Oral ribose supplementation in dystroglycanopathy: A single case study.

Three forms of muscular dystrophy-dystroglycanopathies are linked to the ribitol pathway. These include mutations in the isoprenoid synthase domain-containing protein (ISPD), fukutin-related protein (FKRP), and fukutin (FKTN) genes. The aforementioned enzymes are required for generation of the ribitol phosphate linkage in the O-glycan of alpha-dystroglycan. Mild cases of dystroglycanopathy present with slowly progressive muscle weakness, while in severe cases the eyes and brain are also involved. Previous research showed that ribose increased the intracellular concentrations of cytidine diphosphate-ribitol (CDP-ribitol) and had a therapeutic effect. Here, we report the safety and effects of oral ribose supplementation during 6 months in a patient with limb girdle muscular dystrophy type 2I (LGMD2I) due to a homozygous FKRP mutation. Ribose was well tolerated in doses of 9 g or 18 g/day. Supplementation with 18 g of ribose resulted in a decrease of creatine kinase levels of 70%. Moreover, metabolomics showed a significant increase in CDP-ribitol levels with 18 g of ribose supplementation (p < 0.001). Although objective improvement in clinical and patient-reported outcome measures was not observed, the patient reported subjective improvement of muscle strength, fatigue, and pain. This case study indicates that ribose supplementation in patients with dystroglycanopathy is safe and highlights the importance for future studies regarding its potential effects.

Pulmonary artery pressure monitoring in chronic heart failure: effects across clinically relevant subgroups in the MONITOR-HF trial.

BACKGROUND AND AIMS: In patients with chronic heart failure (HF), the MONITOR-HF trial demonstrated the efficacy of pulmonary artery (PA)-guided HF therapy over standard of care in improving quality of life and reducing HF hospitalizations and mean PA pressure. This study aimed to evaluate the consistency of these benefits in relation to clinically relevant subgroups. METHODS: The effect of PA-guided HF therapy was evaluated in the MONITOR-HF trial among predefined subgroups based on age, sex, atrial fibrillation, diabetes mellitus, left ventricular ejection fraction, HF aetiology, cardiac resynchronisation therapy, and implantable cardioverter defibrillator. Outcome measures were based upon significance in the main trial and included quality of life, clinical, and PA pressure endpoints, and were assessed for each subgroup. Differential effects in relation to the subgroups were assessed with interaction terms. Both unadjusted and multiple testing adjusted interaction terms were presented. RESULTS: The effects of PA monitoring on quality of life, clinical events, and PA pressure were consistent in the predefined subgroups, without any clinically relevant heterogeneity within or across all endpoint categories (all adjusted interaction P-values were nonsignificant). In the unadjusted analysis of the primary endpoint quality-of-life change, weak trends towards a less pronounced effect in older patients (Pinteraction = 0.03; adjusted Pinteraction = 0.33) and diabetics (Pinteraction = 0.01; adjusted Pinteraction = 0.06) were observed. However, these interaction effects did not persist after adjusting for multiple testing. CONCLUSIONS: This subgroup analysis confirmed the consistent benefits of PA-guided HF therapy observed in the MONITOR-HF trial across clinically relevant subgroups, highlighting its efficacy in improving quality of life, clinical, and PA pressure endpoints in chronic HF patients.

Exploring patients' experience using PROMs within routine post-discharge follow-up assessment after stroke: a mixed methods approach.

