow for assessment of dose and fidelity.
The intervention consists of six 1-hourly art sessions, implemented at the bedside whilst the participant is receiving haemodialysis and facilitated by the researcher. Each participant will receive the sessions over a course of 3 weeks, receiving two sessions a week. This time frame was chosen in consultation with the study’s interdisciplinary advisory group who recommended each participant receive a day off each week to reduce the potential of fatigue influencing participation, in consultation with experts in the field of arts in health who established six sessions was an adequate dose [68 ], and reviewing previous literature that identified 1 h is the optimal time frame for implementing an art activity [69 (link)]. The activities on offer will consist of a selection of discrete choices, either creative writing and visual art, but will involve a person-centred approach that will allow patients to adapt the activities to their interests and their abilities. This person-centred approach is modelled on the arts-in-medicine programmes that have shown evidence of being sustainable in clinical settings over prolonged periods of time [43 (link)–45 (link)].
Each participant will receive their own individual arts pack that will contain a standardised set of materials that were selected by the study’s interdisciplinary advisory group. The items were selected according to their ease of use and their ability to be implemented without impacting the clinical setting. Each participant will receive:

Sketch book

Graphite pencils

Graphic pens

Watercolour paints

Watercolour brush pen with in-built water container

Colouring pencils

Drawing board

Drawing board clip

Eraser

Sharpener

Pencil grip

Individual packs will be provided to each participant to maintain infection control and reduce any issue of cross-contamination between participants. All participants will keep the packs at the end of the study. Each session will involve one to one facilitation to ensure the activities are accessible for the majority of patients, as arteriovenous fistulas and problems with dexterity can limit a person’s ability to use the materials unassisted. Patient preference of activity, materials and engagement will be captured in activity logs by the researcher implementing the intervention.

All animal studies and experiments were approved by the University of Alabama at Birmingham Institutional Animal Care and Use Committee (IACUC) and performed in accordance with National Institutes of Health guidelines. Our studies utilized male C57BL/6J mice (n = 3, Taconic Biosciences, Hudson, NY) aged 8-12 weeks.
After mice (n = 2) with AVF were anesthetized with isoflurane, buprenorphine, xyalazine, and ketamine, a midline incision of the surgical area was performed. Using a surgical microscope, the right carotid artery and jugular vein were then exposed. Using 10-0 monofilament microsurgical sutures, a side-to-end anastomosis was created using the carotid artery (side) and jugular vein (end) (Fig. 1a). After unclamping, dilation of the vein and patency was confirmed visually. The mice were maintained on a warming blanket following surgery and buprenorphine was administered two times at 12 hours apart. NH was consistently observed by day 21 post-op (Fig. 1b). The control blood vessels were the pre-surgical carotid artery and jugular vein (n = 1), and the contralateral non-surgery carotid artery and jugular vein in the AVF mice at day 7 (n = 1) and day 21 (n = 1) post-operatively.Fig. 1

Surgical procedure and histology: (a) Arteriovenous fistula (AVF) mouse model using jugular vein (end) to carotid artery (side) configuration. Asterisk (*) depicts the arteriovenous anastomosis. The white arrow indicates the direction of blood flow in the venous outflow tract. (b) Representative histology of AVF dysfunction (Movat’s stain). Neointimal hyperplasia (NH) was present at 21 Days

We identified candidate predictors from the literature and input from clinicians with expertise in kidney failure and perioperative medicine. The final list of variables included demographics of age and sex. Surgeries were categorized into 11 surgery types based on CCI codes, including categories that are specific to people with kidney failure (kidney transplant, peritoneal dialysis catheter insertion, and AV fistula creation). Surgery setting was classified using the administrative data as ambulatory elective, inpatient elective, or inpatient urgent/emergent. We considered comorbidities of previous AMI, cancer, chronic pulmonary disease, dementia, diabetes, heart failure, hypertension, liver disease, obesity, peripheral vascular disease, and stroke. These were defined using validated algorithms of International Statistical Classification of Diseases and Related Health Problems Ninth and Tenth Revision (ICD-9-CM and ICD-10-CA) codes [17 (link)] with an unrestricted lookback period for permanent conditions and 3 years for temporary conditions (Supplementary Tables 3 and 4). Kidney failure treatment modality was categorized as non-dialysis, hemodialysis, or peritoneal dialysis. Preoperative outpatient serum albumin (in g/L) and serum hemoglobin (in g/L) within the year before surgery were included as candidates. There were no missing values for variables except for albumin (15%) and hemoglobin (0.2%), which were imputed using multivariable normal regression with an iterative Markov chain Monte Carlo method.

We prospectively and consecutively recruited patients with an acute attack or a history of TM who visited a tertiary referral center (Asan Medical Center, Seoul, South Korea) between July 2018 and April 2020. TM attacks were determined when the following criteria were fulfilled^{1 (link)}: (1) presence of signs or symptoms of sensory, motor, or autonomic dysfunction attributable to the spinal cord; (2) documentation of T2 high signal intensity on spinal MRI. Patients who had experienced clinical attacks within the last two months were regarded as being in an acute attack phase, while all others were regarded as being in the remission phase. For acute attack phase, we only included patients whose last attack was exclusively TM.
A diagnosis of ITM was made based on the previously suggested criteria^{30 (link)}. All patients underwent a detailed diagnostic workup including brain MRI, spinal MRI, cell-based assaying for anti-aquaporin-4 antibody (AQP4-Ab) and anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab)^{13 (link)}, anti-nuclear antibody (ANA), anti-SS-A/SS-B antibody, anti-neutrophil cytoplasmic (ANCA), screening test for HIV and syphilis and routine laboratory test. Patients with evidence of active infections, active malignancy, a history of systemic autoimmune diseases or signs of other various conditions mimicking ITM, such as mechanical compression, spinal cord infarction or spinal arteriovenous fistula were not diagnosed as ITM.
Among the patients with confirmed etiologies, we included AQP4 + NMOSD and RRMS patients for comparison. The diagnoses of AQP4 + NMOSD and RRMS were based on the 2015 International Panel for NMO diagnostic criteria for NMOSD^{31 (link)} and the 2017 revised McDonald criteria^{32 (link)}, respectively. We did not include patients with other etiologies due to small sample sizes. Additionally, healthy controls (HCs), defined as those who complained of mild neurologic symptoms such as headache or dizziness but had normal brain MRI findings, were recruited for further comparison.
All participants were over 18 years of age. Patients were sampled for blood and evaluated for the EDSS score on the day of enrollment.