Immune-related adverse event in the emergency department: methodology of the immune-related emergency disposition index (IrEDi).

For many cancer patients, immune checkpoint inhibitors (ICIs) can be life-saving. However, the immune-related adverse events (irAEs) from ICIs can be debilitating and can quickly become severe or even be fatal. Often, irAEs will precipitate visits to the emergency department (ED). Therefore, early recognition and the decision to admit, observe, or discharge these patients from the ED can be key to a cancer patient's morbidity and mortality. ED clinicians typically make their decision for disposition (admit, observe, or discharge) within 2-6 h from their patient's ED presentation. However, irAEs are particularly challenging in the ED because of atypical presentations, the absence of classic symptoms, the delayed availability of diagnostic tests during the ED encounter, and the fast pace in the ED setting. At present, there is no single sufficiently large ED data source with clinical, biological, laboratory, and imaging data that will allow for the development of a tool that will guide early recognition and appropriate ED disposition of patients with potential irAEs. We describe an ongoing federally funded project that aims to develop an immune-related emergency disposition index (IrEDi). The project capitalizes on a multi-site collaboration among 4 members of the Comprehensive Oncologic Emergency Research Network (CONCERN): MD Anderson Cancer Center, Ohio State University, Northwestern University, and University of California San Diego. If the aims are achieved, the IrEDi will be the first risk stratification tool derived from a large racial/ethnically and geographically diverse population of cancer patients. The future goal is to validate irEDi in general EDs to improve emergency care of cancer patients on ICIs.

A case series of adrenal insufficiency (likely due to hypophysitis) in cancer patients treated with immune checkpoint inhibitors.

The number of approved immune checkpoint inhibitors (ICIs) and their indications have significantly increased over the past decade. Immune-related adverse effects (irAEs) of ICIs vary widely in presentation and symptoms and can present diagnostic challenges to emergency department (ED) physicians. Moreover, when ICIs are combined with radiotherapy, cytotoxic chemotherapy, or targeted therapy, the attribution of signs and symptoms to an immune-related cause is even more difficult. Here, we report a series of 5 ED cases of adrenal insufficiency in ICI-treated cancer patients. All 5 patients presented with severe fatigue and nausea. Four patients definitely had and one patient possibly had central adrenal insufficiency, and 4 patients had undetectable serum cortisol levels. The majority of the patients had nonspecific symptoms that were not recognized at their first ED presentation. These cases illustrate the need for a heightened level of suspicion for adrenal insufficiency in ICI-treated cancer patients with hypotension, nausea and/or vomiting, abdominal pain, fatigue, or hypoglycemia. As ICI use increases, irAE-associated oncologic emergencies will become more prevalent. Thus, ED physicians must update their knowledge regarding the diagnosis and management of irAEs and routinely inquire about the specific antineoplastic therapies that their ED patients with cancer are receiving. A random cortisol level (results readily available in most EDs) with interpretation taking the circadian rhythm and the current level of physiological stress into consideration can inform the differential diagnosis and whether further investigation of this potential irAE is warranted.

Long-term overall survival of patients who undergo breast-conserving therapy or mastectomy for early operable HER2-Positive breast cancer after preoperative systemic therapy: an observational cohort study.

