Lipocalin 2 increases after high-intensity exercise in humans and influences muscle gene expression and differentiation in mice.

Lipocalin 2 (LCN2) is an adipokine that accomplishes several functions in diverse organs. However, its importance in muscle and physical exercise is currently unknown. We observed that following acute high-intensity exercise ("Gran Sasso d'Italia" vertical run), LCN2 serum levels were increased. The Wnt pathway antagonist, DKK1, was also increased after the run, positively correlating with LCN2, and the same was found for the cytokine Interleukin 6. We, therefore, investigated the involvement of LCN2 in muscle physiology employing an Lcn2 global knockout (Lcn2-/- ) mouse model. Lcn2-/- mice presented with smaller muscle fibres but normal muscle performance (grip strength metre) and muscle weight. At variance with wild type (WT) mice, the inflammatory cytokine Interleukin 6 was undetectable in Lcn2-/- mice at all ages. Intriguingly, Lcn2-/- mice did not lose gastrocnemius and quadriceps muscle mass and muscle performance following hindlimb suspension, while at variance with WT, they lose soleus muscle mass. In vitro, LCN2 treatment reduced the myogenic differentiation of C2C12 and primary mouse myoblasts and influenced their gene expression. Treating myoblasts with LCN2 reduced myogenesis, suggesting that LCN2 may negatively affect muscle physiology when upregulated following high-intensity exercise.

The VES-13 and G-8 tools as predictors of toxicity associated with aromatase inhibitors in the adjuvant treatment of breast cancer in elderly patients: A single-center study.

Background: Adjuvant hormone treatment of postmenopausal breast cancer is mainly based on aromatase inhibitors. Adverse events associated with such class of drugs are particularly severe in elderly patients. Therefore, we investigated the possibility of ab initio predict which elderly patients could encounter toxicity. Methods: In light of national and international oncological guidelines recommending the use of screening tests for multidimensional geriatric assessment in elderly patients aged ≥70 years and eligible for active cancer treatment, we assessed whether the Vulnerable Elder Survey (VES)-13 and the Geriatric (G)-8 could be predictors of toxicity associated with aromatase inhibitors. Seventy-seven consecutive patients aged ≥70 diagnosed with non-metastatic hormone-responsive breast cancer and therefore eligible for adjuvant hormone therapy with aromatase inhibitors, were screened with the VES-13 and the G-8, and underwent a six-monthly clinical and instrumental follow-up in our medical oncology unit, from September 2016 to March 2019 (30 months). Said patients were identified as vulnerable (VES-13 score ≥3 or G-8 score ≤14) and fit (VES-13 score <3 or G-8 score >14). The likelihood of experiencing toxicity is greater among vulnerable patients. Results: The correlation between the VES-13 or the G-8 tools and the presence of adverse events is equal to 85.7% (p = 0.03). The VES-13 demonstrated 76.9% sensitivity, 90.2% specificity, 80.0% positive predictive value, 88.5% negative predictive value. The G-8 demonstrated 79.2% sensitivity, 88.7% specificity, 76% positive predictive value, 90.4% negative predictive value. Conclusion: The VES-13 and the G-8 tools could be valuable predictors of the onset of toxicity associated with aromatase inhibitors in the adjuvant treatment of breast cancer in elderly patients aged ≥70.

NSCLC Immunotherapy and Related Rare Toxicities: A Monocentric Real-Life Experience.

BACKGROUND: In the last years immunotherapy has revolutionized the treatment of non-small cell lung cancer (NSCLC) not supported by a driver mutation. Immunotherapy related adverse events (irAEs) have a unique toxicity profiles distinct from the toxicities of classical chemotherapy treatment relating to their mechanism of action. We analyzed some serious and uncommon life-threatening irAEs, needing a change in the therapeutic strategy. METHOD: Between October 2018 and October 2020, 63 NSCLC patients underwent immunotherapy. Thirty-eight patients underwent first-line Pembrolizumab, 200 mg every 21 days (Group A). Twenty patients were treated in second line with Pembrolizumab 200 mg every 21 days or Nivolumab 240 mg every 14 days or Atezolizumab 800 mg every 14 days (Group B). Five stage III patients treated after radio chemotherapy with Durvalumab 1500 mg every 14 days (Group C). RESULTS: We experienced: a) 2 bowel perforations (3.2%), necessitating Hartmann's resection. Only one of the two patients restored immunotherapy; b) 1 chronic renal insufficiency (1.6%, creatinine up to 8 mg/dL) and 2 severe hypertransaminasemias (3.2%, up to 65 U/L), requiring the immediate and definitive interruption of ICIs; c) 2 pericardial effusions (3.2%), of which one needed subxiphoid pericardiocentesis for cardiac tamponade. Patient restored immunotherapy after resolution of the acute event. CONCLUSIONS: Immunotherapy include monoclonal antibodies reducing the suppression of effector T cells and improving the tumor-specific immune responses. Most common irAEs are evident in mild and reversible form, but sometimes life-threatening irEAs show up. Therefore, further clinical trials needed to increase knowledge of drugs and prevent unexpected irAEs.

The VES-13 and G-8 tools as predictors of toxicity associated with aromatase inhibitors in the adjuvant treatment of breast cancer in elderly patients: A single-center study.

Background: Adjuvant hormone treatment of postmenopausal breast cancer is mainly based on aromatase inhibitors. Adverse events associated with such class of drugs are particularly severe in elderly patients. Therefore, we investigated the possibility of ab initio predict which elderly patients could encounter toxicity. Methods: In light of national and international oncological guidelines recommending the use of screening tests for multidimensional geriatric assessment in elderly patients aged ≥70 years and eligible for active cancer treatment, we assessed whether the Vulnerable Elder Survey (VES)-13 and the Geriatric (G)-8 could be predictors of toxicity associated with aromatase inhibitors. Seventy-seven consecutive patients aged ≥70 diagnosed with non-metastatic hormone-responsive breast cancer and therefore eligible for adjuvant hormone therapy with aromatase inhibitors, were screened with the VES-13 and the G-8, and underwent a six-monthly clinical and instrumental follow-up in our medical oncology unit, from September 2016 to March 2019 (30 months). Said patients were identified as vulnerable (VES-13 score ≥3 or G-8 score ≤14) and fit (VES-13 score <3 or G-8 score >14). The likelihood of experiencing toxicity is greater among vulnerable patients. Results: The correlation between the VES-13 or the G-8 tools and the presence of adverse events is equal to 85.7% (p = 0.03). The VES-13 demonstrated 76.9% sensitivity, 90.2% specificity, 80.0% positive predictive value, 88.5% negative predictive value. The G-8 demonstrated 79.2% sensitivity, 88.7% specificity, 76% positive predictive value, 90.4% negative predictive value. Conclusion: The VES-13 and the G-8 tools could be valuable predictors of the onset of toxicity associated with aromatase inhibitors in the adjuvant treatment of breast cancer in elderly patients aged ≥70.

Financial distress and its impact on symptom expression in advanced cancer patients.

AIM: To assess financial distress (FD) and its impact on symptom expression and other quality of life issues PATIENTS AND METHODS: Advanced cancer patients admitted to inpatient and outpatient clinics were selected. Standard epidemiological data including age, gender, primary cancer diagnosis, and Karnofsky level were recorded. Data regarding marital status, number of cohabitants, religious belief, educational level, and family income (< 1000, 1000-3.000, > 3000 euros), as well as extra costs not covered by health care system, were collected. Symptom burden including FD was measured by Edmonton Symptom Assessment Scale (ESAS), FACT-G (Functional Assessment of Cancer Therapy-General), and HADS (Hospital Anxiety Depression scale) were measured. RESULTS: Two hundred thirty-six patients were evaluated. The mean FD was 3.55 (SD 3.1). One hundred patients (42%) had a FD of ≥ 4. There was an inverse correlation between FD and income (P = 0.032). Most patients incurred in extra-costs, the most frequent being for drugs (n, 114). FD was inversely associated with age (P = 0.024), marital status (divorced or separated, P = 0.005), ESAS anxiety (P = 0.006), total ESAS (P = 0.019), physical well-being (P = 0.033), poor social family well-being (P = 0.004), emotional well-being (P = 0.045), poor functional well-being (P = 0.019), HADS-A (P = 0.003), and global HADS (P = 0.034). Family income was inversely related to age (P = 0.023), education level (P < 0.0005), less number of hospital admissions in the last month (P = 0.020), physical well-being (P = 0.039), social/family well-being (P = 0.020), and total well-being (P = 0.001). CONCLUSION: FD is very common in advanced cancer patients. FD was associated with anxiety, depression, and poor quality of life. The screening of FD may allow to develop effective interventions of social support.

The lower the expectations in controlling the symptoms of advanced cancer patients, the better the clinical response.

AIM: The aim of this study was to compare patients' global impression (PGI) and the achievement of personalised symptom goal response (PSGR), after a comprehensive palliative care treatment in advanced cancer patients having high (HPSG) and low symptom goals (LPSG). PATIENTS AND METHODS: Advanced cancer patients admitted to palliative care units rated symptoms intensity by the Edmonton Symptom Assessment Score (ESAS) at admission and then after one week of comprehensive palliative care treatment. For each symptom, patients were divided into two groups, according to their patient symptom goal (PSG): ≥4 (HPSG), and 0-2 (LPSG). PGI and PSGR were evaluated after one week of palliative care. The Memorial Delirium Assessment Scale (MDAS) was assessed at admission. RESULTS: After one week of palliative care, changes in ESAS items were significantly larger in the HPSG group. HPSG patients had a better PGI and reached their target more frequently than LPSG patients for pain, weakness, and poor well-being. LPSG patients were more likely to obtain their target for appetite and insomnia. HPSG patients were more likely to have a lower Karnofsky, a lower educational level, older age, or higher MDAS values for the different ESAS items. CONCLUSION: Advanced cancer patients with low expectations (HPSG) were more likely to achieve their PSGR after a comprehensive palliative care treatment, reporting also a better PGI for some leading symptoms such as pain, weakness, and poor well-being. More fragile patients seem to have lower expectations and to be more likely to be satisfied.

Breakthrough Cancer Pain Clinical Features and Differential Opioids Response: A Machine Learning Approach in Patients With Cancer From the IOPS-MS Study.

PURPOSE: A large proportion of patients with cancer suffer from breakthrough cancer pain (BTcP). Several unmet clinical needs concerning BTcP treatment, such as optimal opioid dosages, are being investigated. In this analysis the hypothesis, we explore with an unsupervised learning algorithm whether distinct subtypes of BTcP exist and whether they can provide new insights into clinical practice. METHODS: Partitioning around a k-medoids algorithm on a large data set of patients with BTcP, previously collected by the Italian Oncologic Pain Survey group, was used to identify possible subgroups of BTcP. Resulting clusters were analyzed in terms of BTcP therapy satisfaction, clinical features, and use of basal pain and rapid-onset opioids. Opioid dosages were converted to a unique scale and the BTcP opioids-to-basal pain opioids ratio was calculated for each patient. We used polynomial logistic regression to catch nonlinear relationships between therapy satisfaction and opioid use. RESULTS: Our algorithm identified 12 distinct BTcP clusters. Optimal BTcP opioids-to-basal pain opioids ratios differed across the clusters, ranging from 15% to 50%. The majority of clusters were linked to a peculiar association of certain drugs with therapy satisfaction or dissatisfaction. A free online tool was created for new patients' cluster computation to validate these clusters in future studies and provide handy indications for personalized BTcP therapy. CONCLUSION: This work proposes a classification for BTcP and identifies subgroups of patients with unique efficacy of different pain medications. This work supports the theory that the optimal dose of BTcP opioids depends on the dose of basal opioids and identifies novel values that are possibly useful for future trials. These results will allow us to target BTcP therapy on the basis of patient characteristics and to define a precision medicine strategy also for supportive care.

Individualized Whole-Body Vibration: Neuromuscular, Biochemical, Muscle Damage and Inflammatory Acute Responses.

Objective. We aimed to investigate the acute residual hormonal, biochemical, and neuromuscular responses to a single session of individualized whole-body vibration (WBV) while maintaining a half-squat position. Methods. Twenty male sport science students voluntarily participated in the present study and were randomly assigned to an individualized WBV group (with the acceleration load determined for each participant) or an isometric group (ISOM). A double-blind, controlled parallel study design with repeated measures was employed. Results. Testosterone and growth hormone increased significantly over time in the WBV group (P < .05 and P < .01, respectively; effect size [ES] ranged from 1.00 to 1.23), whereas cortisol increased over time in both groups (P < .01; ES ranged from 1.04 and 1.36). Interleukin-6 and creatine kinase increased significantly over time only in the WBV group (P < .05; ES = 1.07). The maximal voluntary contraction decreased significantly over time in the ISOM group (P = .019; ES = 0.42), whereas in the WBV group, the decrease did not reach a significant level (P = .05). The ratio of electromyographic activity and power decreased significantly over time in the WBV group (P < .01; ES ranged from 0.57 to 0.72). Conclusion. Individualized WBV increased serum hormonal concentrations, muscle damage, and inflammation to levels similar to those induced by resistance training and hypertrophy exercises.

Breakthrough Pain in Patients with Lung Cancer. A Secondary Analysis of IOPS MS Study.

AIM: To characterize breakthrough cancer pain (BTcP) in patients with lung cancer. METHODS: This was a secondary analysis of multicenter study of patients with BTcP. Background pain intensity and opioid dose were recorded. The number of BTcP episodes, their intensity, predictability, onset, duration and interference with daily activities were collected. Opioids used for BTcP, the mean time to meaningful pain relief after taking medication, satisfaction and adverse effects were assessed. RESULTS: 1087 patients with lung cancer were examined. In comparison with other tumors, patients with lung cancer showed: higher background pain intensity (p = 0.006), lower opioid doses (p = 0.005), higher intensity of BTcP (p = 0.005), movement (79.5%) and cough (8.2%), as principal triggers for predictable BTcP (p < 0.009), larger BTcP interference with daily activity (p = 0.0001), higher use of adjuvants (p = 0.0001). No relevant differences in the other parameters examined were found. CONCLUSION: Patients with lung cancer have their own peculiarities, including higher basal and BTcP pain intensity and the use of more adjuvant drugs for background pain. The most frequent triggers for predictable BTcP are movement and cough. Future studies should be performed to analyze the prevalence of BTcP in patients with different lung cancers as well as the optimal management strategy for background pain and BTcP.

Personalized goal for insomnia and clinical response in advanced cancer patients.

AIM: The aim of this study was to assess the Personalized Insomnia Intensity Goal (PIIG), the achievement of Personalized Goal Response (PGR), and Patient Global Impression (PGI) after a comprehensive symptom management. PATIENTS AND METHODS: Advanced cancer patients admitted to palliative care units rated pain and symptoms intensity and their PIIG by using the Edmonton Symptom Assessment Score (ESAS) (T0). In patients with significant levels of insomnia, the achievement of target expected (PIIG) was measured (patient goal response, PIGR), as well the patient global impression (PGI), by the minimal clinically important difference (MCID), after a comprehensive symptom management (T7). RESULTS: Three hundred ninety-seven patients with a level of insomnia of ≥ 3 on ESAS were analyzed in this study. The mean values of PIIG at T0 and T7 were 1.2 (SD 1.5) and 0.9 (SD 1.4), respectively. Most patients (n = 406, 89.8%) indicated a PIIG of ≤ 3 as a target at T0. Such target was significantly lower at T7 (p = < 0.0005). PGI, expressed as MCID, was perceived with a mean decrease in insomnia intensity of - 2.3. In a minority of patients (n = 26; 5.8%) insomnia worsened, with a MCID of 0.50 (SD 2.8). Higher insomnia intensity at T0 and lower insomnia intensity at T7 were independently related to PGI. PIGR was achieved in 87.9% of patients. PIGR was associated with PIIG at T0, and inversely associated to insomnia intensity at T0 and T7, and PIIG at T7. CONCLUSION: PGIR and PGI seem to be relevant for evaluating the effects of a comprehensive management of insomnia, suggesting therapeutic decisions according to PIIG. Some factors influencing the individual target and clinical response have been detected.

Personalized Pain Goals and Responses in Advanced Cancer Patients.

OBJECTIVE: To assess the personalized pain intensity goal (PPIG), the achievement of a personalized pain goal response (PPGR), and patients' global impression (PGI) in advanced cancer patients after a comprehensive pain and symptom management. DESIGN: Prospective, longitudinal. SETTING: Acute pain relief and palliative/supportive care. SUBJECTS: 689 advanced cancer patients. METHODS: Measurement of Edmonton Symptom Assessment Score (ESAS) and personalized pain intensity goal (PPIG) at admission (T0). After a week (T7) personalized pain goal response (PPGR) and patients' global impression (PGI) were evaluated. RESULTS: The mean PPIG was 1.33 (SD 1.59). A mean decrease in pain intensity of - 2.09 was required on PPIG to perceive a minimal clinically important difference (MCID). A better improvement corresponded to a mean change of - 3.41 points, while a much better improvement corresponded to a mean of - 4.59 points. Patients perceived a MCID (little worse) with a mean increase in pain intensity of 0.25, and a worse with a mean increase of 2.33 points. Higher pain intensity at T0 and lower pain intensity at T7 were independently related to PGI. 207 (30.0%) patients achieved PPGR. PPGR was associated with higher PPIG at T0 and T7, and inversely associated to pain intensity at T0 and T7, and Karnofsky level. Patients with high pain intensity at T0 achieved a favorable PGI, even when PPIG was not achieved by PPGR. CONCLUSION: PPIG, PPGR and PGI seem to be relevant for evaluating the effects of a comprehensive management of pain, assisting decision-making process according to patients' expectations. Some factors may be implicated in determining the individual target and the clinical response.

Breakthrough Cancer Pain in Patients Receiving Low Doses of Opioids for Background Pain.

BACKGROUND: This study aimed to assess the characteristics of breakthrough cancer pain (BTcP) in patients receiving low doses of opioids for background pain in comparison with patients receiving at least 60 mg of oral morphine equivalents (OME). MATERIALS AND METHODS: Patients with advanced cancer receiving less than 60 mg/day of OME with episodes of BTcP were included in the analysis (group L). Data were compared with patients receiving doses of opioids ≥60 mg of OME (group H). Pain intensity, current analgesic therapy, number of BTcP episodes, intensity of BTcP, its predictability and triggers, onset duration, interference with daily activities, BTcP medications, and time to meaningful pain relief were collected. Adverse effects imputable to a BTcP medication were recorded. RESULTS: A total of 1,418 and 2,474 patients were included in groups L and H, respectively. A lower number of BTcP episodes (p = .005), a lower BTcP intensity (p = .0001), a faster BTcP onset (p = .024), and a longer time to meaningful pain relief after taking a BTcP medication (p = .009) were found in group L as compared with group H. In group L, BTcP interference on daily activity was less than in group H (p = .009). Patients in group L were less likely to be prescribed an opioid as BTcP medication in comparison with patients in group H (p = .0001). Opioid doses used for BTcP were significantly higher in group H. Patients in group L were more likely to be less satisfied (p = .003) than patients in group H. No adverse effects of severe intensity were reported in both groups. CONCLUSION: Patients receiving lower doses of opioids exhibit some differences in BTcP presentation: fewer episodes with lower intensity and a faster onset, a longer time to meaningful pain relief, and less satisfaction with BTcP medication. A relevant percentage of patients was receiving fentanyl preparations normally reserved for patients receiving higher doses of opioids. IMPLICATIONS FOR PRACTICE: Breakthrough pain is present in patients receiving low doses of opioids. It has its own peculiarities: less frequent, lower intensity, faster onset, longer time to meaningful pain relief, and less satisfaction with medication. Many patients were prescribed fentanyl preparations, which are normally reserved for patients receiving higher doses of opioids.

