Implementation of Pelvic Floor Rehabilitation after rectal cancer surgery: A qualitative study guided by the Consolidated Framework for Implementation Research (CFIR).

BACKGROUND: Pelvic Floor Rehabilitation (PFR) is effective in a selection of patients with low anterior resection syndrome (LARS) after rectal cancer surgery. This study aimed to identify barriers and enablers to prepare for successful implementation into clinical practice. METHODS: A qualitative study was performed, guided by the Consolidated Framework for Implementation Research (CFIR). Individual interviews (n = 27) and two focus groups were conducted to synthesize the perspectives of rectal cancer patients, pelvic floor (PF) physiotherapists, and medical experts. RESULTS: Barriers were found to be the absence of guidelines about LARS treatment, underdeveloped network care, suboptimal patient information, and expectation management upfront to PFR. Financial status is frequently a barrier because insurance companies do not always reimburse PFR. Enablers were the current level of evidence for PFR, the positive relationship between patients and PF physiotherapists, and the level of self-motivation by patients. CONCLUSION: The factors identified in our study play a crucial role in ensuring a successful implementation of PFR after rectal cancer surgery.

Long-Term Functional Outcome After Early vs. Late Stoma Closure in Rectal Cancer Surgery: Sub-analysis of the Multicenter FORCE Trial.

PURPOSE: The aim of this study was to assess the effect of early stoma closure on bowel function after low anterior resection (LAR) for rectal cancer. METHODS: Patients participating in the FORCE trial who underwent LAR with protective stoma were included in this study. Patients were subdivided into an early closure group (< 3 months) and late closure group (> 3 months). Endpoints of this study were the Wexner Incontinence, low anterior resection syndrome (LARS), EORTC QLQ-CR29, and fecal incontinence quality of life (FIQL) scores at 1 year. RESULTS: Between 2017 and 2020, 38 patients had received a diverting stoma after LAR for rectal cancer and could be included. There was no significant difference in LARS (31 vs. 30, p = 0.63) and Wexner score (6.2 vs. 5.8, p = 0.77) between the early and late closure groups. Time to stoma closure in days was not a predictor for LARS (R2 = 0.001, F (1,36) = 0.049, p = 0.83) or Wexner score (R2 = 0.008, F (1,36) = 0.287, p = 0.60) after restored continuity. There was no significant difference between any of the FIQL domains of lifestyle, coping, depression, and embarrassment. In the EORTC QLQ-29, body image scored higher in the late closure group (21.3 vs. 1.6, p = 0.004). CONCLUSION: Timing of stoma closure does not appear to affect long-term bowel function and quality of life, except for body image. To improve functional outcome, attention should be focused on other contributing factors.

Surgical treatment of esophago-tracheobronchial fistulas after esophagectomy.

The aim of this study was to evaluate the surgical treatment of esophago-tracheobronchial fistulas (ETBFs) that occurred after esophagectomy with gastric conduit reconstruction in a tertiary referral center for esophageal surgery. All patients who underwent surgical repair for an ETBF after esophagectomy with gastric conduit reconstruction were included in a tertiary referral center. The primary outcome was successful recovery after surgical treatment for ETBF, defined as a patent airway at 90 days after the surgical fistula repair. Secondary outcomes were details on the clinical presentation, diagnostics, and postoperative course after fistula repair. Between 2007 and 2022, 14 patients who underwent surgical repair for an ETBF were included. Out of 14 patients, 9 had undergone esophagectomy with cervical anastomosis and 5 esophagectomy with intrathoracic anastomosis after which 13 patients had developed anastomotic leakage. Surgical treatment consisted of thoracotomy to cover the defect with a pericardial patch and intercostal flap in 11 patients, a patch without interposition of healthy tissue in 1 patient, and fistula repair via cervical incision with only a pectoral muscle flap in 2 patients. After surgical treatment, 12 patients recovered (86%). Mortality occurred in two patients (14%) due to multiple organ failure. This study evaluated the techniques and outcomes of surgical repair of ETBFs following esophagectomy with gastric conduit reconstruction in 14 patients. Treatment was successful in 12 patients (86%) and generally consisted of thoracotomy and coverage of the defect with a bovine pericardial patch followed by interposition with an intercostal muscle.