BACKGROUND: Patient Reported Outcomes Measures (PROMs) are being used increasingly to measure health problems in stroke clinical practice. However, the implementation of these PROMs in routine stroke care is still in its infancy. To understand the value of PROMs used in ischemic stroke care, we explored the patients' experience with PROMs and with the consultation at routine post-discharge follow-up after stroke. METHODS: In this prospective mixed methods study, patients with ischemic stroke completed an evaluation questionnaire about the use of PROMs and about their consultation in two Dutch hospitals. Additionally, telephone interviews were held to gain in-depth information about their experience with PROMs. RESULTS: In total, 63 patients completed the evaluation questionnaire of which 10 patients were also interviewed. Most patients (82.2-96.6%) found completing the PROMs to be feasible and relevant. Half the patients (49.2-51.6%) considered the PROMs useful for the consultation and most patients (87.3-96.8%) reported the consultation as a positive experience. Completing the PROMs provided 51.6% of the patients with insight into their stroke-related problems. Almost 75% of the patients found the PROMs useful in giving the healthcare provider greater insight, and 60% reported discussing the PROM results during the consultation. Interviewed patients reported the added value of PROMs, particularly when arranging further care, in gaining a broader insight into the problems, and in ensuring all important topics were discussed during the consultation. CONCLUSIONS: Completing PROMs appears to be feasible for patients with stroke attending post-discharge consultation; the vast majority of patients experienced added value for themselves or the healthcare provider. We recommend that healthcare providers discuss the PROM results with their patients to improve the value of PROMs for the patient. This could also improve the willingness to complete PROMs in the future.

Non-ammoniagenic proliferation and differentiation media for cultivated adipose tissue.

Ammonia (Amm), and its aqueous solved state, ammonium, which is produced from glutamine (Gln) metabolism, is a known inhibitor of stem cell proliferation in vitro. In the context of cultivated beef, primary bovine fibro-adipogenic progenitor cells (FAPs) need to be grown and differentiated for several weeks in vitro for the production of cultivated fat. In this study, the ammonium sensitivity of these cells was investigated by introducing ammonium chloride, which was found to inhibit their proliferation when above 5 mM and their adipogenic differentiation when above 2 mM. Novel serum-free proliferation and differentiation media were hence developed with the aim to suppress Amm production during expansion and adipogenesis. Glutamine substitutes, such as a-ketoglutarate (aKG), glutamate (Glt) and pyruvate (Pyr) were investigated. It was found that aKG based proliferation medium (PM) was the most effective in promoting and maintaining FAPs growth over several passages while the specific Amm production rate was reduced more than 5-fold. In terms of differentiation capacity, the substitution of glucose (Gluc) and Gln with galactose (Gal) and Pyr was shown to be the most effective in promoting FAPs differentiation into mature adipocytes, resulting in over 2-fold increase of fat volume per cell, while suppressing Amm production. Our findings suggest that FAPs do not require Gln as an essential nutrient but, on the contrary, possess all the necessary metabolic pathways to proliferate and subsequently differentiate in a Gln-free medium, resulting in decreased Amm production rates and seemingly synthesising glutamine de novo. These findings are important for prolonging the lifespan of culture medium, allowing for reduced costs and process interventions.

Evolution of Pulmonary Arteriovenous Malformations: The Role of Contrast Echocardiography.

BACKGROUND: Pulmonary arteriovenous malformations (PAVMs) are direct connections between the pulmonary artery and the pulmonary vein, mostly associated with hereditary hemorrhagic telangiectasia (HHT). PAVMs can lead to severe neurologic complications such as stroke and brain abscess. The risk of complications decreases after embolization. Therefore, screening for PAVMs using transthoracic contrast echocardiography (TTCE) is recommended, including a rescreening interval of 5 years. RESEARCH QUESTION: Is extension of the interval for rescreening patients without a pulmonary right-to-left shunt (RLS) of up to 10 years appropriate? STUDY DESIGN AND METHODS: Adult patients with HHT with 5- or 10-year follow-up TTCE, or both, were included. Patients who underwent PAVM embolization in the past or at baseline were excluded. The RLS grades and presence of a treatable PAVM were compared with baseline. RESULTS: In total, 387 patients (median age, 45 years [interquartile range, 33-54 years]; 56% women) involving 5- and 10-year follow-up data in 363 and 166 patients, respectively, were included. None of the patients (n = 148) without a pulmonary RLS at baseline demonstrated a treatable PAVM after 5 and 10 years. Of the patients with a pulmonary RLS at baseline, 20 patients (9%) and three patients (3%) demonstrated a treatable PAVM at the 5- and 10-year follow-up, respectively. In most patients, the RLS grade remained stable over time. INTERPRETATION: On the basis of the results of this retrospective study, we believe that the rescreening interval for patients with HHT without a pulmonary RLS at initial screening may be extended to 10 years. Those with a pulmonary RLS should be rescreened every 5 years because treatable PAVMs can evolve.

