Non-syndromic retinal dystrophy associated with biallelic variation of SUMF1 and reduced leukocyte sulfatase activity.

Biallelic variants in SUMF1 are associated with multiple sulfatase deficiency (MSD), a rare lysosomal storage disorder typically diagnosed in early infancy or childhood, marked by severe neurodegeneration and early mortality. We present clinical and molecular characterisation of three unrelated patients aged 13 to 58 years with milder clinical manifestations due to SUMF1 disease variants, including two adult patients presenting with apparent non-syndromic retinal dystrophy. Whole genome sequencing identified biallelic SUMF1 variants in all three patients; Patient 1 homozygous for a complex allele c.[290G>T;293T>A]; p.[(Gly97Val);(Val98Glu)], Patient 2 homozygous for c.866A>G; p.(Tyr289Cys), and Patient 3 compound heterozygous for c.726-1G>C and p.(Tyr289Cys). Electroretinography indicated a rod-cone dystrophy with additional possible inner retinal dysfunction in all three patients. Biochemical studies confirmed reduced, but not absent, sulfatase enzyme activity in the absence of extra-ocular disease (Patient 1) or only mild systemic disease (Patients 2, 3). These cases are suggestive that non-null SUMF1 genotypes can cause an attenuated clinical phenotype, including retinal dystrophy without systemic complications, in adulthood.

Clinical, biochemical and molecular analysis in a cohort of individuals with gyrate atrophy.

BACKGROUND: Gyrate atrophy of the choroid and retina is a rare autosomal recessive metabolic disorder caused by biallelic variants in the OAT gene, encoding the enzyme ornithine δ-aminotransferase. Impaired enzymatic activity leads to systemic hyperornithinaemia, which in turn underlies progressive chorioretinal degeneration. In this study, we describe the clinical and molecular findings in a cohort of individuals with gyrate atrophy. METHODS: Study participants were recruited through a tertiary UK clinical ophthalmic genetic service. All cases had a biochemical and molecular diagnosis of gyrate atrophy. Retrospective phenotypic and biochemical data were collected using electronic healthcare records. RESULTS: 18 affected individuals from 12 families (8 male, 10 female) met the study inclusion criteria. The median age at diagnosis was 8 years (range 10 months - 33 years) and all cases had hyperornithinaemia (median: 800 micromoles/L; range: 458-1244 micromoles/L). Common features at presentation included high myopia (10/18) and nyctalopia (5/18). Ophthalmic findings were present in all study participants who were above the age of 6 years. One third of patients had co-existing macular oedema and two thirds developed pre-senile cataracts. Compliance with dietary modifications was suboptimal in most cases. A subset of participants had extraocular features including a trend towards reduced fat-free mass and developmental delay. CONCLUSIONS: Our findings highlight the importance of multidisciplinary care in families with gyrate atrophy. Secondary ophthalmic complications such as macular oedema and cataract formation are common. Management of affected individuals remains challenging due to the highly restrictive nature of the recommended diet and the limited evidence-base for current strategies.

Clinical and genetic findings in TRPM1-related congenital stationary night blindness.

PURPOSE: Congenital stationary night blindness (CSNB) is a heterogeneous group of Mendelian retinal disorders that present in childhood. Biallelic variants altering the protein-coding region of the TRPM1 gene are one of the commonest causes of CSNB. Here, we report the clinical and genetic findings in 10 unrelated individuals with TRPM1-retinopathy. METHODS: Study subjects were recruited through a tertiary clinical ophthalmic genetic service at Manchester, UK. All participants underwent visual electrodiagnostic testing and panel-based genetic analysis. RESULTS: Study subjects had a median age of 8 years (range: 3-20 years). All probands were myopic and had electroretinographic findings in keeping with complete CSNB. Notably, three probands reported no night vision problems. Fourteen different disease-associated TRPM1 variants were detected. One individual was homozygous for the NM_001252024.2 (TRPM1):c.965 + 29G>A variant and a mini-gene assay highlighted that this change results in mis-splicing and premature protein termination. Additionally, two unrelated probands who had CSNB and mild neurodevelopmental abnormalities were found to carry a 15q13.3 microdeletion. This copy number variant encompasses seven genes, including TRPM1, and was encountered in the heterozygous state and in trans with a missense TRPM1 variant in each case. CONCLUSION: Our findings highlight the importance of comprehensive genomic analysis, beyond the exons and protein-coding regions of genes, for individuals with CSNB. When this characteristic retinal phenotype is accompanied by extraocular findings (including learning and/or behavioural difficulties), a 15q13.3 microdeletion should be suspected. Focused analysis (e.g. microarray testing) is recommended to look for large-scale deletions encompassing TRPM1 in patients with CSNB and neurodevelopmental abnormalities.

Impact of the Coronavirus (COVID-19) pandemic on surgical practice - Part 2 (surgical prioritisation).

The Coronavirus (COVID-19) Pandemic represents a once in a century challenge to human healthcare with over 4.5 million cases and over 300,000 deaths thus far. Surgical practice has been significantly impacted with all specialties writing guidelines for how to manage during this crisis. All specialties have had to triage the urgency of their daily surgical procedures and consider non-surgical management options where possible. The Pandemic has had ramifications for ways of working, surgical techniques, open vs minimally invasive, theatre workflow, patient and staff safety, training and education. With guidelines specific to each specialty being implemented and followed, surgeons should be able to continue to provide safe and effective care to their patients during the COVID-19 pandemic. In this comprehensive and up to date review we assess changes to working practices through the lens of each surgical specialty.