Eculizumab Rescue Therapy in Patients With Recurrent Atypical Hemolytic Uremic Syndrome After Kidney Transplantation.

Introduction: Since 2016, kidney transplantation in patients with atypical hemolytic uremic syndrome (aHUS) in the Netherlands is performed without eculizumab prophylaxis. Eculizumab is given in case of posttransplant aHUS recurrence. Eculizumab therapy is monitored in the CUREiHUS study. Methods: All participating kidney transplant patients who received eculizumab therapy for a suspected posttransplant aHUS recurrence were evaluated. Overall recurrence rate was monitored prospectively at Radboud University Medical Center. Results: In the period from January 2016 until October 2020, we included 15 (12 females, 3 males; median age 42 years, range 24-66 years) patients with suspected aHUS recurrence after kidney transplantation in this study. The time interval to recurrence showed a bimodal distribution. Seven patients presented early after transplantation (median 3 months, range 0.3-8.8 months), with typical aHUS features: rapid loss of estimated glomerular filtration rate (eGFR) and laboratory signs of thrombotic microangiopathy (TMA). Eight patients presented late (median 46 months, range 18-69 months) after transplantation. Of these, only 3 patients had systemic TMA, whereas 5 patients presented with slowly deteriorating eGFR without systemic TMA. Treatment with eculizumab resulted in improvement or stabilization of eGFR in 14 patients. Eculizumab discontinuation was tried in 7 patients; however, it was successful only in 3. At the end of the follow-up (median 29 months, range 3-54 months after start of eculizumab), 6 patients had eGFR <30 ml/min per 1.73 m2. Graft loss had occurred in 3 of them. Overall, aHUS recurrence rate without eculizumab prophylaxis was 23%. Conclusions: Rescue treatment of posttransplant aHUS recurrence is effective; however, some patients suffer from irreversible loss of kidney function, likely caused by delayed diagnosis and treatment and/or too aggressive discontinuation of eculizumab. Physicians should be aware that recurrence of aHUS can present without evidence of systemic TMA.

Prognostic value of strain by feature-tracking cardiac magnetic resonance in arrhythmogenic right ventricular cardiomyopathy.

AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by ventricular dysfunction and ventricular arrhythmias (VA). Adequate arrhythmic risk assessment is important to prevent sudden cardiac death. We aimed to study the incremental value of strain by feature-tracking cardiac magnetic resonance imaging (FT-CMR) in predicting sustained VA in ARVC patients. METHODS AND RESULTS: CMR images of 132 ARVC patients (43% male, 40.6 ± 16.0 years) without prior VA were analysed for global and regional right and left ventricular (RV, LV) strain. Primary outcome was sustained VA during follow-up. We performed multivariable regression assessing strain, in combination with (i) RV ejection fraction (EF); (ii) LVEF; and (iii) the ARVC risk calculator. False discovery rate adjusted P-values were given to correct for multiple comparisons and c-statistics were calculated for each model. During 4.3 (2.0-7.9) years of follow-up, 19% of patients experienced sustained VA. Compared to patients without VA, those with VA had significantly reduced RV longitudinal (P ≤ 0.03) and LV circumferential (P ≤ 0.04) strain. In addition, patients with VA had significantly reduced biventricular EF (P ≤ 0.02). After correcting for RVEF, LVEF, and the ARVC risk calculator separately in multivariable analysis, both RV and LV strain lost their significance [hazard ratio 1.03-1.18, P > 0.05]. Likewise, while strain improved the c-statistic in combination with RVEF, LVEF, and the ARVC risk calculator separately, this did not reach statistical significance (P ≥ 0.18). CONCLUSION: Both RV longitudinal and LV circumferential strain are reduced in ARVC patients with sustained VA during follow-up. However, strain does not have incremental value over RVEF, LVEF, and the ARVC VA risk calculator.

Initiation of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for cardiogenic shock during out of hours versus working hours is not associated with increased mortality.

