Supporting positive patient experiences for rare disease care during disruptive times: findings from a national study

Aim: We describe the perceptions and experiences of healthcare services during the pandemic of those newly diagnosed with a rare, chronic eye disorder. Methods: A cross-sectional mixed-methods study nested within a multi-center inception cohort study. Participants were UK families and adolescents newly affected by childhood uveitis. Using a validated tool (Health Foundation COVID-19 Survey), we captured quantitative (analyzed using descriptive statistics) and qualitative (analyzed using content and thematic analysis) data. Results: Responses received from 60 families (September 2020–March 2022), of whom 92% felt comfortable accessing healthcare services, despite 40% reporting challenges in accessing medication. Thematic analysis identified five themes: the value of protected spaces; the positive role of digital health tools, negative experience of immature telemedicine, disintegration of care; and dealing with uncertainty. Conclusion: Our findings will support ongoing developments in care with an aim to making services more robust to future periods of disruption

The Role of Intrinsically Unstructured Proteins in Neurodegenerative Diseases

The number and importance of intrinsically disordered proteins (IUP), known to be involved in various human disorders, are growing rapidly. To test for the generalized implications of intrinsic disorders in proteins involved in Neurodegenerative diseases, disorder prediction tools have been applied to three datasets comprising of proteins involved in Huntington Disease (HD), Parkinson's disease (PD), Alzheimer's disease (AD). Results show, in general, proteins in disease datasets possess significantly enhanced intrinsic unstructuredness. Most of these disordered proteins in the disease datasets are found to be involved in neuronal activities, signal transduction, apoptosis, intracellular traffic, cell differentiation etc. Also these proteins are found to have more number of interactors and hence as the proportion of disorderedness (i.e., the length of the unfolded stretch) increased, the size of the interaction network simultaneously increased. All these observations reflect that, “Moonlighting” i.e. the contextual acquisition of different structural conformations (transient), eventually may allow these disordered proteins to act as network “hubs” and thus they may have crucial influences in the pathogenecity of neurodegenerative diseases

2. Pathways to detection of non-infectious childhood uveitis in the UK: findings from the UNICORN cohort study

Introduction Prompt detection of childhood uveitis is key to minimising negative impact. From an internationally unique inception cohort, we report pathways to disease detection. UNICORNS is a national childhood non-infectious uveitis study with longitudinal collection of a standardised clinical dataset and patient reported outcomes. Descriptive analysis of baseline characteristics are reported. Amongst 150 recruited children (51% female, 31% non-white ethnicity) age at detection ranged from 2–18yrs (median 10). In 69%, uveitis was diagnosed following onset of symptoms: time from first symptoms to uveitis detection ranged from 0-739days (median 7days), with longer time to detection for those presenting initially to their general practitioner. Non symptomatic children were detected through JIA/other disease surveillance (16%), routine optometry review (5%) or child visual health screening (1%). Commonest underlying diagnoses at uveitis detection were JIA (17%), TINU (9%, higher than pre-pandemic reported UK disease frequency) and sarcoid (1%). 60% had no known systemic disease at uveitis detection. At disease detection, in at least one eye: 34% had structural complications (associated with greater time to detection – 17 days versus 4 days for uncomplicated presentation). The larger relative proportions of children with non-JIA uveitis reported here increase the importance of improving awareness of childhood uveitis amongst the wider clinical communities. There is scope for improvement of pathways to detection. Forthcoming analysis on the full cohort (251 recruited to date across 33 hospitals and 4 nations) will provide nationally representative data on management and the determinants of visual and broader developmental/well-being outcomes

