Decrease in treatment intensity predicts worse outcome in patients with locally advanced head and neck squamous cell carcinoma undergoing radiochemotherapy.

PURPOSE: Radiochemotherapy (RCT) is an effective standard therapy for locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Nonetheless, toxicity is common, with patients often requiring dose modifications. METHODS: To investigate associations of RCT toxicities according to CTCAE version 5.0 and subsequent therapy modifications with short- and long-term treatment outcomes, we studied all 193 patients with HNSCC who received RCT (70 Gy + platinum agent) at an academic center between 03/2010 and 04/2018. RESULTS: During RCT, 77 (41%, 95% CI 34-49) patients developed at least one ≥ grade 3 toxicity, including seven grade 4 and 3 fatal grade 5 toxicities. The most frequent any-grade toxicities were xerostomia (n = 187), stomatitis (n = 181), dermatitis (n = 174), and leucopenia (n = 98). Eleven patients (6%) had their radiotherapy schedule modified (mean radiotherapy dose reduction = 12 Gy), and 120 patients (64%) had chemotherapy modifications (permanent discontinuation: n = 67, pause: n = 34, dose reduction: n = 7, change to other chemotherapy: n = 10). Objective response rates to RCT were 55% and 88% in patients with and without radiotherapy modifications (p = 0.003), and 84% and 88% in patients with and without chemotherapy modifications (p = 0.468), respectively. Five-year progression-free survival estimates were 20% and 50% in patients with and without radiotherapy modifications (p = < 0.001), and 53% and 40% in patients with and without chemotherapy modifications (p = 0.88), respectively. CONCLUSIONS: Reductions of radiotherapy dose were associated with impaired long-term outcomes, whereas reductions in chemotherapy intensity were not. This suggests that toxicities during RCT should be primarily managed by modifying chemotherapy rather than radiotherapy.

Visualizing tropoelastin in a long-term human elastic fibre cell culture model.

Elastin is an essential protein found in a variety of tissues where resilience and flexibility are needed, such as the skin and the heart. When aiming to engineer suitable implants, elastic fibres are needed to allow adequate tissue renewal. However, the visualization of human elastogenesis remains in the dark. To date, the visualization of human tropoelastin (TE) production in a human cell context and its fibre assembly under live cell conditions has not been achieved. Here, we present a long-term cell culture model of human dermal fibroblasts expressing fluorescence-labelled human TE. We employed a lentiviral system to stably overexpress Citrine-labelled TE to build a fluorescent fibre network. Using immunofluorescence, we confirmed the functionality of the Citrine-tagged TE. Furthermore, we visualized the fibre assembly over the course of several days using confocal microscopy. Applying super resolution microscopy, we were able to investigate the inner structure of the elastin-fibrillin-1 fibre network. Future investigations will allow the tracking of TE produced under various conditions. In tissue engineering applications the fluorescent fibre network can be visualized under various conditions or it serves as a tool for investigating fibre degradation processes in disease-in-a-dish-models.

Decrease in treatment intensity predicts worse outcome in patients with locally advanced head and neck squamous cell carcinoma undergoing radiochemotherapy

Purpose Radiochemotherapy (RCT) is an effective standard therapy for locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Nonetheless, toxicity is common, with patients often requiring dose modifications. Methods To investigate associations of RCT toxicities according to CTCAE version 5.0 and subsequent therapy modifications with short- and long-term treatment outcomes, we studied all 193 patients with HNSCC who received RCT (70 Gy + platinum agent) at an academic center between 03/2010 and 04/2018. Results During RCT, 77 (41%, 95% CI 34–49) patients developed at least one ≥ grade 3 toxicity, including seven grade 4 and 3 fatal grade 5 toxicities. The most frequent any-grade toxicities were xerostomia (n = 187), stomatitis (n = 181), dermatitis (n = 174), and leucopenia (n = 98). Eleven patients (6%) had their radiotherapy schedule modified (mean radiotherapy dose reduction = 12 Gy), and 120 patients (64%) had chemotherapy modifications (permanent discontinuation: n = 67, pause: n = 34, dose reduction: n = 7, change to other chemotherapy: n = 10). Objective response rates to RCT were 55% and 88% in patients with and without radiotherapy modifications (p = 0.003), and 84% and 88% in patients with and without chemotherapy modifications (p = 0.468), respectively. Five-year progression-free survival estimates were 20% and 50% in patients with and without radiotherapy modifications (p = < 0.001), and 53% and 40% in patients with and without chemotherapy modifications (p = 0.88), respectively. Conclusions Reductions of radiotherapy dose were associated with impaired long-term outcomes, whereas reductions in chemotherapy intensity were not. This suggests that toxicities during RCT should be primarily managed by modifying chemotherapy rather than radiotherapy (AU)

Effect of aging on manipulative behavior in the cuttlefish, sepia.

