Delayed Versus Early Laparoscopic Appendectomy for Adult Patients With Acute Appendicitis: A Randomized Controlled Trial.

OBJECTIVE: To assess whether delaying appendectomy until the following morning is non-inferior to immediate surgery in those with acute appendicitis presenting at night. BACKGROUND: Despite a lack of supporting evidence, those with acute appendicitis who present at night frequently have surgery delayed until the after morning. METHODS: The delay trial is a noninferiority randomized controlled trial conducted between 2018 and 22 at 2 tertiary care hospitals in Canada. Adults with imaging confirmed acute appendicitis who presented at night (8:00 pm -4:00 am ). Delaying surgery until after 6:00 am was compared with immediate surgery. The primary outcome was 30-day postoperative complications. An a prior noninferiority margin of 15% was deemed clinically relevant. RESULTS: One hundred twenty-seven of the planned 140 patients were enrolled in the Delayed Versus Early Laparoscopic Appendectomy (DELAY) trial (59 in the delayed group and 68 in the immediate group). The two groups were similar at baseline. The mean time between the decision to operate and surgery was longer in the delayed group (11.0 vs 4.4 hours, P < 0.0001). The primary outcome occurred in 6/59 (10.2%) of those in the delayed group versus 15/67 (22.4%) of those in the immediate group ( P = 0.07). The difference between groups met the a priori noninferiority criteria of +15% (risk difference -12.2%, 95% CI: -24.4% to +0.4%, test of noninferiority P < 0.0001). CONCLUSIONS: The DELAY study is the first trial to assess delaying appendectomy in those with acute appendicitis. We demonstrate the noninferiority of delaying surgery until the after morning.

Efficacy and safety of avacincaptad pegol in patients with geographic atrophy (GATHER2): 12-month results from a randomised, double-masked, phase 3 trial.

BACKGROUND: Geographic atrophy is an advanced form of dry age-related macular degeneration that can lead to irreversible vision loss and high burden of disease. We aimed to assess efficacy and safety of avacincaptad pegol 2 mg in reducing geographic atrophy lesion growth. METHODS: GATHER2 is a randomised, double-masked, sham-controlled, 24-month, phase 3 trial across 205 retina clinics, research hospitals, and academic institutions globally. To be eligible, patients had to be aged 50 years or older with non-centrepoint-involving geographic atrophy and best corrected visual acuity between 20/25 and 20/320 in the study eye. Eligible patients were randomly assigned (1:1) to monthly avacincaptad pegol 2 mg administered as a 100 µL intravitreal injection or sham for the first 12 months. Randomisation was performed using an interactive response technology system with stratification by factors known to be of prognostic importance in age-related macular degeneration. Patients, investigators, study centre staff, sponsor personnel, and data analysts were masked to treatment allocation. The primary endpoint was geographic atrophy lesion size measured by fundus autofluorescence at baseline, month 6, and month 12. Efficacy and safety analyses were done in the modified intention-to-treat and safety populations, respectively. This trial is registered with ClinicalTrials.gov, NCT04435366. FINDINGS: Between June 22, 2020, and July 23, 2021, 1422 patients were screened for eligibility, of whom 448 were enrolled and randomly assigned to avacincaptad pegol 2 mg (n=225) or sham (n=223). One patient in the sham group did not receive study treatment and was excluded from analyses. There were 154 (68%) female patients and 71 (32%) male patients in the avacincaptad pegol 2 mg group, and 156 (70%) female patients and 66 (30%) male patients in the sham group. From baseline to month 12, the mean rate of square-root-transformed geographic atrophy area growth was 0·336 mm/year (SE 0·032) with avacincaptad pegol 2 mg and 0·392 mm/year (0·033) with sham, a difference in growth of 0·056 mm/year (95% CI 0·016-0·096; p=0·0064), representing a 14% difference between the avacincaptad pegol 2 mg group and the sham group. Ocular treatment-emergent adverse events in the study eye occurred in 110 (49%) patients in the avacincaptad pegol 2 mg group and 83 (37%) in the sham group. There were no endophthalmitis, intraocular inflammation, or ischaemic optic neuropathy events over 12 months. To month 12, macular neovascularisation in the study eye occurred in 15 (7%) patients in the avacincaptad pegol 2 mg group and nine (4%) in the sham group, with exudative macular neovascularisation occurring in 11 (5%) in the avacincaptad pegol 2 mg group and seven (3%) in the sham group. INTERPRETATION: Monthly avacincaptad pegol 2 mg was well tolerated and showed significantly slower geographic atrophy growth over 12 months than sham treatment, suggesting that avacincaptad pegol might slow disease progression and potentially change the trajectory of disease for patients with geographic atrophy. FUNDING: Iveric Bio, An Astellas Company.

