bluuebunny/crossref_metadata_2025_split huggingface dataset:
040  MS disease modifying therapy (DMT) sequencing – natalizumab to cladribine tablets – experience in 20 patients
Authors: Das Joyutpal , Lewis Thomas , Lusher William , Vernon Karen , Rog David , Paul Talbot , Sharaf Nazar , Kalatha Thaleia , Mihalova Tatiana 
Published: May 2022

BackgroundNatalizumab has been used for treatment of rapidly evolving sever relapsing remitting multiple sclerosis (MS) and is associated with risk of progressive multifocal leukoencephalopathy (PML). Patients can switch treatment after two years if JCV antibody-index is positive. One of the alternative treatment options include a weight based adjusted cladribine tablets that have been approved for treatment of highly active relapsing-remitting MS in Europe since 2017.MethodsWe reviewed 20 patients with prior natalizumab-treatment that switched to oral cladribine. The objective for treatment modification was JCV-index positivity. Data was collected regarding MS relapses, disease progression, or any possible adverse events.ResultsPatients started cladribine treatment between 01/2018 and 07/2019 with a follow-up observation period from 3 weeks to 18 months. Treatment was well tolerated and there were no severe opportunistic infections.ConclusionAccording to this review of 20 patients, treatment with cladribine tablets was safe even when used in patients previously treated with natalizumab and at high risk for PML. So far, no serious adverse events other than transient lymphopenia have been observed, especially no cases of PML.j.das@doctors.org.uk
041  Determinants of prolonged time to diagnosis in relapsing-remitting multiple sclerosis in Scotland
Authors: Brown Fraser , Kearns Patrick , Martin Sarah-Jane , Connick Peter , Hunt David , Chandran Siddharthan 
Published: May 2022

BackgroundThere is increasing emphasis on earlier diagnosis in patients with relapsing remitting multiple sclerosis (RRMS) as evidence is accumulating that earlier treatment reduces long-term disability accumu- lation. Much inter-individual variability in time to diagnosis remains unexplained.ObjectivesTo examine factors associated with longer time to diagnosis in a cohort of adult patients diagnosed with RRMS in Scotland between January 2016 and February 2019.MethodsClinical and demographic features were collected as part of an incidence cohort study. Time to diagnosis was defined as interval between date of first symptom to date of diagnosis and considered prolonged if it was greater than the median value. Age at onset, sex, weight, smoking status, employ- ment status, socioeconomic status and onset symptom type were examined for association with time to diagnosis using logistic regression.ResultsWe recruited 440 patients. Median time to diagnosis was 1.75 years. Current employment (OR2.016 [1.186–3.428] p=0.010) was associated with longer time to diagnosis. We found no association with other variables measured.ConclusionsTime to diagnosis in RRMS in Scotland is employment status-dependent. A considerable proportion of variance in time to diagnosis remains unexplained in RRMS.fraser@tonnard.co.uk
046  Familial multiple sclerosis: a community-based epidemiology study in Cumbria
Authors: Nwe May , Footitt David 
Published: May 2022

BackgroundThe Prevalence of Multiple Sclerosis varies according to the geographical location and certain ethnic group. Genetic susceptibility to MS has also been linked to allelic variation It has been suggested that Viking genes’ can make people more susceptible to MS. Given the northern latitude and genetic background of the indigenous population, one might expect the higher prevalence of Multiple sclerosis.Cumbria Neurology Service: The Cumbria Neurology service has established in 2011, which used a single electronic patient record which has linked to the general practice. It is based within a community trust; and which is a single consultant-led service.ObjectiveTo study the prevalence of familial multiple sclerosis in Cumbria Region.ResultsOur estimated prevalence rate of multiple sclerosis is higher than a McKenzie et’s report. However, the data for the familial Multiple Sclerosis is lower than those of the global data (the data collecting is still ongoing).maythaenwe@gmail.com
Effects of VNS stimulation on electrocorticography in patients with dual neuro- stimulation devices
Authors: Joseph Navya Mary , Steffan Paul , Becker Danielle , Wernovsky Magda , Datta Proleta , Ernst Lia 
Published: May 2022

