Urine Biopsy as Dynamic Biomarker to Enhance Clinical Staging of Bladder Cancer in Radical Cystectomy Candidates.

PURPOSE: There is significant interest in identifying complete responders to neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) to potentially avoid removal of a pathologically benign bladder. However, clinical restaging after NAC is highly inaccurate. The objective of this study was to develop a next-generation sequencing-based molecular assay using urine to enhance clinical staging of patients with bladder cancer. METHODS: Urine samples from 20 and 44 patients with bladder cancer undergoing RC were prospectively collected for retrospective analysis for molecular correlate analysis from two clinical trials, respectively. The first cohort was used to benchmark the assay, and the second was used to determine the performance characteristics of the test as it correlates to responder status as measured by pathologic examination. RESULTS: First, to benchmark the assay, known mutations identified in the tissue (MT) of patients from the Accelerated Methotrexate, Vinblastine, Doxorubicin, Cisplatin trial (ClinicalTrials.gov identifier: NCT01611662, n = 16) and a cohort from University of California-San Francisco (n = 4) were cross referenced against mutation profiles from urine (MU). We then determined the correlation between MU persistence and residual disease in pre-RC urine samples from a second prospective clinical trial (The pT0 trial; ClinicalTrials.gov identifier: NCT02968732). Residual MU status correlated strongly with residual disease status (pT0 trial; n = 44; P = .0092) when MU from urine supernatant and urine pellet were assessed separately and analyzed in tandem. The sensitivity, specificity, PPV, and NPV were 91%, 50%, 86%, and 63% respectively, with an overall accuracy of 82% for this second cohort. CONCLUSION: MU are representative of MT and thus can be used to enhance clinical staging of urothelial carcinoma. Urine biopsy may be used as a reliable tool that can be further developed to identify complete response to NAC in anticipation of safe RC avoidance.

Circadian regulation of macromolecular complex turnover and proteome renewal.

Although costly to maintain, protein homeostasis is indispensable for normal cellular function and long-term health. In mammalian cells and tissues, daily variation in global protein synthesis has been observed, but its utility and consequences for proteome integrity are not fully understood. Using several different pulse-labelling strategies, here we gain direct insight into the relationship between protein synthesis and abundance proteome-wide. We show that protein degradation varies in-phase with protein synthesis, facilitating rhythms in turnover rather than abundance. This results in daily consolidation of proteome renewal whilst minimising changes in composition. Coupled rhythms in synthesis and turnover are especially salient to the assembly of macromolecular protein complexes, particularly the ribosome, the most abundant species of complex in the cell. Daily turnover and proteasomal degradation rhythms render cells and mice more sensitive to proteotoxic stress at specific times of day, potentially contributing to daily rhythms in the efficacy of proteasomal inhibitors against cancer. Our findings suggest that circadian rhythms function to minimise the bioenergetic cost of protein homeostasis through temporal consolidation of protein turnover.

Video-assisted thoracic surgery and robotic-assisted first-rib excision and thoracic outlet syndrome decompression.

Multiple surgical approaches have been used in the management of thoracic outlet syndrome. These approaches have traditionally been "open" approaches and have been associated with the inherent morbidities of an open approach, including a risk of injury to the neurovascular structures due to traction and trauma while resecting the first rib. In addition, there has been concern that recurrence of symptoms may be related to incomplete resection of the rib with conventional open techniques. With the advent of minimally invasive thoracic surgery, surgeons began to explore first-rib resection via a thoracoscopic approach. Unfortunately, the existing video-assisted thoracic surgery technology and equipment was not well suited to working in the apex of the chest. With the introduction and subsequent progress in robotic surgery and instrumentation, this dissection can be performed with all the advantages of robotics, but also with minimal traction and trauma to the neurovascular structures, and incorporates almost complete resection of the rib with minimal residual stump. Robotics has developed as a reliable, safe, and less invasive approach to first-rib resection, yielding excellent results while limiting the morbidity of the procedure.