A Phase 2 Trial of Intravesical Gemcitabine and Docetaxel in the Treatment of Bacillus Calmette-Guérin‒Naïve Nonmuscle-Invasive Urothelial Carcinoma of the Bladder.

PURPOSE: Combination intravesical gemcitabine and docetaxel (GemDoce) has demonstrated efficacy as second-line therapy for patients with bacillus Calmette-Guérin (BCG)‒unresponsive nonmuscle-invasive urothelial carcinoma of the bladder (NMIBC). In the context of widespread BCG shortages, we performed a phase 2 prospective trial to assess GemDoce for BCG-naïve NMIBC. MATERIALS AND METHODS: This study is a prospective, single-arm, open-label phase 2 trial for patients with BCG-naïve high-risk NMIBC. Intravesical GemDoce was given weekly for 6 weeks as induction followed by monthly maintenance therapy for 2 years among responders. The primary end point was 3-month complete response, and key secondary end points included adverse events (AEs) and 12-month recurrence-free survival. RESULTS: Twenty-five patients were enrolled between August 2020 and August 2022 with median follow-up of 19.6 months. The pretreatment pathologic stages were high-grade (HG) T1 with carcinoma in situ (CIS; n = 7), HGT1 without CIS (n = 6), HGTa (n = 9), and CIS alone (n = 3). The 3-month complete response rate was 100% and recurrence-free survival at 12 months was 92%. Two patients with pretreatment HGT1 had HGT1 recurrences at 9 and 12 months. No patients progressed to T2 disease, underwent radical cystectomy, or had any radiographic evidence of progressive disease. Grade 1 AEs were common (23/25 patients) including hematuria, urinary frequency, urgency, and fatigue. Five patients (20%) experienced a grade 3 AE including hematuria and UTI. CONCLUSIONS: In this single-arm phase 2 trial, GemDoce was well tolerated with promising efficacy for patients with BCG-naïve high-risk NMIBC.

Venous invasion detectable only by elastic stain shows weak prognostic value in colon cancer.

AIMS: Large venous invasion (VI) is prognostically significant in colon cancer. The increased use of elastic stains by pathologists results in higher VI detection rates compared to routine stains alone. This study assesses the prognostic value of VI detected by elastic versus routine stains. METHODS AND RESULTS: Colon cancers resected between 2014 and 2017 underwent pathology slide review for VI. Cases without VI on routine stain were stained by elastic trichrome and re-examined. Demographic, clinical, pathological and outcome data were gathered by retrospective review. Kaplan-Meier curves with log-rank tests were performed for survival categorised by VI status. Cox regression was performed for multivariate analysis. Of 277 cases, 97 (35%) showed VI by routine stain alone, with an additional 58 (21%) discovered by subsequent elastic stains. Thus, elastic trichrome increased VI detection by 60%. However, only VI detected by routine stain showed worse overall survival (P < 0.001). VI detected by elastic stain only was not prognostically different from cases without VI (P = 0.428). For stage 2 cancers, VI was not prognostically significant regardless of method of detection. For stage 3 cases, only VI detected by routine stain was prognostic for overall survival (P = 0.002) with a hazard ratio of 4.04 by multivariate regression (P = 0.028). CONCLUSIONS: VI detectable only by elastic stains do not show prognostic significance for survival in colon cancer. For pathologists with high baseline VI detections rates on routine stain, reflexive use of elastic stain may be of limited value.

Smartphone Application Versus Standard Instruction for Colonoscopic Preparation: A Randomized Controlled Trial.