The Self-Regulation Assessment (SeRA) questionnaire: development and exploratory analyses of a new patient-reported outcome measure for rehabilitation.

PURPOSE: To develop and explore underlying dimensions of the Self-Regulation Assessment (SeRA) and psychometric features of potential components. Further, to identify associations between the SeRA and disability-management self-efficacy, type of diagnosis, and type of rehabilitation. MATERIALS AND METHODS: Based on a previously developed model of self-regulation, expert and patient opinions, and cognitive interviews, a list of 22 items on self-regulation (the SeRA) was constructed. The SeRA was included in a cross-sectional survey among a multi-diagnostic group of 563 former rehabilitation patients. Exploratory analyses were conducted. RESULTS: Respondents had a mean age of 56.5 (SD 12.7) years. The largest diagnostic groups were chronic pain disorder and brain injury. Four components were found within the SeRA, labelled as "insight into own health condition," "insight into own capabilities," "apply self-regulation," and "organization of help." Cronbach's alpha was high (total scale: 0.93, subscales: range 0.85-0.89). Only scores on the first subscale showed a ceiling effect. Subscale three showed the highest correlation with a self-efficacy measure. Small differences in SeRA total scores (range 71.6-78.1) were found between different diagnostic groups. CONCLUSION: The SeRA is a new self-regulation measure with four subscales. Further research is needed to establish the validity and reliability of the SeRA. IMPLICATIONS FOR REHABILITATIONThe Self-Regulation Assessment (SeRA) was developed to provide a comprehensive measurement of self-regulation among rehabilitation populations.The SeRA could potentially be used to identify persons with self-regulation problems at the start of rehabilitation treatment and measure outcomes of rehabilitation for self-regulation.The SeRA could potentially be used to help analyse outcomes of rehabilitation practice as well as evaluate interventions on self-regulation.

Intra- and interpersonal effects of coping style and self-efficacy on anxiety, depression and life satisfaction in patient-partner couples after stroke.

Many stroke patients and partners suffer from anxiety, depression, and low life satisfaction. Psychological factors such as coping style and self-efficacy can be protective factors within individuals. The close relationship between stroke patients and partners suggests that there may be interdependence in psychological functioning. The aim of this study was to examine intra- and interpersonal effects of coping style and self-efficacy on anxiety, depression, and life satisfaction in patient-partners couples. In this prospective cohort study, pro-active coping (UPCC), general self-efficacy (GSES), anxiety (HADS-A), depression (HADS-D), and life satisfaction (1-6 scale) were assessed in 215 couples at 2 and 12 months post-stroke. Effects within couples were assessed using structural equation modelling. Several intra- and interpersonal effects of coping style and self-efficacy at 2 months post-stroke were related to emotional health at 12 months post-stroke. Most effects were intrapersonal effects. The interpersonal effects were small but showed that pro-active coping by the patient was associated with lower anxiety of the partner. Higher self-efficacy of the partner was associated with lower depression scores and higher life satisfaction of the patient. This study underscores the importance of a dyadic approach to post-stroke functioning. It supports a family-based approach for treating post-stroke emotional problems.

Measures of self-regulation used in adult rehabilitation populations: A systematic review and content screening.