The cuttlefish is an active predator that is able to catch crabs of a size that is large relative to its own. The capture is followed by a complex manipulative behavior leading to paralysis of the prey by injection of a cephalotoxin. This manipulative behavior is relatively stereotyped, and earlier research has shown that the cuttlefish concentrates its bite on the articular basi-ischiocoxopodite membrane of the crab's fifth pair of pereiopods. By placing mechanical constraints on the base of the fifth pereiopods, we were able to demonstrate that this manipulative behavior presents a marked degree of stereotypy but is not rigidly fixed. Substantial behavioral differences, however, were observed between subadult and senescent cuttlefish. The existence of a reduction in behavioral flexibility in the older animals in reaction to the constraints is discussed.

Significance of yeasts and moulds occurring in maize dough fermentation for 'kenkey' production.

Yeasts and moulds associated with the fermentation of maize dough during the processing of the West African traditional food 'kenkey' were investigated. A mixed flora comprising Candida, Saccharomyces, Trichosporon, Kluyveromyces and Debaryomyces species were isolated from raw maize, during steeping and early phases of fermentation. After 24-48 h of fermentation, Candida krusei and Saccharomyces cerevisiae dominated reaching counts exceeding 10(6) cfu/g. This succession of yeast populations and the significant multiplication of C. krusei and S. cerevisiae were observed in all cases for both the fermentation and the production sites investigated. Penicillium, Aspergillus and Fusarium species, including potential mycotoxin producers, were isolated from raw maize. Initial high counts of 10(5) cfu/g for moulds were reduced to less than 10(2)cfu/g within 24 h of fermentation. High levels of aflatoxins were observed in raw maize, and they were not affected during the fermentations.

Microbiological and aromatic characteristics of fermented maize doughs for kenkey production in Ghana.

A very uniform microflora was demonstrated in 15 samples of fermented maize dough from different larger commercial production sites. At the advanced stage of fermentation, more than 96% of the bacteria present were morphologically and biochemically uniform, obligatively heterofermentative lactobacilli occurring in concentrations about 10(9) cfu/g. Yeast occurred in levels of about 10(6) cfu/g, dominated by Candida and Saccharomyces spp. Studies on microbial successions indicated a selection towards a micropopulation dominated by lactic acid bacteria. The Gram-negative bacteria, catalase-positive Gram-positive bacteria and moulds underwent three to four decimal reductions during the early phase of the process. The aroma components detected were dominated by lactic acid, acetic, butyric and propionic acids. Volatile aroma components demonstrated by gas chromatography and mass spectrometry were characteristic for lactic acid bacteria with acetoin and related products as typical examples.

Lactic acid tolerance determined by measurement of intracellular pH of single cells of Candida krusei and Saccharomyces cerevisiae isolated from fermented maize dough.

Strains of Candida krusei and Saccharomyces cerevisiae were grown together at 30 degrees C in MYGP broth, pH 2.5, in the presence of 106.4 mM undissociated lactic acid. The two C. krusei strains investigated grew within 48 h from initial counts of 2 x 10(4) to approximately 10(7) cells/ml whereas the two S. cerevisiae strains investigated survived but did not grow in the presence of 106.4 mM undissociated lactic acid at pH 2.5. To explain the differences in lactic acid tolerance of the two yeast species, we used fluorescence-ratio-imaging microscopy and a perfusion system to determine the short-term intracellular pH (pH(i)) changes in single cells of C. krusei and S. cerevisiae. The changes were investigated both in the presence of low (20.7 mM) and high (106.4 mM) concentrations of undissociated lactic acid. For both the investigated species 20.7 mM undissociated lactic acid did not seem to influence the initial pH(i) which for C. krusei was found to be approximately 8.0 and for S. cerevisiae 6.9-7.5. For both C. krusei strains, perfusion with 106.4 mM undissociated lactic acid induced only weak short-term pH(i) responses with a decrease in pH(i) of less than one pH unit. Contrary, for both strains of S. cerevisiae perfusion with 106.4 mM undissociated lactic acid resulted in a significant decrease in pH(i) from initially 6.9-7.5 to 6.2-6.4 after 1 min and further to a pH(i) of < or = 5.5 after 3 min after which it remained constant. The results obtained show that C. krusei is more resistant to short-term pH(i) changes caused by lactic acid than S. cerevisiae, and this, in turn, may be part of the explanation why C. krusei is more tolerant to lactic acid than S. cerevisiae.