Potassium rhythms couple the circadian clock to the cell cycle.

Circadian (~24 h) rhythms are a fundamental feature of life, and their disruption increases the risk of infectious diseases, metabolic disorders, and cancer1-6. Circadian rhythms couple to the cell cycle across eukaryotes7,8 but the underlying mechanism is unknown. We previously identified an evolutionarily conserved circadian oscillation in intracellular potassium concentration, [K+]i9,10. As critical events in the cell cycle are regulated by intracellular potassium11,12, an enticing hypothesis is that circadian rhythms in [K+]i form the basis of this coupling. We used a minimal model cell, the alga Ostreococcus tauri, to uncover the role of potassium in linking these two cycles. We found direct reciprocal feedback between [K+]i and circadian gene expression. Inhibition of proliferation by manipulating potassium rhythms was dependent on the phase of the circadian cycle. Furthermore, we observed a total inhibition of cell proliferation when circadian gene expression is inhibited. Strikingly, under these conditions a sudden enforced gradient of extracellular potassium was sufficient to induce a round of cell division. Finally, we provide evidence that interactions between potassium and circadian rhythms also influence proliferation in mammalian cells. These results establish circadian regulation of intracellular potassium levels as a primary factor coupling the cell- and circadian cycles across diverse organisms.

Lung-Mimetic Hydrofoam Sealant to Treat Pulmonary Air Leak.

Pulmonary air leak is the most common complication of lung surgery, contributing to post-operative morbidity in up to 60% of patients; yet, there is no reliable treatment. Available surgical sealants do not match the demanding deformation mechanics of lung tissue; and therefore, fail to seal air leak. To address this therapeutic gap, a sealant with structural and mechanical similarity to subpleural lung is designed, developed, and systematically evaluated. This "lung-mimetic" sealant is a hydrofoam material that has alveolar-like porous ultrastructure, lung-like viscoelastic properties (adhesive, compressive, tensile), and lung extracellular matrix-derived signals (matrikines) to support tissue repair. In biocompatibility testing, the lung-mimetic sealant shows minimal cytotoxicity and immunogenicity in vitro. Human primary monocytes exposed to sealant matrikines in vitro upregulate key genes (MARCO, PDGFB, VEGF) known to correlate with pleural wound healing and tissue repair in vivo. In rat and swine models of pulmonary air leak, this lung-mimetic sealant rapidly seals air leak and restores baseline lung mechanics. Altogether, these data indicate that the lung-mimetic sealant can effectively seal pulmonary air leak and promote a favorable cellular response in vitro.

A phase 1 study of nivolumab in combination with interferon-gamma for patients with advanced solid tumors.

This phase I, dose-escalation trial evaluates the safety of combining interferon-gamma (IFN-γ) and nivolumab in patients with metastatic solid tumors. Twenty-six patients are treated in four cohorts assessing increasing doses of IFN-γ with nivolumab to evaluate the primary endpoint of safety and determine the recommended phase two dose (RP2D). Most common adverse events are low grade and associated with IFN-γ. Three dose limiting toxicities are reported at the highest dose cohorts. We report only one patient with any immune related adverse event (irAE). No irAEs ≥ grade 3 are observed and no patients require corticosteroids. The maximum tolerated dose of IFN-γ is 75 mcg/m2, however based on a composite of safety, clinical, and correlative factors the RP2D is 50 mcg/m2. Exploratory analyses of efficacy in the phase I cohorts demonstrate one patient with a complete response, and five have achieved stable disease. Pre-planned correlative assessments of circulating immune cells demonstrate intermediate monocytes with increased PD-L1 expression correlating with IFN-γ dose and treatment duration. Interestingly, post-hoc analysis shows that IFN-γ induction increases circulating chemokines and is associated with an observed paucity of irAEs, warranting further evaluation. ClinicalTrials.gov Trial Registration: NCT02614456.

