Hinchingbrooke Hospital

PurposeTo investigate the impact of central serous chorioretinopathy on sleep and mood in patients with acute and chronic central serous chorioretinopathy.MethodsThis cross-sectional study compared sleep and mood differences between central serous chorioretinopathy and control patients recruited from Ophthalmology clinics at the John Radcliffe Hospital, Oxford between 2012 and 2020. Data including visual acuity, type of central serous chorioretinopathy (acute or chronic; aCSC/cCSC), sex, and chronotype were obtained. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI); the Hospital Anxiety and Depression Scale (HADS) was used to evaluate anxiety (HADS-A) and depression (HADS-D).ResultsA total of 247 age matched controls and 109 patients with central serous chorioretinopathy participated. There were no significant differences in PSQI or HADs (P > 0.05) between the two groups. Females exhibited significantly higher PSQI scores than males both for control and central serous chorioretinopathy groups (P < 0.05). Within the central serous chorioretinopathy group, 88 (81%) had chronic central serous chorioretinopathy and 21 (19%) had acute central serous chorioretinopathy, and an increase in daytime dysfunction was seen in the acute phenotype compared to chronic (P = 0.018).ConclusionIn our study, no significant differences in sleep quality or mood scores were identified in central serous chorioretinopathy patients, when compared to controls. Worsened sleep for females was present when compared to males, both in central serous chorioretinopathy and control groups. Within central serous chorioretinopathy groups, worsened daytime function was observed in acute versus chronic – a larger study would help distinguish the effect of chronicity on sleep.

IntroductionSarcoidosis is a rare disease primarily affecting the pulmonary system in approximately 90% of cases. (1) Cutaneous involvement occurs in 20-35% of sarcoidosis patients and can present without systemic manifestations (2). The skin is the second most commonly affected organ after the lungs in sarcoidosis (3).Clinical CaseWe report a unique case of cutaneous sarcoidosis presenting with asymptomatic hypercalcemia. An 81-year-old White British woman with a medical history of type 2 diabetes mellitus, anemia, hypertension, and polymyalgia rheumatica (PMR) was managed for left leg cellulitis. Examination revealed a systolic murmur, clear chest, bilateral erythema, raised temperature, and pitting edema at the infection site. An admission chest x-ray showed a known large hiatus hernia. Routine blood tests revealed adjusted calcium levels of 3.52 mmol/L (2.20-2.60 mmol/L), and PTH levels were low at 0.9 pmol/L (1.6-6.9 pmol/L), indicating PTH-independent hypercalcemia.Further blood tests showed normal vitamin D (129nmol/L, n>50nmol/L), ACE levels (<5 IU/L), and thyroid funct,on tests (TSH 7.17mU/L, n0.30-4.20mU/L, T4 15.6pmol/L, n11.9-21.6pmol/L, TPO antibody<10IU/mL, n0-34). Myeloma screen (no monoclonal bands, Serum Kappa Free Light Chain:31.03 mg/L,n 3.30 - 19.40; Serum Lambda Free Light Chain:22.57 mg/L,n:5.71 - 26.30) and autoimmune screens (IgG:7.8 g/L,n:6.0 - 16.0; IgA:1.26 g/L,n:0.80 - 4.00; IgM*0.41 g/L,n:0.50 - 2.00) were negative. Elevated 1,25-dihydroxy vitamin D (calcitriol) was noted at 246 pmol/L. Occult malignancy was ruled out via normal CT chest, abdomen, and pelvis, gastroscopy with biopsy, and CT head scans. Initial PET CT results were reported as normal.Hypercalcemia management included intravenous fluids, zoledronic acid, denosumab, steroids, and cinacalcet. Subsequent detailed PET CT report revealed extensive moderate FDG uptake in the subcutaneous tissue of both arms. Physical examination identified subcutaneous nodules, and histology confirmed a florid dermal non-necrotizing granulomatous reaction, diagnosing extra-pulmonary cutaneous sarcoidosis.Interestingly, the patient had been on long-term prednisolone (10 mg) for PMR, recently reduced to 4 mg prior to admission. Her calcium levels normalized (2.57 mmol/L) after weaning off prednisolone.ConclusionHypercalcemia in cutaneous sarcoidosis without pulmonary involvement is rare. Long-term follow-up is essential, as patients with cutaneous sarcoidosis may develop systemic involvement. She was referred to pulmonary and dermatology specialists for further evaluation.