OBJECTIVE: We aimed to identify generic measures of self-regulation and to examine the degree to which these measures fit a recently developed conceptual model of self-regulation in a rehabilitation context. DATA SOURCES: Pubmed, Embase, PsycInfo, and CINAHL were searched. REVIEW METHODS: Articles were included if they were published between January 2015 and August 2020 and reported on empirical studies (trials and observational studies) using a measure of self-regulation or a related concept, in an adult rehabilitation population. Main content was analysed by linking all items of the selected measures to one or more of the six sub-themes of self-regulation: (1) insight into physical and cognitive impairments, (2) insight into the consequences of the impairments, (3) insight into abilities, (4) to be able to communicate limitations, (5) trust in body and functioning, and (6) make use of abilities. RESULTS: Two reviewers independently screened 7808 abstracts, resulting in the inclusion of 236 articles. In these articles, 80 different measures were used to assess self-regulation or related concept. Nineteen of these measures met the inclusion criteria and were included for the content analyses. Nine of these were self-efficacy measures. No measures covered four or more of the six sub-themes of self-regulation. The three sub-themes on gaining insights were covered less compared to the sub-domains 'trust' and 'make use of abilities'. CONCLUSIONS: Many measures on self-regulation exist None of these measures cover all six sub-themes of self-regulation considered important to measure self-regulation as a rehabilitation outcome.

Four-year survival rate in pulmonary sarcoidosis with extensive pulmonary hypertension screening.

BACKGROUND: Sarcoidosis is a systemic disease of unknown aetiology with significant morbidity and mortality. The PULSAR study prospectively performed cardiac analysis including systematic pulmonary hypertension screening in sarcoidosis patients newly referred to a tertiary sarcoidosis center. In this manuscript we studied the four-year mortality of this population. METHODS AND MAIN FINDINGS: Between august 2015 and October 2017, 399 patients (58% male, mean age 49.4 years, 90.5% Caucasian) were included and followed for a mean period of 4.3±0.7 years. In total, 10 patients had died at the time of analysis. 1-, 2-, 3- and 4-year survival rate was 100% (n=399), 99.0% (n=399), 98.2% (n=399) and 94.6% (n=276). Most patients died of respiratory failure, other causes were heterogeneous including cardiac, neurological and non-sarcoidosis origin. A low CPI score or modified Walsh score was associated with higher mortality, similar for high PH probability on echocardiography and elevated right ventricular systolic pressure. CONCLUSION: This study highlights that elevated RVSP and presence of PH on echocardiography and progression of fibrotic disease with subsequent decline in pulmonary function test are important factors for mortality in sarcoidosis patients.

Right atrial and ventricular strain detects subclinical changes in right ventricular function in precapillary pulmonary hypertension.

Right ventricular (RV) ejection fraction (EF) by cardiac magnetic resonance (CMR) correlates to outcome in precapillary pulmonary hypertension (pPH) patients, but is insensitive to early changes. Strain might provide incremental information. In this study, we compare right atrial (RA) and RV strain in pPH patients to healthy controls, and evaluate the prognostic value of strain in pPH. In this cross-sectional study, 45 pPH patients and 20 healthy controls underwent CMR, and feature-tracking derived RA and RV strain were evaluated. pPH patients had impaired RA reservoir and conduit strain, and RV longitudinal strain (LS), compared to healthy controls. In pPH patients with preserved RVEF (≥ 50%, n = 18), RA reservoir (35% ± 9 vs. 41% ± 6, p = 0.02) and conduit strain (16% ± 8 vs. 23% ± 5, p = 0.004), and RV-LS (-25% ± 4 vs. -31% ± 4, p < 0.001) remained impaired, compared to healthy controls. The association of strain with the primary endpoint (combination of all-cause death, lung transplantation, and heart failure hospitalization) was evaluated using a multivariable Cox regression model. RV-LS (HR 1.18, 95%-CI 1.04-1.34, p = 0.01) and RA strain (reservoir: HR 0.87, 95%-CI 0.80-0.94, p = 0.001; conduit: HR 0.85, 95%-CI 0.75-0.97, p = 0.02, booster: HR 0.81, 95%-CI 0.71-0.92, p = 0.001) were independent predictors of outcome, beyond clinical and imaging features. In conclusion, pPH patients have impaired RA strain and RV-LS, even when RVEF is preserved. In addition, RA strain and RV-LS were independent predictors of adverse prognosis. These results emphasize the incremental value of RA and RV strain analyses, to detect alterations in RV function, even before RVEF declines.