OBJECTIVE: To compare smartphone application (Colonoscopic Preparation) instructions versus paper instructions for bowel preparation for colonoscopy. BACKGROUND: Adhering to bowel preparation instructions is important to ensure a high-quality colonoscopy. PATIENTS AND METHODS: This randomized controlled trial included individuals undergoing colonoscopy at a tertiary care hospital. Individuals were randomized (1:1) to receive instructions through a smartphone application or traditional paper instructions. The primary outcome was the quality of the bowel preparation as measured by the Boston Bowel Preparation Score. Secondary outcomes included cecal intubation and polyp detection. Patient satisfaction was assessed using a previously developed questionnaire. RESULTS: A total of 238 individuals were randomized (n = 119 in each group), with 202 available for the intention-to-treat analysis (N = 97 in the app group and 105 in the paper group). The groups had similar demographics, indications for colonoscopy, and type of bowel preparation. The primary outcome (Boston Bowel Preparation Score) demonstrated no difference between groups (Colonoscopic Preparation app mean: 7.26 vs paper mean: 7.28, P = 0.91). There was no difference in cecal intubation (P = 0.37), at least one polyp detected (P = 0.43), or the mean number of polyps removed (P = 0.11). A higher proportion strongly agreed or agreed that they would use the smartphone app compared with paper instructions (89.4% vs 70.1%, P = 0.001). CONCLUSIONS: Smartphone instructions performed similarly to traditional paper instructions for those willing to use the application. Local patient preferences need to be considered before making changes in the method of delivery of medical instructions.

A systematic review and meta-analysis of oncological outcomes with transanal total mesorectal excision for rectal cancer.

AIM: Transanal total mesorectal (taTME) excision is a method used to assist in the radical removal of the rectum. By adopting the concept of natural orifice surgery, it offers potential benefits over conventional techniques. Early enthusiasm for this strategy led to its rapid and widespread adoption. The imposing of a local moratorium was precipitated by the discovery in Norway of an uncommon multifocal pattern of locoregional recurrence. The aim of this systematic review and meta-analysis was to determine the incidence of local recurrence after taTME for rectal cancer. METHOD: Conforming to the Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines checklist, a systematic review and meta-analysis was conducted. This included case series and comparative studies between taTME and preferentially laparoscopic procedures published between 2010 and 2021. RESULTS: There were a total of 1175 studies retrieved. After removal and screening for quality and relevance, the final analysis contained 40 studies. The local recurrence rate following taTME was 3.4% (95% CI 2.9%-3.9%, I2 = 0%) in 4987 patients with follow-up durations ranging from 0.7 to 5.5 years. Compared with laparoscopic TME, local recurrence was not statistically different for the taTME group (p = 0.076); however, it was less probable (OR = 0.51, 95% CI 0.24-1.09, I2 = 0%). Systemic recurrence and circumferential resection margin status were secondary outcomes; however, the differences were not statistically significant. CONCLUSION: Our data suggest that the local recurrence for regular laparoscopic and transanal TME surgeries may be comparable, suggesting that taTME can be performed without influencing locoregional oncological outcomes in patients treated at specialized institutions and who have been cautiously selected.

Toxic potential assessment of hair dye developer 2,4,5,6-tetraaminopyrimidine sulfate exposed under ambient UVB radiation.

Synthetic cosmetics, particularly hair dyes, are becoming increasingly popular among people of all ages and genders. 2,4,5,6-tetraaminopyrimidine sulfate (TAPS) is a key component of oxidative hair dyes and is used as a developer in several hair dyes. TAPS has previously been shown to absorb UVB strongly and degrade in a time-dependent manner, causing phototoxicity in human skin cells. However, the toxic effects of UVB-degraded TAPS are not explored in comparison to parent TAPS. Therefore, this research work aims to assess the toxicity of UVB-degraded TAPS than TAPS on two different test systems, that is, HaCaT (mammalian cell) and Staphylococcus aureus (a bacterial cell). Our result on HaCaT has illustrated that UVB-degraded TAPS is less toxic than parent TAPS. Additionally, UVB-exposed TAPS and parent TAPS were given to S. aureus, and the bacterial growth and their metabolic activity were assessed via CFU and phenotype microarray. The findings demonstrated that parent TAPS reduced bacterial growth via decreased metabolic activity; however, bacteria easily utilized the degraded TAPS. Thus, this study suggests that the products generated after UVB irradiation of TAPS is considered to be safer than their parent TAPS.

The impact of robotic rectal cancer surgery at a Canadian regional cancer centre: a retrospective cohort study.