Background: Understanding the survival outcomes associated with breast-conserving therapy (BCT) and mastectomy after preoperative systemic therapy (PST) enables clinicians to provide more personalized treatment recommendations. However, lack of firm survival benefit data limits the breast surgery choices of human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients who receive PST. We sought to determine whether BCT or mastectomy after PST for early operable HER2-positive breast cancer is associated with better long-term survival outcomes and determine the degree to which PST response affects this association. Methods: In this observational cohort study, we compared the long-term survival outcomes of BCT and mastectomy after PST for HER2-positive breast cancer and evaluated the impact of PST response on the relationship between breast surgery performed and survival outcomes. Our cohort included 625 patients with early operable HER2-positive breast cancer who received PST followed by BCT or mastectomy between January 1998 and October 2009. These patients also received standard postoperative radiation, trastuzumab, and endocrine therapy as indicated clinically. We used propensity score matching to assemble mastectomy and BCT cohorts with similar baseline characteristics and used Kaplan-Meier plots and Cox proportional hazards regression to detect associations between surgery types and outcomes. Furthermore, in this study, we analyzed the original data of 625 patients using the inverse probability of treatment weighting (IPTW) method to enhance the reliability of the comparison between the mastectomy and BCT cohorts by addressing potential confounding variables. Findings: Propensity score matching yielded cohorts of 221 patients who received BCT and 221 patients who underwent mastectomy. At the median follow-up time of 9.9 years, compared with BCT, mastectomy was associated with worse overall survival (hazard ratio, 1.66; 95% confidence interval [CI]: 1.08-2.57; P = 0.02). In patients who had axillary lymph node pathological complete response, mastectomy was associated with worse overall survival before matching (hazard ratio, 2.17; 95% CI: 1.22-3.86; P < 0.01) and after matching (hazard ratio, 2.12; 95% CI: 1.15-3.89; P = 0.02). Among patients with pathological complete response in the breast, the survival results did not differ significantly between BCT and mastectomy patients. IPTW method validated that BCT offers better overall survival in patients who had axillary lymph node pathological complete response. Interpretation: People with HER2-positive breast cancer who have already had PST are more likely to survive after BCT, especially if they get a pathological complete response in the axillary lymph nodes. These findings underscore the necessity for further investigation into how responses to PST can inform the choice of surgical intervention and the potential impact on overall survival. Such insights could lead to the development of innovative tools that support personalized surgical strategies in the management of breast cancer. Funding: This work was supported by grants from the Nantong Science and Technology Project (JCZ2022079), Nantong Health Commission Project (QA2021031, MSZ2023040) and National Natural Science Foundation of China (No. 82394430).

Cardiovascular events after cancer immunotherapy as oncologic emergencies: Analyses of 610 head and neck cancer patients treated with immune checkpoint inhibitors.

BACKGROUND: Cardio-oncology and emergency medicine are closely collaborative, as many cardiac events in cancer patients require evaluation and treatment in the emergency department (ED). Immune checkpoint inhibitors (ICIs) have become a common treatment for patients with head and neck cancer (HNC). However, the immune-related adverse events (irAEs) from ICIs can be clinically significant. METHODS: We reviewed and analyzed cardiovascular diagnoses among HNC patients who received ICI during the period April 1, 2016-December 31, 2020 in a large tertiary cancer center. Demographics, clinical and cancer-related data were abstracted, and billing databases were queried for cardiovascular disease (CVD)-related diagnosis using International Classification of Disease-version10 (ICD-10) codes. We recorded receipt of care at the ED as one of the outcome variables. RESULTS: A total of 610 HNC patients with a median follow-up time of 12.3 months (median, interquartile range = 5-30 months) comprised our study cohort. Overall, 25.7% of patients had pre-existing CVD prior to ICI treatment. Of the remaining 453 patients without pre-existing CVD, 31.5% (n = 143) had at least one CVD-related diagnosis after ICI initiation. Tachyarrhythmias (91 new events) was the most frequent CVD-related diagnosis after ICI. The time to diagnosis of myocarditis from initiation of ICI occurred the earliest (median 2.5 months, 1.5-6.8 months), followed by myocardial infarction (3.7, 0.5-9), cardiomyopathy (4.5, 1.6-7.3), and tachyarrhythmias (4.9, 1.2-11.4). Patients with myocarditis and tachyarrhythmias mainly presented to the ED for care. CONCLUSION: The use of ICI in HNC is still expanding and the spectrum of delayed manifestation of ICI-induced cardiovascular toxicities is yet to be fully defined in HNC survivors.

Long QT syndrome after using EGFR-TKIs in older patients with advanced non-small cell lung cancer.

BACKGROUND: Long QT syndrome (LQTS) has been reported in older patients with advanced non-small cell lung cancer (NSCLC) following the use of osimertinib, the third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). However, there have not been analytic epidemiology studies on this topic. We aimed to compare the risk of LQTS between osimertinib and first/second-generation EGFR-TKIs in older patients with advanced NSCLC. RESEARCH DESIGN AND METHODS: This retrospective observational study used the 2006-2019 Surveillance, Epidemiology, and End Results (SEER)-Medicare data and included older patients with advanced NSCLC who were treated with either osimertinib or first/second-generation EGFR-TKIs during 2007-2017. Inverse probability of treatment weighting (IPTW) was used to balance the two groups with propensity scores estimated based on the patients' socioeconomic and clinical characteristics. Crude incidence rate (IR) and adjusted hazard ratio (HR) of the primary outcome, incident LQTS, were estimated. RESULTS: A total of 545 and 1,135 patients were included in the osimertinib and first/second-generation EGFR-TKI groups, which increased to 1,614 and 1,659, respectively, after IPTW. The osimertinib group had a higher IR of LQTS (2.62 per 100 person-years, 95% CI 2.03-3.38) compared to the first/second-generation EGFR-TKI group (1.33 per 100 person-years, 95% CI 0.92-1.92). After adjusting for covariates, the osimertinib group had a higher risk of LQTS than the first/second-generation EGFR-TKI group, with an HR of 1.94 (95% CI 1.23-3.08). The increased LQTS risk in the osimertinib group was even higher in females, whites and patients aged ≥ 75. CONCLUSIONS: Given the elevated risk of LQTS associated with osimertinib user, close monitoring for cardiac rhythm irregularities of high-risk patients following initiation of EGFR-TKI is recommended.

