People withdrew from PT in relation to life stages and reasons that are unknown. Our findings emphasise the importance of: (i) adherence to internationally recommended guidelines for PT; (ii) the role of the multidisciplinary team in risk minimisation; and (iii) patient selection.
Background: The prognosis of malignant pleural mesothelioma has traditionally been poor. Whether this remains the case compared to historical data and within a specific geographical location is uncertain. Knowledge of predictive factors for survival with malignant pleural mesothelioma is also inadequate. Methods: We conducted a retrospective local database analysis to determine overall prognosis of patients with malignant pleural mesothelioma and evaluate the influence of demographic characteristics, histological subtype and laboratory parameters. Patients with histological diagnoses of malignant pleural mesothelioma held on the NHS Grampian pathology database between 2002 and 2012 were analysed. Data on baseline demographics, mode of diagnosis, histological sub-type, and survival and serum laboratory parameters, were analysed; time to death was examined using Cox regression analyses. Results: A total of 114 patients with malignant pleural mesothelioma were included in the analysis. The median survival was 345 days (IQR 99-600). Sarcomatoid malignant pleural mesothelioma carried a significantly worse prognosis with median survival of 125 days (IQR 44-289) vs 334 days (IQR 126-715) for biphasic, 412 days (IQR 201-656) for epithelioid and 345 days (IQR 99-600) for those with no definitive typing. Individuals who did not receive chemotherapy experienced a significantly worse prognosis (hazard ratio 2.7; 95%CI 1.5-4.7; p = 0.001), while a low albumin and raised urea at time of diagnosis were also associated with a significantly poorer prognosis. Conclusion:The survival of patients with malignant pleural mesothelioma remains poor and typically around 1 year. The presence of raised urea and low albumin is associated with a poorer prognosis, while patients with a good performance status and few co-morbidities should be encouraged to receive chemotherapy.
NHS genetics centres in Scotland sought to investigate the Genomics England 100,000 Genomes Project diagnostic utility to evaluate genome sequencing for in rare, inherited conditions. Four regional services recruited 999 individuals from 394 families in 200 rare phenotype categories, with negative historic genetic testing. Genome sequencing was performed at Edinburgh Genomics, and phenotype and sequence data were transferred to Genomics England for variant calling, gene-based filtering and variant prioritisation. NHS Scotland genetics laboratories performed interpretation, validation and reporting. New diagnoses were made in 23% cases – 19% in genes implicated in disease at the time of variant prioritisation, and 4% from later review of additional genes. Diagnostic yield varied considerably between phenotype categories and was minimal in cases with prior exome testing. Genome sequencing with gene panel filtering and reporting achieved improved diagnostic yield over previous historic testing but not over now routine trio-exome sequence tests. Re-interpretation of genomic data with updated gene panels modestly improved diagnostic yield at minimal cost. However, to justify the additional costs of genome vs exome sequencing, efficient methods for analysis of structural variation will be required and / or cost of genome analysis and storage will need to decrease.
Andersen Tawil Syndrome (ATS) is a neurological channelopathy caused by mutations in the KCNJ2 gene that encodes the ubiquitously expressed Kir2.1 potassium channel. The syndrome is characterised by episodic weakness, cardiac arrythmias and dysmorphic features. However, the full extent of the multi-system phenotype is not well described. In-depth, multi-system phenotyping is required to inform diagnosis, and guide management. We report our findings following deep multimodal phenotyping across all systems in a large case series of 69 total patients, with comprehensive data for 52. As a national referral centre, we assessed point prevalence and showed it is higher than previously reported, at 0.105 per 100 000 population in England. While the classical phenotype of episodic weakness is recognised, we found that a quarter of our cohort have fixed myopathy and 13.5% required a wheelchair or gait aid. We identified frequent fatty infiltration on MRI and tubular aggregates on muscle biopsy emphasising the active myopathic process underpinning the potential for severe neuromuscular disability. Long exercise testing (LET) was not reliable in predicting neuromuscular symptoms. A normal LET was seen in five patients of whom four had episodic weakness. 67% of patients treated with acetazolamide reported a good neuromuscular response. 13% of the cohort required cardiac defibrillator or pacemaker insertion. An additional 23% reported syncope. Baseline electrocardiograms were not helpful in stratifying cardiac risk, but holter monitoring was. A subset of patients had no cardiac symptoms, but had abnormal holter monitor recordings which prompted medication treatment. We describe the utility of loop recorders to guide management in two such asymptomatic patients. Micrognathia was the most commonly reported skeletal feature, however 8% of patients did not have dysmorphic features and one third of patients had only mild dysmorphic features. We describe novel phenotypic features including abnormal echocardiogram in nine patients, prominent pain, fatigue and fasciculations. Five patients exhibited executive dysfunction and slowed processing which may be linked to central expression of KCNJ2. We report eight new KCNJ2 variants with in vitro functional data. Our series illustrates that ATS is not benign. We report marked neuromuscular morbidity and cardiac risk with multi-system involvement. Our key recommendations include proactive genetic screening of all family members of a proband. This is required, given the risk of cardiac arrhythmias among asymptomatic individuals, and a significant subset of ATS patients have no (or few) dysmorphic features or negative LET. We discuss recommendations for increased cardiac surveillance and neuropsychometry testing.
Paediatric neurology syndromes are a broad and complex group of conditions with a large spectrum of clinical phenotypes. Joubert syndrome is a genetically heterogeneous neurological ciliopathy syndrome with molar tooth sign as the neuroimaging hallmark. We reviewed the clinical, radiological and genetic data for several families with a clinical diagnosis of Joubert syndrome but negative genetic analysis. We detected biallelic pathogenic variants in LAMA1, including novel alleles, in each of the four cases we report, thereby establishing a firm diagnosis of Poretti-Boltshauser syndrome. Analysis of brain MRI revealed cerebellar dysplasia and cerebellar cysts, associated with Poretti-Boltshauser syndrome and the absence of typical molar tooth signs. Using large UK patient cohorts, the relative prevalence of Joubert syndrome as a cause of intellectual disability was 0.2% and of Poretti-Boltshauser syndrome was 0.02%. We conclude that children with congenital brain disorders that mimic Joubert syndrome may have a delayed diagnosis due to poor recognition of key features on brain imaging and the lack of inclusion of LAMA1 on molecular genetic gene panels. We advocate the inclusion of LAMA1 genetic analysis on all intellectual disability and Joubert syndrome gene panels and promote a wider awareness of the clinical and radiological features of these syndromes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.