BackgroundOne-third of epilepsy patients become refractory to anti-epileptic medications. In these patients neurostimulation devices are considered as potential treatment options. The FDA has approved vagal nerve stimulation (VNS) and responsive neurostimulation (RNS system) for the treatment of focal epilepsy. There is limited data on interaction between the two devices and their mechanism of action is actively being researched. Limited prior evidence suggests that acute VNS stimulation may reduce epileptiform activity and cause EEG desynchronization. Our study aims to isolate the effects of VNS on electrocorticography (ECoG) as recorded by the RNS system.MethodsECoG from 20 patients were obtained. For each patient, five pairs of ‘on’ recordings of 60-second VNS stimulation on ECoGs were compared to ‘off’ baseline 60s recordings. ECoGs were analyzed for differences in spectral content.ResultsPreliminary results show that acute VNS stimulation is associated with significant decrease in power (i.e. desynchronization) in the theta, beta, and (50–70 Hz) gamma bands.ConclusionThis study demonstrates desynchronization as a mechanism of action of VNS, as recorded by the RNS system. As more patients receive dual neurostimulators, it will be crucial to understand isolated effects of each device to optimize programming and improve therapeutic efficacy.navya.joseph@unmc.edu
056  OCT screening prior to starting fingolimod: is it truly justified?
Authors: Fisniku Leonora , Tageldin Amr 
Published: May 2022

Background andAimFingolimod, an oral immunomodulating drug is used in the management of relaps- ing-remitting MS (RRMS)-patients. Fingolimod-related macular oedema is reported in 0.4% of cases. Whereas pre-treatment optical coherence tomography (OCT) was used in the pivotal trials, the licensing of Fingolimod did not require this. We sought to assess the rate of abnormal pre-treatment OCTs in the patients treated with Fingolimod at Brighton and Sussex University Hospital (BSUH).MethodsWe reviewed the OCTs of all RRMS-patients screened at BSUH prior to being started on Fingoli- mod from November 2013-September 2019. Patients screened elsewhere, were not included.Results135 patients were screened. 21(15%) were males; mean age 39 (range 25–74). Macular-OCT was normal in 133/135(98.5%) patients; in one patient a tiny cyst but no frank edema was noted; no post Fin- golimod macular oedema was noted; subretinal fluid was noted in another patient; this patient did not tolerate Fingolimod. No macular eodema was observed in any of the patients started on Fingolimod.ConclusionsOur data suggest the routine use of OCT as part of Fingolimod pre-screening is not justified. Rationalizating pre-screening investigations prior to starting disease-modifying-therapies, could avoid unnecessary delay in starting such treatments and provide better use of the resources. This data re- enforces the need for reviewing and auditing our protocols and guidelines.leonora.fisniku@nhs.net
057  Clinical experience of cladribine use in a large UK cohort – side effect profiles, including lymphocytopaenia
Authors: Suslak Thomas , Murray Lesley , MacDougall Niall 
Published: May 2022

Cladribine is a novel disease-modifying therapy that has been licensed for treatment of highly active relapsing-remitting multiple sclerosis. This study examines the prescribing of cladribine in a cohort of real-world patients (n=120), over two health boards in Scotland, assessing the workability of the Scottish Medicines Consortium prescribing guidelines, as well as examining the safety-netting that exists to manage adverse events.One significant issue with the current guidelines is identified - the imaging criteria - and it is proposed that these are redundant in clinical practice. Mild to moderate lymphocytopaeniais the main adverse effect of cladribine, present in 78% of patients within treatment year 1. Adequate infection prophylaxis and counselling are noted to be key aspects of pre-assessment. The average lag to peak lymphocytopaenia is was two to four months after first treatment (n patients = 75%), indi- cating the optimal time frame for routine follow-up screening. Other adverse effects were noted in 25 patients (21%), most commonly fatigue (incidence = 0.07), hair loss (incidence = 0.05) and nausea (incidence = 0.03). Allergic-type reactions were also observed in 2% of patients, but these were mild and treatable, without interruption to therapy.This study represents interim follow-up data for this patient cohort, who have completed their first round of cladribine treatment. This therapy is reported to have maximum efficacy after two treatment cycles therefore, this study represents the groundwork for subsequent, annual follow-up.thomas.suslak@gmail.com
Swampland criteria in Chaplygin-braneworld warm inflation scenario
Authors: Maqsood Sadaf , Jawad Abdul 
Published: May 2022