BACKGROUND: Initiation of veno-arterial (VA) Extracorporeal Membrane Oxygenator (ECMO) is associated with severe complications. It is unknown whether these adverse consequences occur more often after initiations during out of hours service compared to working hours. METHODS: All patients receiving VA-ECMO for cardiogenic shock between 2009 and 2020 were categorized into a working hours group (between 8 am and 5 pm on weekdays) and an out of hours service group (between 5 pm and 8 am, or between Friday 5 pm and Monday 8 am). Primary outcome was all-cause mortality at 30 days. Secondary outcomes included vascular complications (including limb ischemia and/or bleeding), bloodstream infections and length of ICU stay. Propensity scores were used to adjust for potential confounding effects. RESULTS: Among 250 patients (median (IQR) age 56 (42-64) years) receiving VA-ECMO (median duration 3.5 (1.0-9.0) days), 160 (64%) runs were initiated between 5 pm and 8 am whereas the remainder (36%) started during working hours. Characteristic did not differ between the working hours- and out of hours-group. By day 30, 37 (41.1%), and 68 (42.5%) patients in either group had died, respectively (p = 0.831). VA-ECMO support duration and length of stay on the ICU did not differ significantly in both crude and adjusted analyses. More complications occurred during out of hours service (p = 0.039). CONCLUSIONS: Out of hours- versus working hours-initiation of VA-ECMO for cardiogenic shock was not associated with higher mortality, longer VA-ECMO support duration, or longer length of stay on the intensive care. Vascular complications were more common in the out of hours group.

Pelvic Floor Rehabilitation After Rectal Cancer Surgery: A Multicenter Randomized Clinical Trial (FORCE Trial).

OBJECTIVE: To investigate the effects of PFR after LAR compared to usual care without PFR. SUMMARY OF BACKGROUND DATA: Functional complaints, including fecal incontinence, often occur after LAR for rectal cancer. Controversy exists about the effectiveness of PFR in improving such postoperative functional outcomes. METHODS: This was a multicenter, randomized controlled trial involving 17 Dutch centers. Patients after LAR for rectal cancer were randomly assigned (1:1) to usual care or PFR and stratified by sex and administration of neoadjuvant therapy. Selection was not based on severity of complaints at baseline. Baseline measurements were taken 3 months after surgery without temporary stoma construction or 6 weeks after stoma closure. The primary outcome measure was the change in Wexner incontinence scores 3 months after randomization. Secondary outcomes were fecal incontinence-related quality of life, colorectal-specific quality of life, and the LARS scores. RESULTS: Between October 2017 and March 2020, 128 patients were enrolled and 106 randomly assigned (PFR n = 51, control n = 55); 95 patients (PFR n = 44, control n = 51) were assessable for final analysis. PFR did not lead to larger changes in Wexner incontinence scores in nonselected patients after LAR compared to usual care [PFR: -2.3, 95% confidence interval (CI) -3.3 to -1.4, control: -1.3, 95% CI -2.2 to -0.4, P = 0.13]. However, PFR was associated with less urgency at follow-up (odds ratio 0.22, 95% CI 0.06-0.86). Patients without near-complete incontinence reported larger Wexner score improvements after PFR (PFR: -2.1, 95% CI -3.1 to -1.1, control: -0.7, 95% CI -1.6 to 0.2, P = 0.045). For patients with at least moderate incontinence PFR resulted in relevant improvements in all fecal incontinence-related quality of life domains, while the control group deteriorated. These improvements were even larger when patients with near-complete incontinence were excluded. No serious adverse PFR-related events occurred. CONCLUSION: No benefit was found of PFR in all patients but several subgroups were identified that did benefit from PFR, such as patients with urgency or with at least moderate incontinence and no near-complete incontinence. A selective referral policy (65%-85% of all patients) is suggested to improve postoperative functional outcomes for patients after LAR for rectal cancer. TRIAL REGISTRATION: Netherlands Trial Registration, NTR5469, registered on 3 September 2015.

Rationale and design of the PHOspholamban RElated CArdiomyopathy intervention STudy (i-PHORECAST).