The influence of psychological factors and mood on the course of participation up to four years after stroke.

PURPOSE: (1) To explore the course of participation from two months up to four years after stroke, and (2) to examine if adaptive and maladaptive psychological factors and mood measured at two months after stroke are determinants of the course of participation during this period. MATERIALS AND METHODS: Prospective cohort study in which 369 individuals with stroke were assessed at stroke onset, two months, six months, one year, two years and three to four years after stroke. The Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-Participation) restrictions subscale was used to measure participation. Psychological factors were clustered into adaptive (proactive coping, self-efficacy, extraversion and optimism) and maladaptive (passive coping, neuroticism and pessimism) psychological factors. The Hospital Anxiety and Depression Scale was used to assess mood. RESULTS: Although improvements in participation were observed up to one year after stroke, considerable long-term restrictions in social and physical domains persisted. More mood problems and less adaptive psychological factors were independent determinants of worse participation up to four years after stroke. CONCLUSIONS: Participation improves in the first 12 months after stroke and stabilizes afterwards. Mood problems and less adaptive psychological factors negatively influence the course of participation over time up to four years after stroke.Implications for rehabilitationFollow-up assessments after stroke should not only focus on cognitive and motor impairment, but also encompass screening on mood problems and adaptive psychological factors.Implementation of a routine follow-up assessment one year after stroke can be beneficial as restrictions in participation are unlikely to diminish spontaneously from then onwards.

The European Rare Disease Network for HHT Frameworks for management of hereditary haemorrhagic telangiectasia in general and speciality care.

Hereditary haemorrhagic telangiectasia (HHT) is a complex, multisystemic vascular dysplasia affecting approximately 85,000 European Citizens. In 2016, eight founding centres operating within 6 countries, set up a working group dedicated to HHT within what became the European Reference Network on Rare Multisystemic Vascular Diseases. By launch, combined experience exceeded 10,000 HHT patients, and Chairs representing 7 separate specialties provided a median of 24 years' experience in HHT. Integrated were expert patients who focused discussions on the patient experience. Following a 2016-2017 survey to capture priorities, and underpinned by more than 40 monthly meetings, and new data acquisitions, VASCERN HHT generated position statements that distinguish expert HHT care from non-expert HHT practice. Leadership was by specialists in the relevant sub-discipline(s), and 100% consensus was required amongst all clinicians before statements were published or disseminated. One major set of outputs targeted all healthcare professionals and their HHT patients, and include the new Orphanet definition; Do's and Don'ts for common situations; Outcome Measures suitable for all consultations; COVID-19; and anticoagulation. The second output set span aspects of vascular pathophysiology where greater understanding will assist organ-specific specialist clinicians to provide more informed care to HHT patients. These cover cerebral vascular malformations and screening; mucocutaneous telangiectasia and differential diagnosis; anti-angiogenic therapies; circulatory interplays between anaemia and arteriovenous malformations; and microbiological strategies to counteract loss of normal pulmonary capillary function. Overall, the integrated outputs, and documented current practices, provide frameworks for approaches that augment the health and safety of HHT patients in diverse health-care settings.

Self-regulation as rehabilitation outcome: what is important according to former patients?

PURPOSE: Self-regulation refers to self-management and self-control, with or without disability. Outcomes of rehabilitation with respect to self-regulation are unclear. This study aims to identify elements of self-regulation that former patients consider important in the context of medical rehabilitation. MATERIALS AND METHODS: Qualitative exploration based on focus group discussions (FGDs). Transcripts were analysed using thematic analysis as well as open coding. Forty individuals participated in seven diagnosis-related FGDs. RESULTS: Six subthemes were raised in the FGDs which could be merged into three main themes. Two main themes are conditional for regaining self-regulation: 1) having insight into one's condition and abilities (i.e., insight into impairments. consequences of impairments. abilities); 2) to know how to cope with the consequences of the condition (be able to communicate limitations; have to trust in body and functioning). The subject of the last theme 3) is how to apply self-regulation in one's own life (to make use of abilities and optimize functioning). CONCLUSIONS: Three main themes of self-regulation in the context of medical rehabilitation were identified by former patients, partly relating to the ability to self-regulate and partly to the execution of self-regulation. This knowledge can be used to define specific rehabilitation goals and further develop rehabilitation outcome measurement.IMPLICATIONS FOR REHABILITATIONAwareness of the fundamental subthemes of self-regulation in rehabilitation will positively contribute to theory building and improve clinical practice (e.g., goal setting).Paying explicit attention to the six subthemes as standard elements of rehabilitation will help to provide a comprehensive view concerning self-regulation.The conceptual model of self-regulation, based on patient perspectives, can contribute to the measurement of rehabilitation outcomes.