BACKGROUND: Although robotic surgery has several advantages over other minimally invasive surgery (MIS) techniques for rectal cancer surgery, the uptake in Canada has been limited owing to a perceived increase in cost and lack of training. The objective of this study was to determine the impact of access to robotic surgery in a Canadian setting. METHODS: We conducted a retrospective cohort study involving consecutive adults undergoing surgical resection for rectal cancer between 2017 and 2020. The primary exposure was access to robotic surgery. Outcomes included MIS utilization, short-term outcomes, total cost of care, and quality of surgical resection. We completed univariate and multivariate analyses. RESULTS: We included 171 individuals in this cohort study (85 in the prerobotic period and 86 in the robotic period). The 2 groups had similar baseline characteristics. A higher proportion of individuals underwent successful MIS in the robotic phase (86% v. 46%, p < 0.001). Other benefits included a shorter mean length of hospital stay (5.1 d v. 9.2 d, p < 0.001). The quality of surgical resection was similar between groups. The total cost of care was $16 746 in the robotic period and $18 808 in the prerobotic period (mean difference -$1262, 95% confidence interval -$4308 to $1783; p = 0.4). CONCLUSION: Access to robotic rectal cancer surgery increased successful completion of MIS and shortened hospital stay, with a similar total cost of care. Robotic rectal cancer surgery can enhance patient outcomes in the Canadian setting.

Digital health literacy among the ageing population: A comparative cross-sectional study between rural and urban Telangana, India.

Background: Digital health literacy (DHL) is the confluence where health literacy meets digital literacy. DHL has been labelled as one of the digital determinants of health by the World Health Organization. The present study estimated and compared the DHL between Telangana's urban and rural ageing adults, and their potential determinants. Methods: A cross-sectional study was undertaken among 318 of the ageing individuals (≥45 years) of Hyderabad, visiting the primary health centres in the rural and urban field practice during March 2023. A Telugu version of the eHealth literacy scale (eHEALS) and health literacy scale tools were administered by the interviewers. Adjusted analysis was conducted by multiple linear regression method. Results: Overall, 20.4% of the study participants had good DHL, with a similar proportion between rural and urban areas (rural-20.1% and urban-20.8%, p value-0.889). The median eHealth literacy score among the study participants was 8. While 36.5% and 45.9% had smartphones and standard analogue phones, respectively in urban areas, only 19.5% and 38.4% had smartphones and standard analogue phones, respectively in rural areas. Computer usage in the past month, higher educational qualification, and ownership of mobile phones were significant determinants of DHL. A mild but significant correlation between DHL and health literacy screening scores was found. Conclusion: Considering the low DHL among the ageing population, enabling environment with enhanced access to mobile phones/smartphones and familiarity with information and communication technology gadgets must be established to improve their DHL.

Environmental impact of single-use and reusable flexible cystoscopes.

OBJECTIVES: To compare the carbon footprint and environmental impact of single-use and reusable flexible cystoscopes. MATERIALS AND METHODS: We analysed the expected clinical lifecycle of single-use (Ambu aScope™ 4 Cysto) and reusable (Olympus CYF-V2) flexible cystoscopes, from manufacture to disposal. Performance data on cumulative procedures between repairs and before decommissioning were derived from a high-volume multispecialty practice. We estimated carbon expenditures per-case using published data on endoscope manufacturing, energy consumption during transportation and reprocessing, and solid waste disposal. RESULTS: A fleet of 16 reusable cystoscopes in service for up to 135 months averaged 207 cases between repairs and 3920 cases per lifecycle. Based on a manufacturing carbon footprint of 11.49 kg CO2 /kg device for reusable flexible endoscopes and 8.54 kg CO2 /kg device for single-use endoscopes, the per-case manufacturing cost was 1.37 kg CO2 for single-use devices and 0.0017 kg CO2 for reusable devices. The solid mass of single-use and reusable devices was 0.16 and 0.57 kg, respectively. For reusable devices, the energy consumption of reusable device reprocessing using an automated endoscope reprocessor was 0.20 kg CO2 , and per-case costs of device repackaging and repair were 0.005 and 0.02 kg CO2 , respectively. The total estimated per-case carbon footprint of single-use and reusable devices was 2.40 and 0.53 kg CO2 , respectively, favouring reusable devices. CONCLUSION: In this lifecycle analysis, the environmental impact of reusable flexible cystoscopes is markedly less than single-use cystoscopes. The primary contributor to the per-case carbon cost of reusable devices is energy consumption of reprocessing.