BACKGROUND: The p.Arg14del (c.40_42delAGA) phospholamban (PLN) pathogenic variant is a founder mutation that causes dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM). Carriers are at increased risk of malignant ventricular arrhythmias and heart failure, which has been ascribed to cardiac fibrosis. Importantly, cardiac fibrosis appears to be an early feature of the disease, occurring in many presymptomatic carriers before the onset of overt disease. As with most monogenic cardiomyopathies, no evidence-based treatment is available for presymptomatic carriers. AIMS: The PHOspholamban RElated CArdiomyopathy intervention STudy (iPHORECAST) is designed to demonstrate that pre-emptive treatment of presymptomatic PLN p.Arg14del carriers using eplerenone, a mineralocorticoid receptor antagonist with established antifibrotic effects, can reduce disease progression and postpone the onset of overt disease. METHODS: iPHORECAST has a multicentre, prospective, randomised, open-label, blinded endpoint (PROBE) design. Presymptomatic PLN p.Arg14del carriers are randomised to receive either 50 mg eplerenone once daily or no treatment. The primary endpoint of the study is a multiparametric assessment of disease progression including cardiac magnetic resonance parameters (left and right ventricular volumes, systolic function and fibrosis), electrocardiographic parameters (QRS voltage, ventricular ectopy), signs and/or symptoms related to DCM and ACM, and cardiovascular death. The follow-up duration is set at 3 years. BASELINE RESULTS: A total of 84 presymptomatic PLN p.Arg14del carriers (n = 42 per group) were included. By design, at baseline, all participants were in New York Heart Association (NHYA) class I and had a left ventricular ejection fraction > 45% and < 2500 ventricular premature contractions during 24-hour Holter monitoring. There were no statistically significant differences between the two groups in any of the baseline characteristics. The study is currently well underway, with the last participants expected to finish in 2021. CONCLUSION: iPHORECAST is a multicentre, prospective randomised controlled trial designed to address whether pre-emptive treatment of PLN p.Arg14del carriers with eplerenone can prevent or delay the onset of cardiomyopathy. iPHORECAST has been registered in the clinicaltrials.gov-register (number: NCT01857856).

Predictors of undergoing multivisceral resection, margin status and survival in Dutch patients with locally advanced colorectal cancer.

BACKGROUND: The aim of this nationwide observational study was to evaluate factors associated with multivisceral resection (MVR), margin status and overall survival in locally advanced colorectal cancer (CRC). MATERIAL AND METHODS: Patients with (y)pT4, cM0 CRC between 2006 and 2017 were selected from the Netherlands Cancer Registry. Cox-proportional hazards modelling was used for survival analysis, stratified for T4a and T4b. Annual hospital volume cut-off was 75 for colon and 40 for rectal resections. RESULTS: A total of 11.930 patients were included and 2410 patients (20.2%) underwent MVR. Factors associated with MVR for colon and rectal cancer besides cT4 category were more recent diagnosis (OR 3.61, CI 95% 3.06-4.25 (colon) and OR 2.72, CI 95% 1.82-4.08 (rectum)) and high hospital volume (OR 1.20, CI 95% 1.05-1.38 (colon) and OR 2.17, CI 95% 1.55-3.04 (rectum)). Patients ≥70 year were less likely to undergo MVR for colon cancer (OR 0.80, 95% CI 0.70-0.90). Risk factors for incomplete resection were cT4 (OR 3.08, CI 95% 2.35-4.04 (colon) and OR 1.82, CI 95% 1.13-2.94 (rectum)) and poor/undifferentiated tumors (OR 1.41, CI 95% 1.14-1.72 (colon) and OR 1.69, CI 95% 1.05-2.74 (rectum)). More recent diagnosis was independently associated with less incomplete resections in colon cancer (OR 0.58, CI 95% 0.40-0.76). Independent predictors of survival were age, resection margin, nodal status and adjuvant chemotherapy, but not MVR. CONCLUSION: Treatment of locally advanced CRC with MVR at population level was influenced by year of diagnosis and hospital volume. Margin status in colon cancer improved substantially over time.

Transanal total mesorectal excision and low anterior resection syndrome.

