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Background: Accurate risk stratification of pulmonary embolism (PE) can reduce unnecessary imaging. We investigated the extent to which the American College of Physicians (ACP) guideline for evaluation of patients with suspected PE could be applied to cancer patients in the emergency department of a comprehensive cancer center.Materials and Methods: Data from cancer patients who underwent CT pulmonary angiography (CTPA) between August 1, 2015, and October 31, 2015, were collected. We assessed each patient's diagnostic workup for its adherence to the ACP guideline in terms of clinical risk stratification and age-adjusted d-dimer level and the degree to which these factors were associated with PE.Results: Of the 380 patients identified, 213 (56%) underwent CTPA indicated per the ACP guideline, and 78 (21%) underwent CTPA not indicated per the guideline. Only one of the patients who underwent nonindicated CTPA had a PE. Fifty-seven patients underwent unnecessary d-dimer evaluation, and 71 patients with negative d-dimer test results underwent nonindicated CTPA. PEs were found in 6 of 108 (6%) low-risk patients, 22 of 219 (10%) intermediate-risk patients, and 13 of 53 (25%) high-risk patients. The ACP guideline had negative predictive value of 99% (95% confidence interval: 93%-100%) and sensitivity of 97% (95% confidence interval: 86%-100%) in predicting PE.Conclusion: The ACP guideline has good sensitivity for detecting PE in cancer patients and thus can be applied in this population. Compliance with the ACP guideline when evaluating cancer patients with suspected PE could reduce the use of unnecessary imaging and laboratory studies. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the postrelapse survival of relapsed osteosarcoma with pulmonary metastases in patients who received pulmonary metastasectomy using intent to treat and propensity score analysis. Patients with osteosarcoma who relapsed with pulmonary metastases between 2004 and 2018 who were treated in a hospital affiliated with a medical school were included. All the enrolled patients were evaluated as operable with assessment algorithm at the time of diagnosis of pulmonary relapse and intent to treat analysis was done. Multiple propensity score methods (eg, matching, stratification, covariate adjustment, and inverse probability of treatment weighting) were performed to balance confounding bias. Cox proportional hazards regression and the Kaplan-Meier method were used to evaluate patient survival. A total of 125 patients met the study criteria. Of these, 59 (47.2%) patients received pulmonary metastasectomy combined with chemotherapy and 66 (52.8%) received chemotherapy alone. The 2-year and 5-year postrelapse survival rate of metastasectomy group and nonmetastasectomy group were 68.4% versus 25.0% and 41.0% versus 0%, respectively. The median postrelapse survival was 24.9 versus 13.5 months, respectively. Pulmonary metastasectomy was independently associated with improved survival (hazard ratio, 0.185; 95% confidence interval, 0.103-0.330; P <.001). These results were confirmed by multiple propensity score analyses. Further stratified analysis revealed that the survival advantage associated with metastasectomy was not significant in patients with metastases involving ≥3 lung lobes and patients with very high pretreatment serum alkaline phosphatase (more than twice the upper limit). Pulmonary metastasectomy is associated with improved survival in patients with recurrent osteosarcoma. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: The role of surgical treatment for juvenile myasthenia gravis (MG) remains unclear. Here, we performed a retrospective study to evaluate the predictors of clinical outcome of juvenile MG treated with extended transsternal thymectomy. Methods: A total of 141 consecutive juvenile MG patients underwent extended transsternal thymectomy at an academic hospital over a 20-year period were reviewed. Thymectomy was performed in patients resistant to pyridostigmine therapy, with generalized symptoms or ocular MG with partial response to pyridostigmine for more than 2 years. Variables potentially affecting responses to extended transsternal thymectomy were evaluated using Kaplan-Meier analysis and Cox regression modeling. Complete stable remission (CSR) is defined as asymptomatic without medication for more than 12 months. Results: There were 96 patients with ocular MG and 45 generalized MG, the median age at disease onset was 6 years and that at operation was 12 years. Among 135 patients with complete postoperative follow-up, 34 (25.2%) achieved CSR, 28 (20.7%) experienced pharmacologic remission, 61 (45.2%) improved, 5 (3.7%) remained stable, and 7 (5.2%) deteriorated. The results indicated the disease-onset age greater than 6 years and age at operation greater than 12 years were both positively associated with CSR responses. Postoperative steroid treatments in ocular MG and preoperative disease duration in generalized MG (>12 months) were negatively associated with CSR responses. Conclusions: Extended transsternal thymectomy for Chinese juvenile MG patients has an efficacy comparable with reports from other ethnicities. Juvenile patients with disease-onset age greater than 6 years, age at operation greater than 12 years, and shorter disease duration of generalized MG are associated with favorable clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: The optimal treatment for ocular myasthenia gravis (OMG) remains controversial. We conducted a review of the long-term clinical outcomes of Chinese patients with OMG after extended transsternal thymectomy (ETT) to determine the efficacy of this procedure as a treatment for OMG. Methods: We reviewed the cases of 115 consecutive patients with OMG who underwent ETT at our Myasthenia Gravis Research Center between January 2006 and December 2008. Extended transsternal thymectomy was done in patients who had thymoma, resistance to pyridostigmine therapy, or relapse after immunosuppressive therapy. The patients'' postoperative responses were defined as strict complete remission (SCR), consisting of an asymptomatic status without medication for more than 12 months; general complete remission (GCR), consisting of an asymptomatic status with low-dose single-drug therapy or without medication for more than 12 months; or improvement, consisting of fewer symptoms or less of a need for medication than before surgery. Results: The overall complication rate was 7.8%. None of the patients experienced a myasthenic crisis, progression to generalized myasthenia gravis, or mortality. Hyperplasia of the thymus was present in 106 of the 115 patients (92.2%). Among 110 patients on whom follow-up was done postoperatively, 29 (26.4%) were in SCR, 64 (58.2%) showed improvement, 7 (6.4%) remained unchanged, and 10 (9.1%) had a worsening of their conditions. Kaplan-Meier analysis revealed rates of GCR of 41.8% at 24 months and 47.3% at 48 months after surgery, and rates of SCR of 24.5% at 24 months and 26.4% at 48 months. Both univariate analysis and multivariate Cox regression analysis revealed that only preoperative duration of illness was positively associated with GCR (p < 0.001). Conclusions: The results of the review indicate that ETT is a safe and effective treatment for OMG, especially in patients with illness of shorter duration. [Copyright &y& Elsevier]