In recent times, it has been perceived that incorporation of branes in higher dimensional theories of quantum gravity is very effective to differentiate those theories which successfully satisfy the swampland criteria. Moreover, warm inflation is considered to be most appropriate single scalar field inflationary model in the framework of swampland criteria. In this regard, we study two well-known Chaplygin gas (CG) models embedded in Randall–Sundrum braneworld. It is known that the de Sitter constraint is derived by taking into account Bousso’s covariant entropy bound. We discuss the application of this result in the context of Chaplygin-brane models and find the condition on the slope of the potential. Furthermore, it is demonstrated that in view of warm inflation dynamics this condition remains essentially unchanged indicating the compatibility of the models with swampland criteria. In addition, we investigate the constraint on the warm inflation parameter imposed by the de Sitter conjecture which shows that the warm inflation is in accordance with de Sitter bound in the strong as well as in weak dissipative regime for both models of Chaplygin gas.
Clinical Analysis of C-Shaped Embedded Pancreaticojejunostomy in Pancreaticoduodenectomy
Authors: Huang Hui , Sun Jichun , Li Zhiqiang , Zang Longjun , Zhu Hongwei , Zhang Xianlin , Yu Xiao 
Published: May 2022

Background. Comparing the effects of C-shaped embedded anastomosis and pancreatic duct-jejunal mucosal anastomosis on the incidence of pancreatic fistula after pancreaticoduodenectomy (PD) to find a better pancreaticojejunal anastomosis method that can reduce the occurrence of complications during the operation and benefit the patients. Methods. A retrospective subresearch method was used to select the clinical data of patients who have undergone pancreaticoduodenectomy in our hospital from December 2019 to March 2021. The indicators to be collected for this study include gender, age, body mass index, preoperative liver function (total bilirubin, alanine aminotransferase, and albumin), preoperative comorbidities (diabetes, chronic pancreatitis), and pancreatic condition (texture, pancreatic duct diameter). The patients were divided into two groups according to the method of pancreaticojejunostomy: C-shaped embedded anastomosis group (

n
=
38

) and pancreatic duct-jejunal mucosal anastomosis group (

n
=
30

). The duration of pancreaticojejunostomy, biliary-enteric anastomosis, gastrointestinal anastomosis, intraoperative blood loss, upper abdominal surgery history, pathological type, intraoperative blood loss, pancreaticojejunostomy time, combined pancreatic fistula, biliary fistula, hemorrhage, and abdominal infection were observed and compared. According to the different methods of pancreaticojejunostomy during operation, they were divided into group A: C-shaped embedded pancreaticojejunostomy group (38 cases), and group B: pancreatic duct-jejunal mucosal anastomosis group (30 cases). The postoperative complications were compared between the two groups, and the observed indicators were analyzed with statistical methods. Results. The average pancreaticojejunostomy time in group A was

32.13
±
4.52

min, and the average pancreaticojejunostomy time in group B was

43.23
+
4.31

min. The difference was statistically significant (

p
<
0.05

). Neither group A nor group B had a grade C fistula. The incidence of biochemical fistula in group A was 21.05% (8/38), and the incidence of biochemical fistula in group B was 13.3% (4/30). The difference was not statistically significant (

p
>
0.05

). The incidence of grade B fistula in group A was 5.20% (2/38), and the incidence of grade B fistula in group B was 26.67% (8/30). The difference was statistically significant (

p
<
0.0

5). There were no perioperative deaths in the two groups. Conclusion. According to the results of data analysis, it can be seen that both the two types of pancreaticojejunostomy have good clinical effects, but that in terms of reducing the grade of pancreatic fistula, the C-shaped embedded pancreaticojejunostomy is obviously better and safer. At the same time, the C-shaped embedded pancreaticojejunostomy can shorten the time of pancreaticojejunostomy and is easier to operate, thus worthy of clinical promotion.
Mapping Atrial Fibrillation After Surgical Therapy to Guide Endocardial Ablation
Authors: Bhatia Neal K. , Shah Rajan L. , Deb Brototo , Pong Terrence , Kapoor Ridhima , Rogers Albert J. , Badhwar Nitish , Brodt Chad , Wang Paul J. , Narayan Sanjiv M. , Lee Anson M. 
Published: May 2022

BACKGROUND:
Surgical ablation for atrial fibrillation (AF) can be effective, yet has mixed results. It is unclear which endocardial lesions delivered as part of hybrid therapy‚ will best augment surgical lesion sets in individual patients. We addressed this question by systematically mapping AF endocardially after surgical ablation and relating findings to early recurrence, then performing tailored endocardial ablation as part of hybrid therapy.