Long QT syndrome (LQTS) indicates a disorder of heart beats with prolonged QT intervals. There have been reports of LQTS in older patients with advanced non-small cell lung cancer (NSCLC) who were treated with osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). We conducted a retrospective study using Surveillance, Epidemiology, and End Results (SEER)-Medicare database, including older patients aged ≥ 65 with advanced NSCLC who were treated with EGFR-TKIs. Our results show higher incidence of LQTS after using osimertinib than first/second-generation EGFR-TKIs. After adjusting for patients' characteristics that might have affected the incidence of LQTS, the risk of LQTS was significantly higher in osimertinib users than in earlier generation EGFR-TKI users. Females, whites, and patients aged ≥ 75 had an even higher risk of LQTS when treated with osimertinib. Close monitoring for cardiac rhythm irregularities in high-risk patients after osimertinib initiation is recommended.

Hemoptysis in Cancer Patients.

Hemoptysis in cancer patients can occur for various reasons, including infections, tumors, blood vessel abnormalities and inflammatory conditions. The degree of hemoptysis is commonly classified according to the quantity of blood expelled. However, volume-based definitions may not accurately reflect the clinical impact of bleeding. This review explores a more comprehensive approach to evaluating hemoptysis by considering its risk factors, epidemiology and clinical consequences. In particular, this review provides insight into the risk factors, identifies mortality rates associated with hemoptysis in cancer patients and highlights the need for developing a mortality prediction score specific for cancer patients. The use of hemoptysis-related variables may help stratify patients into risk categories; optimize the control of bleeding with critical care; implement the use of tracheobronchial or vascular interventions; and aid in treatment planning. Effective management of hemoptysis in cancer patients must address the underlying cause while also providing supportive care to improve patients' quality of life.

Anti-miR-93-5p therapy prolongs sepsis survival by restoring the peripheral immune response.

Sepsis remains a leading cause of death for humans and currently has no pathogenesis-specific therapy. Hampered progress is partly due to a lack of insight into deep mechanistic processes. In the past decade, deciphering the functions of small noncoding miRNAs in sepsis pathogenesis became a dynamic research topic. To screen for new miRNA targets for sepsis therapeutics, we used samples for miRNA array analysis of PBMCs from patients with sepsis and control individuals, blood samples from 2 cohorts of patients with sepsis, and multiple animal models: mouse cecum ligation puncture-induced (CLP-induced) sepsis, mouse viral miRNA challenge, and baboon Gram+ and Gram- sepsis models. miR-93-5p met the criteria for a therapeutic target, as it was overexpressed in baboons that died early after induction of sepsis, was downregulated in patients who survived after sepsis, and correlated with negative clinical prognosticators for sepsis. Therapeutically, inhibition of miR-93-5p prolonged the overall survival of mice with CLP-induced sepsis, with a stronger effect in older mice. Mechanistically, anti-miR-93-5p therapy reduced inflammatory monocytes and increased circulating effector memory T cells, especially the CD4+ subset. AGO2 IP in miR-93-KO T cells identified important regulatory receptors, such as CD28, as direct miR-93-5p target genes. In conclusion, miR-93-5p is a potential therapeutic target in sepsis through the regulation of both innate and adaptive immunity, with possibly a greater benefit for elderly patients than for young patients.

Emergency department use by patients who received chimeric antigen receptor T cell infusion therapy.

