Linda S. Elting

Bio: Linda S. Elting is an academic researcher from University of Texas MD Anderson Cancer Center. The author has contributed to research in topics: Cancer & Population. The author has an hindex of 63, co-authored 199 publications receiving 17485 citations. Previous affiliations of Linda S. Elting include University of Texas at Austin & University of Texas System.

Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients

Abstract: BACKGROUND A frequent complication of anticancer treatment, oral and gastrointestinal (GI) mucositis, threatens the effectiveness of therapy because it leads to dose reductions, increases healthcare costs, and impairs patients' quality of life. The Multinational Association of Supportive Care in Cancer and the International Society for Oral Oncology assembled an international multidisciplinary panel of experts to create clinical practice guidelines for the prevention, evaluation, and treatment of mucositis. METHODS The panelists examined medical literature published from January 1966 through May 2002, presented their findings at two separate conferences, and then created a writing committee that produced two articles: the current study and another that codifies the clinical implications of the panel's findings in practice guidelines. RESULTS New evidence supports the view that oral mucositis is a complex process involving all the tissues and cellular elements of the mucosa. Other findings suggest that some aspects of mucositis risk may be determined genetically. GI proapoptotic and antiapoptotic gene levels change along the GI tract, perhaps explaining differences in the frequency with which mucositis occurs at different sites. Studies of mucositis incidence in clinical trials by quality and using meta-analysis techniques produced estimates of incidence that are presented herein for what to our knowledge may be a broader range of cancers than ever presented before. CONCLUSIONS Understanding the pathobiology of mucositis, its incidence, and scoring are essential for progress in research and care directed at this common side-effect of anticancer therapies. Cancer 2004;100(9 Suppl):1995–2025. © 2004 American Cancer Society.

MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy

Abstract: BACKGROUND: Mucositis is a highly significant, and sometimes dose-limiting, toxicity of cancer therapy. The goal of this systematic review was to update the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) Clinical Practice Guidelines for mucositis. METHODS: A literature search was conducted to identify eligible published articles, based on predefined inclusion/exclusion criteria. Each article was independently reviewed by 2 reviewers. Studies were rated according to the presence of major and minor flaws as per previously published criteria. The body of evidence for each intervention, in each treatment setting, was assigned a level of evidence, based on previously published criteria. Guidelines were developed based on the level of evidence, with 3 possible guideline determinations: recommendation, suggestion, or no guideline possible. RESULTS: The literature search identified 8279 papers, 1032 of which were retrieved for detailed evaluation based on titles and abstracts. Of these, 570 qualified for final inclusion in the systematic reviews. Sixteen new guidelines were developed for or against the use of various interventions in specific treatment settings. In total, the MASCC/ISOO Mucositis Guidelines now include 32 guidelines: 22 for oral mucositis and 10 for gastrointestinal mucositis. This article describes these updated guidelines. CONCLUSIONS: The updated MASCC/ISOO Clinical Practice Guidelines for mucositis will help clinicians provide evidence-based management of mucositis secondary to cancer therapy.

Updated clinical practice guidelines for the prevention and treatment of mucositis

Abstract: Considerable progress in research and clinical application has been made since the original guidelines for managing mucositis in cancer patients were published in 2004, and the first active drug for the prevention and treatment of this condition has been approved by the United States Food and Drug Administration and other regulatory agencies in Europe and Australia. These changes necessitate an updated review of the literature and guidelines. Panel members reviewed the biomedical literature on mucositis published in English between January 2002 and May 2005 and reached a consensus based on the criteria of the American Society of Clinical Oncology. Changes in the guidelines included recommendations for the use of palifermin for oral mucositis associated with stem cell transplantation, amifostine for radiation proctitis, and cryotherapy for mucositis associated with high-dose melphalan. Recommendations against specific practices were introduced: Systemic glutamine was not recommended for the prevention of gastrointestinal mucositis, and sucralfate and antimicrobial lozenges were not recommended for radiation-induced oral mucositis. Furthermore, new guidelines suggested that granulocyte-macrophage-colony stimulating factor mouthwashes not be used for oral mucositis prevention in the transplantation population. Advances in mucositis treatment and research have been complemented by an increased rate of publication on mucosal injury in cancer. However, additional and sustained efforts will be required to gain a fuller understanding of the pathobiology, impact on overall patient status, optimal therapeutic strategies, and improved educational programs for health professionals, patients, and caregivers. These efforts are likely to have significant clinical and economic impact on the treatment of cancer patients. Cancer 2007;109:820-31. (c) 2007 American Cancer Society.

