Idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive devastating lung disease with substantial morbidity. It is associated with cough, dyspnea and impaired quality of life. If left untreated, IPF has a median survival of 3 years. IPF affects ∼3 million people worldwide, with increasing incidence in older patients. The current concept of pathogenesis is that pulmonary fibrosis results from repetitive injury to the lung epithelium, with fibroblast accumulation, myofibroblast activation, and deposition of matrix. These injuries, in combination with innate and adaptive immune responses, dysregulated wound repair and fibroblast dysfunction, lead to recurring tissue remodeling and self-perpetuating fibrosis as seen in IPF. The diagnostic approach includes the exclusion of other interstitial lung diseases or underlying conditions and depends on a multidisciplinary team-based discussion combining radiological and clinical features and well as in some cases histology. In the last decade, considerable progress has been made in the understanding of IPF clinical management, with the availability of two drugs, pirfenidone and nintedanib, that decrease pulmonary lung function decline. However, current IPF therapies only slow disease progression and prognosis remains poor. Fortunately, there are multiple clinical trials ongoing with potential new therapies targeting different disease pathways. This review provides an overview of IPF epidemiology, current insights in pathophysiology, diagnostic and therapeutic management approaches. Finally, a detailed description of current and evolving therapeutic approaches is also provided.</p

The CODECS study:COgnitive DEficits in Cerebellar Stroke

Part of the extra-pyramidal system, the cerebellum is more and more recognized by its non-motor functions known as the cerebellar cognitive affective syndrome. Several studies have identified disturbances specifically in executive and attentional functions after focal cerebellar lesions. However, most studies were performed in small and heterogeneous patient groups. Furthermore, there is a substantial variation in the methodology of assessment. Here, we present the results of a large and homogeneous cohort of patients with isolated uniform cerebellar lesions. After three months post-stroke all patients underwent structural neuroimaging to confirm an isolated lesion and were given neuropsychological testing. The results show that cerebellar lesions relate to mild but long-term cognitive impairment in a broad spectrum of neurocognitive functions compared to normative values. These findings confirm involvement of the cerebellum in cognitive processing and supports the theory of ‘dysmetria of thought’ based upon uniform cerebellar processing in multiple cognitive domains. This study highlights the following results: 1-Cognitive impairments after isolated cerebellar stroke is confirmed in several cognitive domains. 2-Semantic and phonemic fluency are most affected in cerebellar stroke patients. 3-Verbal deficits show an age-independent long term effect post-stroke and should be studied further in depth. 4-Cognitive disorders after cerebellar stroke are more prominent in women than men.</p

Disease management with home telemonitoring aimed at substitution of usual care in the Netherlands: Post-hoc analyses of the e-Vita HF study

BACKGROUND: Home telemonitoring in heart failure (HF) patients may reduce workload of HF nurses by reducing face-to-face contacts. The aim of this study is to assess whether telemonitoring as a substitution could have negative effects as expressed by less reduction in circulating natriuretic peptide levels between baseline and one-year of follow up compared to usual care. METHODS: A post-hoc analysis of the e-Vita HF trial, a three-arm parallel randomized trial conducted in stable HF patients. Patients were randomized into three arms: (i) usual HF outpatient care, (ii) usual care combined with the use of the website heartfailurematters.org, and (iii) telemonitoring (e-Vita HF platform) instead of face-to-face consultations. Mixed linear model analyses were applied to assess differences in the N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels between the three arms over a year. RESULTS: A total of 223 participants could be included (mean age 67.1 ± 10.1 years, 27% women, New York Heart Association class I–IV; 39%, 38%, 14%, and 9%). The mean left ventricular ejection fraction was 35 ± 10%. The median of routine face-to-face contacts over a year was 1.0 lower (2.0 vs. 3.0) in the third arm compared with usual care. Median NT-proBNP levels did not significantly differ between the three arms. CONCLUSION: In stable and optimally treated HF patients, telemonitoring causing a reduction of routine face-to-face contacts seems not to negatively affect hemodynamic status as measured by NT-proBNP levels over time

Healthcare use and direct medical costs in a cleft lip and palate population:an analysis of observed and protocolized care and costs