Background: The diagnosis of myasthenia gravis (MG) remains challenging. We performed a proteome-wide search for potential serum protein diagnostic markers for MG using surface-enhanced laser desorption/ionization (SELDI) time-of-flight mass spectrometry (TOFMS). Methods: Proteomic spectra from 80 MG patients and 80 healthy individuals were generated by SELDI. Samples from 56 MG patients and 56 healthy individuals in the training set were analyzed to set up the decision tree. Samples from 24 MG patients and 24 healthy individuals were used for cross-validation testing. Results: The SELDI TOFMS analysis generated 101 peaks, representing differentially expressed proteins between 1000 and 20000 Da. Among them, 9 peaks were down-regulated and 30 others were up-regulated in the MG sera compared with the controls. The decision tree used the peak at M4168.94 Da and M1122.57 Da as splitters in the classification process. In the training set, 112 samples were classified as MG or control group, with a sensitivity of 100% and specificity of 89.3%; the 10-fold cross-validated analysis identified the optimal decision tree with the lowest relative cross-validated cost of 0.080. In the test set, the decision tree generated was able to identify 20 of 24 MG patients and 21 of 24 healthy individuals with a sensitivity of 83.3% and a specificity of 87.5%. Conclusions: SELDI TOFMS is a useful tool for the detection and identification of potential serum biomarkers that can diagnose MG with high sensitivity and specificity. [Copyright &y& Elsevier]

Background & Aims: Antidiabetic drugs have been found to have various effects on cancer in experimental systems and in epidemiologic studies, although the association between these therapeutics and the risk of human pancreatic cancer has not been explored. We investigated the effect of antidiabetic therapies on the risk of pancreatic cancer. Methods: A hospital-based case-control study was conducted at M. D. Anderson Cancer Center from 2004 to 2008 involving 973 patients with pancreatic adenocarcinoma (including 259 diabetic patients) and 863 controls (including 109 diabetic patients). Information on diabetes history and other risk factors was collected by personal interview. The frequencies of use of insulin, insulin secretagogues, metformin, and other antidiabetic medications among diabetic patients were compared between cases and controls. The risk of pancreatic cancer was estimated using unconditional logistic regression analysis. Results: Diabetic patients who had taken metformin had a significantly lower risk of pancreatic cancer compared with those who had not taken metformin (odds ratio, 0.38; 95% confidence interval, 0.22–0.69; P = .001), with adjustments for potential confounders. This difference remained statistically significant when the analysis was restricted to patients with a duration of diabetes >2 years or those who never used insulin. In contrast, diabetic patients who had taken insulin or insulin secretagogues had a significantly higher risk of pancreatic cancer compared with diabetic patients who had not taken these drugs. Conclusions: Metformin use was associated with reduced risk, and insulin or insulin secretagogue use was associated with increased risk of pancreatic cancer in diabetic patients. [Copyright &y& Elsevier]

