Citations

AimsWe compiled two cohorts of colorectal adenosquamous carcinoma (ASC) to describe its histologic and molecular aspects using modern parameters to compare them with literature reports using meta‐analysis of cohorts and individual case series.Methods and ResultsWe identified 53 colorectal ASC from 19 North American academic medical centres, in addition to national database reports on 94 Dutch cases. We analysed available clinical, histologic, and immunohistochemical features and patient outcome. ASC comprised 0.02% of colorectal cancers in the Dutch database. The median cohort patient ages at resection were 65 and 69 years (North American and Dutch cohorts, respectively), with a roughly equal male:female ratio. The squamous component represented between 5% and 95% of each tumour, with a median of 50%. Tumour‐infiltrating lymphocytes (TILs) were generally low (66%), and tumour budding was often Bd1 (64%). Most cases were pT3 (55%) or pT4 (40%), with nodal metastases in more than half (58%). Twenty‐three cases (43%) metastasized distantly, most commonly to the liver. Mismatch repair (MMR) deficiency was identified in 34% of the cases. Follow‐up was available for 48 patients; 13 (27%) had recurrent disease and 29 (60%) died. A total of 31 patients progressed, with median time to progression of 18 months. Available data for the Dutch cohort revealed largely similar findings, as did review of cases in the literature.ConclusionColorectal ASC usually presents at an advanced stage. Despite high rates of MMR deficiency and low tumour budding, TILs were generally low, and there is a high recurrence rate and poor prognosis.

Background: Multiple randomized clinical trials failed to show benefit of anticoagulation over antiplatelets in the secondary prevention for embolic stroke of undetermined source (ESUS). However, the benefit of combination antithrombotic regimens remains unexplored in the same patient population. Methods: This is a subgroup analysis of a multicenter retrospective observational cohort of consecutive adult patients with ESUS (n=27 sites, 2015-2024). Comparisons were made between patients treated with single (SAPT) or dual antiplatelet therapy (DAPT), exclusive anticoagulation (AC) (direct oral anticoagulant, vitamin K antagonist, low molecular weight heparin) and combination anticoagulation and antiplatelet therapy initiated within the first 7 days of index stroke. The primary composite outcome of recurrent ischemic stroke, major bleeding, or death was assessed using unadjusted and adjusted Cox proportional hazards regression. Secondary outcomes were individual outcomes of recurrent ischemic stroke, major bleeding, or death. Results: Of the 2201 included patients, 1456 (66.1%) were on SAPT, 527 (23.9%) were on DAPT, 195 (8.8%) were on exclusive AC and 23 (1.0%) were on AC+AP (all of which were on DAPT). Patients treated with AC+AP were older (median 66 years [IQR 51-78]), more likely to have history of hypertension, stroke, hyperlipidemia, PFO and left atrial enlargement. Compared to SAPT, all treatment strategies were associated with similar risk of the primary outcomes in the unadjusted and adjusted cox regression. Similarly, there was no difference in individual outcomes including recurrent stroke, major bleeding and death in the adjusted cox regression. However, there was an increased risk of major bleeding with AC+AP in the unadjusted cox regression (HR 4.0, [95% CI 1.2-12.8], p=0.02) but not in the adjusted model when compared to SAPT. Also, DAPT was associated with lower risk of death than SAPT in the unadjusted model (HR 0.61 [95% CI 0.4-0.8],p=0.005) but not the adjusted model. Additionally, when adjusted by the HASBLED score, there was no difference in major bleeding when AC+AP was compared to SAPT. Conclusion: Over 90% of ESUS patients in this cohort were prescribed SAPT or DAPT. Antithrombotic therapy with DAPT, exclusive AC, or AC+AP was not associated with any lower risk of recurrent ischemic stroke, major bleeding and death compared with SAPT in an unselected cohort of ESUS patients.

