Citations

Background: Primary colorectal sarcomatoid carcinoma is a rare and aggressive malignant neoplasm that displays mixed epithelial and mesenchymal differentiation, with uncertain histogenesis. First described in 1986, there is a paucity of literature related to this condition and there are no evidence-based treatment guidelines. The aim of our study is to present our 30-year experience with primary colorectal sarcomatoid carcinoma. Methods: Retrospective single-center analysis of all patients treated for primary colorectal sarcomatoid carcinoma from 1992 to 2022. The primary outcome was response to treatment strategy and overall survival. Results: A total of six cases met eligibility criteria. Three were male (50%) with a mean age at diagnosis of 59 years (range, 49-72). Four neoplasms were located in the rectum (66%) and two in the colon. Mean tumor size at diagnosis was 4.8 cm (range, 2.8-7.0). Three patients were treated endoscopically and three underwent oncologic surgical resection. Five experienced recurrence and one expired from other comorbidities. The mean survival among those with colonic and rectal sarcomatoid carcinoma was 7 months (range, 3-11) and 39 months (range, 9-60), respectively. Discussion: Primary colorectal sarcomatoid carcinoma is a rare malignant tumor with poor prognosis. Treatment modalities have not been standardized and despite multimodal therapy, disease recurrence and/or metastasis is likely to occur. Further studies are necessary to determine optimal treatment to improve outcomes.

Cutaneous paraneoplastic syndromes due to Hodgkin lymphoma present with a wide spectrum of clinical manifestations from generalized pruritus to exfoliative erythroderma. We summarize the clinical findings and outcomes of 14 patients with Hodgkin lymphoma and associated cutaneous paraneoplastic syndromes treated at Mayo Clinic over the past 3 decades. Cutaneous paraneoplastic syndromes may be present at the time of lymphoma diagnosis, whereas in other patients, it may appear at the time of relapse, including patients with initial absence of cutaneous manifestations during the initial lymphoma presentation. Our results indicate that complete resolution of the paraneoplastic syndrome is associated with significantly improved overall survival. Recognition of cutaneous paraneoplastic syndromes is a crucial surrogate of relapsed malignancy and treatment requires targeting the underlying malignancy.

ObjectiveOur objective was to evaluate the effect of glucocorticoid regimens on renal response, infections, and mortality among patients with lupus nephritis (LN).MethodsWe performed a systematic review and meta‐analysis of the control arms of randomized clinical trials (RCTs). We included RCTs of biopsy‐proven LN that used a protocolized regimen of glucocorticoids in combination with mycophenolic acid analogs or cyclophosphamide and reported the outcomes of complete response (CR), serious infections, and death. The starting dosage of glucocorticoids, tapering method, and administration of glucocorticoid pulses were abstracted. Meta‐analysis of proportions, meta‐regression, and subgroup meta‐analysis were performed at 6 and 12 months for all outcomes.ResultsFifty RCT arms (3,231 patients with LN) were included. The predicted rates of CR, serious infections, and death when starting on oral prednisone at 25 mg/day without pulses were 19.5% (95% confidence interval [CI] 7.3–31.5), 3.2% (95% CI 2.4–4.0), and 0.2% (95% CI 0.0–0.4), respectively. Starting on prednisone at 60 mg/day (without pulses) increased the rates to 34.6% (95% CI 16.9–52.3), 12.1% (95% CI 9.3–14.9), and 2.7% (95% CI 0.0–5.3), respectively. Adding glucocorticoid pulses increased the rates of CR and death but not serious infections. We observed a dose–response gradient between the initial glucocorticoid dosage and all the outcomes at six months after accounting for the administration of glucocorticoid pulses, underlying immunosuppressant, and baseline proteinuria.ConclusionA higher exposure to glucocorticoids during the initial therapy of LN was associated with better renal outcomes at the cost of increased infections and death.

Magnetic resonance imaging (MRI) can facilitate accurate organ delineation and optimal dose distributions in high-dose-rate (HDR) MRI-Assisted Radiosurgery (MARS). Its use for this purpose has been limited by the lack of positive-contrast MRI markers that can clearly delineate the lumen of the HDR applicator and precisely show the path of the HDR source on T1- and T2-weighted MRI sequences. We investigated a novel MRI positive-contrast HDR brachytherapy or interventional radiotherapy line marker, C4:S, consisting of C4 (visible on T1-weighted images) complexed with saline. Longitudinal relaxation time (T1) and transverse relaxation time (T2) for C4:S were measured on a 1.5 T MRI scanner. High-density polyethylene (HDPE) tubing filled with C4:S as an HDR brachytherapy line marker was tested for visibility on T1- and T2-weighted MRI sequences in a tissue-equivalent female ultrasound training pelvis phantom. Relaxivity measurements indicated that C4:S solution had good T1-weighted contrast (relative to oil [fat] signal intensity) and good T2-weighted contrast (relative to water signal intensity) at both room temperature (relaxivity ratio > 1; r2/r1 = 1.43) and body temperature (relaxivity ratio > 1; r2/r1 = 1.38). These measurements were verified by the positive visualization of the C4:S (C4/saline 50:50) HDPE tube HDR brachytherapy line marker on both T1- and T2-weighted MRI sequences. Orientation did not affect the relaxivity of the C4:S contrast solution. C4:S encapsulated in HDPE tubing can be visualized as a positive line marker on both T1- and T2-weighted MRI sequences. MRI-guided HDR planning may be possible with these novel line markers for HDR MARS for several types of cancer.