Background: Chimeric antigen receptor T cell infusion (CAR T) therapy has revolutionized the treatment of hematologic malignancies, but treatment-related toxicities are of concern. Understanding the timing and reasons for which patients present to the emergency department (ED) after CAR T therapy can assist with the early recognition and management of toxicities. Methods: A retrospective observational cohort study was conducted for patients who had undergone CAR T therapy in the past 6 months and visited the ED of The University of Texas MD Anderson Cancer Center between 04/01/2018 and 08/01/2022. The timing of presentation after CAR T product infusion, patient characteristics, and outcomes of the ED visit were examined. Survival analyses were conducted using Cox proportional hazards regression and Kaplan-Meier estimates. Results: 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. Conclusion: Cancer patients who receive CAR T therapy commonly visit the ED, and most are admitted and/or require urgent or emergent care. During early ED visits patients mainly present with constitutional symptoms such as fever and fatigue, and these early visits are associated with better overall survival.

The prevalence and spectrum of reported incidental adrenal abnormalities in abdominal computed tomography of cancer patients: The experience of a comprehensive cancer center.

Background: The increasing use of computed tomography (CT) has identified many patients with incidental adrenal lesions. Further evaluation of these lesions is often dependent on the language used in the radiology report. Compared to the general population, patients with cancer have a higher risk for adrenal abnormalities, yet data on the prevalence and type of incidental adrenal lesions reported on radiologic reports in cancer patients is limited. In this study, we aimed to determine the prevalence and nature of adrenal abnormalities as an incidental finding reported on radiology reports of cancer patients evaluated for reasons other than suspected adrenal pathology. Methods: Radiology reports of patients who underwent abdominal CT within 30 days of presentation to a tertiary cancer center were reviewed and analyzed. We used natural language processing to perform a multi-class text classification of the adrenal reports. Patients who had CT for suspected adrenal mass including adrenal protocol CT were excluded. Three independent abstractors manually reviewed abnormal and questionable results, and we measured the interobserver agreement. Results: From June 1, 2006, to October 1, 2017, a total of 600,399 abdominal CT scans were performed including 66,478 scans obtained within 30 days of the patient's first presentation. Of these, 58,512 were eligible after applying the exclusion criteria. Adrenal abnormalities were identified in 7,817 (13.4%) reports, with adrenal nodularity (3,401 [43.5%]), adenomas (1,733 [22.2%]), and metastases (1,337 [17.1%]) being the most reported categories. Only 10 cases (0.1%) were reported as primary adrenal carcinomas and 2 as pheochromocytoma. Interobserver agreement using 300 reports yielded a Fleiss kappa of 0.893, implying almost perfect agreement between the abstractors. Conclusions: Incidental adrenal abnormalities are commonly reported in abdominal CT reports of cancer patients. As the terminology used by radiologists to describe these findings greatly determine the subsequent management plans, further studies are needed to correlate some of these findings to the actual confirmed diagnosis based on hormonal, histological and follow-up data and ascertain the impact of such reported findings on patients' outcomes.

Characteristics and Outcomes of Patients with Cancer Pain Placed in an Emergency Department Observation Unit.

Pain remains an undertreated complication of cancer, with poor pain control decreasing patients' quality of life. Traditionally, patients presenting to an emergency department with pain have only had two dispositions available to them: hospitalization or discharge. A third emerging healthcare environment, the emergency department observation unit (EDOU), affords patients access to a hospital's resources without hospitalization. To define the role of an EDOU in the management of cancer pain, we conducted a retrospective study analyzing patients placed in an EDOU with uncontrolled cancer pain for one year. Patient characteristics were summarized using descriptive statistics and predictors of disposition from the EDOU and were identified with univariate and multivariate analyses. Most patients were discharged home, 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. We concluded that an EDOU appears to be the appropriate venue to care for a subsegment of patients presenting to an emergency department with cancer pain, with patients receiving safe care as well as appropriate consultation and admission when indicated.

Concomitant Deep Vein Thrombosis in Cancer Patients with Unsuspected Pulmonary Embolism.