Background: Studies have demonstrated that manumycin, a farnesyltransferase inhibitor, enhances the cytotoxic effect of paclitaxel in anaplastic thyroid cancer cells and in xenografts, but the mechanism of this effect is unknown. Parathyroid hormone–related protein (PTHrP) may function as an oncoprotein that inhibits apoptosis and enhances cell proliferation, in addition to its role as the mediator of humoral hypercalcemia of malignancy. We hypothesized that this protein might have a novel role in anaplastic thyroid cancer. Methods: Five anaplastic thyroid cancer cell lines (ARO, DRO, KAT-4, Hth-74, C-643) were examined for PTHrP expression in vitro by immunohistochemistry (IHC), radioimmunoassay, and Western blot (IP/WB) analyses. PTHrP expression was also examined in an in vivo xenograft model. The effects of manumycin and paclitaxel on PTHrP expression were studied. Results: All 5 ATC cell lines were found to robustly express PTHrP by IHC of fixed cells and radioimmunoassay of cell lysates and conditioned culture media (range, 468 ± 55 to 1410 ± 195 pg/mg cellular protein). Manumycin (54 μmol/L), but not paclitaxel (22 μmol/L), decreased the amount of PTHrP. Further, PTHrP was decreased in KAT-4 xenografts in nude mice that had been treated for 3 weeks with biweekly intraperitoneal injections of manumycin (7.5 mg/kg), compared with control mice by IHC. On Western blot analyses, fractionation of radiolabeled proteins showed that manumycin decreased synthesis of PTHrP in cytoplasm, with the amount of newly synthesized PTHrP in the nucleus and increased ubiquitination of PTHrP suggesting increased degradation of PTHrP through the proteasome pathway. Conclusions: Manumycin inhibits cell proliferation and decreases PTHrP levels in anaplastic thyroid cancer cells in vitro and in vivo and decreases the PTHrP level in the nucleus where PTHrP may function as an oncoprotein. These data suggest that PTHrP has a novel role in anaplastic thyroid cancer and that modulation of PTHrP levels may be of therapeutic benefit in this lethal malignancy. [Copyright &y& Elsevier]

In recent years, a dramatic breakthrough in cancer treatment has arisen with the advent of immune-checkpoint inhibitor (ICI) therapy. However, these therapies are accompanied by multiple unique immune-related adverse effects that can present as an oncologic emergency to emergency department (ED). Here we describe the characteristics of cancer patients with no previous diagnosis of adrenal insufficiency who present to the emergency with low adrenocorticotropic hormone and cortisol levels following ICI therapy. Using data from a comprehensive cancer center, we conducted a retrospective cohort study of patients 18 years and older who received ICI between April 1 st, 2018, and December 31st, 2022, and presented to the ED with low ACTH and total cortisol levels. The billing database was used to exclude patients with prior diagnosis of adrenal insufficiency based on the ICD-10 codes. Demographics, clinical and cancerrelated data were collected from the institution's data warehouse. Descriptive statistics were used to analyze the data. A total of 101 cancer patients were identified based on the eligibility criteria, with a median age of 63 years (interquartile range= 58-72 years), who were mostly White race (83.2 %) and Not Hispanic or Latino ethnic group (86.1%). Melanoma, lung, renal and head and neck cancer were the most common cancer types for these patients. The median Charlson comorbidity index was 8 (interquartile range: 7–9). Most (98%) of the patients presented as level 2 or 3 on the emergency severity index. Almost all patients (94%) were admitted, of these, 26 patients (25.7%) were placed in the observation unit. Of the patients who got admitted, around 10% were placed in the intensive care unit during their hospital stay. The clinical use of ICI is continually broadening and certain ICI-induced toxicities including endocrinopathies requires immediate medical attention. We found that most patients presenting to the ED with low ACTH and cortisol levels with no previous diagnosis of adrenal insufficiency after ICI therapy require admission and close monitoring. Further studies are needed to better evaluate the incidence and outcomes of ICI-induced adrenal insufficiency among cancer patients after ICI therapy. [ABSTRACT FROM AUTHOR]