Whether endothelium derived Nitric Oxide (NO) uptake by the blood is limited by a boundary layer, the red cell membrane or its interior is the subject of continued debate. Whether lung uptake of NO in the single-breath DLNO test is limited by blood or not is also debated. To understand which processes are limiting blood NO uptake we have modelled NO chemical kinetics and we have derived a shrinking core model, Thiele Modulus and FTCS (Euler) numerical solution. In a rapid reaction apparatus, NO uptake appears limited by a boundary layer, and throughout the red cell, by diffusion. In the single breath situation, and arguably with endogenous NO in vivo, NO uptake appears limited by a boundary layer and a pseudo first order chemical reaction in the outer molecular layers of the red cell. We have not found evidence to support red cell membrane limitation.

Abstract Introduction: Identification of Molecular Residual Disease (MRD) in patients with breast cancer with circulating tumor DNA (ctDNA) presents a strategy to identify patients at high risk of relapse. Approaches that detect ctDNA at lower concentrations are required to increase sensitivity and improve on the lead time between ctDNA detection and clinical relapse. Here we present results using novel highly sensitive tumor-informed sequencing assays for ctDNA detection of MRD based on detection of multiple patient specific mutations in ctDNA. Methods: 62 stage II-III breast cancer patients (23 hormone receptor positive HER2 negative (HR+HER2-), 20 HER2+, 15 triple negative breast cancer (TNBC) and 4 unknown receptor status) enrolled in the ChemoNEAR sample collection study were included. All patients received neoadjuvant chemotherapy, followed up by surgery, with samples taken at diagnosis, and post-surgery every 3 months for the first two years, followed by every 6 months for up to five years. Tumor DNA from FFPE samples and germline was Whole Exome Sequenced to identify patient specific mutations and design anchored-multiplex PCR (AMP™) Personalized Cancer Monitoring (PCMTM) assays to track mutations in plasma. Cell free DNA was extracted from 613 plasma samples (median volume 4ml, range 0.5-4.5ml) and sequenced with PCMTM assays, with 37-177 variants (median 52) per panel, to a depth of 100,000x per locus. A proprietary algorithm was used to identify ctDNA. Results: At a median follow-up of 52.7 months post-surgery (range 15.3-96.4 months), ctDNA was detected in 25.8% (16/62) of patients, with detected ctDNA levels ranging from allele frequency (AF) of 0.01%, to 32.5%) (median 0.24% AF). Detection of ctDNA was associated with a high risk of future relapse (HR 65.4, 95% CI 14.5-293.7), with a median lead-time from ctDNA detection to clinical relapse of 13.7 months (range 3.9-58.9). MRD was identified in 76.9% (10/13) of patients who relapsed. ctDNA was detected prior to relapse in both patients with brain only relapse, but with a reduced lead time over clinical relapse (5.73 and 3.90 months), which was previously not achievable with digital PCR MRD-detection assays. Of patients with assessable baseline samples, 81% (39/48) had ctDNA detected. No patients with undetected ctDNA, or detectable ctDNA with AF&amp;lt; 0.1%, relapsed during follow-up, whereas ctDNA was detected at baseline in all 10 patients who relapsed during follow-up (p=0.1). Conclusions: PCMTM detected breast cancer relapse with a long lead-time over clinical relapse, and strong association with relapse free survival, an advancement over previously published data with digital PCR MRD detection. Prospective, interventional trials are now required to assess whether treatment on the basis of MRD detection improves outcome, including the TRAK ER Trial (NCT04985266). Citation Format: Isaac Garcia-Murillas, Giselle Walsh-Crestani, Edward Phillips, Rosalind Cutts, Sarah Hrebien, Kathryn Dunne, Kally Sidhu, Robert Daber, Amber C. Carter, Lorena De La Peña, Stephen Johnston, Alistair Ring, Simon Russell, Abigail Evans, Anthony Skene, Duncan Wheatley, Ian Smith, Nicholas Turner. Personalized Cancer Monitoring (PCM): a novel ctDNA tool to detect molecular residual disease in patients with early-stage breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-05-01.