Abstract Background Precision medicine, sometimes referred to as personalized medicine, is rapidly changing the possibilities for how people will engage health care in the near future. As technology to support precision medicine exponentially develops, there is an urgent need to proactively improve our understanding of precision medicine and pose important research questions (RQs) related to its inclusion in the education and training of future emergency physicians. Methods A seven‐step process was employed to develop a research agenda exploring the intersection of precision and emergency medicine education/training. A literature search of articles about precision medicine was conducted first, which informed the creation of future four scenarios in which trainees and practicing physicians regularly discuss and incorporate precision medicine tools into their discussions and work. Based on these futurist narratives, potential education RQs were generated by an expert panel. A total of 59 initial questions were subsequently categorized and refined to a priority list through a nominal group voting method. The top/priority questions were presented at the 2023 SAEM Consensus Conference on Precision Medicine, Austin, Texas, for further input. Results Eight high‐value education RQs were developed, reflecting a holistic view of the challenges and opportunities for precision medicine education in the knowledge, skills, and attitudes relevant to emergency medicine. These questions contend with topics such as most effective pedagogical methods; intended resulting outcomes and behaviors; the generational differences between practicing emergency physicians, educators, and future trainees; and the desires and expectations of patients. Conclusions Emergency medicine and emergency physicians must be prepared to understand precision medicine and incorporate this information into their “toolbox” of thinking, problem solving, and communication with patients and colleagues. This research agenda on how best to educate future emergency physicians in the use of personalized data to provide optimal health care is the focus of this article.

Background and Aims: Acute-on-chronic liver failure (ACLF) is a complication of cirrhosis characterized by multiple organ failure and high short-term mortality. The pathophysiology of ACLF involves elevated systemic inflammation leading to organ failure, along with immune dysfunction that heightens susceptibility to bacterial infections. However, it is unclear how these aspects are associated with recovery and nonrecovery in ACLF. Approach and Results: Here, we mapped the single-cell transcriptome of circulating immune cells from patients with ACLF and acute decompensated (AD) cirrhosis and healthy individuals. We further interrogate how these findings, as well as immunometabolic and functional profiles, associate with ACLF-recovery (ACLF-R) or nonrecovery (ACLF-NR). Our analysis unveiled 2 distinct states of classical monocytes (cMons). Hereto, ACLF-R cMons were characterized by transcripts associated with immune and stress tolerance, including anti-inflammatory genes such as RETN and LGALS1. Additional metabolomic and functional validation experiments implicated an elevated oxidative phosphorylation metabolic program as well as an impaired ACLF-R cMon functionality. Interestingly, we observed a common stress-induced tolerant state, oxidative phosphorylation program, and blunted activation among lymphoid populations in patients with ACLF-R. Conversely, ACLF-NR cMon featured elevated expression of inflammatory and stress response genes such as VIM, LGALS2, and TREM1, along with blunted metabolic activity and increased functionality. Conclusions: This study identifies distinct immunometabolic cellular states that contribute to disease outcomes in patients with ACLF. Our findings provide valuable insights into the pathogenesis of ACLF, shedding light on factors driving either recovery or nonrecovery phenotypes, which may be harnessed as potential therapeutic targets in the future.

Abstract Background and Aims Non-invasive cross-sectional imaging via magnetic resonance enterography [MRE] offers excellent accuracy for the diagnosis of stricturing complications in Crohn’s disease [CD] but is limited in determining the degrees of fibrosis and inflammation within a stricture. We developed and validated a radiomics-based machine-learning model for separately characterizing the degree of histopathological inflammation and fibrosis in CD strictures and compared it to centrally read visual radiologist scoring of MRE. Methods This single-centre, cross-sectional study included 51 CD patients [n = 34 for discovery; n = 17 for validation] with terminal ileal strictures confirmed on diagnostic MRE within 15 weeks of resection. Histopathological specimens were scored for inflammation and fibrosis and spatially linked with corresponding pre-surgical MRE sequences. Annotated stricture regions on MRE were scored visually by radiologists as well as underwent 3D radiomics-based machine learning analysis; both were evaluated against histopathology. Results Two distinct sets of radiomic features capturing textural heterogeneity within strictures were linked with each of severe inflammation or severe fibrosis across both the discovery (area under the curve [AUC = 0.69, 0.83] and validation [AUC = 0.67, 0.78] cohorts. Radiologist visual scoring had an AUC = 0.67 for identifying severe inflammation and AUC = 0.35 for severe fibrosis. Use of combined radiomics and radiologist scoring robustly augmented identification of severe inflammation [AUC = 0.79] and modestly improved assessment of severe fibrosis [AUC = 0.79 for severe fibrosis] over individual approaches. Conclusions Radiomic features of CD strictures on MRE can accurately identify severe histopathological inflammation and severe histopathological fibrosis, as well as augment performance of the radiologist visual scoring in stricture characterization.