Patient and surgeon preferences for early ileostomy closure following restorative proctectomy for rectal cancer: why aren't we doing it?

BACKGROUND: Early ileostomy closure (EIC), ≤ 2 weeks from creation, is a relatively new practice. Multiple studies have demonstrated that this approach is safe, feasible, and cost-effective. Despite the demonstrated benefits, this is neither routine practice, nor has it been studied, in North America. This study aimed to assess patient and surgeon perspectives about EIC. METHODS: A mixed-methods, cross-sectional study of patients and surgeons was performed. Rectal cancer survivors from a single institution who underwent restorative proctectomy with diverting loop ileostomy and subsequent closure within the last 5 years were contacted. North American surgeons with high rectal cancer volumes (> 20 cases/year) were included. Surveys (patients) and semi-structured interviews (surgeons) were conducted. Analysis employed descriptive statistics and thematic analysis, respectively. RESULTS: Forty-eight patients were surveyed (mean age 65.1 ± 11.8 years; 54.2% male). Stoma closure occurred after a median of 7.7 months (IQR 4.8-10.9) and 50.0% (24) found it "difficult" or "very difficult" to live with their stoma. Patients considered improvement in quality of life and quicker return to normal function the most important advantages of EIC, whereas the idea of two operations in two weeks being too taxing on the body was deemed the biggest disadvantage. Most patients (35, 72.9%) would have opted for EIC. Surgeon interviews (15) revealed 4 overarching themes: (1) there are many benefits to EIC; (2) specific patient characteristics would make EIC an appropriate option; (3) many barriers to implementing EIC exist; and (4) many logistical hurdles need to be addressed for successful implementation. Most surgeons (12, 80.0%) would "definitely want to participate" in a North American randomized-controlled trial (RCT) on EIC for rectal cancer patients. CONCLUSIONS: Implementing EIC poses many logistical challenges. Both patients and surgeons are interested in further exploring EIC and believe it warrants a North American RCT to motivate a change in practice.

Sinonasal undifferentiated carcinoma with metastasis to the extradural spine.

Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive cancer of the sinonasal tract and is often characterized by intracranial invasion. However, SNUC rarely metastasizes to the spine. In this paper, we present a case of extradural metastasis and invasion of the adjacent spine by SNUC. A 42-year-old man presented to our hospital with two-month history of anosmia and nosebleeds. Imaging studies showed a neoplasm of the ethmoid sinus with extension into the anterior cranial fossa. The patient underwent resection of the carcinoma and began chemoradiotherapy. After completing chemoradiotherapy the patient complained of neck pain radiating down the right arm, and imaging showed an extradural mass at the C5 vertebral level. The patient underwent laminectomy for debulking of this tumor. One month later, the patient complained of recurrent weakness and pain in the right shoulder and arm. Imaging showed an extradural tumor wrapping around the C7 and C8 nerve roots, as well as a separate tumor at C2 adherent to the dura. The extradural tumor at C2 was surgically resected. Further imaging showed multiple new soft tissue masses at the thoracic level. We present a case of SNUC metastasis to the extradural spine representing the second case reported in the literature. Peri-dural metastasis and resulting symptoms should be included in the differential diagnosis and assessment of patients with SNUC.

Reviewing the Reviewers Potential Financial Conflicts of Interest in Editorial Boards of Surgery Journals.

OBJECTIVE: To assess the prevalence, magnitude, and disclosure status of industry funding in editorial boards of surgery journals. SUMMARY OF BACKGROUND DATA: Financial COI can bias research. Although authors seeking to publish in peer-reviewed surgery journals are required to provide COI disclosures, editorial board members' COI disclosures are generally not disclosed to readers. METHODS: We present a cross-sectional analysis of industry funding to editorial board members of high-impact surgery journals. We reviewed top US-based surgery journals by impact factor to determine the presence of financial COI in members of each journal's editorial board. The prevalence and magnitude of COI was determined using 2018 industry reported payments found in the Centers for Medicare and Medicaid Services Open Payments database. Journal websites were also reviewed looking for the presence of editorial board disclosure statements. RESULTS: A total of 1002 names of editorial board members from the top 10 high-impact American surgery journals were identified. Of 688 individual physicians based in the USA, 452 (65.7%) were found to have received industry payments in 2018, totaling $21,916,503 with a median funding amount per physician of $1253 (interquartile range $156-$10,769). Funding levels varied by surgical specialty and journal. Editorial board disclosure information was found in only 3.3% of physicians. CONCLUSIONS: Industry funding to editorial board members of high impact surgery journals is prevalent and underreported. Mechanisms of disclosure for COI are needed at the editorial board level to provide readers full transparency. This would acknowledge this COI of editorial board members, and thereby attempt to potentially further reduce the risk of bias in editorial decisions.