Abstract Background Acute upper gastrointestinal bleed (AUGIB) is associated with a 10% in-patient mortality and this outcome has not significantly improved over the past 50 years (1). The UK's National Institute for Health and Care Excellence (NICE) has developed guidance for the management of patients presenting with AUGIB, which highlights several priorities that should be addressed such as: a) risk assessment using the Blatchford and Rockall scores, b) the optimal timing of endoscopy, c) management of non-variceal bleeds (NVB's), d) management of variceal bleeds (VB's), and e) guidance on controlling bleeding and preventing re-bleeding in patients on non-steroidal anti-inflammatory drugs, aspirin or clopidogrel (1). Methods This study aimed to assess the compliance of AUGIB management in a district general hospital against the NICE quality standards. In the first cycle, we retrospectively reviewed case notes from 52 patients who presented with AUGIB and were admitted between September 1 and December 31, 2019. A re-audit was performed between December 1, 2020 to March 31, 2021 where we reviewed the case notes of 22 patients. We allowed for a 1-year interval between the first and second cycle where we educated doctors about the NICE quality standards of AUGIB management. The primary outcome of the study was the compliance of local management of AUGIB in a district hospital compared to NICE quality standards. Results Intervention indications in the first cycle were: haematemesis in 26.9% (14/52); melaena in 50% (26/52); both haematemesis and melaena in 23.1% (12/52). Indications in the second cycle were haematemesis in 64% (14/22); melaena in 18% (4/22); both haematemesis and melaena in 8% (4/22). Compliance with discontinuing aspirin during AUGIB was 60% (3/5) in the first cycle, and 80% (4/5) in the second. Blatchford risk score was used in 12.5% (5/40) in the first cycle, and 50% (11/22) in the second. Among haemodynamically unstable patients, endoscopy was performed immediately after resuscitation in 100% in both the first (4/4) and second (3/3) cycles. Among haemodynamically stable patients, 91.4% (32/35) had endoscopy &amp;lt;24 hours in the first cycle, and 53% (10/19) in the second. For NVB's, proton pump inhibitors were used in 74.4% (29/39) in the first cycle and 77% (17/22) in the second. For NVB endoscopy, there was 100% compliance in using clips with/without adrenaline in both cycles. Dual therapy with thermal coagulation and adrenaline was performed in 100% (1/1) of patients in the first cycle, and none in the second. For VB's, 100% of patients in the first (4/4) and second (5/5) cycle were given terlipressin, antibiotics, and band ligation. Conclusions In our district hospital, pre-endoscopic management of AUGIB such as PPI use, and time to endoscopy were adequate, but did not fully meet the quality standards stipulated by NICE. Endoscopic management for AUGIB, however, was fully compliant with NICE standards.

The ankle syndesmosis is a critical structure, conferring a great degree of stability to the ankle mortise comprising part of a complex framework of ligaments responsible for 90% of the resistance to lateral displacement of the fibula [1]. The components of the syndesmosis are the Anterior-Inferior Tibiofibular Ligament (AITFL), Posterior- Inferior Tibiofibular Ligament (PITFL), Transverse Tibiofibular Ligament (TTFL) and Interosseous Ligament (IOL). With approximately one in seven ankle fractures associated with a syndesmotic injury it is a common pattern [2]. The injury itself is most often found intra-operatively after stable fixation of malleolar fractures, indicated by persistent instability. This instability is often dealt with through the use of a bridging syndesmotic screw which restores the ankle mortise, confers stability but leaves the original syndesmotic injury relatively untouched.

