Hybrid Imaging in Head and Neck Sarcoidosis

To determine the prevalence of head and neck sarcoidosis (HNS) and evaluate the role of hybrid molecular imaging in HNS. Between 2010 and 2018, 222 patients with chronic sarcoidosis and presence of prolonged symptoms of active disease were referred to FDG PET/CT. Active disease was found in 169 patients, and they were all screened for the presence of HNS. All patients underwent MDCT and assessment of the serum ACE level. Follow-up FDG PET/CT examination was done 19.84 ± 8.98 months after the baseline. HNS was present in 38 out of 169 patients. FDG uptake was present in: cervical lymph nodes (38/38), submandibular glands (2/38), cerebrum (2/38), and bone (1/38). The majority of patients had more than two locations of disease. After FDG PET/CT examination, therapy was changed in most patients. Fourteen patients returned to follow-up FDG PET/CT examination in order to assess the therapy response. PET/CT revealed active disease in 12 patients and complete remission in two patients. Follow-up ACE levels had no correlation with follow-up SUVmax level (ρ = −0.18, p = 0.77). FDG PET/CT can be useful in the detection of HNS and in the evaluation of the therapy response. It may replace the use of non-purposive mounds of insufficiently informative laboratory and radiological procedures

The Prognostic Effect of Circadian Blood Pressure Pattern on Long-Term Cardiovascular Outcome is Independent of Left Ventricular Remodeling

We aimed to investigate the predictive value of 24 h blood pressure (BP) patterns on adverse cardiovascular (CV) outcome in the initially untreated hypertensive patients during long-term follow-up. This study included 533 initially untreated hypertensive patients who were involved in this study in the period between 2007 and 2012. All participants underwent laboratory analysis, 24 h BP monitoring, and echocardiographic examination at baseline. The patients were followed for a median period of nine years. The adverse outcome was defined as the hospitalization due to CV events (atrial fibrillation, myocardial infarction, myocardial revascularization, heart failure, stroke, or CV death). During the nine-year follow-up period, adverse CV events occurred in 85 hypertensive patients. Nighttime SBP, non-dipping BP pattern, LV hypertrophy (LVH), left atrial enlargement (LAE), and LV diastolic dysfunction (LV DD) were risk factors for occurrence of CV events. However, nighttime SBP, non-dipping BP pattern, LVH, and LV DD were the only independent predictors of CV events. When all four BP pattern were included in the model, non-dipping and reverse dipping BP patterns were associated with CV events, but only reverse-dipping BP pattern was independent predictor of CV events. The current study showed that reverse-dipping BP pattern was predictor of adverse CV events independently of nighttime SBP and LV remodeling during long-term follow-up. The assessment of BP patterns has very important role in the long-time prediction in hypertensive population

High-normal blood pressure, functional capacity and left heart mechanics: is there any connection?

Objective. To evaluate the relationship between functional capacity and left ventricular (LV) and left atrial (LA) myocardial deformation, assessed by two- and three-dimensional (2DE and 3DE) strain analysis, in subjects with high-normal blood pressure (BP). Methods. This cross-sectional study included 64 subjects with optimal BP and 75 subjects with high-normal BP of similar gender and age. All the subjects underwent a complete 2DE and 3DE examination and cardiopulmonary exercise testing. Results. 3DE global longitudinal strain was significantly lower in the group with high-normal BP than in the optimal BP group (- 20.1 ± 2.4 vs - 18.5 ± 2.3%, p < 0.001). Similar results were obtained for 3DE global circumferential strain (- 21.8 ± 2.6 vs - 19.3 ± 2.4%, p < 0.001), as well as for 3DE global radial strain (45.1 ± 8.8 vs 42.3 ± 7.2%, p = 0.042), and 3DE global area strain (- 30.1 ± 4.2 vs - 28.1 ± 3.8%, p < 0.001). LV twist was similar between the observed groups, whereas untwisting rate was significantly decreased in the subjects with high-normal BP (- 123 ± 30 vs - 112 ± 26°/s, p = 0.023). Peak VO2 was significantly lower in the high-normal BP group (30.8 ± 4 vs 28.3 ± 3.7 ml/kg/min, p < 0.001). 2DE LV ejection fraction (β = 0.38, p = 0.014), 2DE global longitudinal strain (β = 0.35, p = 0.019) and 3DE global longitudinal strain (β = 0.27, p = 0.042) were independently associated with peak VO2. Conclusion. LV and LA mechanics, as well as functional capacity are significantly impaired in the subjects with high-normal BP. LV and LA myocardial deformations are associated with peak oxygen uptake

Social and Emotional Education - Building inclusive schools and ownership of values - Programme of activities

Young people need to have a balanced set of cognitive, social and emotional competences in order to help them navigate successfully through the developmental tasks, situational challenges, and transitions they are set to face in their pathway to adulthood