Breakthrough pain in patients with head & neck cancer. A secondary analysis of IOPS MS study.

AIM: To characterize breakthrough pain (BTcP) in patients with Head and neck (H&N) cancer. METHODS: This was a secondary analysis of multicenter study of BTcP. Background pain intensity and opioid dose were recorded. The number of BTcP episodes, their intensity, predictability, onset, duration and interference with daily activities were collected. Opioids used for BTcP, and the mean time to meaningful pain relief after taking medication, were assessed. The presence of mucositis was also assessed. RESULTS: 205 patients with H&N cancer were examined. The mean number of BTcP episodes was 2.8/day, which was higher than in general population. The mean intensity of BTcP was 7.4. BTcP was more predictable in H&N cancer than in other tumors. The main trigger of predictable BTcP was the ingestion of food (76.5%). BTcP onset was fast in 148 patients (72.2%). The mean time to meaningful pain relief after taking a BTcP medication was 15.3 min and BTcP interference with daily activity was relevant in most patients (89.2%). Transdermal drugs and nasal fentanyl preparations were more frequently used for background pain and BTcP, respectively. A consistent number of patients with H&N cancer (38.5%) exhibited different levels of oral mucositis. CONCLUSION: BTcP in patients with H&N cancer is characterized by a larger number of episodes/day and the predictability, particularly with ingestion of food. The use of drugs for background analgesia and BTcP were conditioned by the possible interference with swallowing or local mucosal damage.

Breakthrough Cancer Pain in Patients With Abdominal Visceral Cancer Pain.

OBJECTIVE: The objective of this study was to assess the characteristics of breakthrough cancer pain (BTcP) in patients with abdominal cancer pain, and the eventual factors associated with its presentation. METHODS: Patients with abdominal visceral cancer presenting BTcP were included in the analysis. Pain intensity, current analgesic therapy, number of BTcP episodes, intensity of BTcP, its predictability and triggers, onset (≤10 minutes or >10 minutes), duration, interference with daily activities, medications and doses currently used for BTcP, and time to meaningful pain relief were collected. Adverse effects imputable to a BTcP medication were recorded. RESULTS: Four hundred fourteen patients were included in the study. The mean background pain was 2.7 (SD 1.19) and most patients (97.6%) were receiving opioids. The mean number of BTcP episodes/day was 2.2 (SD 1.51). The mean intensity of BTcP was 7.3 (SD 1.32). BTcP onset was ≤10 minutes and >10 minutes in 271 (65.5%) and 143 patients (35.5%), respectively, and the mean duration was 52.6 minutes (SD 38.1). Interference of BTcP with daily activity was relevant for 340 patients (82%). In 122 patients (29.5%), BTcP was predictable and ingestion of food (n = 63, 51.6%) was the most frequent trigger. In comparison with unpredictable BTcP, postprandial BTcP had a lower intensity (P = 0.039), had a faster onset (P = 0.042), and was associated with the use of oxycodone/naloxone (P = 0.003), and less use of nonsteroidal anti-inflammatory drugs (P = 0.006). CONCLUSION: Patients with abdominal visceral BTcP represent a subgroup with specific features of BTcP, particularly those with predictable BTcP. Ingestion of food was the prominent trigger for BTcP, having a faster onset and a lower intensity. This group of patients more frequently used oxycodone/naloxone or no anti-inflammatory drugs. These findings suggest consequential therapeutic decisions.