Incidental venous thromboembolism (VTE) is common in cancer patients and identifying factors associated with these events can improve the management plan. We studied the characteristics of concomitant deep vein thrombosis (C-DVT) in cancer patients presenting with unsuspected pulmonary embolism (PE) and the association of C-DVT with VTE recurrence and survival outcomes. Patients presenting to our emergency department with confirmed unsuspected/incidental PE between 1 January 2006 and 1 January 2016, were identified. Radiologic reports were reviewed to confirm the presence or absence of C-DVT. Logistic regression analyses and cox regression modeling were used to determine the effect of C-DVT on VTE recurrence and survival outcomes. Of 904 eligible patients, 189 (20.9%) had C-DVT. Patients with C-DVT had twice the odds of developing VTE recurrence (odds ratio 2.07, 95% confidence interval 1.21-3.48, p = 0.007). The mortality rates among C-DVT were significantly higher than in patients without. C-DVT was associated with reduced overall survival in patients with unsuspected PE (hazard ratio 1.33, 95% confidence interval 1.09-1.63, p = 0.005). In conclusion, C-DVT in cancer patients who present with unsuspected PE is common and is associated with an increased risk of VTE recurrence and poor short- and long-term survival. Identifying other venous thrombi in cancer patients presenting with unsuspected PE is recommended and can guide the management plan. For patients with isolated incidental subsegmental pulmonary embolism and concomitant deep vein thrombosis, initiating anticoagulants if no contraindications exist is recommended.

Characteristics and predictors of venous thrombosis recurrence in patients with cancer and catheter-related thrombosis.

Background: Central venous catheters raise the risk of catheter-related thrombosis (CRT) in patients with cancer, typically affecting the upper extremity. Management of CRT involves catheter removal and anticoagulation. However, robust evidence is lacking on the optimal timing of anticoagulation relative to catheter removal. Objectives: Our goal is to provide a better understanding of the factors that increase the risk of recurrent venous thromboembolism (VTE) in these patients. Patients and Methods: We conducted a retrospective chart review of all consecutive patients with cancer in our hospital affected by CRT between January 1, 2015, and December 31, 2017. We measured recurrence of VTE as thrombosis in any vascular bed or pulmonary embolism, for up to 2 years after diagnosis. Logistic and competing risk regression analyses were used to determine the association between different clinical factors and any VTE recurrence in patients with cancer and CRT. Results: Of the 257 individuals meeting the inclusion criteria, 80.2% had their catheter removed; of these, 50.5% did not receive anticoagulation before the removal. Patients who did not receive anticoagulation before the removal had increased 3-month and 1-year risks of recurrent VTE (odds ratio, 5.07 [95% confidence interval [CI], 1.53-23.18]; and hazard ratio, 3.47 [95% CI, 1.34-9.01]), respectively. Conclusions: Our study supports the use of anticoagulants before catheter removal in patients with CRT. Randomized clinical trials are recommended to establish stronger evidence pertaining to the long-term risk of VTE recurrence and the effect of catheter reinsertion.

Characteristics and Outcomes of Intracranial Hemorrhage in Cancer Patients Visiting the Emergency Department.

Intracranial hemorrhage (ICH) is a dreaded complication of both cancer and its treatment. To evaluate the characteristics and clinical outcomes of cancer patients with ICH, we identified all patients with ICH who visited The University of Texas MD Anderson Cancer Center emergency department between 1 September 2006 and 16 February 2016. Clinical and radiologic data were collected and compared. Logistic regression analyses were used to determine the association between clinical variables and various outcomes. During the period studied, 704 confirmed acute ICH cases were identified. In-hospital, 7-day, and 30-day mortality rates were 15.1, 11.4, and 25.6%, respectively. Hypertension was most predictive of intensive care unit admission (OR = 1.52, 95% CI = 1.09-2.12, p = 0.013). Low platelet count was associated with both in-hospital mortality (OR = 0.96, 95% CI = 0.94-0.99, p = 0.008) and 30-day mortality (OR = 0.98, 95% CI = 0.96-1.00, p = 0.016). Radiologic findings, especially herniation and hydrocephalus, were strong predictors of short-term mortality. Among known risk factors of ICH, those most helpful in predicting cancer patient outcomes were hypertension, low platelet count, and the presence of hydrocephalus or herniation. Understanding how the clinical presentation, risk factors, and imaging findings correlate with patient morbidity and mortality is helpful in guiding the diagnostic evaluation and aggressiveness of care for ICH in cancer patients.

The Value Proposition of Observation Medicine in Managing Acute Oncologic Pain.