Genetic and molecular pathogenesis of Parkinson's disease

Parkinson's disease (PD), a common progressive degenerative disease of the central nervous system, affects about 1% of adults aged older than 60 years. PD is characterized by rigidity, tremor, postural instability and bradykinesia, and is attributed to selective degeneration of the nigrostriatal dopaminergic neurons. Recent studies indicate the presence of both genetic and environmental factors in the pathogenesis of PD. While PD is usually sporadic, familial PD cases have been reported, following mostly a Mendelian pattern of inheritance (autosomal dominant or recessive pattern). Six genes have been implicated so far in the pathogenesis of PD (α-synuclein, parkin, UCH-L1, DJ-I, PINK1, and LRRK2), and additional genetic loci are currently under investigation. The proteins encoded by the first three genes are closely related to proteasome function, either as components of the ubiquitin-proteasome system (UPS) function (parkin and UCH-L1) or as degradable substrates (α-synuclein), thereby implicating aberrations in UPS function and protein aggregation as causative events in the pathogenesis of PD. This review describes the genetics and molecular pathogenesis of PD, emphasizing the role of UPS and α-synuclein and commenting on the role of Lewy bodies, the pathological hallmark in sporadic forms and in the majority of inherited forms of PD. Identification of underlying pathogenic mechanisms in PD opens a new era in drug design and intervention

Sphenoid sinus aspergilloma with sixth nerve palsy

[No abstract available

Microcirculation-guided treatment improves tissue perfusion and hemodynamic coherence in surgical patients with septic shock

Purpose: Severe sepsis and septic shock may impair microcirculatory perfusion and cause organ dysfunction. The aim of this pilot study was to assess a new microcirculation-guided resuscitation strategy in patients with septic shock undergoing emergency abdominal surgery. Methods: A microcirculation-guided treatment algorithm was developed and applied intraoperatively following restoration of systemic hemodynamics. Sublingual microcirculation was monitored with Sidestream DarkField (SDF +) imaging technique. The primary objective was to investigate the change in De Backer score, Consensus Proportion of Perfused Vessels (Consensus PPV), and Consensus PPV (small) and its association with venous-to-arterial carbon dioxide difference (v-aPCO2). Results: Thirteen consecutive patients were included in the study. Microcirculation-guided resuscitation resulted in an increase of 0.49 mm−1 in the De Backer score (p < 0.001), an increase of 2.28% in the Consensus PPV (p < 0.001), and an increase of 2.26% in the Consensus PPV (small) (p < 0.001) for every 30 min of additional intraoperative time. All microcirculation variables were negatively correlated with v-aPCO2 (rho = − 0.656, adj-p < 0.001; rho = − 0.623; adj-p < 0.001; rho = − 0.597, adj-p < 0.001, respectively) at each intraoperative time point. Lactate levels were negatively correlated with Consensus PPV (rho = − 0.464; adj-p = 0.002) and Consensus PPV (small) (rho = − 0.391, adj-p < 0.001). Survival at 30 days, 90 days, and 1 year were 76.9%, 76.9%, and 61.5%, respectively. Conclusions: The intraoperative use of microcirculation-guided resuscitation strategy may improve tissue perfusion and hemodynamic coherence in patients with septic shock. © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany

2 Pathways to detection of non-infectious childhood uveitis in the UK: findings from the UNICORN cohort study

Introduction Prompt detection of childhood uveitis is key to minimising negative impact. From an internationally unique inception cohort, we report pathways to disease detection. UNICORNS is a national childhood non-infectious uveitis study with longitudinal collection of a standardised clinical dataset and patient reported outcomes. Descriptive analysis of baseline characteristics are reported. Amongst 150 recruited children (51% female, 31% non-white ethnicity) age at detection ranged from 2–18yrs (median 10). In 69%, uveitis was diagnosed following onset of symptoms: time from first symptoms to uveitis detection ranged from 0-739days (median 7days), with longer time to detection for those presenting initially to their general practitioner. Non symptomatic children were detected through JIA/other disease surveillance (16%), routine optometry review (5%) or child visual health screening (1%). Commonest underlying diagnoses at uveitis detection were JIA (17%), TINU (9%, higher than pre-pandemic reported UK disease frequency) and sarcoid (1%). 60% had no known systemic disease at uveitis detection. At disease detection, in at least one eye: 34% had structural complications (associated with greater time to detection – 17 days versus 4 days for uncomplicated presentation). The larger relative proportions of children with non-JIA uveitis reported here increase the importance of improving awareness of childhood uveitis amongst the wider clinical communities. There is scope for improvement of pathways to detection. Forthcoming analysis on the full cohort (251 recruited to date across 33 hospitals and 4 nations) will provide nationally representative data on management and the determinants of visual and broader developmental/well-being outcomes