Episodic ataxia type 1 (EA1) is a rare autosomal potassium channelopathy, due to mutations in KCNA1. Patients have childhood onset of intermittent attacks of ataxia, dizziness or imbalance. In order to quantify the natural history of EA1, its effect on quality of life and in preparation for future clinical trials, we set up an international multi-centre study of EA1. We recruited thirty-three participants with EA1: twenty-three completed 1-year follow-up and eighteen completed 2-year follow-up. There was very little accumulation of disability or impairment over the course of the 2 years of the study. The outcome measures of ataxia (SARA and functional rating of ataxia) and the activities of daily living scale were largely stable over time. Self-reported health-related quality of life (SF-36) scores were lower across all domains than controls, in keeping with a chronic condition. Physical subdomain scores appeared to deteriorate over time, which seems to be driven by the female participants in the study. This is an interesting finding and warrants further study. Attacks of EA1 reported by participants in real time via an interactive voice response system showed that symptoms were not stereotyped; however, attack duration and frequency was stable between individuals. This large prospective study is the first ever completed in subjects with EA1. We document the natural history of the disorder over 2 years. These data will enable the development of outcome measures for clinical trials of treatment.

Background: Oesophageal adenocarcinoma (OAC) is a lethal cancer with an overall 5-year survival of <20%. Given the presence of a pre-invasive disease stage, also known as Barrett’s oesophagus (BO), and the availability of minimally invasive treatments for BO-related neoplasia, it is thought that early detection is the best strategy to improve patient outcomes. Clinical guidelines recommend endoscopic screening in patients with symptoms of acid reflux and additional risk factors. This strategy is flawed by the cost and invasiveness of endoscopy as well as by the fact that a significant proportion of OAC patients deny a history of reflux symptoms. Summary: New research on the use of epidemiologic and clinical data has allowed the creation of risk-prediction algorithms to identify the population at risk. In addition, newer less-invasive devices such as transnasal endoscopy, Cytosponge, volumetric laser endomicroscopy, and volatile organic compounds are emerging as promising options to allow screening in the primary care setting. Finally, there is an opportunity to intervene at the pre-invasive stage with pharmacological strategies to reduce the risk burden. Key Messages: In this review, we provide a critical appraisal of the different screening approaches and chemopreventive strategies and a guide to readers on how to implement research evidence in clinical practice.

Tibial plateau and distal femoral fractures are common injuries presenting a significant operative challenge. Complexity of the fracture often needs multi-planar surgical access. A combined two-staged procedure is frequently suggested both in supine and prone position to address this issue. However, this will significantly increase the operative time and eventually impact the outcome, in addition to the complications associated with prone positioning. In this study we used a standard orthopaedic table to position these patients in order to grant access to the postro-medial and a postro-lateral structures while the patient stays in supine setup, at the same time, giving the flexibility to change the alignment from valgus to varus and vice versa. This facilitates fracture reduction while addressing the anatomical structure of the knee. A further advantage is the unobstructed imaging access throughout the surgical fixation. This facilitates the reduction in operative time hence leading to a better outcome in these difficult fractures. We tested this positioning technique in more than 40 patients over a 4-year period at two different centres in the United Kingdome. We found that this approach is safe, reproducible and relatively easy to set up in the two centres.

IntroductionAnti‐vascular endothelial growth factors (anti‐VEGFs) are considered standard of care therapy for diabetic macular oedema (DME). This study examined treatment patterns and outcomes in patients with DME treated with anti‐VEGF therapy.MethodsUsing anonymized electronic medical record data collected from three UK sites, this retrospective cohort study assessed rates of anti‐VEGF intravitreal injections in adults with treatment‐naïve DME who received their first treatment between 1 September 2010 and 31 July 2018. The proportion of patients with at least one interval of at least 12 weeks between injections; the distribution of injection intervals; the discontinuation rates; and the number of anti‐VEGF injection‐, injection‐free‐ and total visits were assessed during the first and second years of treatment.ResultsOverall, 1606 patient eyes with DME were included, with no minimum follow‐up. During the first and second year of treatment, 63.2% and 73.1% of eyes had at least one anti‐VEGF injection interval of at least 12 weeks, respectively. In the first and second years of treatment, the mean (standard deviation) numbers of injections were 7.7 (1.9) and 5.6 (2.2), with 14.2 (5.7) and 13.4 (6.4) total clinic visits, and 6.6 (5.0) and 7.8 (5.8) injection‐free visits, respectively. In total, 27.8% of patient eyes discontinued treatment during the first 2 years.ConclusionsThe high number of clinic visits and high discontinuation rates demonstrate a significant unmet need for a treatment to enable sustainable extended injection intervals, while maintaining visual acuity. This could improve patient adherence and health‐related quality of life for patients with DME.