PURPOSE OF REVIEW: Despite recommended best practice guidelines, pain remains an ongoing but undertreated symptom in patients with cancer, many of whom require emergency department evaluation for acute oncologic pain. A significant proportion of these patients are hospitalized for pain management, which increases healthcare costs and exposes patients to the risks of hospitalization. We reviewed the literature on observation medicine: an emerging mode of healthcare delivery which can offer patients with acute pain access to a hospital's pain management solutions and specialists without an inpatient hospitalization. Specifically, we appraised the role of observation medicine in acute pain management and its financial implications in order to consider its potential impact on the management of acute oncologic pain. RECENT FINDINGS: Recent evidence shows that observation medicine has the potential to decrease short-stay hospitalizations in cancer patients presenting with various concerns, including pain. Observation medicine is reported to be successful in providing comprehensive and cost-effective care for non-cancer patients with acute pain, making it a promising alternative to short-stay hospitalizations for cancer patients with acute oncologic pain.

Outcomes of Patients Placed in an Emergency Department Observation Unit of a Comprehensive Cancer Center.

PURPOSE: Emergency department observation units (EDOUs) have been shown to decrease length of stay and improve cost effectiveness. Yet, compared with noncancer patients, patients with cancer are placed in EDOUs less often. In this study, we aimed to describe patients who were placed in a cancer center's EDOU to discern their clinical characteristics and outcomes. METHODS: We performed a retrospective observational study that included all patients age 18 years and older who presented to our emergency department (ED) and were placed in the EDOU between March 1, 2019, and February 29, 2020. The patients' electronic medical records were queried for demographics, comorbidities, diagnosis at the time of placement in the EDOU, length of stay, disposition from the EDOU, ED return within 72 hours after discharge from the EDOU, and mortality outcomes at 14 and 30 days. RESULTS: A total of 2,461 visits were eligible for analysis. Cancer-related pain was the main reason for observation in more than one quarter of the visits. The median length of stay in the EDOU was approximately 23 hours, and 69.6% of the patients were discharged. The ED return rate for unscheduled visits at 72 hours was 1.9%. The 14- and 30-day mortality rates were significantly higher for patients who were admitted than for those who were discharged (14 days: 1.7% v 0.3%, P < .001; 30 days: 5.9% v 1.8%, P < .001). CONCLUSION: Our data suggest that placing patients with cancer in EDOUs is safe, reduces admissions, and reserves hospital resources for patients who can receive the most benefit without compromising care.

Prognostic Value of Procalcitonin, C-Reactive Protein, and Lactate Levels in Emergency Evaluation of Cancer Patients with Suspected Infection.

Cancer patients have increased risk of infections, and often present to emergency departments with infection-related problems where physicians must make decisions based on a snapshot of the patient's condition. Although C-reactive protein, procalcitonin, and lactate are popular biomarkers of sepsis, their use in guiding emergency care of cancer patients with infections is unclear. Using these biomarkers, we created a prediction model for short-term mortality in cancer patients with suspected infection. We retrospectively analyzed all consecutive patients who visited the emergency department of MD Anderson Cancer Center between 1 April 2018 and 30 April 2019. A clinical decision model was developed using multiple logistic regression for various clinical and laboratory biomarkers; coefficients were used to generate a prediction score stratifying patients into four groups according to their 14-day mortality risk. The prediction score had an area under the receiver operating characteristic curve value of 0.88 (95% confidence interval 0.85-0.91) in predicting 14-day mortality. The prediction score also accurately predicted intensive care unit admission and 30-day mortality. Our simple new scoring system for mortality prediction, based on readily available clinical and laboratory data, including procalcitonin, C-reactive protein, and lactate, can be used in emergency departments for cancer patients with suspected infection.

Association of Cardiovascular Disease Risk Factors with Late Cardiotoxicity and Survival in HER2-positive Breast Cancer Survivors.