Acute gastrointestinal complications after cardiac surgery.

Gastrointestinal problems, with an incidence of about 1%, may complicate the postoperative period after cardiovascular surgery, increasing morbidity, length of stay, and mortality. Several risk factors for the development of these complications, including preexisting conditions; advancing age; surgical procedure, especially valve, combined bypass/valve, emergency, reoperative, and aortic dissection repair; iatrogenic conditions; stress; ischemia; and postpump complications, have been identified in multiple research studies. Ischemia is the most significant of these risk factors after cardiovascular surgery. Mechanisms that have been implicated include longer cardiopulmonary bypass and aortic cross-clamp times and hypoperfusion states, especially if inotropic or intra-aortic balloon pump support is required. These risk factors have been linked to upper and lower gastrointestinal bleeding, paralytic ileus, intestinal ischemia, acute diverticulitis, acute cholecystitis, hepatic dysfunction, hyperamylasemia, and acute pancreatitis. Gastrointestinal bleeding accounts for almost half of all complications, followed by hepatic dysfunction, intestinal ischemia, and acute cholecystitis. Identification of these gastrointestinal complications may be difficult because manifestations may be masked by postoperative analgesia or not reported by patients because they are sedated or require prolonged mechanical ventilation. Furthermore, clinical manifestations may be nonspecific and not follow the "classic" clinical picture. Therefore, astute assessment skills are needed to recognize these problems in high-risk patients early in their clinical course. Such early recognition will prompt aggressive medical and/or surgical management and therefore improve patient outcomes for the cardiovascular surgical population.

Emotional responses of family members during a critical care hospitalization.

BACKGROUND: The needs and satisfaction levels of family members of critically ill patients have received much attention in the literature. The feelings of family members, however, have not been thoroughly investigated. To develop appropriate nursing interventions to assist family members in coping with a critical care hospitalization, accurate information about their emotional response to the situation is needed. OBJECTIVE: To examine emotional responses of family members and their descriptions of supportive behaviors of others during a critical care hospitalization. METHODS: An exploratory design was used to study 52 subjects with critically ill family members in the pediatric, neonatal, medical, surgical and cardiovascular intensive care units in a large tertiary care hospital. The subjects kept daily logs of their feelings and the supportive behaviors of others. Thematic analysis was used to identify major themes. RESULTS: Analysis revealed a broad range of powerful emotions throughout the intensive care unit stay. Negative and positive emotions such as despair and joy were sometimes identified by subjects within a 24-hour period. Although fear, worry, anger and exhaustion were dominant themes during the first 24 hours and when the family received bad news about the patient, there was no pattern of emotional response evident as the stay progressed. Some differences between subjects drawn from the medical and neonatal intensive care units were evident. CONCLUSIONS: The findings suggest that family members of critically ill patients experience deep emotional turmoil throughout the intensive care unit stay. Specific nursing interventions to promote adaptive coping are needed throughout the experience.

Women and coronary disease: relationship between descriptors of signs and symptoms and diagnostic and treatment course.

BACKGROUND: Heart disease is the No. 1 killer among women in the United States. Differences in the clinical features of coronary heart disease among men and women have been reported, along with various approaches to the diagnostic workup and therapeutic interventions. PURPOSE: To explore the relationship between descriptors of signs and symptoms of coronary heart disease and follow-up care and to investigate any differences between male and female patients. METHODS: Structured interviews with patients and chart audits were used to assess initial signs and symptoms, associated cardiac-related signs and symptoms, and the diagnostic tests and interventions used for treatment. The sample consisted of 98 patients (51 women and 47 men) who were admitted with a medical diagnosis of myocardial infarction. RESULTS: Chest pain was the most common sign or symptom reported by both men and women. The 4 most common associated signs and symptoms were identical in men and women: fatigue, rest pain, shortness of breath, and weakness. However, significantly more women than men reported loss of appetite, paroxysmal nocturnal dyspnea, and back pain. Women were also less likely than men to have angiography and to receive i.v. nitroglycerin, heparin, and thrombolytic agents as part of acute management of myocardial infarction. CONCLUSION: Chest pain remains the initial symptom of acute myocardial infarction in both men and women. However, women may experience some different associated signs and symptoms than do men. Despite these similarities, men still are more likely than women to have angiography and to receive a number of therapies.