Clinical practice guidelines for the prevention and treatment of cancer therapy–induced oral and gastrointestinal mucositis†

Abstract: BACKGROUND Oral and gastrointestinal (GI) mucositis can affect up to 100% of patients undergoing high-dose chemotherapy and hematopoietic stem cell transplantation, 80% of patients with malignancies of the head and neck receiving radiotherapy, and a wide range of patients receiving chemotherapy. Alimentary track mucositis increases mortality and morbidity and contributes to rising health care costs. Consequently, the Multinational Association of Supportive Care in Cancer and the International Society for Oral Oncology assembled an expert panel to evaluate the literature and to create evidence-based guidelines for preventing, evaluating, and treating mucositis. METHODS Thirty-six panelists reviewed literature published between January 1966 and May 2002. An initial meeting in January 2002 produced a preliminary draft of guidelines that was reviewed at a second meeting the same year. Thereafter, a writing committee produced a report on mucositis pathogenesis, epidemiology, and scoring (also included in this issue), as well as clinical practice guidelines. RESULTS Panelists created recommendations from higher levels of evidence and suggestions when evidence was of a lower level and there was a consensus regarding the interpretation of the evidence by the panel. Panelists identified gaps in evidence that made it impossible to recommend or not recommend use of specific agents. CONCLUSIONS Oral/GI mucositis is a common side effect of many anticancer therapies. Evidence-based clinical practice guidelines are presented as a benchmark for clinicians to use for routine care of appropriate patients and as a springboard to challenge clinical investigators to conduct high-quality trials geared toward areas in which data are either lacking or conflicting. Cancer 2004;100(9 Suppl):2026–2046. © 2004 American Cancer Society.

Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.

Abstract: Objective:To provide an update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” last published in 2008.Design:A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at ke

Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012

Abstract: To provide an update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” last published in 2008. A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 h of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1B); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients (1C); fluid challenge technique continued as long as hemodynamic improvement is based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7–9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a Pao 2/Fio 2 ratio of ≤100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 h) for patients with early ARDS and a Pao 2/Fi o 2 180 mg/dL, targeting an upper blood glucose ≤180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 h after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 h of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5–10 min (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven “absolute”’ adrenal insufficiency (2C). Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients.

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

Abstract: To provide an update to “Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012”. A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

A systematic review of the literature

Abstract: OBJECTIVE — To systematically review the incidence of posttransplantation diabetes (PTD), risk factors for its development, prognostic implications, and optimal management. RESEARCH DESIGN AND METHODS — We searched databases (MEDLINE, EMBASE, the Cochrane Library, and others) from inception to September 2000, reviewed bibliographies in reports retrieved, contacted transplantation experts, and reviewed specialty journals. Two reviewers independently determined report inclusion (original studies, in all languages, of PTD in adults with no history of diabetes before transplantation), assessed study methods, and extracted data using a standardized form. Meta-regression was used to explain between-study differences in incidence. RESULTS — Nineteen studies with 3,611 patients were included. The 12-month cumulative incidence of PTD is lower (10% in most studies) than it was 3 decades ago. The type of immunosuppression explained 74% of the variability in incidence (P 0.0004). Risk factors were patient age, nonwhite ethnicity, glucocorticoid treatment for rejection, and immunosuppression with high-dose cyclosporine and tacrolimus. PTD was associated with decreased graft and patient survival in earlier studies; later studies showed improved outcomes. Randomized trials of treatment regimens have not been conducted. CONCLUSIONS — Physicians should consider modification of immunosuppressive regimens to decrease the risk of PTD in high-risk transplant recipients. Randomized trials are needed to evaluate the use of oral glucose-lowering agents in transplant recipients, paying particular attention to interactions with immunosuppressive drugs. Diabetes Care 25:583–592, 2002