METHODS:
We studied 81 consecutive patients undergoing epicardial surgical ablation (stage 1 hybrid), of whom 64 proceeded to endocardial catheter mapping and ablation (stage 2). Stage 2 comprised high-density mapping of pulmonary vein (PV) or posterior wall (PW) reconnections, low-voltage zones (LVZs), and potential localized AF drivers. We related findings to postsurgical recurrence of AF.

RESULTS:

Mapping at stage 2 revealed PW isolation reconnection in 59.4%, PV isolation reconnection in 28.1%, and LVZ in 42.2% of patients. Postsurgical recurrence of AF occurred in 36 patients (56.3%), particularly those with long-standing persistent AF (
P
=0.017), but had no relationship to reconnection of PVs (
P
=0.53) or PW isolation (
P
=0.75) when compared with those without postsurgical recurrence of AF. LVZs were more common in patients with postsurgical recurrence of AF (
P
=0.002), long-standing persistent AF (
P
=0.002), advanced age (
P
=0.03), and elevated CHA
2
DS
2
-VASc (
P
=0.046). AF mapping revealed 4.4±2.7 localized focal/rotational sites near and also remote from PV or PW reconnection. After ablation at patient-specific targets, arrhythmia freedom at 1 year was 81.0% including and 73.0% excluding previously ineffective antiarrhythmic medications.

CONCLUSIONS:
After surgical ablation, AF may recur by several modes particularly related to localized mechanisms near low voltage zones, recovery of posterior wall or pulmonary vein isolation, or other sustaining mechanisms. LVZs are more common in patients at high clinical risk for recurrence. Patient-specific targeting of these mechanisms yields excellent long-term outcomes from hybrid ablation.
Impact of Adenosine on Wavefront Propagation in Persistent Atrial Fibrillation: Insights From Global Noncontact Charge Density Mapping of the Left Atrium
Authors: Pope Michael T. B. , Kuklik Pawel , Briosa e Gala Andre , Leo Milena , Mahmoudi Michael , Paisey John , Betts Timothy R. 
Published: May 2022

Background
Adenosine shortens action potential duration and refractoriness and provokes atrial fibrillation. This study aimed to evaluate the effect of adenosine on mechanisms of wavefront propagation during atrial fibrillation.

Methods and Results

The study included 22 patients undergoing catheter ablation for persistent atrial fibrillation. Left atrial mapping was performed using the AcQMap charge density system before and after administration of intravenous adenosine at 1 or more of 3 time points during the procedure (before pulmonary vein isolation, after pulmonary vein isolation, and after nonpulmonary vein isolation ablation). Wave‐front propagation patterns were evaluated allowing identification and quantification of localized rotational activation (LRA), localized irregular activation, and focal firing. Additional signal processing was performed to identify phase singularities and calculate global atrial fibrillation cycle length and dominant frequency. A total of 35 paired maps were analyzed. Adenosine shortened mean atrial fibrillation cycle length from 181.7±14.3 to 165.1±16.3, (mean difference 16.6 ms; 95% CI, 11.3–21.9,
P
<0.0005) and increased dominant frequency from 6.0±0.7 Hz to 6.6±0.8 Hz (95% CI, 0.4–0.9,
P
<0.0005). This was associated with a 50% increase in the number of LRA occurrences (16.1±7.6–24.2±8.1; mean difference 8.1, 95% CI, 4.1–12,
P
<0.0005) as well as a 20% increase in the number of phase singularities detected (30.1±7.8–36.6±9.3; mean difference 6.5; 95% CI, 2.6–10.0,
P
=0.002). The percentage of left atrial surface area with LRA increased with adenosine and 42 of 70 zones (60%) with highest density of LRA coincided with high density LRA zones at baseline with only 28% stable across multiple maps.