Sound-guided assessment and localization of pulmonary air leak.

Pulmonary air leak is the most common complication of lung surgery, with air leaks that persist longer than 5 days representing a major source of post-surgery morbidity. Clinical management of air leaks is challenging due to limited methods to precisely locate and assess leaks. Here, we present a sound-guided methodology that enables rapid quantitative assessment and precise localization of air leaks by analyzing the distinct sounds generated as the air escapes through defective lung tissue. Air leaks often present after lung surgery due to loss of tissue integrity at or near a staple line. Accordingly, we investigated air leak sounds from a focal pleural defect in a rat model and from a staple line failure in a clinically relevant swine model to demonstrate the high sensitivity and translational potential of this approach. In rat and swine models of free-flowing air leak under positive pressure ventilation with intrapleural microphone 1 cm from the lung surface, we identified that: (a) pulmonary air leaks generate sounds that contain distinct harmonic series, (b) acoustic characteristics of air leak sounds can be used to classify leak severity, and (c) precise location of the air leak can be determined with high resolution (within 1 cm) by mapping the sound loudness level across the lung surface. Our findings suggest that sound-guided assessment and localization of pulmonary air leaks could serve as a diagnostic tool to inform air leak detection and treatment strategies during video-assisted thoracoscopic surgery (VATS) or thoracotomy procedures.

Point-of-care ultrasound thoracic "Quick Look" identifies potentially dangerous chest tube insertion sites.

PURPOSE: Emergency and trauma physicians typically rely on anatomic landmarks to determine the proper intercostal space for emergent tube thoracostomy. However, physicians using this technique select a potentially dangerous insertion site too inferior in nearly one-third of cases, which have the potential to result in subdiaphragmatic puncture. We investigated a point-of-care ultrasound (POCUS) thoracic "Quick Look" procedure as a technique to allow visualization of underlying structures to avoid tube misplacement. METHODS: We performed an observational study of adult emergency department patients and their treating physicians. The patient's emergency physician was asked to rapidly identify and mark a hypothetical tube thoracostomy insertion site on the patient's chest wall. An ultrasound fellow then performed a POCUS thoracic "Quick Look" exam with a phased-array probe placed directly over the marked site. Over one regular respiratory cycle, the identification of standard lung pattern was considered a negative scan whereas visualization of the diaphragm with underlying liver or spleen was considered a positive scan. Time for completion of the "Quick Look" scan was measured and inter-rater reliability was determined through image review by a single, blinded ultrasound director. RESULTS: Seventy-six thoracic "Quick Look" scans were performed on patient subjects, of which 17% (13/76, 95%CI 8-26%) were positive. The average time for performing the "Quick Look" exam was 43 s (95%CI 30-57). Inter-rater reliability of the thoracic "Quick Look" was excellent (κ = 0.95). CONCLUSION: Thoracic "Quick Look" exams performed at mock chest tube insertion sites demonstrated potentially dangerous insertions in 17% of the cases. POCUS thoracic "Quick Look" may be a rapid and reliable technique that improves safety when placing an emergent chest tube.

Post-infarction ventricular septal defect: percutaneous or surgical management in the UK national registry.

AIMS: Post-infarction ventricular septal defect (PIVSD) is a mechanical complication of acute myocardial infarction (AMI) with a poor prognosis. Surgical repair is the mainstay of treatment, although percutaneous closure is increasingly undertaken. METHODS AND RESUTS: Patients treated with surgical or percutaneous repair of PIVSD (2010-2021) were identified at 16 UK centres. Case note review was undertaken. The primary outcome was long-term mortality. Patient groups were allocated based upon initial management (percutaneous or surgical). Three-hundred sixty-two patients received 416 procedures (131 percutaneous, 231 surgery). 16.1% of percutaneous patients subsequently had surgery. 7.8% of surgical patients subsequently had percutaneous treatment. Times from AMI to treatment were similar [percutaneous 9 (6-14) vs. surgical 9 (4-22) days, P = 0.18]. Surgical patients were more likely to have cardiogenic shock (62.8% vs. 51.9%, P = 0.044). Percutaneous patients were substantially older [72 (64-77) vs. 67 (61-73) years, P < 0.001] and more likely to be discussed in a heart team setting. There was no difference in long-term mortality between patients (61.1% vs. 53.7%, P = 0.17). In-hospital mortality was lower in the surgical group (55.0% vs. 44.2%, P = 0.048) with no difference in mortality after hospital discharge (P = 0.65). Cardiogenic shock [adjusted hazard ratio (aHR) 1.97 (95% confidence interval 1.37-2.84), P < 0.001), percutaneous approach [aHR 1.44 (1.01-2.05), P = 0.042], and number of vessels with coronary artery disease [aHR 1.22 (1.01-1.47), P = 0.043] were independently associated with long-term mortality. CONCLUSION: Surgical and percutaneous repair are viable options for management of PIVSD. There was no difference in post-discharge long-term mortality between patients, although in-hospital mortality was lower for surgery.

Pathological remodeling of distal lung matrix in end-stage cystic fibrosis patients.

BACKGROUND: Manifestations of cystic fibrosis, although well-characterized in the proximal airways, are understudied in the distal lung. Characterization of the cystic fibrosis lung 'matrisome' (matrix proteome) has not been previously described, and could help identify biomarkers and inform therapeutic strategies. METHODS: We performed liquid chromatography-mass spectrometry, gene ontology analysis, and multi-modal imaging, including histology, immunofluorescence, and electron microscopy for a comprehensive evaluation of distal human lung extracellular matrix (matrix) structure and composition in end-stage cystic fibrosis. RESULTS: Quantitative proteomic profiling identified sixty-eight (68) matrix constituents with significantly altered expression in end-stage cystic fibrosis. Over 90% of significantly different matrix peptides detected, including structural and basement membrane proteins, were expressed at lower levels in cystic fibrosis. However, the total abundance of matrix in cystic fibrosis lungs was not significantly different from control lungs, suggesting that cystic fibrosis leads to loss of diversity among lung matrix proteins rather than an absolute loss of matrix. Visualization of distal lung matrix via immunofluorescence and electron microscopy revealed pathological remodeling of distal lung tissue architecture and loss of alveolar basement membrane, consistent with significantly altered pathways identified by gene ontology analysis. CONCLUSIONS: Dysregulation of matrix organization and aberrant wound healing pathways are associated with loss of matrix protein diversity and obliteration of distal lung tissue structure in end-stage cystic fibrosis. While many therapeutics aim to functionally restore defective cystic fibrosis transmembrane conductance regulator (CFTR), drugs that target dysregulated matrix pathways may serve as adjunct interventions to support lung recovery.

Targeting Metabolic Adaptations in the Breast Cancer-Liver Metastatic Niche Using Dietary Approaches to Improve Endocrine Therapy Efficacy.

Estrogen receptor-positive (ER+) metastatic tumors contribute to nearly 70% of breast cancer-related deaths. Most patients with ER+ metastatic breast cancer (MBC) undergo treatment with the estrogen receptor antagonist fulvestrant as standard of care. Yet, among such patients, metastasis in liver is associated with reduced overall survival compared with other metastasis sites. The factors underlying the reduced responsiveness of liver metastases to ER-targeting agents remain unknown, impeding the development of more effective treatment approaches to improve outcomes for patients with ER+ liver metastases. We therefore evaluated site-specific changes in MBC cells and determined the mechanisms through which the liver metastatic niche specifically influences ER+ tumor metabolism and drug resistance. We characterized ER activity of MBC cells both in vitro, using a novel system of tissue-specific extracellular matrix hydrogels representing the stroma of ER+ tumor metastatic sites (liver, lung, and bone), and in vivo, in liver and lung metastasis mouse models. ER+ metastatic liver tumors and MBC cells grown in liver hydrogels displayed upregulated expression of glucose metabolism enzymes in response to fulvestrant. Furthermore, differential ERα activity, but not expression, was detected in liver hydrogels. In vivo, increased glucose metabolism led to increased glycogen deposition in liver metastatic tumors, while a fasting-mimicking diet increased efficacy of fulvestrant treatment to reduce the metastatic burden. Our findings identify a novel mechanism of endocrine resistance driven by the liver tumor microenvironment. IMPLICATIONS: These results may guide the development of dietary strategies to circumvent drug resistance in liver metastasis, with potential applicability in other metastatic diseases.

