Biallelic variants in CEP164 cause a motile ciliopathy-like syndrome.

Ciliopathies may be classed as primary or motile depending on the underlying ciliary defect and are usually considered distinct clinical entities. Primary ciliopathies are associated with multisystem syndromes typically affecting the brain, kidney, and eye, as well as other organ systems such as the liver, skeleton, auditory system, and metabolism. Motile ciliopathies are a heterogenous group of disorders with defects in specialised motile ciliated tissues found within the lung, brain, and reproductive system, and are associated with primary ciliary dyskinesia, bronchiectasis, infertility and rarely hydrocephalus.

Case Report and Literature Review of Giant Cutaneous Malignant Melanoma: What's Keeping Patients Away?

Giant cutaneous malignant melanoma (MM) is a term that has previously been used to define lesions that are at least 10 cm in diameter or 48 mm in thickness. Such tumours are rare. There is no substantial body of evidence considering why patients may delay presentation with MM until they reach this size.

Analysis of Fibroblast Growth Factor 14 (FGF14) structural variants reveals the genetic basis of the early onset nystagmus locus NYS4 and variable ataxia.

Nystagmus (involuntary, rhythmical eye movements) can arise due to sensory eye defects, in association with neurological disorders or as an isolated condition. We identified a family with early onset nystagmus and additional neurological features carrying a partial duplication of FGF14, a gene associated with spinocerebellar ataxia type 27 (SCA27) and episodic ataxia. Detailed eye movement analysis revealed oculomotor anomalies strikingly similar to those reported in a previously described four-generation family with early onset nystagmus and linkage to a region on chromosome 13q31.

Endoscope-assisted Surgical Removal of an Ectopic Wisdom Tooth Below Lower Border of the Mandible - A Case Report.

The Rationale: Presentation of a case where using an endoscope aided the removal of a significantly displaced mandibular third molar.

Patient Concerns: Pain and infection associated with the ectopic wisdom tooth, increased risks with conventional surgical removal.

Diagnosis: Chronic infection associated with the displaced, ectopic left lower third molar (LL8).

Bladder tumor Resection Weight as a Prognostic Factor for Recurrence and Progression in Patients With High-Risk Non-Muscle Invasive Bladder Treated With BCG.

Introduction: Predicting outcomes of patients with high-risk non-muscle invasive bladder cancer (HR-NMIBC) is critical. Here, we evaluate whether bladder tumor resection weight might serve as a prognostic factor for recurrence and progression of HR-NMIBC patients treated with Bacillus Calmette-Guérin (BCG).

Methods: In this retrospective, single-centre study in the UK, we analysed a consecutive cohort of HR-NMIBC patients who have received adequate intravesical BCG immunotherapy between 2009 and 2019.

Pigmentary anomaly caused by mosaic 3q22.2q29 duplication.

A 39-year-old woman sought advice regarding potential risks to her offspring due to previous possible diagnosis of incontinentia pigmenti. She had linear hyperpigmentation along the lines of Blaschko affecting the upper and lower limbs, and skin-coloured papules on the left palm. Ophthalmoscopy revealed hypopigmented spots in the macular region of the retina in each eye due to focal areas of depigmentation of the retinal pigment epithelium.

The Effect of a Brief Physician-Delivered Neurobiologically Oriented, Cognitive Behavioural Therapy (Brief-CBT) Intervention on Chronic Pain Acceptance in Youth with Chronic Pain-A Randomized Controlled Trial.

At the Stollery Children’s Chronic Pain Clinic, new referrals are assessed by an interdisciplinary team. The final part of the intake assessment typically involves an explanation and compassionate validation of the etiology of chronic pain and an invitation to the youth to attend the group outpatient Cognitive Behavioural Therapy (CBT) program, called Pain 101, or to individual outpatient CBT. It was hypothesized that a brief physician-delivered CBT (brief-CBT) intervention at first point of contact improves subsequent pain acceptance.

Adjuvant Intravesical Chemohyperthermia Versus Passive Chemotherapy in Patients with Intermediate-risk Non-muscle-invasive Bladder Cancer (HIVEC-II): A Phase 2, Open-label, Randomised Controlled Trial.

Background: Adjuvant intravesical chemotherapy following tumour resection is recommended for intermediate-risk non-muscle-invasive bladder cancer (NMIBC).

Objective: To assess the efficacy and safety of adjuvant intravesical chemohyperthermia (CHT) for intermediate-risk NMIBC.

Design, Setting, And Participants: HIVEC-II is an open-label, phase 2 randomised controlled trial of CHT versus chemotherapy alone in patients with intermediate-risk NMIBC recruited at 15 centres between May 2014 and December 2017 (ISRCTN 23639415).

Continuous pressure monitoring of inpatient spinal cord injured patients: implications for pressure ulcer development.

Study Design: Cohort observational study.