This study was performed to describe observed healthcare utilization and medical costs for patients with a cleft, compare these costs to the expected costs based on the treatment protocol, and explore the additional costs of implementing the International Consortium for Health Outcomes Measurement (ICHOM) Standard Set for Cleft Lip and Palate (CL/P). Forty patients with unilateral CL/P between 0 and 24 years of age, treated between 2012 and 2019 at Erasmus University Medical Center, were included. Healthcare services (consultations, diagnostic and surgical procedures) were counted and costs were calculated. Expected costs based on the treatment protocol were calculated by multiplying healthcare products by the product prices. Correspondingly, the additional expected costs after implementing the ICHOM Standard Set (protocol + ICHOM) were calculated. Observed costs were compared with protocol costs, and the additional expected protocol + ICHOM costs were described. The total mean costs were highest in the first year after birth (€5596), mainly due to surgeries. The mean observed total costs (€40,859) for the complete treatment (0–24 years) were 1.6 times the expected protocol costs (€25,198) due to optional, non-protocolized procedures. Hospital admissions including surgery were the main cost drivers, accounting for 42% of observed costs and 70% of expected protocol costs. Implementing the ICHOM Standard Set increased protocol-based costs by 7%.</p

Occurrence and predictors of persistent impaired glucose tolerance after acute ischemic stroke or transient ischemic attack

Background Impaired glucose tolerance is often present in patients with a transient ischemic attack (TIA) or ischemic stroke and doubles the risk of recurrent stroke. This impaired glucose tolerance can be transient, reflecting an acute stress response, or persistent, representing undiagnosed impaired glucose metabolism possibly requiring treatment. We aimed to assess the occurrence of persistent impaired glucose tolerance after a stroke or TIA and to develop a prediction model to identify patients at risk of persistent impaired glucose tolerance. Methods Patients admitted to the str

Does Heterogeneity Exist in Treatment Associations With Renin–Angiotensin–System Inhibitors or Beta-blockers According to Phenotype Clusters in Heart Failure with Preserved Ejection Fraction?

BACKGROUND: We explored the association between use of renin–angiotensin system inhibitors and beta-blockers, with mortality/morbidity in 5 previously identified clusters of patients with heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: We analyzed 20,980 patients with HFpEF from the Swedish HF registry, phenotyped into young–low comorbidity burden (12%), atrial fibrillation–hypertensive (32%), older–atrial fibrillation (24%), obese–diabetic (15%), and a cardiorenal cluster (17%). In Cox proportional hazard models with inverse probability weighting, there was no heterogeneity in the association between renin–angiotensin system inhibitor use and cluster membership for any of the outcomes: cardiovascular (CV) mortality, all-cause mortality, HF hospitalisation, CV hospitalisation, or non-CV hospitalisation. In contrast, we found a statistical interaction between beta-blocker use and cluster membership for all-cause mortality (P = .03) and non-CV hospitalisation (P = .001). In the young–low comorbidity burden and atrial fibrillation–hypertensive cluster, beta-blocker use was associated with statistically significant lower all-cause mortality and non-CV hospitalisation and in the obese–diabetic cluster beta-blocker use was only associated with a statistically significant lower non-CV hospitalisation. The interaction between beta-blocker use and cluster membership for all-cause mortality could potentially be driven by patients with improved EF. However, patient numbers were diminished when excluding those with improved EF and the direction of the associations remained similar. CONCLUSIONS: In patients with HFpEF, the association with all-cause mortality and non-CV hospitalisation was heterogeneous across clusters for beta-blockers. It remains to be elucidated how heterogeneity in HFpEF could influence personalized medicine and future clinical trial design

Three-Dimensional Handheld Scanning to Quantify Head-Shape Changes in Spring-Assisted Surgery for Sagittal Craniosynostosis

