Cardiac Development at a Single-Cell Resolution.

Mammalian cardiac development is a complex, multistage process. Though traditional lineage tracing studies have characterized the broad trajectories of cardiac progenitors, the advent and rapid optimization of single-cell RNA sequencing methods have yielded an ever-expanding toolkit for characterizing heterogeneous cell populations in the developing heart. Importantly, they have allowed for a robust profiling of the spatiotemporal transcriptomic landscape of the human and mouse heart, revealing the diversity of cardiac cells-myocyte and non-myocyte-over the course of development. These studies have yielded insights into novel cardiac progenitor populations, chamber-specific developmental signatures, the gene regulatory networks governing cardiac development, and, thus, the etiologies of congenital heart diseases. Furthermore, single-cell RNA sequencing has allowed for the exquisite characterization of distinct cardiac populations such as the hard-to-capture cardiac conduction system and the intracardiac immune population. Therefore, single-cell profiling has also resulted in new insights into the regulation of cardiac regeneration and injury repair. Single-cell multiomics approaches combining transcriptomics, genomics, and epigenomics may uncover an even more comprehensive atlas of human cardiac biology. Single-cell analyses of the developing and adult mammalian heart offer an unprecedented look into the fundamental mechanisms of cardiac development and the complex diseases that may arise from it.

Early Breast Angiosarcoma Development After Radiotherapy: A Cautionary Tale.

This is a short clinical report depicting an exceptionally early presentation of radiation-induced angiosarcoma and overview of the literature. This case highlights the need for a high level of clinical suspicion in those patients presenting with unresolving cutaneous skin changes after radiotherapy for breast cancer.Breast-conserving therapy, comprising breast-conserving surgery and adjuvant radiotherapy, has largely replaced mastectomy in the treatment of early-stage breast carcinoma. Breast angiosarcoma is a rare but severe long-term complication associated with postoperative radiotherapy (Int J Radiat Oncol Biol Phys. 2002;52:1231-1237). It often presents as a bluish/purple skin lesion in a breast previously treated for breast cancer. This case explores an unexpectedly early presentation of radiation-induced breast angiosarcoma, which was initially thought to be benign bruising. Management remains challenging and prognosis is poor because of its aggressive local and regional invasion and early metastasis, commonly to the lungs and liver. Early surgical resection with wide margins is the treatment of choice (J Plast Reconstr Aesthet Surg. 2011;64:1036-1042).

ORthopaedic trauma hospital outcomes - Patient operative delays (ORTHOPOD) Study: The management of day-case orthopaedic trauma in the United Kingdom.

INTRODUCTION: ORTHOPOD: Day Case Trauma is a multicentre prospective service evaluation of day-case trauma surgery across four countries. It is an epidemiological assessment of injury burden, patient pathways, theatre capacity, time to surgery and cancellation. It is the first evaluation of day-case trauma processes and system performance at nationwide scale. METHODS: Data was prospectively recorded through a collaborative approach. Arm one captured weekly caseload burden and operating theatre capacity. Arm two detailed patient and injury demographics, and time to surgery for specific injury groups. Patients scheduled for surgery between 22/08/22 and 16/10/22 and operated on before 31/10/22, were included. For this analysis, hand and spine injuries were excluded. RESULTS: Data was obtained from 86 Data Access Groups (70 in England, 2 in Wales, 10 in Scotland and 4 in Northern Ireland). After exclusions, 709 weeks worth of data representing 23,138 operative cases were analysed. Day-case trauma patients (DCTP) accounted for 29.1% of overall trauma burden and utilised 25.7% of general trauma list capacity. They were predominantly adults aged 18 to 59 (56.7%) with upper limb Injuries (65.7%). Across the four nations, the median number of day-case trauma lists (DCTL) available per week was 0 (IQR 1). 6 of 84 (7.1%) hospitals had at least five DCTLs per week. Rates of cancellation (13.2% day-case; 11.9% inpatient) and escalation to elective operating lists (9.1% day-case; 3.4% inpatient) were higher in DCTPs. For equivalent injuries, DCTPs waited longer for surgery. Distal radius and ankle fractures had median times to surgery within national recommendations: 3 days and 6 days respectively. Outpatient route to surgery was varied. Dominant pathways (>50% patients listed at that episode) in England and Wales were uncommon but the most frequently seen was listing patients in the emergency department, 16 of 80 hospitals (20%). CONCLUSION: There is significant mismatch in DCTP management and resource availability. There is also considerable variation in DCTP route to surgery. Suitable DCTL patients are often managed as inpatients. Improving day-case trauma services reduces the burden on general trauma lists and this study demonstrates there is considerable scope for service and pathway development and improved patient experience.

Lack of regional pathways impact on surgical delay: Analysis of the Orthopaedic Trauma Hospital Outcomes-Patient Operative Delays (ORTHOPOD) study.