Not to Miss: Intronic Variants, Treatment, and Review of the Phenotypic Spectrum in VPS13D-Related Disorder

VPS13D is one of four human homologs of the vacuolar sorting protein 13 gene (VPS13). Biallelic pathogenic variants in the gene are associated with spastic ataxia or spastic paraplegia. Here, we report two patients with intronic pathogenic variants: one patient with early onset severe spastic ataxia and debilitating tremor, which is compound-heterozygous for a canonical (NM_018156.4: c.2237−1G &gt; A) and a non-canonical (NM_018156.4: c.941+3G&gt;A) splice site variant. The second patient carries the same non-canonical splice site variant in the homozygous state and is affected by late-onset spastic paraplegia. We confirmed altered splicing as a result of the intronic variants and demonstrated disturbed mitochondrial integrity. Notably, tremor in the first patient improved significantly by bilateral deep brain stimulation (DBS) in the ventralis intermedius (VIM) nucleus of the thalamus. We also conducted a literature review and summarized the phenotypical spectrum of reported VPS13D-related disorders. Our study underscores that looking for mutations outside the canonical splice sites is important not to miss a genetic diagnosis, especially in disorders with a highly heterogeneous presentation without specific red flags

Detection of duodenal villous atrophy on endoscopic images using a deep learning algorithm

Background and aims Celiac disease with its endoscopic manifestation of villous atrophy is underdiagnosed worldwide. The application of artificial intelligence (AI) for the macroscopic detection of villous atrophy at routine esophagogastroduodenoscopy may improve diagnostic performance. Methods A dataset of 858 endoscopic images of 182 patients with villous atrophy and 846 images from 323 patients with normal duodenal mucosa was collected and used to train a ResNet 18 deep learning model to detect villous atrophy. An external data set was used to test the algorithm, in addition to six fellows and four board certified gastroenterologists. Fellows could consult the AI algorithm’s result during the test. From their consultation distribution, a stratification of test images into “easy” and “difficult” was performed and used for classified performance measurement. Results External validation of the AI algorithm yielded values of 90 %, 76 %, and 84 % for sensitivity, specificity, and accuracy, respectively. Fellows scored values of 63 %, 72 % and 67 %, while the corresponding values in experts were 72 %, 69 % and 71 %, respectively. AI consultation significantly improved all trainee performance statistics. While fellows and experts showed significantly lower performance for “difficult” images, the performance of the AI algorithm was stable. Conclusion In this study, an AI algorithm outperformed endoscopy fellows and experts in the detection of villous atrophy on endoscopic still images. AI decision support significantly improved the performance of non-expert endoscopists. The stable performance on “difficult” images suggests a further positive add-on effect in challenging cases

EIF2AK2 Missense Variants Associated with Early Onset Generalized Dystonia

Objective: The study was undertaken to identify a monogenic cause of early onset, generalized dystonia. Methods: Methods consisted of genome-wide linkage analysis, exome and Sanger sequencing, clinical neurological examination, brain magnetic resonance imaging, and protein expression studies in skin fibroblasts from patients. Results: We identified a heterozygous variant, c.388G&gt;A, p.Gly130Arg, in the eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2) gene, segregating with early onset isolated generalized dystonia in 5 patients of a Taiwanese family. EIF2AK2 sequencing in 191 unrelated patients with unexplained dystonia yielded 2 unrelated Caucasian patients with an identical heterozygous c.388G&gt;A, p.Gly130Arg variant, occurring de novo in one case, another patient carrying a different heterozygous variant, c.413G&gt;C, p.Gly138Ala, and one last patient, born from consanguineous parents, carrying a third, homozygous variant c.95A&gt;C, p.Asn32Thr. These 3 missense variants are absent from gnomAD, and are located in functional domains of the encoded protein. In 3 patients, additional neurological manifestations were present, including intellectual disability and spasticity. EIF2AK2 encodes a kinase (protein kinase R [PKR]) that phosphorylates eukaryotic translation initiation factor 2 alpha (eIF2α), which orchestrates the cellular stress response. Our expression studies showed abnormally enhanced activation of the cellular stress response, monitored by PKR-mediated phosphorylation of eIF2α, in fibroblasts from patients with EIF2AK2 variants. Intriguingly, PKR can also be regulated by PRKRA (protein interferon-inducible double-stranded RNA-dependent protein kinase activator A), the product of another gene causing monogenic dystonia. Interpretation: We identified EIF2AK2 variants implicated in early onset generalized dystonia, which can be dominantly or recessively inherited, or occur de novo. Our findings provide direct evidence for a key role of a dysfunctional eIF2α pathway in the pathogenesis of dystonia. ANN NEUROL 2021;89:485–497.</p

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks