Single-line macular optic coherence tomography to confirm optic neuropathies in awake infants and young children.

BACKGROUND: Handheld optical coherence tomography (HH-OCT) can image awake, young children but lacks integrated segmentation/analysis software. OCT imaging of eyes with optic neuropathies demonstrates ganglion cell layer (GCL) and ganglion cell complex (GCC) thinning, with a normal or thickened inner nuclear layer (INL). We compared pediatric normative data with GCL/INL and GCC/INL ratios from HH-OCT macular scans of awake young children with clinically diagnosed optic neuropathies. METHODS: Macular HH-OCT from awake children with optic neuropathies was prospectively obtained using Bioptigen (Leica Microsystems, Wetzlar, Germany). The GCL, GCC, and INL were manually measured by two readers using ImageJ from single-line macular scans at the thickest points nasal and temporal to the fovea, respectively, and the GCL/INL and GCC/INL ratios were calculated and compared with normative data. RESULTS: HH-OCT images from 17 right eyes of 17 children (mean age, 4.3 ± 2.9 years) with optic neuropathies were analyzed. Mean nasal (17 eyes) and temporal (16 eyes) GCL/INL ratios with optic neuropathies were 0.44 ± 0.38 (95% CI, 0.26-0.62) and 0.26 ± 0.22 (95% CI, 0.15-0.36), respectively. Corresponding normative GCL/INL ratios are 1.26 ± 0.20 (95% CI, 1.19-1.34) and 1.23 ± 0.27 (95% CI, 1.13-1.33), respectively (P < 0.0001). Severe thinning precluded GCL measurements in 2 eyes nasally and 5 eyes temporally, resulting in GCL measurements of zero. Mean nasal (17 eyes) and temporal (16 eyes) GCC/INL ratios were 1.93 ± 0.70 (95% CI,1.60-2.27) and 1.67 ± 0.44 (95% CI,1.46-1.87). Corresponding normative ratios are 2.85 ± 0.38 (95% CI, 2.71-2.99) and 2.87 ± 0.42 (95% CI, 2.70-3.03), respectively (P < 0.0001). CONCLUSIONS: GCL/INL and GCC/INL ratios calculated from single-line macular HH-OCT scans in awake young children with optic neuropathies differ significantly from normative values and may thus have utility in helping to establish a diagnosis of optic neuropathy.

Tissue-Free Liquid Biopsies Combining Genomic and Methylation Signals for Minimal Residual Disease Detection in Patients with Early Colorectal Cancer from the UK TRACC Part B Study.

PURPOSE: The absence of postoperative circulating tumor DNA (ctDNA) identifies patients with resected colorectal cancer (CRC) with low recurrence risk for adjuvant chemotherapy (ACT) de-escalation. Our study presents the largest resected CRC cohort to date with tissue-free minimal residual disease (MRD) detection. EXPERIMENTAL DESIGN: TRACC (tracking mutations in cell-free tumor DNA to predict relapse in early colorectal cancer) included patients with stage I to III resectable CRC. Prospective longitudinal plasma collection for ctDNA occurred pre- and postsurgery, post-ACT, every 3 months for year 1 and every 6 months in years 2 and 3 with imaging annually. The Guardant Reveal assay evaluated genomic and methylation signals. The primary endpoint was 2-year recurrence-free survival (RFS) by postoperative ctDNA detection (NCT04050345). RESULTS: Between December 2016 and August 2022, 1,203 were patients enrolled. Plasma samples (n = 997) from 214 patients were analyzed. One hundred forty-three patients were evaluable for the primary endpoint; 92 (64.3%) colon, 51 (35.7%) rectal; two (1.4%) stage I, 64 (44.8%) stage II, and 77 (53.8%) stage III. Median follow-up was 30.3 months (95% CI, 29.5-31.3). Two-year RFS was 91.1% in patients with ctDNA not detected postoperatively and 50.4% in those with ctDNA detected [HR, 6.5 (2.96-14.5); P < 0.0001]. Landmark negative predictive value (NPV) was 91.2% (95% CI, 83.9-95.9). Longitudinal sensitivity and specificity were 62.1% (95% CI, 42.2-79.3) and 85.9% (95% CI, 78.9-91.3), respectively. The median lead time from ctDNA detection to radiological recurrence was 7.3 months (IQR, 3.3-12.5; n = 9). CONCLUSIONS: Tissue-free MRD detection with longitudinal sampling predicts recurrence in patients with stage I to III CRC without the need for tissue sequencing. The UK TRACC Part C study is currently investigating the potential for ACT de-escalation in patients with undetectable postoperative ctDNA, given the high NPV indicating a low likelihood of residual disease.

The effects of coagulation factors and their inhibitors on proliferation and migration in colorectal cancer.

BACKGROUND/AIM: Clotting factors promote cancer development. We investigated if coagulation proteins promote proliferation and migration in colorectal cancer (CRC) cell lines and whether their direct inhibitors can attenuate these effects. MATERIALS AND METHODS: DLD-1 and SW620 cells were treated with tissue factor (0, 50, 100 and 500 pg/mL ± 10 µg/mL 10H10 [anti-tissue factor antibody]), thrombin (0.0, 0.1, 1.0 and 10.0 U/mL ± 0.5 µM dabigatran [thrombin inhibitor]) and Factor Xa, FXa (0.0, 0.1, 1.0 and 10.0 U/mL ± 100 ng/mL rivaroxaban [FXa inhibitor]) and their effects on proliferation and migration were quantified using the PrestoBlue® and transwell migration assays, respectively. RESULTS: Thrombin increased proliferation from 48 h treatment compared to its control (48 h 6.57 ± 1.36 u vs. 2.42 ± 0.13 u, p = 0.001, 72 h 9.50 ± 1.54 u vs. 4.50 ± 0.47 u, p = 0.004 and 96 h 10.77 ± 1.72 u vs. 5.57 ± 0.25 u, p = 0.008). This increase in proliferation was attenuated by dabigatran at 72 h (2.23 ± 0.16 u vs. 3.26 ± 0.43 u, p = 0.04). Tissue factor (0 pg/mL 20.7 ± 1.6 cells/view vs. 50 pg/mL 32.4 ± 1.9 cells/view, p = 0.0002), FXa (0.0 U/mL 8.9 ± 1.1 cells/view vs. 10.0 U/mL 17.7 ± 1.7 cells/view, p < 0.0001) and thrombin (0.0 U/mL 8.9 ± 1.3 cells/view vs. 10.0 U/mL 20.2 ± 2.0 cells/view, p < 0.0001) all increased migration compared to their controls. However, their direct inhibitors did not attenuate these increases. CONCLUSION: Thrombin, FXa and TF all increase migration in CRC in vitro. Thrombin induced increase in proliferation is abrogated by dabigatran. Dabigatran may have potential as an anti-cancer therapy in CRC.

Managing surgical demand when needs outstrip resource: qualitative investigation of colorectal cancer surgery provision in the first wave of the COVID-19 pandemic.

BACKGROUND: At the onset of the COVID-19 pandemic, elective surgical provision was severely affected by the need for hospital reorganization to care for critically ill patients. In response, National Health Service (NHS) England issued national guidance proposing acceptable time intervals for postponing different types of surgical procedure. This study reports healthcare professionals' private accounts of the strategies adopted to manage the imbalance of demand and resource, using colorectal cancer surgery as a case study. METHODS: Twenty-seven semistructured interviews were conducted with healthcare professionals between June and November 2020. A key informant sampling approach was used, followed by snowballing to achieve maximum regional variation across the UK. Data were analysed thematically using the constant comparison approach. RESULTS: In the context of considerable resource constraint, surgical teams overcame challenges to continue elective cancer provision. They achieved this by pursuing a combination of strategies: relocating surgical services; prioritizing patients within and across surgical specialties; adapting patient treatment plans; and introducing changes to surgical team working practices. Despite national guidance, prioritization decisions were framed as complex, and the most challenging of the strategies to implement, both practically and emotionally. CONCLUSION: There is a need to better support surgeons tasked with prioritizing patients when capacity exceeds demand.

Branch Retinal Vein Occlusion in a COVID-19 Positive Patient.

Retinal vein occlusions (RVOs), including central retinal vein occlusions (CRVOs) and branch retinal vein occlusions (BRVOs), are a common cause of morbidity in elderly patients. We present the case of a healthy 74-year-old female patient who initially presented with blurry vision in her left eye in the setting of a symptomatic COVID-19 infection. She was diagnosed with a branch retinal vein occlusion that did not immediately require treatment. Three months later, she again presented with worsening vision and was found to have cystoid macular edema (CME) secondary to the vein occlusion, thus was treated with an intravitreal dexamethasone implant. This case serves to highlight the growing evidence of increased thromboembolic risk associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the possible correlation of COVID-19 infections with ocular pathology, including retinal vein occlusions.

A Prospective Study to Identify Rates of SARS-CoV-2 Virus in the Peritoneum and Lower Genital Tract of Patients Having Surgery: An Observational Study.

STUDY OBJECTIVE: The risks to surgeons of carrying out aerosol-generating procedures during the coronavirus disease 2019 (COVID-19) pandemic are unknown. To start to define these risks, in a systematic manner, we investigated the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus in the abdominal fluid and lower genital tract of patients undergoing surgery. DESIGN: Prospective cross-sectional observational study. SETTING: Single, large United Kingdom hospital. PATIENTS: Total of 113 patients undergoing abdominal surgery or instrumentation of the lower genital tract. INTERVENTIONS: We took COVID-19 swabs from the peritoneal cavity and from the vagina from all eligible patients. Results were stratified by preoperative COVID-19 status. MEASUREMENTS AND MAIN RESULTS: In patients who were presumed COVID-19 negative at the time of surgery, SARS-CoV-2 virus RNA was detected in 0 of 102 peritoneal samples and 0 of 98 vaginal samples. Both cohorts included 4 patients who were antibody positive but nasopharyngeal swab test negative at the time of surgery. Peritoneal and vaginal swabs were also negative in 1 patient who had a positive nasopharyngeal swab immediately before surgery. CONCLUSION: The presence of SARS-CoV-2 RNA in the abdominal fluid or lower genital tract of presumed negative patients is nil or extremely low. These data will inform surgeons of the risks of restarting laparoscopic surgery at a time when COVID-19 is endemic in the population.

The Association of Coloproctology of Great Britain and Ireland consensus guidelines in emergency colorectal surgery.

AIM: There is a requirement for an expansive and up to date review of the management of emergency colorectal conditions seen in adults. The primary objective is to provide detailed evidence-based guidelines for the target audience of general and colorectal surgeons who are responsible for an adult population and who practise in Great Britain and Ireland. METHODS: Surgeons who are elected members of the Association of Coloproctology of Great Britain and Ireland Emergency Surgery Subcommittee were invited to contribute various sections to the guidelines. They were directed to produce a pathology-based document using literature searches that were systematic, comprehensible, transparent and reproducible. Levels of evidence were graded. Each author was asked to provide a set of recommendations which were evidence-based and unambiguous. These recommendations were submitted to the whole guideline group and scored. They were then refined and submitted to a second vote. Only those that achieved >80% consensus at level 5 (strongly agree) or level 4 (agree) after two votes were included in the guidelines. RESULTS: All aspects of care (excluding abdominal trauma) for emergency colorectal conditions have been included along with 122 recommendations for management. CONCLUSION: These guidelines provide an up to date and evidence-based summary of the current surgical knowledge in the management of emergency colorectal conditions and should serve as practical text for clinicians managing colorectal conditions in the emergency setting.

Coluber Constrictor Bite to the Eye: A Novel Case Report of a Wild Snake Bite to the Eye in North America and Review of Literature.

Snake bites involving the eye are an uncommon cause of ocular trauma; herein, we present one of the few known instances of a snake bite directly to the globe, specifically by the way of a Coluber constrictor, also known as the "Black Racer." In this case report, we describe a nine-year-old girl who presented immediately following a snake bite to the right eye. The patient's vision was unaffected despite visualized puncture wounds through the conjunctiva with associated near-total subconjunctival hemorrhage. The patient was taken to the operating room emergently for globe exploration. Circumferential peritomy and direct view to the sclera did not reveal any lacerations or puncture and subconjunctival vancomycin, gentamycin, and dexamethasone were administered intraoperatively. Post-operatively, the patient was discharged on a regimen of oral Cephalexin. Throughout multiple follow-ups, she continued to maintain excellent vision without sequelae. Trauma to the globe via snake bite is an exceedingly rare occurrence. Upon literature review, three out of three cases involving venomous snakes resulted in "No Light Perception" vision despite anti-venom. While nonvenomous snake bites may lend a better visual outcome, if not treated properly they may also yield poor final visual potential. Methods of treatment include oral or subconjunctival antibiotic administration with or without a steroid or cycloplegic agent. All reported cases of nonvenomous cases ultimately resulted in excellent visual potential (20/40 or better) and no reports of endophthalmitis. As such, it is evident that identifying the species of snake is of the utmost importance when considering visual prognosis. Due to very few reported incidences of globe trauma via snake bite, there is no mainstay therapy for either the venomous or nonvenomous snake bite variety. Despite this, we encourage careful pursuance of the appropriate therapy on a case-by-case basis, considering operative treatment, antivenom (if necessary), and antibiotic coverage with possible cycloplegia and steroid administration.

Treatment of Coats' disease: an analysis of pooled results.

AIM: To elucidate the association of treatment modality to vitreoretinal fibrosis and traction retinal detachment (TRD) in Coats' disease. METHODS: A PubMed search for Coats' disease with included studies describing eyes with clinical features and treatment course of Coats' disease. Binary logistic regression with fibrosis at presentation and treatment type as independent variables was performed to determine predictors of TRD historically (since 1921) and in the anti-vascular endothelial growth factor (VEGF) era (since 2007). Odds ratios (OR) with 95% confidence intervals (CI) reported. RESULTS: Of 175 articles described 1183 eyes. Vitreoretinal fibrosis increased from presentation (5.4%) to follow-up (15.5%) and TRD increased from 0.44% to 3.9% at follow up. Laser was protective against vitreoretinal fibrosis (OR 0.6, 95%CI 0.4-0.9) but TRD was borderline (OR 0.6, 95%CI 0.3-1.1). Cryotherapy showed a higher association with TRD (OR 1.9, 95%CI 1.0-3.7) than with vitreoretinal fibrosis (OR 0.8, 95%CI 0.5-1.2). Similarly, intravitreal anti-VEGF alone was not associated with fibrosis (OR 1.1, 95%CI 0.6-1.8) nor TRD (OR 1.1, 95%CI 0.5-2.6) but the combination of laser and anti-VEGF therapy was protective [Fibrosis: 0.1 (0.03, 0.35); TRD: 0.05 (0.01, 0.23)] compared to anti-VEGF plus cryotherapy (P<0.001). Disease stage ≤2B or ≥3A was not associated with TRD. CONCLUSION: Vitreoretinal fibrosis and TRD increase after treatment in Coats' disease. The combination of anti-VEGF agents and cryotherapy may lead to higher risk for TRD. Presence of pre-treatment fibrosis is the highest risk factor for post-treatment worsening of vitreoretinal fibrosis and TRD.