Effects of support groups on anxiety of family members during critical illness.

A critical illness event may precipitate anxiety and a state of crisis for members of the patient's family. Many stressors produce anxiety, such as an unexpected onset of illness and fragmented support provided in critical care settings. This quasi-experimental study examined the effectiveness of support groups in reducing state anxiety of adult family members during a relative's critical illness. A target sample was used to assign subjects to the treatment groups. The control group (n = 30) received bedside support from nurses and other health professionals during visiting hours or condition reports. Experimental subjects (n = 25) attended a support group to share feelings and experiences in coping with illness. No significant differences were found in prestate or poststate anxiety scores between the two groups, but experimental subjects had a significant reduction in anxiety from premeasures to postmeasures (p less than or equal to 0.01). These findings provide a basis for continued research on the effectiveness of interventions in reducing the anxiety associated with the crisis of critical illness in the family system.

Effects of child visitation in adult critical care units: a pilot study.

OBJECTIVE: To examine the behavioral and emotional responses of the child and of the nonhospitalized adult family member (NHAFM) to facilitated child visitation in the critical care setting. DESIGN: Quasi-experimental, posttreatment design. SETTING: An adult surgical intensive care unit at a large Midwestern teaching hospital. PARTICIPANTS: Twenty families participated in the study, 10 families in a restricted and 10 families in a facilitated visitation group. Each family unit had a child, an NHAFM, and a critically ill family member. In the control group the NHAFMs visited the patient in the customary routine, but children were restricted from visiting. After a 2-week waiting period a facilitated child visitation intervention was implemented for the experimental group. OUTCOME MEASURES: The child completed measures on anxiety as measured by the Manifest Anxiety Scale and behavioral and emotional changes as measured by the Perceived Change Scale. The NHAFM completed measures on anxiety as measured by the State-Trait Anxiety Inventory and mood as measured by the Mood Adjective Check List. Family functioning, as measured by the Feetham Family Functioning Survey, and life event changes, as measured by the Life Event Scale, were examined as extraneous variables. INTERVENTION: The Child Visitation Intervention encompassed systematic facilitation and supervision of children visiting a critically ill adult family member in a surgical intensive care unit and provision of emotional support before, during, and after visitation (the intervention protocol may be obtained from the investigators on request). RESULTS: Children in the facilitated visitation group had a greater reduction (t = 4.0, df = 18, p = 0.0004) in negative behavioral and emotional changes as measured by the Child-Perceived Change Scale when compared with children in the restricted visitation group. CONCLUSION: Facilitated child visitation may help children deal with the critical illness of an adult family member and deserves further study.

Behavioral responses of family members during critical illness.

This articles describes the behavioral responses of adult family members to critical illness and how these responses change over the course of the hospitalization. A convenience sample of 52 family members of patients in intensive units completed the Iowa ICU Family Scale, a self-report tool measuring sleep, eating, activity, family role, and support behaviors. Scales were completed by family members each day during the first week and then weekly throughout the patient's ICU stay. Family members reported sleeping less with a poorer quality of sleep, less nutritional intake, an increased use of cigarettes, alcohol, and over-the-counter and prescription medications, and spending more time talking, visiting the patient, and waiting. Stress was highest at the time of the ICU admission, began to plateau at Day 6, and then dropped considerably by Day 28. These findings suggest that crisis intervention is important during the early phase of caring for critically ill patients and their family members.

Epidural analgesia for effective pain control.

Over the past decade, awareness of the harmful effects of postoperative pain has increased. These effects seem to be intensified in critically ill patients. Epidural analgesia has been shown to improve pulmonary function in the critically ill, including a reduction in frequency of intubation and tracheostomies and decreased length of mechanical ventilatory support. In addition, the heightened metabolic-stress response associated with pain may be averted, thereby reducing problems with fluid retention that may further compromise pulmonary status. As a result, epidural analgesia can lead to: shortened length of stay in the ICU overall decreased mortality rate improvement in quality of life As a pain-control method, epidural analgesia is gaining popularity in a variety of ICU patient populations. Therefore, critical care nurses need to update their knowledge base and nursing practice to provide safe and effective nursing care. State nurse practice acts and agency policies dictate the amount and type of involvement nurses have in caring for patients receiving epidural pain therapy. Potential life-threatening problems with epidural analgesia are rare. Many side effects can be controlled or prevented with appropriate patient selection and nursing management.

Family needs: an annotated bibliography.