Introduction: Four randomized clinical trials have not demonstrated the superiority of anticoagulation over antiplatelet therapy in the prevention of recurrent embolic stroke of undetermined source (ESUS). In this multicenter observational cohort study, we evaluated long-term outcomes associated with various antithrombotic strategies according to potential embolic sources. Methods: A multicenter retrospective observational cohort of consecutive adult patients with ESUS was queried (n=27 sites). Comparisons were made between patients treated with single or combination antiplatelet therapy versus anticoagulation (direct oral anticoagulant, vitamin K antagonist, low molecular weight heparin) with or without antiplatelet therapy initiated within 7 days of stroke. The primary composite outcome of recurrent stroke, major bleeding, or death was assessed using unadjusted and adjusted Cox proportional hazards regression, with clustering by site. Causal inference was assessed using inverse probability of treatment weighted regression adjustment (IPTWRA), accounting for propensity for antiplatelet treatment, with effect estimates summarized as the average treatment effect (ATE) over time (in days). Adjusted models accounted for age, stroke severity, vascular risk factors, and major categories of potential embolic sources. Results: Of the 2201 included patients (n=218 treated with anticoagulation) followed over a median of 564 days (interquartile range [IQR] 154-1124), the median age was 65y (IQR 54-74) and 49.8% were female. Patients treated with anticoagulation were older with more frequent previous stroke, concomitant left ventricular dysfunction, and more severe deficits. Over 4541 person-years of follow-up, the annualized incidence rate of the primary outcome was 14.6% (95% confidence interval [CI], 13.6%-15.8%). Compared to anticoagulation, antiplatelet(s) use was not associated with a lower risk of the primary outcome in the adjusted Cox model (HR 0.91, 95% CI, 0.64-1.29) or in the IPTWRA model (average treatment effect 0.14, 95% CI, -1376.6 to 1376.9). Major bleeding events trended toward significance in the adjusted Cox model (HR 0.51, 95% CI 0.25-1.04) but were no different with IPTWRA (ATE 58.9, 95% CI, -125.4 to 243.2). Conclusions: These results validate the observations of randomized trials indicating a lack of benefit of anticoagulation over antiplatelet therapy in ESUS. A more detailed analysis of heterogeneity of treatment effect is under way.

Background: It is known that there are discrepancies between insurance status and access to care for a variety of health conditions. In addition, differences have been shown in initial in-hospital management of stroke as well as outcomes in the acute setting. We sought to examine the relationship between insurance status and risk of recurrent stroke, major bleeding or death following an incident cryptogenic stroke. Methods: Patients with cryptogenic stroke included in a multicenter (n=27 sites) retrospective observational cohort and complete insurance status were evaluated for a primary composite outcome of recurrent stroke, major bleeding, or death. Insurance providers were categorized by Private/Veterans Administration, Medicare, Other, and Medicaid/pending/None, with the primary carrier ranked in that order when multiple insurance carriers applied. Descriptive statistics and an adjusted Cox proportional hazards regression were used to associate the primary insurance provider with the composite outcome, and with each unique secondary outcome, adjusting for age, stroke severity, pre-stroke disability, atherosclerotic risk factors, and potential embolic sources (e.g., patent foramen ovale). Results: Of the 2201 patients, 2006 (91.1%) had reported insurance information and were followed for a median of 1.50 years (interquartile range [IQR 0.41 - 2.99y]). The majority of patients were primary Medicare beneficiaries (42.3%), followed by private insurance (36.7%), Medicaid/none (18.1%) and Other (2.9%). Although there were important differences in demographic and neurodiagnostic results across insurance groups, compared to Private/VA beneficiaries, beneficiaries for Medicaid/pending/none had a higher rate of the composite outcome in adjusted regression (adjusted hazard ratio [HR] 1.35, 95% confidence interval [CI], 1.07-1.69) which was driven largely by the higher rate of recurrent stroke (adjusted HR 1.33, 95%CI, 1.02-1.73) with no significant difference in rate of major bleeding or death (p>0.05 for both). Conclusions: Independent of age, race, pre-existing disability, and atherosclerotic risk factors, insurance status was independently predictive of recurrent stroke in this diverse cohort of cryptogenic stroke.

Abstract Globally, an estimated 300 million individuals have sickle cell trait (SCT), the carrier state for sickle cell disease (SCD). Although SCD is associated with increased morbidity and shortened life span, SCT has a life span comparable with that of the general population. However, “sickle cell crisis” has been used as a cause of death for decedents with SCT in reports of exertion-related death in athletes, military personnel, and individuals in police custody. To appraise this practice, the American Society of Hematology convened an expert panel of hematologists and forensic pathologists to conduct a systematic review of the literature relating to the occurrence of sickle cell pain crises and exertion-related mortality in people with SCT. Multiple bibliographic databases were searched with controlled vocabulary and keywords related to “sickle cell trait,” “vaso-occlusive pain,” and “death,” yielding 18 of 1474 citations. Independent pairs of reviewers selected studies and extracted data. We found no studies comparing uncomplicated acute pain crises in individuals with SCT and SCD. Additionally, no study was identified to support the occurrence of acute vaso-occlusive pain crises in individuals with SCT. Furthermore, this systematic review did not identify any evidence to support an association between SCT and sudden unexplained death in the absence of exertion-related rhabdomyolysis. We conclude that there are no data to support the diagnosis of acute vaso-occlusive sickle cell crisis as a cause of death in SCT, nor does the available evidence support the use of SCT as a cause of exertion-related death without rhabdomyolysis.