BACKGROUND: Bowel dysfunction after rectal cancer surgery is common, with some experiencing low anterior resection syndrome (LARS) is common after rectal cancer surgery. This study examined if transanal total mesorectal excision (TaTME) has a similar risk of LARS and altered quality of life (QoL) as patients who undergo low anterior resection (LAR). METHODS: Patients who underwent TaTME or traditionally approached total mesorectal excision in a prospective colorectal cancer cohort study (2014-2019) were propensity score matched in a 1 : 1 ratio. LARS and QoL scores were assessed before and after surgery with a primary endpoint of major LARS at 12 months analysed for possible association between factors by logistic regression. RESULTS: Of 61 TaTME and 317 LAR patients eligible, 55 from each group were propensity score matched. Higher LARS scores (30.6 versus 25.4, P = 0.010) and more major LARS (65 versus 42 per cent, P = 0.013; OR 2.64, 95 per cent c.i. 1.22 to 5.71) were reported after TaTME. Additionally, QoL score differences (body image, bowel frequency, and embarrassment) were worse in the TaTME group. CONCLUSIONS: TaTME may be associated with more severe bowel dysfunction than traditional approaches to rectal cancer.

Twelve years of circulatory extracorporeal life support at the University Medical Centre Utrecht.

INTRODUCTION: Circulatory extracorporeal life support (ECLS) has been performed at the University Medical Centre Utrecht for 12 years. During this time, case mix, indications, ECLS set-ups and outcomes seem to have substantially changed. We set out to describe these characteristics and their evolution over time. METHODS: All patients receiving circulatory ECLS between 2007 and 2018 were retrospectively identified and divided into six groups according to a 2-year period of time corresponding to the date of ECLS initiation. General characteristics plus data pertaining to comorbidities, indications and technical details of ECLS commencement as well as in-hospital, 30-day, 1­year and overall mortality were collected. Temporal trends in these characteristics were examined. RESULTS: A total of 347 circulatory ECLS runs were performed in 289 patients. The number of patients and ECLS runs increased from 8 till a maximum of 40 runs a year. The distribution of circulatory ECLS indications shifted from predominantly postcardiotomy to a wider set of indications. The proportion of peripheral insertions with or without application of left ventricular unloading techniques substantially increased, while in-hospital, 30-day, 1­year and overall mortality decreased over time. CONCLUSION: Circulatory ECLS was increasingly applied at the University Medical Centre Utrecht. Over time, indications as well as treatment goals broadened, and cannulation techniques shifted from central to mainly peripheral approaches. Meanwhile, weaning success increased and mortality rates diminished.

Functional complaints and quality of life after transanal total mesorectal excision: a meta-analysis.

BACKGROUND: Total mesorectal excision (TME) gives excellent oncological results in rectal cancer treatment, but patients may experience functional problems. A novel approach to performing TME is by single-port transanal minimally invasive surgery. This systematic review evaluated the functional outcomes and quality of life after transanal and laparoscopic TME. METHODS: A comprehensive search in PubMed, the Cochrane Library, Embase and the trial registers was conducted in May 2019. PRISMA guidelines were used. Data for meta-analysis were pooled using a random-effects model. RESULTS: A total of 11 660 studies were identified, from which 14 studies and six conference abstracts involving 846 patients (599 transanal TME, 247 laparoscopic TME) were included. A substantial number of patients experienced functional problems consistent with low anterior resection syndrome (LARS). Meta-analysis found no significant difference in major LARS between the two approaches (risk ratio 1·13, 95 per cent c.i. 0·94 to 1·35; P = 0·18). However, major heterogeneity was present in the studies together with poor reporting of functional baseline assessment. CONCLUSION: No differences in function were observed between transanal and laparoscopic TME.