Conclusions
Adenosine accelerates atrial fibrillation and promotes rotational activation patterns with no impact on focal activation. There is little evidence that rotational activation seen with adenosine represents promising targets for ablation aimed at sites of stable arrhythmogenic sources in the left atrium.
Same‐Day Discharge After Transcatheter Aortic Valve Implantation: Insights from the Nationwide Readmission Database 2015 to 2019
Authors: Zahid Salman , Rai Devesh , Tanveer Ud Din Mian , Khan Muhammad Zia , Ullah Waqas , Usman Khan Muhammad , Thakkar Samarthkumar , Hussein Ahmed , Baibhav Bipul , Rao Mohan , Abtahian Farhad , Bhatt Deepak L. , Depta Jeremiah P. 
Published: May 2022

Background
There is a paucity of data on the feasibility of same‐day discharge (SDD) following transcatheter aortic valve implantation (TAVI) at a national level.

Methods and Results

This study used data from the Nationwide Readmission Database from the fourth quarter of 2015 through 2019 and identified patients undergoing TAVI using the claim code 02RF3. A total of 158 591 weighted hospitalizations for TAVI were included in the analysis. Of the patients undergoing TAVI, 961 (0.6%) experienced SDD. Non‐SDDs included 65 814 (41.5%) patients who underwent TAVI who were discharged the next day, and 91 816 (57.9%) discharged on the second or third day. The 30‐day readmission rate for SDD after TAVI was similar to non‐SDD TAVI (9.8% versus 8.9%,
P
=0.31). The cumulative incidence of 30‐day readmissions for SDD was higher compared with next‐day discharge (log‐rank
P
=0.01) but comparable to second‐ or third‐day discharge (log‐rank
P
=0.66). At 30 days, no differences were observed in major or minor vascular complications, heart failure, or ischemic stroke for SDD compared with non‐SDD. Acute kidney injury, pacemaker implantation, and bleeding complications were lower with SDD. Predictors associated with SDD included age <85 years, male sex, and prior pacemaker placement, whereas left bundle‐branch block, right bundle‐branch block, second‐degree heart block, heart failure, prior percutaneous coronary intervention, and atrial fibrillation were negatively associated with SDD.

Conclusions
SDD following TAVI is associated with similar 30‐day readmission and complication rates compared with non‐SDD. Further prospective studies are needed to assess the safety and feasibility of SDD after TAVI.
Lipoprotein(a) and the Risk for Coronary Heart Disease and Ischemic Stroke Events Among Black and White Adults With Cardiovascular Disease
Authors: Colantonio Lisandro D. , Bittner Vera , Safford Monika M. , Marcovina Santica , Brown Todd M. , Jackson Elizabeth A. , Li Mei , López J. Antonio G. , Monda Keri L. , Plante Timothy B. , Kent Shia T. , Muntner Paul , Rosenson Robert S. 
Published: May 2022

Background
It is unclear whether lipoprotein(a) is associated with coronary heart disease (CHD) and ischemic stroke events in White and Black adults with atherosclerotic cardiovascular disease (ASCVD).

Methods and Results

We conducted a case‐cohort analysis, including Black and White REGARDS (Reasons for Geographic and Racial Differences in Stroke) study participants ≥45 years of age with prevalent ASCVD (ie, CHD or stroke) at baseline between 2003 and 2007. Baseline lipoprotein(a) molar concentration was measured in participants with ASCVD who experienced a CHD event by December 2017 (n=1166) or an ischemic stroke by September 2019 (n=492) and in a random subcohort of participants with prevalent ASCVD (n=1948). The hazard ratio (HR) for CHD events per 1 SD (1.5 units) higher log‐transformed lipoprotein(a) was 1.26 (95% CI, 1.02–1.56) among Black participants and 1.16 (95% CI, 1.02–1.31) among White participants (
P
value comparing HRs, 0.485). The HR for CHD events per 1 SD higher log‐lipoprotein(a) within subgroups with hs‐CRP (high‐sensitivity C‐reactive protein) ≥2 and <2 mg/L was 1.31 (95% CI, 0.99–1.73) and 1.23 (95% CI, 0.85–1.80), respectively (
P
value comparing HRs, 0.836), among Black participants, and 1.07 (95% CI, 0.91–1.27) and 1.36 (95% CI, 1.10–1.70), respectively (
P
value comparing HRs, 0.088), among White participants. There was no evidence that the association between lipoprotein(a) and CHD events differed by statin use. There was no evidence of an association between lipoprotein(a) and ischemic stroke events among Black or White participants.

Conclusions
Higher lipoprotein(a) levels were associated with an increased risk for CHD events in Black and White adults with ASCVD.