The usefulness of repeated CMR and FDG PET/CT in the diagnosis of patients with initial possible cardiac sarcoidosis.

BACKGROUND: Cardiac sarcoidosis (CS) diagnosis is usually based on advanced imaging techniques and multidisciplinary evaluation. Diagnosis is classified as definite, probable, possible or unlikely. If diagnostic confidence remains uncertain, cardiac imaging can be repeated. The objective is to evaluate the usefulness of repeated cardiac magnetic resonance imaging (CMR) and fluorodeoxyglucose positron emission tomography (FDG PET/CT) for CS diagnosis in patients with an initial "possible" CS diagnosis. METHODS: We performed a retrospective cohort study in 35 patients diagnosed with possible CS by our multidisciplinary team (MDT), who received repeated CMR and FDG PET/CT within 12 months after diagnosis. Imaging modalities were scored on abnormalities suggestive for CS and classified as CMR+/PET+, CMR+/PET-, CMR-/PET+ and CMR-/PET-. Primary endpoint was final MDT diagnosis of CS. RESULTS: After re-evaluation, nine patients (25.7%) were reclassified as probable CS and 16 patients (45.7%) as unlikely CS. Two patients started immunosuppressive treatment after re-evaluation. At baseline, eleven patients (31.4%) showed late gadolinium enhancement (LGE) on CMR (CMR+) and 26 (74.3%) patients showed myocardial FDG-uptake (PET+). At re-evaluation, nine patients (25.7%) showed LGE (CMR+), while 16 patients (45.7%) showed myocardial FDG-uptake (PET+). When considering both imaging modalities together, 82.6% of patients with CMR-/PET+ at baseline were reclassified as possible or unlikely CS, while 36.4% of patients with CMR+ at baseline were reclassified as probable CS. Three patients with initial CMR-/PET+ showed LGE at re-evaluation. CONCLUSION: Repeated CMR and FDG PET/CT may be useful in establishing or rejecting CS diagnosis, when initial diagnosis is uncertain. However, clinical relevance has to be further determined.

Idiopathic and hereditary haemorrhagic telangiectasia associated pulmonary arteriovenous malformations: comparison of clinical and radiographic characteristics.

AIM: To determine whether there are differences between idiopathic and hereditary haemorrhagic telangiectasia (HHT) associated pulmonary arteriovenous malformations (PAVMs) (HHT-PAVM) regarding clinical and radiographic characteristics, and the results of embolotherapy. MATERIALS AND METHODS: A retrospective analysis was undertaken of all adult and adolescent patients who were diagnosed with a PAVM on chest computed tomography (CT) from January 2006 until August 2019. RESULTS: In total, 41 patients with idiopathic PAVMs and 194 patients with genetically confirmed HHT and PAVMs were included. Idiopathic PAVMs were more frequently observed in female patients, were more solitary, and predominantly located in the lower lobes. The diameter of the feeding artery and type of PAVM (simple versus complex) were similar. Embolotherapy results were comparable between both groups with similar re-embolisation rates. CONCLUSIONS: PAVMs of idiopathic origin are predominantly found in women, more frequently located in the lower lobes, and solitary compared to HHT-PAVMs; however, the outcome of treatment is the same, suggesting that treatment and follow-up should be similar in both groups.