Four versus 3 Cycles of Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: Implications for Pathological Response and Survival.

PURPOSE: The ideal number of neoadjuvant chemotherapy (NAC) cycles for muscle-invasive bladder cancer is uncertain with 3 to 4 representing the standard of care (SOC). We compared ypT0 rates and survival between patients receiving 4 versus 3 cycles of NAC with evaluation of chemotherapy-related toxicity for correlation with tumor chemosensitivity and pathological response. MATERIALS AND METHODS: Patients receiving NAC followed by radical cystectomy for cT2-4N0M0 urothelial carcinoma from 2 institutions were included. Primary study groups included 4 cisplatin-based NAC cycles, 3 cisplatin-based NAC cycles, and nonSOC NAC (1-2 cycles or noncisplatin-based) to compare ypT0/≤ypT1 rates and survival. A cohort of patients not receiving NAC was included for pathological reference. RESULTS: Of 693 total patients, 318 (45.9%) received NAC. ypT0 and ≤ypT1 rates were 42/157 (26.8%) and 86/157 (54.8%) for 4 cycles, 38/114 (33.3%) and 71/114 (62.3%) for 3 cycles, and 6/47 (12.8%) and 13/47 (27.7%) for nonSOC (p=0.03 and p <0.01, respectively). Pathological response appeared higher among patients receiving 3 cycles due to toxicity (ypT0: 29/77 [37.7%]; ≤ypT1: 51/77 [66.2%]) but did not reach statistical significance. Toxicities leading to treatment modifications were thrombocytopenia (32.1%), neutropenia (27.2%), renal insufficiency (22.2%), and constitutional symptoms (18.5%). NonSOC patients had lower Kaplan-Meier survival (cT2-cT4N0M0: log-rank p=0.07; cT2N0M0: log-rank p=0.02). There were no statistically significant differences in survival between 4 and 3 cycles (HR 1.00 [95% CI 0.57-1.74], p=0.99). CONCLUSIONS: Patients completing 3 cycles of cisplatin-based NAC have similar pathologic response and short-term survival compared to 4 cycles. Further evaluation of patients experiencing toxicity as a potential marker of tumor chemosensitivity is needed.

mRNA Coronavirus Disease 2019 Vaccine-Associated Myopericarditis in Adolescents: A Survey Study.

In this survey study of institutions across the US, marked variability in evaluation, treatment, and follow-up of adolescents 12 through 18 years of age with mRNA coronavirus disease 2019 (COVID-19) vaccine-associated myopericarditis was noted. Only one adolescent with life-threatening complications was reported, with no deaths at any of the participating institutions.

Incidence, Timing, and Outcomes of Venous Thromboembolism in Patients Undergoing Surgery for Esophagogastric Cancer: A Population-Based Cohort Study.