Telehealth voice assessment by speech language pathologists during a global pandemic using principles of a primary contact model: an observational cohort study protocol.

INTRODUCTION: SARS-CoV-2, a highly contagious severe acute respiratory syndrome, has spread to most countries in the world and resulted in a change to practice patterns for the assessment and diagnosis of people with voice disorders. Many services are transitioning to telehealth models to maintain physical distancing measures and conserve personal protective equipment used by healthcare workers during laryngoscopy examinations. The speech-language pathology primary contact (SLPPC) assessment for patients referred to ear, nose and throat (ENT) services in Australia has been shown to reduce waiting times for assessment while streamlining access to ENT assessment and allied health practitioner treatment pathways. METHODS AND ANALYSIS: A prospective observational cohort study will see patients in a newly developed telehealth model which uses the principles from a usual care SLPPC assessment protocol. Participants will be offered an initial telehealth assessment (speech-language pathology primary contact telehealth (SLPPC-T)) prior to being prioritised for a face-to-face laryngoscopy assessment to complete the diagnostic process. The telehealth assessment will collect sociodemographic information, personal and family medical history, key symptoms, onset and variability of symptoms, red-flag signs or symptoms for laryngeal malignancy, and clinical voice assessment data for auditory-perceptual and acoustic analysis. The study outcomes include (1) association of signs, symptoms and specific voice measures collected during SLPPC-T with voice disorder classification provided after laryngoscopy; (2) degree of concordance between voice disorder classification after SLPPC-T and after laryngoscopy; (3) health service and patient-related costs and health outcomes of the SLPPC-T; (4) patient and stakeholder views and beliefs about the SLPPC-T process. ETHICS AND DISSEMINATION: Ethical approval has been granted prior to commencement of the study enrolment by the Gold Coast Hospital and Health Service Human Research Ethics Committee (reference number HREC/2020/QGC/62832). Results will be shared through the publication of articles in peer-reviewed medical journals and presentation at national and international scientific meetings. TRIAL REGISTRATION NUMBER: ACTRN12621000427875.

Triple gallbladder with heterotopic gastric mucosa: a case report.

BACKGROUND: Triple gallbladder is a rare congenital anomaly of the biliary tract that can be associated with heterotopic tissue. Gallbladder triplication results from the failure of rudimentary bile ducts to regress during embryological development, and can be difficult to distinguish from Todani type II choledochal cysts and biliary duplication cysts. CASE PRESENTATION: A 2-year-old patient presented to our institution with intermittent abdominal pain for 1 year. She had elevated transaminases with imaging concerning for a choledochal cyst. After assessment with magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography, she was diagnosed with a gallbladder multiplication and a common bile duct stricture. She underwent laparoscopic cholecystectomy, which confirmed the diagnosis of triple gallbladder. One of the three gallbladders demonstrated heterotopic gastric mucosa on final pathology, including at the cystic duct margin. Follow up testing with a technetium 99 m scan demonstrated a subtle focus of increased activity in the right upper abdomen at the expected location of the common bile duct, concerning for the presence of residual gastric mucosa. The patient remains well without abdominal pain. CONCLUSIONS: We describe the first case of heterotopic gastric mucosa in a triple gallbladder in a young patient presenting with chronic abdominal pain. We also demonstrate the safety and feasibility of laparoscopic cholecystectomy in young children with triple gallbladder. Finally, we propose an interdisciplinary approach to the management of common bile duct strictures in the setting of ectopic acid secretion, involving a combination of medical management, endoscopic intervention, and possible salvage laparoscopic Roux-en-Y hepaticojejunostomy.