Aneurysmal bone cyst is a benign tumor of the skeletal system that rarely occurs in ribs. We report two cases of aneurysmal bone cyst in the first rib. The first patient was a 21-year-old woman with an aneurysmal bone cyst in the left first rib that was resected with an L incision. The second patient was a 42-year-old man with an aneurysmal bone cyst in the right first rib that was resected with a posterolateral incision but recurred 1 year later. An en bloc resection was performed, without recurrence to date. We also review this disease with emphasis on the etiology, clinicopathology, and treatment approaches. [Copyright &y& Elsevier]

Immune checkpoint inhibitors are a new class of anticancer drugs recently approved by the US Food and Drug Administration (FDA) for the treatment of various malignancies. Pembrolizumab is an immune checkpoint inhibitor that targets the programmed cell death protein-1 (PD-1) receptor and blocks its interaction with programmed cell death ligand-1 (PD-L1) and programmed cell death ligand-2 (PD-L2). Pembrolizumab was first approved by the FDA in 2014 for the treatment of advanced melanoma and is currently approved for use in non-small cell lung cancer and several other neoplasms. Immune checkpoint inhibitors such as pembrolizumab have been reported to induce immune-mediated side effects, including type 1 diabetes mellitus in very rare cases (0.1% in clinical trials). Here, we report the case of a woman with no known history of diabetes who presented to our emergency department in a state of diabetic ketoacidosis within 3 weeks of receiving only a single dose of pembrolizumab therapy, and without any previous exposure to immunotherapy. This case of abrupt adult-onset type 1 diabetes mellitus is an example of the undesirable side effects that can emerge after only a brief exposure to an immune checkpoint inhibitor. Close monitoring of patients receiving immune checkpoint inhibitors is warranted for the early diagnosis and management of imminent and potentially life-threatening complications. [ABSTRACT FROM AUTHOR]

Background: The concurrence of ectopic adrenocorticotropic hormone (ACTH) syndrome (ectopic Cushing syndrome) and cancer is uncommon in the emergency department (ED) setting, but a constellation of nonspecific signs and symptoms can suggest the presence of Cushing syndrome.Case Report: A 65-year-old woman with diabetes visited the ED complaining of severe weight loss, generalized weakness, and hypokalemia. She was treated for hypokalemia and thrush. She was found to have a lung mass with a large pleural effusion. Upon discovery of the suspected malignancy, the patient was referred to the ED of a comprehensive cancer center, where she was diagnosed with ectopic Cushing syndrome and admitted to the hospital for further evaluation and treatment. WHY SHOULD THE EMERGENCY PHYSICIAN BE AWARE OF THIS?: The emergency physician should be able to recognize Cushing syndrome in cancer patients so that the paraneoplastic syndrome can be managed to avoid complications during cancer treatment. [ABSTRACT FROM AUTHOR]

Patients with a known cancer diagnosis are frequent visitors to general emergency departments (ED) Since MD Anderson Cancer Center is a dedicated oncologic hospital, new patients present with symptoms suspected to be attributable to a yet unconfirmed cancer diagnosis. The aim was to examine and characterize the oncologic ED presentation of new patients with a suspicion of cancer. Our institutional database was quired for all ED visits for subjects aged 18 and older with no prior cancer diagnosis (using tumor registry and billing database) between 11/1/2020 and 01/01/2022. Chart review was conducted to confirm the absence of previous cancer diagnosis in the identified subjects and to verify they received follow-up in our institution. Demographics, ED presentation and clinical data were collected. Descriptive statistics and Chi-Square test of independence were used to analyze, compare and report the presentation and the outcomes of final eligible patients. During the study period, of the 2727 subjects identified, 358 met the final eligibility criteria. The median age was 57 years (interquartile range: 45-66 years). The majority were male (51.1%), White or Caucasian race (57.0%) and not Hispanic or Latino ethnicity (74.0%). Almost all the patients (99.2%) were presented as emergent or urgent acuity level (i.e., Emergency Severity Index levels 2 or 3 respectively). The most frequent presenting complaint(s) were: Abnormal laboratory results (16.8%); Hypertension (9.8%); infection and/or suspected sepsis (7.5%); nausea/vomiting (7.3%); fatigue (7.0%); shortness of breath (6.7%) or headache (5.9%). Most of the patients were admitted either to the hospital (59.2%) or the observation unit (18.2%). Of the 212 admitted patients, 35 (16.5%) died within one year of the ED presentation, which was significantly (P=0.003) higher than the 5.5% one-year mortality rate for the patients who were discharged or placed in the observation unit. Most patients presenting to an oncologic emergency with unconfirmed suspicion of cancer require hospitalization. The admitted group have higher mortality for reasons that need further elucidation. Further research is also needed to understand why the fairly large segment that do not require hospitalization seek care in the ED setting. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T cell infusion (CAR T) therapy revolutionized and led to a paradigm shift in the treatment of hematologic malignancies, but treatment- related toxicities including cytokine release syndrome and immune effector cell- associated neurotoxicity syndrome are of concern. In this study, we aimed to understand the timing and reasons for which patients present to the emergency department (ED) after CAR T therapy to better assist with early recognition and management of these toxicities. We conducted a retrospective observational study for patients who had undergone CAR T therapy in the past 6 months and visited the ED of our comprehensive cancer center between 04/01/2018 and 08/01/2022. We examined the timing of presentation after CAR T product infusion, patient characteristics, and outcomes of the ED visit. Survival analyses were conducted using Cox proportional hazards regression and Kaplan-Meier estimates. During the period studied, there were 276 ED visits by 168 unique patients. Most patients had diffuse large B-cell lymphoma (103/168; 61.3%), multiple myeloma (21/168; 12.5%), or mantle cell lymphoma (16/168; 9.5%). Almost all 276 visits required urgent (60.5%) or emergent (37.7%) care and 73.5% of visits led to admission to the hospital or observation unit. Fever was the most frequent presenting complaint, reported in 19.6% of the visits. The 30-day and 90-day mortality rates after the index ED visits were 17.0% and 32.2% respectively. Patients who had their first ED visit >14 days after CAR T product infusion had significantly worse overall survival (multivariable hazard ratio 3.27; 95% confidence interval 1.29–8.27; P=0.012) than patients who first visited the ED within 14 days of CAR T product infusion. Cancer patients who receive CAR T therapy frequently visit the ED and most are admitted and/or require urgent or emergent care. Early ED visits may indicate early systemic inflammatory response to CAR T therapy, with patients mainly presenting with constitutional symptoms such as fever and fatigue, and these early visits are associated with better overall survival. [ABSTRACT FROM AUTHOR]