INTRODUCTION: Current practice following injury within the United Kingdom is to receive surgery, at the institution of first contact regardless of ability to provide timely intervention and inconsiderate of neighbouring hospital resource and capacity. This can lead to a mismatch of demand and capacity, delayed surgery and stress within hospital systems, particularly with regards to elective services. We demonstrate through a multicentre, multinational study, the impact of this at scale. METHODOLOGY: ORTHOPOD data collection period was between 22/08/2022 and 16/10/2022 and consisted of two arms. Arm 1 captured orthopaedic trauma caseload and capacity in terms of sessions available per centre and patients awaiting surgery per centre per given week. Arm 2 recorded patient and injury demographics, time of decision making, outpatient and inpatient timeframes as well as time to surgery. Hand and spine cases were excluded. For this regional comparison, regional trauma networks with a minimum of four centres enroled onto the ORTHOPOD study were exclusively analysed. RESULTS: Following analysis of 11,202 patient episodes across 30 hospitals we found no movement of any patient between hospitals to enable prompt surgery. There is no current system to move patients, between regional centres despite clear discrepancies in workload per capacity across the United Kingdom. Many patients wait for days for surgery when simple transfer to a neighbouring hospital (within 10 miles in many instances) would result in prompt care within national guidelines. CONCLUSION: Most trauma patients in the United Kingdom are managed exclusively at the place of first presentation, with no consideration of alternative pathways to local hospitals that may, at that time, offer increased operative capacity and a shorter waiting time. There is no oversight of trauma workload per capacity at neighbouring hospitals within a regional trauma network. This leads to a marked disparity in waiting time to surgery, and subsequently it can be inferred but not proven, poorer patient experience and outcomes. This inevitably leads to a strain on the overall trauma system and across several centres can impact on elective surgery recovery. We propose the consideration of inter-regional network collaboration, aligned with the Major Trauma System.

The ORthopaedic Trauma Hospital Outcomes - Patient Operative Delays (ORTHOPOD) study.

Aims: This is a multicentre, prospective assessment of a proportion of the overall orthopaedic trauma caseload of the UK. It investigates theatre capacity, cancellations, and time to surgery in a group of hospitals that is representative of the wider population. It identifies barriers to effective practice and will inform system improvements. Methods: Data capture was by collaborative approach. Patients undergoing procedures from 22 August 2022 and operated on before 31 October 2022 were included. Arm one captured weekly caseload and theatre capacity. Arm two concerned patient and injury demographics, and time to surgery for specific injury groups. Results: Data was available from 90 hospitals across 86 data access groups (70 in England, two in Wales, ten in Scotland, and four in Northern Ireland). After exclusions, 709 weeks' of data on theatre capacity and 23,138 operations were analyzed. The average number of cases per operating session was 1.73. Only 5.8% of all theatre sessions were dedicated day surgery sessions, despite 29% of general trauma patients being eligible for such pathways. In addition, 12.3% of patients experienced at least one cancellation. Delays to surgery were longest in Northern Ireland and shortest in England and Scotland. There was marked variance across all fracture types. Open fractures and fragility hip fractures, influenced by guidelines and performance renumeration, had short waits, and varied least. In all, nine hospitals had 40 or more patients waiting for surgery every week, while seven had less than five. Conclusion: There is great variability in operative demand and list provision seen in this study of 90 UK hospitals. There is marked variation in nearly all injuries apart from those associated with performance monitoring. There is no evidence of local network level coordination of care for orthopaedic trauma patients. Day case operating and pathways of care are underused and are an important area for service improvement.

Influence of Pre-operative HbA1c on Bariatric Surgery Outcomes-the Sunderland (UK) Experience.

PURPOSE: UK guidelines recommend an HbA1c < 8.5% prior to elective surgery. Optimisation of pre-operative glycaemic control can be often difficult. Aim to correlate the effect of pre-operative HbA1c on the peri-operative complication rates and whether elective bariatric surgery should be delayed in poorly controlled diabetics. MATERIAL AND METHODS: Retrospective data of consecutive patients who underwent laparoscopic Roux-en-Y gastric bypass, one-anastomosis gastric bypass and laparoscopic sleeve gastrectomy during January 2014 and April 2018. Patients were categorised into group 1, non-diabetics with an HbA1c < 6.5%; group 2, well-controlled diabetics with HbA1c between 6.5 and 8.4%; and group 3, poorly controlled diabetics with HbA1c ≥ 8.5%. Primary outcome was peri-operative complication rates. RESULTS: Group 1 (n = 978), 81.8% female, median (i.q.r.) age 44.0 (34-52) years, median (i.q.r.) BMI 42.0 (38.7-46.7); group 2 (n = 350), 66.3% female, age 51.0 (45-59) years, BMI 41.8 (37.5-46.5); and group 3 (n = 90), 60% female, age 52.0 (45-56) years and BMI 41.4(36.9-44.8). Early complication rates in each group were low, 1.0% vs 1.7% vs 1.1% (p = 0.592). Mean length of stay was 2 days across the groups (p > 0.05). There was no difference in 30-day re-admission rates between groups 2.8%, 2.9% and 3.3% (p = 0.983). At 6 months and 1 year, there was sustained and equal reduction in HbA1c in all groups (p < 0.05). CONCLUSION: Patients undergoing metabolic surgery for poorly controlled diabetes achieve non-inferior peri-operative outcomes. Hence, delaying metabolic surgery in an attempt to optimise diabetic control is not justifiable.

devCellPy is a machine learning-enabled pipeline for automated annotation of complex multilayered single-cell transcriptomic data.

A major informatic challenge in single cell RNA-sequencing analysis is the precise annotation of datasets where cells exhibit complex multilayered identities or transitory states. Here, we present devCellPy a highly accurate and precise machine learning-enabled tool that enables automated prediction of cell types across complex annotation hierarchies. To demonstrate the power of devCellPy, we construct a murine cardiac developmental atlas from published datasets encompassing 104,199 cells from E6.5-E16.5 and train devCellPy to generate a cardiac prediction algorithm. Using this algorithm, we observe a high prediction accuracy (>90%) across multiple layers of annotation and across de novo murine developmental data. Furthermore, we conduct a cross-species prediction of cardiomyocyte subtypes from in vitro-derived human induced pluripotent stem cells and unexpectedly uncover a predominance of left ventricular (LV) identity that we confirmed by an LV-specific TBX5 lineage tracing system. Together, our results show devCellPy to be a useful tool for automated cell prediction across complex cellular hierarchies, species, and experimental systems.