Xenogeneic support for the recovery of human donor organs.

VIDEO ABSTRACT.

Homogeneous Distribution of Exogenous Cells onto De-epithelialized Rat Trachea via Instillation of Cell-Loaded Hydrogel.

Injured or diseased airway epithelium due to repeated environmental insults or genetic mutations can lead to a functional decline of the lung and incurable lung diseases. Bioengineered airway tissue constructs can facilitate in vitro investigation of human lung diseases and accelerate the development of effective therapeutics. Here, we report robust tissue manipulation modalities that allow: (i) selective removal of the endogenous epithelium of in vitro cultured airway tissues and (ii) spatially uniform distribution and prolonged cultivation of exogenous cells that are implanted topically onto the denuded airway lumen. Results obtained highlight that our approach to airway tissue manipulation can facilitate controlled removal of the airway epithelium and subsequent homogeneous distribution of newly implanted cells. This study can contribute to the creation of innovative tissue engineering methodologies that can facilitate the treatment of lung diseases, such as cystic fibrosis, primary ciliary dyskinesia, and chronic obstructive pulmonary disease.

A Comprehensive Update of the Treatment and Management of Bertolotti's Syndrome: A Best Practices Review.

Bertolotti's Syndrome is defined as chronic back pain caused by transitional lumbosacral vertebra. The transitional vertebra may present with numerous clinical manifestations leading to a myriad of associated pain types. The most common is pain in the sacroiliac joint, groin, and hip region and may or may not be associated with radiculopathy. Diagnosis is made through a combination of clinical presentations and imaging studies and falls into one of four types. The incidence of transitional vertebra has a reported incidence between 4 and 36%; however, Bertolotti's Syndrome is only diagnosed when the cause of pain is attributed to this transitional anatomy. Therefore, the actual incidence is difficult to determine. Initial management with conservative treatment includes medical management and physical therapy. Injection therapy has been established as an effective second line. Epidural steroid injection at the level of the transitional articulation is effective, with either local anesthetics alone or in combination with steroids. Surgery carries higher risks and is reserved for patients failing previous lines of treatment. Options include surgical removal of the transitional segment, decompression of stenosed foramina, and spinal fusion. Recent evidence suggests that radiofrequency ablation (RFA) around the transitional segment may also provide relief. This manuscript is a comprehensive review of the literature related to Bertolotti's Syndrome. It describes the background, including epidemiology, pathophysiology, and etiology of the Syndrome, and presents the best evidence available regarding management options. Bertolotti's Syndrome is considered an uncommon cause of chronic back pain, though the actual incidence is unclear. Most evidence supporting these therapies is of lower-level evidence with small cohorts, and more extensive studies are required to provide strong evidence supporting best practices.

COVID-19: A Time Like No Other in (the Department of) Neurological Surgery.

Coronavirus disease 2019 (COVID-19) has disrupted lives and indelibly impacted the practice of medicine since emerging as a pandemic in March 2020. For neurosurgery departments throughout the United States, the pandemic has created unique challenges across subspecialties in devising methods of triage, workflow, and operating room safety. Located in New York City, at the early epicenter of the COVID-19 crisis, the Weill Cornell Medicine Department of Neurological Surgery was disrupted and challenged in many ways, requiring adaptations in clinical operations, workforce management, research, and education. Through our department's collective experience, we offer a glimpse at how our faculty and administrators overcame obstacles, and transformed in the process, at the height of the COVID-19 pandemic.

Cystoscopy and Systematic Bladder Tissue Sampling in Predicting pT0 Bladder Cancer: A Prospective Trial.