ANTECEDENTES: La escisión total del mesorrecto (total mesorectal excision, TME) proporciona excelentes resultados oncológicos en el tratamiento del cáncer de recto, pero los pacientes pueden presentar trastornos funcionales. Un abordaje novedoso para realizar la TME es mediante cirugía transanal mínimamente invasiva de puerto único. En esta revisión sistemática se evaluaron los resultados funcionales y la calidad de vida después de TME transanal (TaTME) y TME laparoscópica (LapTME). MÉTODOS: En mayo de 2019 se realizó una búsqueda exhaustiva en las bases de datos de Pubmed, Biblioteca Cochrane, EMBASE y en los registros de ensayos clínicos. Se utilizaron las guías PRISMA. Los datos para el metaanálisis se agruparon utilizando un modelo de efectos aleatorios. RESULTADOS: Se identificaron un total de 11.660 estudios, de los cuales se incluyeron 14 estudios y 6 resúmenes de congresos con 846 pacientes (599 TaTME/247 LapTME). Un número sustancial de pacientes presentó trastornos funcionales consistentes con el síndrome de resección anterior baja (low anterior resection syndrome, LARS). El metaanálisis no encontró diferencias significativas en los porcentajes de LARS grave entre los dos abordajes (razón de oportunidades, odds ratio, OR 1,13; i.c. del 95% 0,94-1,35; P = 0,18). Sin embargo, los estudios globalmente presentaron una gran heterogeneidad, así como una deficiente información sobre la evaluación funcional basal. CONCLUSIÓN: No se observaron diferencias en la función entre TaTME y LapTME.

Pelvic floor rehabilitation to improve functional outcome and quality of life after surgery for rectal cancer: study protocol for a randomized controlled trial (FORCE trial).

BACKGROUND: After low anterior resection (LAR), up to 90% of patients develop anorectal dysfunction. Especially fecal incontinence has a major impact on the physical, psychological, social, and emotional functioning of the patient but also on the Dutch National Healthcare budget with more than €2000 spent per patient per year. No standardized treatment is available to help these patients. Common treatment nowadays is focused on symptom relief, consisting of lifestyle advices and pharmacotherapy with bulking agents or antidiarrheal medication. Another possibility is pelvic floor rehabilitation (PFR), which is one of the most important treatments for fecal incontinence in general, with success rates of 50-80%. No strong evidence is available for the use of PFR after LAR. This study aims to prove a beneficial effect of PFR on fecal incontinence, quality of life, and costs in rectal cancer patients after sphincter-saving surgery compared to standard treatment. METHODS: The FORCE trial is a multicenter, two-armed, randomized clinical trial. All patients that underwent LAR are recruited from the participating hospitals and randomized for either standard treatment or a standardized PFR program. A total of 128 patients should be randomized. Optimal blinding is not possible. Stratification will be done in variable blocks (gender and additional radiotherapy). The primary endpoint is the Wexner incontinence score; secondary endpoints are health-related and fecal-incontinence-related QoL and cost-effectiveness. Baseline measurements take place before randomization. The primary endpoint is measured 3 months after the start of the intervention, with a 1-year follow-up for sustainability research purposes. DISCUSSION: The results of this study may substantially improve postoperative care for patients with fecal incontinence or anorectal dysfunction after LAR. This section provides insight in the decisions that were made in the organization of this trial. TRIAL REGISTRATION: Netherlands Trial Registration, NTR5469, registered on 03-09-2015. Protocol FORCE trial V18, 19-09-2019. Sponsor Radboud University Medical Center, Nijmegen.

The low anterior resection syndrome in a reference population: prevalence and predictive factors in the Netherlands.

AIM: The low anterior resection syndrome (LARS) severely affects quality of life (QoL) after colorectal cancer surgery. There are no data about these complaints and the association with QoL in a reference population. The aim of this study was to assess LARS and the association with QoL in a reference population. METHODS: Six hundred patients who visited the outpatient clinic because of general or trauma surgical indications were asked to participate in this study. They received an invitation letter containing three validated questionnaires to assess LARS (assessed with the LARS score) and both general [European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30] and colorectal-specific (EORTC QLQ-CR29) QoL. RESULTS: Five hundred and one respondents could be included for the analyses. The median age at inclusion was 68 years and 47.3% were men. Major LARS was observed in 15% of patients (11.4% in men and 18.9% in women, P = 0.021). Women reported more urgency (P = 0.070) and incontinence for both flatus (P < 0.001) and stool (P = 0.063) compared to men. In univariate analyses, women reported major LARS significantly more often than men (OR 1.82; 95% CI 1.10-3.01). Patients with major LARS scored significantly worse in most QoL domains compared to patients with no/minor LARS. CONCLUSION: This is the first study demonstrating major LARS and the association with QoL in a reference population of patients without colorectal cancer. Our data can assist in the interpretation of LARS in past and future research about abdominal complaints after colorectal cancer surgery.