Objectives: To examine the movement profiles of individuals with spinal cord injury (SCI) during their inpatient rehabilitative phase using continuous pressure monitoring (CPM), evaluating the trends in those with skin damage.

Setting: SCI specialist rehabilitation centre in the United Kingdom.

Pregnancy and neonatal outcomes of COVID-19: The PAN-COVID study.

Objective: To assess perinatal outcomes for pregnancies affected by suspected or confirmed SARS-CoV-2 infection.

Methods: Prospective, web-based registry. Pregnant women were invited to participate if they had suspected or confirmed SARS-CoV-2 infection between 1st January 2020 and 31st March 2021 to assess the impact of infection on maternal and perinatal outcomes including miscarriage, stillbirth, fetal growth restriction, pre-term birth and transmission to the infant.

A systematic analysis of splicing variants identifies new diagnoses in the 100,000 Genomes Project.

Background: Genomic variants which disrupt splicing are a major cause of rare genetic diseases. However, variants which lie outside of the canonical splice sites are difficult to interpret clinically. Improving the clinical interpretation of non-canonical splicing variants offers a major opportunity to uplift diagnostic yields from whole genome sequencing data.

A comparison of hemiarthroplasty versus dynamic hip screw fixation for intertrochanteric femoral fractures: a systematic review.

Introduction: Intertrochanteric fractures are predominantly treated by dynamic hip screw (DHS) fixation. However, recent evidence has found acceptable clinical results following hemiarthroplasty for these fractures. Thus, a systematic review was conducted to compare hemiarthroplasty with DHS fixation for intertrochanteric fractures.

Symptom control in advanced chronic liver disease: integrating anticipatory palliative and supportive care.

The number of patients coming to hospital with liver disease is increasing. There was a worrying trend before the pandemic, and this has intensified. Despite improvements in the management of patients with advanced cirrhosis many patients will die within 6-12 months of first presentation, and, despite this, the field of palliative and supportive care in liver disease is still in its infancy.

Reclassification of clinically-detected sequence variants: Framework for genetic clinicians and clinical scientists by CanVIG-UK (Cancer Variant Interpretation Group UK).

Purpose: Variant classifications may change over time, driven by emergence of fresh or contradictory evidence or evolution in weighing or combination of evidence items. For variant classifications above the actionability threshold, which is classification of likely pathogenic or pathogenic, clinical actions may be irreversible, such as risk-reducing surgery or prenatal interventions. Variant reclassification up or down across the actionability threshold can therefore have significant clinical consequences.

Optimising the use of cell salvage in revision hip arthroplasty.

Background: Intraoperative cell salvage is an established method to reduce the requirement for and the volume of allogenic blood transfusion but adds to the financial cost of performing surgery.

Aims: The primary aim of this study was to determine which patients and what type of revision hip surgery benefit most from intraoperative cell salvage.

Methods: This observational study included patients who underwent revision hip surgery performed by the senior author at a single orthopaedic unit.

Ongoing Challenges in the Diagnosis of 11p15.5-Associated Imprinting Disorders.

The overgrowth disorder Beckwith-Wiedemann syndrome and the growth restriction disorder Silver-Russell syndrome have been described as 'mirror' syndromes, in both their clinical features and molecular causes. Clinically, their nonspecific features, focused around continuous variables of atypical growth, make it hard to set diagnostic thresholds that are pragmatic without potentially excluding some cases. Molecularly, both are imprinting disorders, classically associated with 'opposite' genetic and epigenetic changes to genes on chromosome 11p15, but both are associated with somatic mosaicism as well as an increasing range of alternative (epi)genetic changes to other genes, which make molecular diagnosis an increasingly complex process.

Generation of a Cone Photoreceptor-specific GNGT2 Reporter Line in Human Pluripotent Stem Cells.

Fluorescent reporter lines generated in human pluripotent stem cells are a highly useful tool to track, isolate, and analyze cell types and lineages in live cultures. Here, we generate the first human cone photoreceptor reporter cell line by CRISPR/Cas9 genome editing of a human embryonic stem cell (hESC) line to tag both alleles of the Guanine nucleotide-binding protein subunit gamma-T2 (GNGT2) gene with a mCherry reporter cassette. Three-dimensional optic vesicle-like structures were produced to verify reporter fidelity and track cones throughout their development in culture.

Early experience of a local pathway on the waiting time for MRI in patients presenting to a UK district general hospital with suspected cauda equina syndrome.

Aim: This study evaluated the impact of the Salisbury Protocol for Assessment of Cauda Equina Syndrome (SPACES) on the waiting time for MRI in patients presenting with suspected Cauda Equina Syndrome (sCES) within a UK district general hospital.

Patients And Methods: All consecutive patients undergoing an MRI scan in our hospital, for sCES, over a 12 month period, prior to and following the introduction of SPACES, were identified. Patient's gender, age, MRI diagnosis, time from MRI request to imaging and outcome were recorded.