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)

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.

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.

Effect of nitric oxide synthase inhibition on the manipulative behaviour of Sepia officinalis.

Nitric oxide (NO), produced by nitric oxide synthase (NOS) in brain tissue, is essential for a variety of kinds of learning in vertebrates. In invertebrates, there are clear examples of an association between NO signalling and olfaction, feeding behaviour and learning. The role of NO as a neurotransmitter in the manipulative behaviour of Sepia officinalis was tested. Manipulative behaviour requires extensive chemotactile sensory processing, fine motor control and probably motor learning processes. NADPH-diaphorase activity (a reliable histochemical marker for nitric oxide synthase) was found in sensory epithelia and in the axial nerve cord of the arms. NOS inhibitor injections (L-NAME) produced an increase in the latency of prey paralysis. By placing mechanical constraints on the base of the fifth periopods of the crab, we prevented the cuttlefish from injecting cephalotoxin and, thus, forced it to change injection sites. We showed that L-NAME pretreatment did not affect the flexibility of the manipulative behaviour. The implications of the involvement of NO in the acquisition of chemo-tactile information and in the programming of the motor skills of the manipulative behaviour is discussed.

The role of cholinergic networks of the anterior basal and inferior frontal lobes in the predatory behaviour of Sepia officinalis.

The predatory behaviour of the cuttlefish has been the subject of a few detailed studies and can be divided into several stages: prey detection, orientation, positioning, prey-seizing, prey-manipulation and ingestion. Nevertheless, the data about its control by the CNS remain fragmentary. By injecting a cholinergic agonist (nicotine) and antagonists (alpha-bungarotoxin, mecamylamine), the implication of cholinergic networks of the anterior basal and inferior frontal lobes in the control of predatory behaviour are demonstrated. Through these cholinergic networks, the anterior basal lobe takes an important part in the orientation and positioning. The inferior frontal lobe seems to play a role in the control of brachial manipulative and buccal mass activities. The implication of cholinergic networks of the anterior basal and inferior frontal lobes in the predatory behaviour and the pharmacology of nicotinic receptors are discussed.

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.

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.

Women and cardiac rehabilitation: referral and compliance patterns.

Heart disease is the primary killer among American women. Differences in referral for cardiac rehabilitation, as well as compliance rates, have been reported between male and female cardiac patients. This study explored the use of Phase I and Phase II cardiac rehabilitation programs by male and female patients. In particular, the study aimed to investigate the relationship between eligibility and subsequent referral to Phase II cardiac rehabilitation in both men and women, as well as their compliance rates in completing Phase II. In addition, for those patients who never started a Phase II program, their reasons for nonparticipation were explored. Structured patient interviews and chart audits were used to explore cardiac rehabilitation eligibility criteria, referral and completion rates. The sample consisted of 87 patients (46 women and 41 men) who were admitted with a medical diagnosis of angina, myocardial infarction, coronary artery bypass grafting, or valve replacement surgery. Men had higher eligibility rates for Phase I, whereas women had higher eligibility rates for Phase II; more men received a referral for Phase II from their physician than women did. Men had a higher completion rate with Phase II compared with women. For those patients who chose not to start a Phase II program, the most common reasons cited included transportation problems, insurance issues, and having exercise equipment at home. Although women are being referred for cardiac rehabilitation, fewer complete the programs. Continued education is essential to teach women the importance of cardiac rehabilitation to overall recovery and adaptation to an acute cardiac event. In addition, cardiac rehabilitation programs must be structured to meet the unique needs of women and thereby remove obstacles that have prevented higher participation rates by women in the past.

Spirit at work: supporting patients and colleagues.

In this article, the authors describe ways to create spirit at work--a sense of teamwork and caring for patients, their families, and colleagues. Defining an ideal role model and striving to emulate that model are the first steps to creating a facility that enriches the lives of patients, families, and health care providers.

Early discharge with home health care in the coronary artery bypass patient.

Early hospital discharge after coronary artery bypass graft surgery has been the standard of practice throughout the United States. This study compared outcomes, readmissions, and costs for patients discharged early with home health care with those of patients discharged a day or more later without home health care. Discharging open-heart surgery patients on postoperative day 4 with home health care was found to be safe and cost-effective.

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.

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.

Restructuring the clinical nurse specialist position to a unit-based role.

Role restructuring can be the key to maximizing efficiency, productivity, and operational effectiveness. The clinical nurse specialist role was restructured from a divisional project focus to a unit-based design to enhance the care of specific patient populations. The authors describe the process used to make this change, the outcomes achieved, and the lessons learned.

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.