Spinal cord injuries and bowel stomas: timing and satisfaction with stoma formation and alterations in quality of life.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: Neurogenic bowel dysfunction (NBD) is frequent among individuals with spinal cord injury (SCI) and is often difficult to treat. A bowel stoma is considered the last-resort treatment option for individuals with SCI and severe NBD. This study aims to explore whether individuals are satisfied with their bowel stoma and how they feel about the timing of stoma formation. Furthermore, we want to explore side effects addressing diversion colitis and changes in quality of life (QOL) after stoma formation. SETTING: Netherlands, community. METHODS: We included participants aged at least 18 years with a traumatic or non-traumatic SCI and bowel stoma. Questions regarding timing of stoma formation, alterations in QOL after stoma formation and experienced side effects of the bowel stoma were addressed in an online questionnaire. RESULTS: In total 23 participants filled out the online survey. Twenty-two participants (96%) were satisfied with their bowel stoma and 83% felt their stoma was placed too late or far too late. The large majority (>80%) reported improvements in the four QOL domains after the procedure. Nine participants reported stoma-related problems in the last month. In the last three months, seven participants (30%) reported to have diversion colitis. Four of these seven participants experienced this at least once a week or more. Two participants stated this had moderate influence on daily activities. CONCLUSIONS: Most participants with SCI experienced improvement in QOL and in retrospect wanted their bowel stoma earlier. Early, extensive conversations to inform individuals about bowel stoma as a treatment option is recommended.

Effectiveness and safety of infliximab in cardiac Sarcoidosis.

BACKGROUND: Immunosuppressive therapy in active cardiac sarcoidosis (CS) might prevent potential life-threatening complications. Infliximab (IFX) is a tumor necrosis factor alpha monoclonal antibody proven to be effective in refractory extracardiac sarcoidosis. It is sparsely used in CS, because of its association with worsening heart failure in prior studies. The goal of this study is to assess the effectiveness and safety of IFX in CS. METHODS AND RESULTS: A retrospective, single center cohort study was performed in sarcoidosis patients treated with IFX based on a cardiac indication between January 2016 and March 2019. Patients received IFX intravenously at a dose of 5 mg/kg at week 0, 2, and subsequently every 4 weeks. After every six months, treatment response was evaluated within the multidisciplinary team using FDG-PET/CT, transthoracic echocardiography, biomarkers and device interrogation reports. Responder analysis definitions were based on; dosage of immunosuppressive drugs, improvement in functional class, left ventricular ejection fraction (LVEF) and SUVmax. Twenty-two patients were included (mean age 51.0 SD10.0 years, male 68.2%) with a mean follow-up of 18.9 months (6 to 44 months) of whom 18 (82%) were classified as responders. Median SUVmax on FDG-PET/CT decreased from SUVmax 5.2 [3.7-8.4] to 2.3 [1.4-2.3], p = 0.015. The target-to-background ratio decreased from 3.2 [2.1-5.1] to 1.0 [0.7-2.4], p = 0.002. The median left ventricular (LV) ejection fraction increased from 45.0% [34.0-60.0] to 55.0% [41.0-60.0], p = 0.02. The majority of patients (73%) experienced no side effects and no patients had worsening of heart failure. CONCLUSION: In this pilot study, patients with refractory CS treated with infliximab, on top of standard of care, had a reduction in inflammation on FDG-PET/CT and an improvement in LV function, without serious adverse events.

Granulomatous amoebic encephalitis caused by Acanthamoeba in a patient with AIDS: a challenging diagnosis.