Three-dimensional (3D) imaging is an important tool for diagnostics, surgical planning, and evaluation of surgical outcomes in craniofacial procedures. Gold standard for acquiring 3D imaging is computed tomography that entails ionizing radiations and, in young children, a general anaesthesia. Three-dimensional photographic imaging is an alternative method to assess patients who have undergone calvarial reconstructive surgery. The aim of this study was to assess the utility of 3D handheld scanning photography in a cohort of patients who underwent spring-assisted correction surgery for scaphocephaly. Pre- and postoperative 3D scans acquired in theater and at the 3-week follow-up in clinic were postprocessed for 9 patients. Cephalic index (CI), head circumference, volume, sagittal length, and coronal width over the head at pre-op, post-op, and follow-up were measured from the 3D scans. Cephalic index from 3D scans was compared with measurements from planar x-rays. Statistical shape modeling (SSM) was used to calculate the 3D mean anatomical head shape of the 9 patients at the pre-op, post-op, and follow-up. No significant differences were observed in the CI between 3D and x-ray. Cephalic index, volume, and coronal width increased significantly over time. Mean shapes from SSM visualized the overall and regional 3D changes due to the expansion of the springs in situ. Three-dimensional handheld scanning followed by SSM proved to be an efficacious and practical method to evaluate 3D shape outcomes after spring-assisted cranioplasty in individual patients and the population

The 3D skull 0–4 years: A validated, generative, statistical shape model

BACKGROUND: This study aims to capture the 3D shape of the human skull in a healthy paediatric population (0–4 years old) and construct a generative statistical shape model. METHODS: The skull bones of 178 healthy children (55% male, 20.8 ± 12.9 months) were reconstructed from computed tomography (CT) images. 29 anatomical landmarks were placed on the 3D skull reconstructions. Rotation, translation and size were removed, and all skull meshes were placed in dense correspondence using a dimensionless skull mesh template and a non-rigid iterative closest point algorithm. A 3D morphable model (3DMM) was created using principal component analysis, and intrinsically and geometrically validated with anthropometric measurements. Synthetic skull instances were generated exploiting the 3DMM and validated by comparison of the anthropometric measurements with the selected input population. RESULTS: The 3DMM of the paediatric skull 0–4 years was successfully constructed. The model was reasonably compact - 90% of the model shape variance was captured within the first 10 principal components. The generalisation error, quantifying the ability of the 3DMM to represent shape instances not encountered during training, was 0.47 mm when all model components were used. The specificity value was <0.7 mm demonstrating that novel skull instances generated by the model are realistic. The 3DMM mean shape was representative of the selected population (differences <2%). Overall, good agreement was observed in the anthropometric measures extracted from the selected population, and compared to normative literature data (max difference in the intertemporal distance) and to the synthetic generated cases. CONCLUSION: This study presents a reliable statistical shape model of the paediatric skull 0–4 years that adheres to known skull morphometric measures, can accurately represent unseen skull samples not used during model construction and can generate novel realistic skull instances, thus presenting a solution to limited availability of normative data in this field

Discovering Distinct Phenotypical Clusters in Heart Failure Across the Ejection Fraction Spectrum: a Systematic Review

Review Purpose: This systematic review aims to summarise clustering studies in heart failure (HF) and guide future clinical trial design and implementation in routine clinical practice. Findings: 34 studies were identified (n = 19 in HF with preserved ejection fraction (HFpEF)). There was significant heterogeneity invariables and techniques used. However, 149/165 described clusters could be assigned to one of nine phenotypes: 1) young, low comorbidity burden; 2) metabolic; 3) cardio-renal; 4) atrial fibrillation (AF); 5) elderly female AF; 6) hypertensive-comorbidity; 7) ischaemic-male; 8) valvular disease; and 9) devices. There was room for improvement on important methodological topics for all clustering studies such as external validation and transparency of the modelling process. Summary: The large overlap between the phenotypes of the clustering studies shows that clustering is a robust approach for discovering clinically distinct phenotypes. However, future studies should invest in a phenotype model that can be implemented in routine clinical practice and future clinical trial design. Graphical Abstract: HF = heart failure, EF = ejection fraction, HFpEF = heart failure with preserved ejection fraction, HFrEF = heart failure with reduced ejection fraction, CKD = chronic kidney disease, AF = atrial fibrillation, IHD = ischaemic heart disease, CAD = coronary artery disease, ICD = implantable cardioverter-defibrillator, CRT = cardiac resynchronization therapy, NT-proBNP = N-terminal pro b-type natriuretic peptide, BMI = Body Mass Index, COPD = Chronic obstructive pulmonary disease