PURPOSE: Breast cancer and cardiovascular (CV) diseases often share the same risk factors. It is increasingly important to identify risk factors for CV events in patients with high-risk breast cancer and explore optimal treatment regimens. EXPERIMENTAL DESIGN: Early HER2-positive breast cancer patients at our institution between January 1998 and October 2009 were reviewed. Primary outcome was late-severe-CV-event-free survival, and late severe CV events were defined as cardiovascular death, cardiomyopathy, symptomatic heart failure, and myocardial infarction developing 2+ years after breast cancer diagnosis. Kaplan-Meier plots, Cox proportional hazard regressions, and restricted mean survival time were used to evaluate outcomes. RESULTS: We identified 2,448 consecutive eligible patients with a median follow-up time of 111.0 months (interquartile range, 52.0-151.8 months). One hundred and thirty-six patients had late severe CV events and 752 died of any cause [533 (70.9%) died of primary breast cancer; 12 (1.6%) died of cardiovascular disease]. Hypertension [HR, 1.546; 95% confidence interval (95% CI), 1.030-2.320; P = 0.036] and history of coronary artery disease (CAD; HR, 3.333; 95% CI, 1.669-6.656; P < 0.001) were associated with worse late-severe-CV-event-free survival. Anthracycline-containing regimens (HR, 1.536; 95% CI, 0.979-2.411; P = 0.062) was not a significant risk factor for CV events in multivariate analysis. Regimens containing both anthracycline and anti-HER2 therapy were prognostic for better OS (HR, 0.515; 95% CI, 0.412-0.643; P < 0.001). CONCLUSIONS: Hypertension and CAD history were independent prognostic factors for late severe CV events. Adding anti-HER2 agents to anthracycline-containing regimens did not substantially increase the risk for late severe cardiotoxicity and conferred better overall survival.

Acupuncture for Cancer-Related Anorexia: a Review of the Current Evidence.

PURPOSE OF REVIEW: Loss of appetite/anorexia is extremely common among cancer patients, affecting as many as half of newly diagnosed patients and 70% of patients with advanced disease. Effective management of this disabling symptom of cancer remains a major challenge in the field of oncology. We conducted a systematic review of the current evidence on acupuncture and/or moxibustion as an intervention for cancer-related anorexia. RECENT FINDINGS: Acupuncture, as a part of traditional Chinese medicine practice, has demonstrated effectiveness in managing many cancer- and treatment-related symptoms, especially chemotherapy-induced or postoperative nausea. However, the efficacy of acupuncture in treating cancer-related anorexia/loss of appetite is not clear. The current level of evidence is insufficient to make a definitive conclusion on the benefit of acupuncture/moxibustion for treating chronic cancer-related anorexia/appetite problems. Future large randomized controlled trials of high methodological quality are needed.

Cyst(e)ine in nutrition formulation promotes colon cancer growth and chemoresistance by activating mTORC1 and scavenging ROS.

Weight loss and cachexia are common problems in colorectal cancer patients; thus, parenteral and enteral nutrition support play important roles in cancer care. However, the impact of nonessential amino acid components of nutritional intake on cancer progression has not been fully studied. In this study, we discovered that gastrointestinal cancer patients who received cysteine as part of the parenteral nutrition had shorter overall survival (P < 0.001) than those who did not. Cystine indeed robustly promotes colon cancer cell growth in vitro and in immunodeficient mice, predominately by inhibiting SESN2 transcription via the GCN2-ATF4 axis, resulting in mTORC1 activation. mTORC1 inhibitors Rapamycin and Everolimus block cystine-induced cancer cell proliferation. In addition, cystine confers resistance to oxaliplatin and irinotecan chemotherapy by quenching chemotherapy-induced reactive oxygen species via synthesizing glutathione. We demonstrated that dietary deprivation of cystine suppressed colon cancer xenograft growth without weight loss in mice and boosted the antitumor effect of oxaliplatin. These findings indicate that cyst(e)ine, as part of supplemental nutrition, plays an important role in colorectal cancer and manipulation of cyst(e)ine content in nutritional formulations may optimize colorectal cancer patient survival.

Hypomagnesemia and incidence of osteoradionecrosis in patients with head and neck cancers.

BACKGROUND: We aimed to determine whether hypomagnesemia predicts osteoradionecrosis development in patients with squamous cell carcinoma of the oropharynx and oral cavity who received platinum-based concurrent chemoradiation with or without induction therapy. METHODS: We reviewed data from patients with head and neck cancers who had undergone chemoradiation with weekly cisplatin/carboplatin between January 1, 2010 and December 31, 2014 at our institution. Pathologic features, laboratory test results, disease stage, and social histories were recorded. The association between hypomagnesemia and osteoradionecrosis was analyzed controlling for known confounding factors. RESULTS: Hypomagnesemia during cancer treatment was associated with osteoradionecrosis development (HR = 2.72, P = .037) independent of total radiation dose (HR = 1.07, P = .260) and smoking history (HR = 2.05, P = .056) among the patients who received platinum-based induction chemotherapy followed by concurrent chemoradiation. CONCLUSIONS: Hypomagnesemia was predictive of the development of osteoradionecrosis in patients with cancers of the oropharynx and oral cavity receiving platinum-based induction followed by concurrent chemoradiation.