Pain remains an undertreated complication of cancer and has been shown to affect patients' quality of life. Patients when presenting to an emergency department (ED) with pain have two routes to management: hospitalization or discharged for outpatient management. With the advent of observation units, there is now an opportunity to utilize hospital resources without an inpatient stay. In this study, we aimed to define the role of an EDOU in the management of cancer pain. We performed a retrospective observational study that included all patients aged 18 years and older who presented to our ED and were placed in the EDOU with uncontrolled cancer pain between 1 March 2019 and 29 February 2020. Patient characteristics were summarized using descriptive statistics and predictors of the disposition from the EDOU were identified with univariate and multivariate analyses. A total of 600 visits were eligible for analysis. The median age of the cohort was 59 years (interquartile range: IQR 48–68 years). Breast, lung, and colorectal cancer were the most common cancer types. The abdomen (29.0%), back (17.3%), and extremities (15.8%) were the most common locations of identified pain. Most patients were discharged home (61.8%), and discharged patients had low 72-hour revisit and 30-day mortality rates. Significant predictors of hospitalization were initial EDOU pain score (odds ratio (OR) = 1.12; 95% CI 1.06–1.19; p < 0.001) and supportive care (OR = 2.04; 95% CI 1.37–3.04; p < 0.001) or pain service (OR = 2.67; 95% CI 1.63–4.40; p < 0.001) consultations. Our data suggest that an EDOU appears to be an appropriate venue to care for a subsegment of patients presenting to an emergency department with cancer pain with low 72- hour ED revisits and 30-day mortality rates. Placing eligible cancer patients with pain in EDOU creates an optimal care environment than immediate admission or discharge for patients who require significant cancer pain management but may not require inpatient hospitalization for their therapy. [ABSTRACT FROM AUTHOR]

Summary Biomarkers for predicting prognosis are critical to treating colorectal cancer (CRC) patients. We found that CSN6, a subunit of COP9 signalosome, is overexpressed in CRC samples and that CSN6 overexpression is correlated with poor patient survival. Mechanistic studies revealed that CSN6 is deregulated by epidermal growth factor receptor (EGFR) signaling, in which ERK2 binds directly to CSN6 Leu163/Val165 and phosphorylates CSN6 at Ser148. Furthermore, CSN6 regulated β-Trcp and stabilized β-catenin expression by blocking the ubiquitin-proteasome pathway, thereby promoting CRC development. High CSN6 expression was positively correlated with ERK2 activation and β-catenin overexpression in CRC samples, and inhibiting CSN6 stability with cetuximab reduced colon cancer growth. Taken together, our study’s findings indicate that the deregulation of β-catenin by ERK2-activated CSN6 is important for CRC development. [ABSTRACT FROM AUTHOR]