BACKGROUND: Abdominal surgery and chemotherapy are well-established risk factors for venous thromboembolism (VTE) in patients with cancer, but their specific contribution in patients with esophageal and gastric cancer is unclear. We aim to quantify the risk of VTE, identify risk factors associated with VTE, and determine the association between VTE and survival in patients undergoing surgery for esophageal or gastric cancer. METHODS: A retrospective, population-based cohort study was conducted using linked administrative healthcare databases. We used the Ontario Cancer Registry to identify patients with esophageal or gastric cancer between January 1, 2007 and December 31, 2016 who underwent surgical resection. Incidence of first VTE event was identified using International Classification of Diseases 9 and 10 codes. VTE incidence was calculated at clinically relevant time points 180 days before and after surgery. Logistic regression was used to identify factors associated with VTE with odds ratios (OR) and 95% confidence intervals (CI) reported. Cox proportional hazards regression models were used to estimate associations between covariates and survival. Kaplan-Meier method was used to compare overall (OS) and cancer-specific survival (CSS) by VTE status. RESULTS: A total of 4894 patients had esophagectomy or gastrectomy, of which 8% (n = 383/4894) had VTE. VTE risk was 2.5% (n = 123/4894) 180 days before surgery, 2.8% (n = 138/4894) within 30 days of surgery, and 2.5% (n = 122/4894) from 31 to ≤ 180 days after surgery. Of the patients with VTE within 30 days of surgery, 34% (n = 47/138) were diagnosed after discharge from hospital. Receipt of preoperative chemotherapy was associated with VTE 180 days before surgery (odds ratio [OR] 3.84, 95% confidence interval [CI] 2.41, 6.11). Increased hospital length of stay (LOS) was associated with VTE 30 days after surgery (OR 1.08, 95% CI 1.02, 1.14, per week). Patients with VTE had inferior median OS and CSS (2.2 vs. 3.7 years; 2.3 vs. 4.4 years, respectively). In adjusted models VTE was associated with inferior OS (HR 1.36, 95% CI 1.13, 1.63) and CSS (HR 1.42, 95% CI 1.16, 1.75). CONCLUSIONS: The highest risk of VTE is within 30 days of surgery with one third of patients diagnosed after discharge from hospital. Longer hospital LOS and receipt of preoperative chemotherapy are associated with increased risk of VTE. VTE is an independent risk factor for inferior survival in patients with esophageal or gastric cancer.

Transanal total mesorectal excision for abdominoperineal resection is associated with poor oncological outcomes in rectal cancer patients: A word of caution from a multicentric Canadian cohort study.

AIM: The main objective of this study was to compare the oncological outcomes of patients undergoing abdominoperineal resection (APR) versus low anterior resection (LAR) through a transanal total mesorectal excision (taTME) approach. METHOD: A total of 360 adult patients with a diagnosis of rectal cancer were enrolled at participating centres from the Canadian taTME Expert Collaboration. Forty-three patients received taTME-APR and received 317 taTME-LAR. Demographic, operative, pathological and follow-up data were collected and merged into a single database. Results are presented as hazard ratio (HR) and 95% confidence interval. All analyses were performed in the R environment (v.3.6). RESULTS: The proportion of patients with a positive circumferential radial margin status was higher in the taTME-APR group than the taTME-LAR group (21% vs. 9%, p = 0.001). Complete TME was achieved in 91% of those undergoing APR compared with 96% of those undergoing LAR (p = 0.25). APR was associated with a greater rate of local recurrence relative to LAR, although it was not significant [crude HR = 3.53 (95% CI 0.92-13.53)]. Circumferential margin positivity was significantly associated with a higher rate of systemic recurrence [crude HR = 3.59 (95% CI 1.38-9.3)]. CONCLUSION: Our results demonstrate inferior outcomes in those undergoing taTME-APR compared with taTME-LAR. The use of this technique for this particular indication needs to be carefully considered.

The impact of robotic surgery on a tertiary care colorectal surgery program, an assessment of costs and short term outcomes: A Canadian perspective.

BACKGROUND: Robotic surgery for colorectal pathology has gained interest as it can overcome technical challenges and limitations of traditional laparoscopic surgery. A lack of training and costs have been cited as reasons for limiting its use in Canada. The objective of this paper was to assess the impact of robotic surgery on outcomes and costs in a Canadian setting. METHODS: This is a retrospective study of consecutive patients undergoing left sided colorectal surgery ("Pre-Robotic Phase" n = 145 vs. "Post Robotic Phase" n = 150) and a single tertiary care centre in Ontario, Canada. Utilization and success of minimally invasive surgery (MIS), length of stay, complications and hospital costs were compared. Univariate and Multivariate analysis was used for these comparisons. RESULTS: Characteristics, diagnosis and type of resection were similar between groups. Robotic Implementation resulted in higher rates of successful MIS (i.e. attempt at MIS without conversion) (85% vs. 47%, P < 0.001), shorter mean length of stay (4.7 days vs. 8.4 days, P < 0.001), and similar mean operative times (3.9 h vs. 3.9 h, P = 0.93). Emergency Department visits were fewer in the Robotic Phase (24% vs. 34%, P = 0.04), with no difference in readmission, anastomotic leak or unplanned reoperation. After robotic implementation, the mean total hospital costs decreased, but this was not statistically significant (-$1453, 95% CI -$3974 to +$1068, P = 0.25). Regression analysis, adjusting for age, gender, obesity, ASA and procedure showed similar findings (Robotic Phase -$657, 95% CI -$3038 to +$1724, vs Pre Robotic Phase [Reference], P = 0.59). INTERPRETATION: Implementation of a robotic colorectal surgery program in a Canadian tertiary care centre showed improved clinical outcomes, without a significant increase in the cost of care. Although this study is from a single institution, we have demonstrated that robotic colorectal surgery is feasible and can be cost effective in the right setting.