The Netherlands Arrhythmogenic Cardiomyopathy Registry: design and status update.

BACKGROUND: Clinical research on arrhythmogenic cardiomyopathy (ACM) is typically limited by small patient numbers, retrospective study designs, and inconsistent definitions. AIM: To create a large national ACM patient cohort with a vast amount of uniformly collected high-quality data that is readily available for future research. METHODS: This is a multicentre, longitudinal, observational cohort study that includes (1) patients with a definite ACM diagnosis, (2) at-risk relatives of ACM patients, and (3) ACM-associated mutation carriers. At baseline and every follow-up visit, a medical history as well information regarding (non-)invasive tests is collected (e. g. electrocardiograms, Holter recordings, imaging and electrophysiological studies, pathology reports, etc.). Outcome data include (non-)sustained ventricular and atrial arrhythmias, heart failure, and (cardiac) death. Data are collected on a research electronic data capture (REDCap) platform in which every participating centre has its own restricted data access group, thus empowering local studies while facilitating data sharing. DISCUSSION: The Netherlands ACM Registry is a national observational cohort study of ACM patients and relatives. Prospective and retrospective data are obtained at multiple time points, enabling both cross-sectional and longitudinal research in a hypothesis-generating approach that extends beyond one specific research question. In so doing, this registry aims to (1) increase the scientific knowledge base on disease mechanisms, genetics, and novel diagnostic and treatment strategies of ACM; and (2) provide education for physicians and patients concerning ACM, e. g. through our website ( www.acmregistry.nl ) and patient conferences.

Prevalence and cardiac phenotype of patients with a phospholamban mutation.

Pathogenic mutations in the phospholamban (PLN) gene may give rise to inherited cardiomyopathies due to its role in calcium homeostasis. Several PLN mutations have been identified, with the R14del mutation being the most prevalent cardiomyopathy-related mutation in the Netherlands. It is present in patients diagnosed with arrhythmogenic cardiomyopathy as well as dilated cardiomyopathy. Awareness of the phenotype of this PLN mutation is of great importance, since many carriers remain to be identified. Patients with the R14del mutation are characterised by older age at onset, low-voltage electrocardiograms and a high frequency of ventricular arrhythmias. Additionally, these patients have a poor prognosis often with left ventricular dysfunction and early-onset heart failure. Therefore, when there is a suspicion of a PLN mutation, cardiac and genetic screening is strongly recommended.

What you should know about the low anterior resection syndrome - Clinical recommendations from a patient perspective.

INTRODUCTION: Functional bowel complaints, referred to as Low Anterior Resection Syndrome (LARS), are common after sphincter-saving surgical procedures and have a severe impact on quality of life (QoL). Care for LARS patients is complex and surgeons underestimate or misinterpret its associated symptoms. This study aimed to explore the impact of LARS from a patient perspective facilitating the construction of a set of recommendations improving current care stratagems. METHODS: In a non-academic Dutch teaching hospital, three focus group sessions were conducted with 16 patients (males = 50%) who had undergone colorectal surgery between 2012 and 2017. A trained moderator orchestrated patient-discussion regarding illness perception and health-care needs. Transcripts were analysed using inductive content analysis. RESULTS: Three themes were identified: illness perception, preoperative care and postoperative supportive care. Specific attention and screening for LARS is deemed necessary for breaking the taboo surrounding it. Extension of preoperative counselling on the normal postoperative course, including ways to optimize social support, were identified as crucial. After discharge, patients experienced a lack of supportive care regarding functional complaints and did not know who to counsel. In addition, they felt intrinsically motivated to actively prepare for surgery, i.e. by participating in prehabilitation programs. CONCLUSION: Exploring perspectives in LARS patients resulted in the identification of potential improvements in current care pathways. Recommendations on ways to improve information provision, screening of LARS and methods to intervene in the gap of supportive care after discharge are presented. We recommend to implement these measures as QoL of patients undergoing colorectal cancer surgery may be improved.

A decade of atrial fibrillation ablation : Shifts in patient characteristics and procedural outcomes.