Hospitalization for a critical illness is not only a crisis for the patient, but also his family. This annotated bibliography can be used as a resource for nurses dealing with the family members of such patients.

Assessment and follow-up of problem wounds in the hyperbaric oxygen setting.

Ongoing wound assessment is essential to track the progress or lack of progress of non-healing wounds treated with HBO. By incorporating the entire HBO team, the assessment tool encourages clinicians to take a comprehensive view of the patient's physiological status and progress toward desired outcomes. Clinical assessment tools are a useful method to monitor and document the effectiveness of HBO as an adjunctive therapy to wound healing. As a result, other treatment measures that are also beneficial for wound healing can be included in the patient's plan of care.

Elimination concerns with acute spinal cord trauma. Assessment and nursing interventions.

Elimination for the spinal cord-injured patient presents a challenge to nurses in both the acute and rehabilitation phases. The most frequent GI and urinary complications associated with spinal shock are gastric dilatation and paralytic ileus, stress ulcers, metabolic disturbances, and neurogenic bowel and bladder. Associated clinical findings are often altered or absent from the lack of sensory, motor, and reflex functions. Nonspecific signs and symptoms such as anorexia, nausea, and vomiting, create the need for complex differential diagnosis. Critical care nurses have a vital role in this diagnostic process by monitoring and reporting significant changes in assessment and laboratory findings. In addition, care measures are directed at preventing complications or supporting the patient's current condition. These interventions include gastric decompression, gastric pH monitoring, administration of antacids, nutritional support, and early bowel and bladder management.

Support and reassurance needs: strategies for practice.

Support and personal needs have been empirically validated as two of the most important family need categories during critical illness. Perhaps over-shadowed during the initial critical care phase by a need for relief of initial anxiety and reassurance of quality care and information, support needs emerge as family members recognize the impact of the stressful illness experience on themselves. Critical care nurses can provide social support to family members through family assessment, counseling, and support groups. Although not empirically tested, it is generally believed that such support will influence the ability of family members to provide support to the patient and thereby influence a positive recovery from critical illness.

Collaborative care: improving patient outcomes in cardiovascular surgery.

Collaborative care, a multidisciplinary process to standardize and streamline care for selected case types, has gained momentum as a care delivery system in health care settings. The major goals of these programs are to improve the quality and continuity of care, while decreasing length of stay and cost. This article will describe key components, issues and challenges of developing, implementing and evaluating a collaborative care program for cardiovascular patients. The initial clinical path focused on bypass surgery, incorporating many of the aggressive bypass surgery recovery guidelines, such as short-acting anesthesia, same-day extubation and decreased laboratory blood analyses and test utilization. Issues that arose focused on patient selection, documentation, determining appropriateness for discontinuing paths and patient/family education. In regard to clinical outcomes, no significant differences were found in mortality or complication rates, such as postoperative bleeding, dysrhythmias and infection rates, between the clinical path group and a comparable group of non-path patients. Both intensive care unit (ICU) and overall hospital length of stay were concomitantly reduced. Other examples of program evaluation are also described, such as variation and patient follow-up data, to highlight quality improvement initiatives that further improve quality of care and reduce length of stay for this patient population.

Heart failure in women.

Heart failure affects more than 5 million Americans. Each year, about 400,000 individuals develop heart failure, making it the nation's most rapidly growing cardiac problem. Almost one third of these individuals have New York Heart Association Functional Class III or IV heart failure and are faced with progressive clinical deterioration and frequent hospital admissions. These figures will continue to escalate as the population ages. The success of interventional procedures and pharmacologic therapies in the management of coronary artery disease has enabled this population to survive acute events, at the same time creating a population with chronic disease. Common etiologies of heart failure in women include coronary artery disease, myocardial infarction, and valvular disease. However, women are at especially high risk for developing heart failure due to diastolic dysfunction associated with hypertension and diabetes. Heart failure in women is best managed across the care continuum, incorporating pharmacologic agents, interventional procedures when appropriate, dietary restrictions, self-monitoring, and psychosocial support. Much of the recent literature has focused on women and heart disease. This emphasis is partly due to public misconception about women's health problems and the growing body of research distinguishing gender differences. Significant advances in therapy have been made to improve the quality and span of life for people with heart disease. Despite therapeutic advances, however, women have high mortality rates from heart disease, including heart failure due to ischemic causes. In fact, women with heart failure present differently than men and have different etiologies and treatment options. As we learn more about women and heart disease, the distinguishing differences unfold and become helpful in establishing a plan of care.