Myopericarditis after messenger RNA Coronavirus Disease 2019 Vaccination in Adolescents 12 to 18 Years of Age.

OBJECTIVES: To characterize the clinical course and outcomes of children 12-18 years of age who developed probable myopericarditis after vaccination with the Pfizer-BioNTech (BNT162b2) coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccine. STUDY DESIGN: A cross-sectional study of 25 children, aged 12-18 years, diagnosed with probable myopericarditis after COVID-19 mRNA vaccination as per the Centers for Disease Control and Prevention criteria for myopericarditis at 8 US centers between May 10, 2021, and June 20, 2021. We retrospectively collected the following data: demographics, severe acute respiratory syndrome coronavirus 2 virus detection or serologic testing, clinical manifestations, laboratory test results, imaging study results, treatment, and time to resolutions of symptoms. RESULTS: Most (88%) cases followed the second dose of vaccine, and chest pain (100%) was the most common presenting symptom. Patients came to medical attention a median of 2 days (range, <1-20 days) after receipt of Pfizer mRNA COVID-19 vaccination. All adolescents had an elevated plasma troponin concentration. Echocardiographic abnormalities were infrequent, and 92% showed normal cardiac function at presentation. However, cardiac magnetic resonance imaging, obtained in 16 patients (64%), revealed that 15 (94%) had late gadolinium enhancement consistent with myopericarditis. Most were treated with ibuprofen or an equivalent nonsteroidal anti-inflammatory drug for symptomatic relief. One patient was given a corticosteroid orally after the initial administration of ibuprofen or an nonsteroidal anti-inflammatory drug; 2 patients also received intravenous immune globulin. Symptom resolution was observed within 7 days in all patients. CONCLUSIONS: Our data suggest that symptoms owing to myopericarditis after the mRNA COVID-19 vaccination tend to be mild and transient. Approximately two-thirds of patients underwent cardiac magnetic resonance imaging, which revealed evidence of myocardial inflammation despite a lack of echocardiographic abnormalities.

C5 Inhibitor Avacincaptad Pegol for Geographic Atrophy Due to Age-Related Macular Degeneration: A Randomized Pivotal Phase 2/3 Trial.

PURPOSE: The complement pathway may play a key role in the pathogenesis of age-related macular degeneration (AMD). The safety and efficacy of avacincaptad pegol (Zimura, IVERIC bio Inc, New York, NY), a C5 inhibitor, were assessed in participants with geographic atrophy (GA) secondary to AMD (GATHER1 Study). DESIGN: International, prospective, randomized, double-masked, sham-controlled, pivotal phase 2/3 clinical trial. PARTICIPANTS: A total of 286 participants with GA secondary to AMD. MAIN OUTCOME MEASURES: The primary efficacy endpoint was the mean rate of change in GA over 12 months measured by fundus autofluorescence (FAF) at 3 timepoints: baseline, month 6, and month 12. RESULTS: The reduction in the mean rate of GA growth (square root transformation) over 12 months was 27.4% (P = 0.0072) for the avacincaptad pegol 2 mg cohort and 27.8% (P = 0.0051) for the avacincaptad pegol 4 mg cohort compared with their corresponding sham cohorts. The results for both dose groups were statistically significant. Avacincaptad pegol was generally well tolerated after monthly administration over 12 months. There were no avacincaptad pegol-related adverse events (AEs) or inflammation. Further, there were no ocular serious AEs (SAEs) and no cases of endophthalmitis. The most frequent ocular AEs were related to the injection procedure. CONCLUSIONS: Intravitreal administration of avacincaptad pegol 2 mg and 4 mg led to a significant reduction of GA growth in eyes with AMD over a 12-month period. Because C5 inhibition theoretically preserves C3 activity, it may offer additional safety advantages. A second confirmatory pivotal clinical trial is underway to confirm the efficacy and safety of avacincaptad pegol in slowing the GA growth (GATHER2 Study).