BACKGROUND: Over the past decade, radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) has evolved into a frequently performed procedure. The aim of this study was to monitor changes in patient characteristics, procedural characteristics, outcomes and complications over the past 10 years. METHODS: All consecutive patients who underwent primary RFCA treatment of AF in the University Medical Center Utrecht from 2005-2015 were included. In all patients, the primary ablation strategy was pulmonary vein (PV) antrum isolation without additional substrate modification. Baseline patient and procedure characteristics, and 1­year follow-up data of 975 patients were prospectively collected. RESULTS: In 2005, 73.4% of patients suffered from paroxysmal AF, which decreased to 45.3% in 2014. Mean age increased from 54 ± 9 to 61 ± 10 years and CHA2DS2-VASc score ≥2 from 18 to 40.6%. History of AF decreased significantly from 7 to 4 years. Mean procedure duration was 237 ± 53 min in 2005 and 163 ± 41 min in 2014. Fluoroscopy time significantly decreased from 41 ± 17 to 19 ± 8 min and total radiation exposure from 465 (263-687) to 210 (118-376) mGy. One-year success remained similar (2005: 55.6%, 2014: 54.8%), as did the amount of PV reconnection observed during redo procedures. Due to a marked reduction in vascular complications and moderate PV stenosis, the total complication rate decreased significantly. CONCLUSION: Over the past decade, AF ablation has increasingly been performed in older patients with persistent AF and more comorbidity. Moreover, it has been performed earlier after AF diagnosis. Although several performance parameters, such as procedure duration and complication rate, improved, 1­year single procedure success remained unchanged.

Dynamics of a single-atom electron pump.

Single-electron pumps based on isolated impurity atoms have recently been experimentally demonstrated. In these devices the Coulomb potential of an atom creates a localised electron state with a large charging energy and considerable orbital level spacings, enabling robust charge capturing processes. In contrast to the frequently used gate-defined quantum dot pumps, which experience a strongly time-dependent potential, the confinement potential in these single-atom pumps is hardly affected by the periodic driving of the system. Here we describe the behaviour and performance of an atomic, single parameter, electron pump. This is done by considering the loading, isolating and unloading of one electron at the time, on a phosphorous atom embedded in a silicon double gate transistor. The most important feature of the atom pump is its very isolated ground state, which is populated through the fast loading of much higher lying excited states and a subsequent fast relaxation process. This leads to a substantial increase in pumping accuracy, and is opposed to the adverse role of excited states observed for quantum dot pumps due to non-adiabatic excitations. The pumping performance is investigated as a function of dopant position, revealing a pumping behaviour robust against the expected variability in atomic position.

Screening for renal involvement in ANCA-associated vasculitis: room for improvement?

BACKGROUND: Renal involvement in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) requires prompt and aggressive immunosuppressive therapy. The aim of this study was to evaluate screening practice for renal involvement in AAV and its potential effect on renal outcomes. METHODS: Between 2005 and 2015, ANCA-positive AAV patients in a teaching hospital in the Netherlands were retrospectively included. Complete screening for renal involvement was defined as: assessment of erythrocyturia, proteinuria and serum creatinine within two weeks of the diagnosis of AAV. Characteristics at presentation and at 12 months were compared between patients with and without complete screening. RESULTS: A total of 109 AAV patients (63% male) were identified with a mean age of 62 ±; 14 years. Complete screening for renal involvement was performed in 90 of the 109 patients (83%). Patients with incomplete screening had a lower serum creatinine (86 ±; 53 vs. 190 ±; 185 µmol/l, p < 0.001) and were more often diagnosed outside the renal department (100% vs. 78%, p = 0.02). Three patients with incomplete screening had a rise in serum creatinine of ≥ 30% at 12 months. Incomplete screening was not associated with the development of end-stage renal disease. Urine analysis of patients with renal biopsy-proven AAV (n = 31) showed erythrocyturia in 58% after one sample and in 94% after three samples. CONCLUSION: Screening for renal involvement in AAV was suboptimal, primarily in patients who presented outside the renal department. A higher sensitivity for erythrocyturia is achieved if urine analysis is repeated. Incomplete screening may lead to renal impairment if renal involvement is not treated appropriately.