Impact of the Coronavirus (COVID-19) pandemic on surgical practice - Part 1.

The Coronavirus (COVID-19) pandemic has resulted in over 4.5 million confirmed cases and over 300,000 deaths. The impact of COVID-19 on surgical practice is widespread, ranging from workforce and staffing issues, procedural prioritisation, viral transmission risk intraoperatively, changes to perioperative practice and ways of working alongside the impact on surgical education and training. Whilst there has been a growing literature base describing the early clinical course of COVID-19 and on aspects of critical care related to treating these patients, there has been a dearth of evidence on how this pandemic will affect surgical practice. This paper seeks to review the current evidence and offers recommendations for changes to surgical practice to minimise the effect of the COVID-19 pandemic.

The socio-economic implications of the coronavirus pandemic (COVID-19): A review.

The COVID-19 pandemic has resulted in over 4.3 million confirmed cases and over 290,000 deaths globally. It has also sparked fears of an impending economic crisis and recession. Social distancing, self-isolation and travel restrictions have lead to a reduced workforce across all economic sectors and caused many jobs to be lost. Schools have closed down, and the need for commodities and manufactured products has decreased. In contrast, the need for medical supplies has significantly increased. The food sector is also facing increased demand due to panic-buying and stockpiling of food products. In response to this global outbreak, we summarise the socio-economic effects of COVID-19 on individual aspects of the world economy.

World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19).

An unprecedented outbreak of pneumonia of unknown aetiology in Wuhan City, Hubei province in China emerged in December 2019. A novel coronavirus was identified as the causative agent and was subsequently termed COVID-19 by the World Health Organization (WHO). Considered a relative of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), COVID-19 is caused by a betacoronavirus named SARS-CoV-2 that affects the lower respiratory tract and manifests as pneumonia in humans. Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 continues to rise, with 90,870 laboratory-confirmed cases and over 3,000 deaths worldwide. In response to this global outbreak, we summarise the current state of knowledge surrounding COVID-19.

Assessing the compliance of systematic review articles published in leading dermatology journals with the PRISMA statement guidelines: A systematic review.

BACKGROUND: Reporting quality of systematic reviews and meta-analyses is of critical importance in dermatology because of their key role in informing health care decisions. OBJECTIVE: To assess the compliance of systematic reviews and meta-analyses in leading dermatology journals with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement guidelines. METHODS: This review was carried out in accordance with PRISMA guidelines. Included studies were reviews published across 6 years in the top 4 highest-impact-factor dermatology journals of 2017. Records and full texts were screened independently. Data analysis was conducted with univariate multivariable linear regression. The primary outcome was to assess the compliance of systematic reviews and meta-analyses in leading dermatology journals with the PRISMA statement. RESULTS: A total of 166 studies were included and mean PRISMA compliance across all articles was 73%. Compliance significantly improved over time (ß = .016; P = <.001). The worst reported checklist item was item 5 (reporting on protocol existence), with a compliance of 15% of articles. CONCLUSION: PRISMA compliance within leading dermatology journals could be improved; however, it is steadily improving.

Percutaneous collagen induction (microneedling) for the management of non-atrophic scars: literature review.

INTRODUCTION: Percutaneous collagen induction (PCI) or needling techniques are increasingly popular in the reconstructive and aesthetic arena. The underlying mechanisms of action rest on producing a pattern of non-ablative and non-confluent puncture wound pattern to the dermis with a resulting regenerative effect to the skin. METHODS: A detailed English literature review was conducted using PubMed Medline, Embase and Web of Science; the manuscripts were appraised and classified according to level of evidence as well risk of bias. Results are presented in descending order of evidence for non-atrophic scars. DISCUSSION: On the basis of level 1 evidence currently available, the combination of needling and silicone gel can improve the short-term pliability, height and vascularity of hypertrophic and keloid scars. According to level 2 evidence, needling alongside spray keratinocytes can produce a statistically significant improvement to patient/observer scar ratings and improve pigmentation in hypopigmented burn scars at 12-month follow-up. Results from mixed cohort studies also point towards needling having a beneficial effect on fat graft retention. Level 3 data suggest that needling can render significant resurfacing effects to both mature and actively hypertrophic burn scars at 12-month follow-up based on objective scar scales; furthermore, favourable histological changes are seen, including better collagen alignment in the dermis and increased epidermal thickness. CONCLUSION: Needling techniques are promising adjuncts to non-atrophic scar management. Further research with long-term follow-up and comparative design protocols incorporating other resurfacing modalities is warranted before the exact value of needling is delineated in scar management protocols.

STROCSS 2019 Guideline: Strengthening the reporting of cohort studies in surgery.

INTRODUCTION: The STROCSS guideline was developed in 2017 to improve the reporting quality of observational studies in surgery. Building on its impact and usefulness, we sought to update the guidelines two years after its publication. METHODS: A steering group was formed to review the existing guideline and propose amendments to the 17-item checklist. A Delphi consensus exercise was utilised to determine agreement across a list of proposed modifications to the STROCSS 2017 guideline. An expert panel of 46 surgeons were invited to assess the proposed updates via Google Forms. RESULTS: The response rate was 91% (n = 42/46). High agreement was reached across all the items and the guideline was finalised in the first round. The checklist maintained 17-items, with modifications primarily considered to improve content and readability. CONCLUSIONS: The STROCSS 2019 guideline is hereby presented as a considered update to improve reporting of cohort, cross-sectional and case-control studies in surgery.