INTRODUCTION: Acanthamoeba spp. is a ubiquitous free-living amoeba that causes human infections affecting predominantly the cornea and central nervous system. The diagnosis and treatment of Acanthamoeba encephalitis is very challenging. CASE SUMMARY: A 53-year-old male with HIV/AIDS was admitted for altered mental status and fever. On initial examination, he had left hemianopia with left-sided weakness and numbness. MRI revealed an inflammatory and enhancing parenchymal mass associated with leptomeningeal enhancement in the occipitoparietal lobe containing multiple punctate hemorrhages. He was treated with empiric antibiotics for presumptive toxoplasmosis, brain abscess, fungal infection and tuberculosis with an unremarkable lymphoma work up. Initial brain biopsy studies were unremarkable except for non-specific granulomas and adjacent necrotic tissue. The patient passed away 2.5 months after initial presentation with no diagnosis. Post-mortem testing by the Centers for Disease Control and Prevention (CDC) confirmed the diagnosis of granulomatous amoebic encephalitis (GAE) by visualization with immunohistochemistry staining and PCR. Recovery is rare from GAE likely due to delay in diagnosis. CONCLUSIONS: This case illustrates the importance of including GAE into the differential diagnosis of brain mass. We advocate early molecular testing of tissue specimen by the CDC to achieve an appropriate diagnosis, and a multidisciplinary approach for the management of this condition.

[Adolescents with concurrent ADHD and substance use disorder; international consensus]. / Jongeren met een stoornis in het gebruik van middelen en ADHD: internationale consensus.

BACKGROUND: Substance use disorder (SUD) is common among youths with attention-deficit/hyperactivity disorder (ADHD). Co-morbid ADHD and SUD in youths complicates screening, diagnosis, and treatment of both disorders and is associated with worse treatment prognosis. Limited research in youths with SUD and co-morbid ADHD provides insufficient basis for firm recommendations. To offer clinicians some guidance on this topic, we present the results of an international consensus procedure. AIM: To summarize an international consensus on diagnosis and treatment of young people with comorbid ADHD and SUD. METHOD: In a modified Delphi-study, a multidisciplinary, international group of 55 experts strived to reach consensus on 37 recommendations. RESULTS: Consensus was reached on 36 recommendations. Routine screening of ADHD and/or SUD is important. For the treatment of co-morbid SUD and ADHD in youths, both psychosocial and pharmacological treatment should be considered. Psychosocial treatment should preferably consist of psychoeducation, motivational interviewing (MI), and cognitive behavioral therapy (CBT) focused on SUD or both disorders. Long-acting stimulants are recommended as first choice pharmacotherapy, preferably embedded in psychosocial treatment. Experts did not agree on the precondition that patients need to be abstinent before starting stimulant treatment. CONCLUSION: Clinicians and youths with co-morbid SUD and ADHD can use this international consensus to choose the best possible treatment.

The aortic root in repaired tetralogy of Fallot: Serial measurements and impact of losartan treatment.

BACKGROUND: Aortic root dilatation is common in adults with repaired tetralogy of Fallot (rTOF) and might lead to aortic dissection. However, little is known on progression of aortic dilatation and the effect of pharmaceutical treatment. This study aims to determine factors associated with aortic growth and investigate effects of losartan. METHODS AND RESULTS: We performed a prespecified analysis from the 1:1 randomized, double-blind REDEFINE trial. Aortic root diameters were measured at baseline and after 2.0 ± 0.3 years of follow-up using cardiovascular magnetic resonance (CMR) imaging. A total of 66 patients were included (68% men, age 40 ± 12 years, baseline aortic root 37 ± 6 mm, 32% aortic dilatation (>40 mm)). There was a trend towards slow aortic root growth (+0.6 ± 2.3 mm after two years, p = 0.06) (n = 60). LV stroke volume was the only factor associated with both a larger baseline aortic root (ß: 0.09 mm/ml (95% C.I.:0.02, 0.15), p = 0.010) and with aortic growth during follow-up (ß: 0.04 mm/ml (95% C.I.:0.005, 0.066), p = 0.024), after correction for age, sex, and body surface area using linear regression analysis. No treatment effect of losartan was found (p = 0.17). CONCLUSIONS: Aortic root dilatation was present in about one-third of rTOF patients. A larger LV stroke volume was associated with both a larger baseline aortic root and ongoing growth. Our findings provide no arguments for lower aortic diameter thresholds for prophylactic surgery compared to the general population.