Abstract Background At the time of hospice enrollment, patients are asked whether they would potentially want antibiotics. This is little information regarding which patients are more likely to receive these antibiotics or the impact on comfort or longevity. To help guide discussions with patients and families and target future stewardship interventions, we sought to characterize the use of antibiotics in the outpatient hospice setting. Methods We performed a retrospective review of patients enrolled in hospice with the Mayo Clinic Health System -Midwest from 1/1/2017 through 1/1/2023. For those with documented Hospice Qualifying Condition (HQC), we assessed age at enrollment, gender, survival time (ST), and Charleston Comorbidity Index (CCI). We documented which antibiotics were prescribed and compared the rate of prescription based on the above characteristics. Results We identified 6452 patients with identifiable HQC. Of these, 1281 patients (19.8%) received 4173 antibiotic prescriptions. After removing refilled prescriptions, there were 2037 new prescriptions. Cephalosporins were the most common class of antibiotics prescribed (24.4% of antibiotics prescribed), followed by fluoroquinolones (19.9%), penicillin derivatives (14.4%), and trimethoprim (10.4%) (fig 1). Pulmonary (28.6%) and GI (31.9%) HQCs were most likely to receive antibiotics, neurologic was least likely (fig 2). There was no difference of age for those receiving antibiotics (80.6 yr) vs those not receiving (80.3 yr [p=0.53]), or for gender (male vs female OR 0.97 [0.86-1.10). CCI was higher in those patients who received antibiotics (4.3) than those not receiving (3.93, p< 0.001). Patients were more likely to receive antibiotics the longer they survived on hospice (4.7% surviving < 7d, 47.7% surviving >6mo – fig 3). Conclusion Antibiotics are an important pharmaceutical tool in the hospice setting. Nearly 20% of patients in hospice will receive antibiotics during their hospice course, with higher chance in those surviving longer periods and those enrolled for GI or pulmonary reasons. Discussions of antibiotic are crucial for these groups, and antimicrobial steward efforts should consider focusing on these patients. Disclosures All Authors: No reported disclosures

Abstract Background Minocycline is a second-generation tetracycline with a broad antimicrobial spectrum. It is often used in chronic suppression of musculoskeletal infections, given activity against gram positive organisms. Efficacy of Minocycline against gram negative skin and soft tissue infection has not previously been defined. In this study, we review in vitro minocycline efficacy against isolates from skin, muscle, and bone sources.Fig 1.Organisms isolated Methods We conducted a retrospective review of all minocycline susceptibility testing performed on musculoskeletal GNB isolates performed at the Mayo Clinic reference lab between 2013-2022. We describe the isolates broken down by site of culture and organism isolated. Then, we calculated the overall susceptibility of these isolates to Minocycline and susceptibility of the most common 6 organisms isolated.Fig 2.Sites of gram negative isolation Results During the study timeframe, we identified 13,567 gram negative isolates from musculoskeletal sites. Of 330 species identified, 19 were identified in at least 100 isolates (fig 1). Of 36 unique sites, 19 sites were each identified in at least 100 isolates (fig 2). 1920 isolates were tested for susceptibility to minocycline. Of these, 1584 (82.5%) were susceptible to minocycline. Of the most common organisms identified and tested for minocycline susceptibility, 99% of Stenotrophomonas maltophilia, 83% of Enterobacter cloacae, 80% of Escherichia coli, 68% of Acinetobacter baumanii, 1% of Proteus mirabilis, 53% of Klebsiella pneumoniae, 65% of Serratia marcescens isolates were susceptible to minocycline (fig 3). Pseudomonas aeruginosa isolates were not tested, due to innate resistance.Fig 3.Minocycline susceptibility compared to key organisms Conclusion A majority of skin and soft tissue cultures positive for Gram negative isolates were below the waist line. Of these, we reported organisms most commonly found. Minocycline showed in vitro activity against some commonly isolated gram negative organisms, especially E.coli, Acinetobacter, and Stenotrophomonas. Further research is needed into the efficacy of minocycline in gram negative skin and soft tissue infections, but it may represent a viable oral option, especially in the end of life. Disclosures All Authors: No reported disclosures