PURPOSE: Concern for discordance between clinical staging and final pathology drives current management of patients deemed appropriate candidates for radical cystectomy. Therefore, we set out to prospectively investigate reliability and shortcomings of cystoscopic evaluation in radical cystectomy candidates. MATERIALS AND METHODS: Patients undergoing radical cystectomy for urothelial carcinoma were enrolled in a prospective single-arm study to evaluate reliability of Systematic Endoscopic Evaluation in predicting pT0 urothelial carcinoma (NCT02968732). Systematic Endoscopic Evaluation consisted of cystoscopy and tissue sampling at the time of radical cystectomy. Systematic Endoscopic Evaluation results were compared to radical cystectomy pathology. The primary end point was the negative predictive value of Systematic Endoscopic Evaluation findings in predicting radical cystectomy pathology. RESULTS: A total of 61 patients underwent Systematic Endoscopic Evaluation and radical cystectomy. Indications included muscle invasive bladder cancer in 42 (68.9%) and high risk nonmuscle invasive bladder cancer in 19 (31.1%). In all, 38 (62.3%, 90.5% of patients with muscle invasive bladder cancer) received neoadjuvant chemotherapy. On Systematic Endoscopic Evaluation, 31 (50.8%) patients demonstrated no visual nor biopsy-based evidence of disease (seeT0), yet 16/31 (51.6%) harbored residual disease (>pT0), including 8 (8/31, 25.8%) with residual ≥pT2 disease upon radical cystectomy. The negative predictive value of Systematic Endoscopic Evaluation predicting a pT0 bladder was 48.4% (CI 30.2-66.9), which was below our prespecified hypothesis. Therefore, the trial was stopped for futility. CONCLUSIONS: Approximately 1 of 4 patients with seeT0 at the time of radical cystectomy harbored residual muscle invasive bladder cancer. These prospective data definitively confirm major limitations of endoscopic assessment for pT0 bladder cancer. Future work should focus on novel imaging and biomarker strategies to optimize evaluations before radical cystectomy for improved decision making regarding bladder preservation.

Acute appendicitis management during the COVID-19 pandemic: A prospective cohort study from a large UK centre.

BACKGROUND: During the Covid-19 pandemic, non-operative management for acute appendicitis (AA) was implemented in the UK. The aim of this study was to determine the efficacy and outcomes of conservative versus surgical management of AA during the pandemic. MATERIALS & METHODS: We conducted an observational study in a tertiary referral centre. Data was collected from all patients (≥16 years) with a diagnosis of AA between November 1, 2019 to March 10, 2020 (pre-COVID period) and March 10, 2020 to July 5, 2020 (COVID period). RESULTS: A total of 116 patients in the pre-COVID period were included versus 91 in the COVID period. 43.1% (n = 50) of patients pre-COVID were classified as ASA 2 compared to 26.4% (n = 24) during the COVID period (p-value = 0.042). 72.5% (n = 66) of the patients during the COVID period scored as high risk using the Alvarado score compared to 24.1% (n = 28) in the pre-COVID period (p-value<0.001). We observed a significant increase in radiological evaluation, 69.8% versus 87.5% of patients had a CT in the pre-COVID and COVID periods respectively (p-value = 0.008). 94.9% of patients were managed operatively in the pre-COVID period compared to 60.4% in the COVID period (p-value<0.001). We observed more open appendicectomies (37.3% versus 0.9%; p-value<0.001) during the COVID period compared to the pre-COVID period. More abscess formation and free fluid were found intraoperatively in the COVID period (p-value = 0.021 and 0.023 respectively). Re-attendance rate due to appendicitis-related issues was significantly higher in the COVID period (p = 0.027). CONCLUSION: Radiological diagnosis of AA was more frequent during the COVID period. More conservative management for AA was employed during the COVID-19 pandemic, and for those managed operatively an open approach was preferred. Intra-operative findings were suggestive of delayed presentation during the COVID period without this affecting the length of hospital stay.