Opioid-induced bowel dysfunction: suggestions from a multidisciplinary expert Board.

Constipation, one of the adverse effects of opioid therapy with a major impact on quality of life, is still an unmet need for cancer patients, particularly those with an advanced and progressive disease, and for non-cancer patients chronically treated with opioids. The awareness of this condition is poor among healthcare providers, despite the recent publication of guidelines and consensus conferences. An early multidisciplinary approach of opioid-induced bowel dysfunction (OIBD), based on available therapies of proven effectiveness, could support clinicians in managing this condition, thus increasing patients' adherence to pain therapy. Several Italian experts involved in the management of patients suffering from pain (anaesthesia pain therapy, oncology, haematology, palliative care, gastroenterology) joined in a Board in order to draw up an expert opinion on OIBD. The most frequent and still unsolved issues in this field were examined, including a more comprehensive definition of OIBD, the benefits of early intervention to prevent its occurrence and the most appropriate use of peripherally acting mu-opioid receptor antagonists (PAMORAs). The use of the recently introduced PAMORA naloxegol was analysed, in light of the current literature. The Board proposed a solution for each open issue in the form of recommendations, integrated with the contribution of representatives from different disciplines and often accompanied by procedural algorithms immediately usable and applicable in daily clinical practice. Safety and quality of life of the patient suffering from pain and from the adverse effects of pain therapies have been the mainstays of this expert opinion, in cooperation with general practitioners and caregivers.

Bone Metastasis Pain, from the Bench to the Bedside.

Bone is the most frequent site of metastasis of the most common cancers in men and women. Bone metastasis incidence has been steadily increasing over the years, mainly because of higher life expectancy in oncologic patients. Although bone metastases are sometimes asymptomatic, their consequences are most often devastating, impairing both life quality and expectancy, due to the occurrence of the skeletal-related events, including bone fractures, hypercalcemia and spinal cord compression. Up to 75% of patients endure crippling cancer-induced bone pain (CIBP), against which we have very few weapons. This review's purpose is to discuss the molecular and cellular mechanisms that lead to CIBP, including how cancer cells convert the bone "virtuous cycle" into a cancer-fuelling "vicious cycle", and how this leads to the release of molecular mediators of pain, including protons, neurotrophins, interleukins, chemokines and ATP. Preclinical tests and assays to evaluate CIBP, including the incapacitance tester (in vivo), and neuron/glial activation in the dorsal root ganglia/spinal cord (ex vivo) will also be presented. Furthermore, current therapeutic options for CIBP are quite limited and nonspecific and they will also be discussed, along with up-and-coming options that may render CIBP easier to treat and let patients forget they are patients.

Personalized Symptom Goals and Patient Global Impression on Clinical Changes in Advanced Cancer Patients.

BACKGROUND: The aim of this study was to assess the patients' global impression (PGI) after symptom management, as well as the achievement of personalized symptom goals (PSG). The secondary outcome was to assess related factors. SUBJECTS, MATERIALS, AND METHODS: Advanced cancer patients admitted to palliative care units rated symptom intensity by using the Edmonton Symptom Assessment Score (ESAS) at admission and then after 1 week. For each symptom, patient-reported PGI and PSG, as well as the rate of PSG response, were evaluated. RESULTS: Eight hundred seventy-six patients were taken into consideration for this study. A mean of 1.71-2.16 points was necessary to perceive a bit better improvement of symptom intensity. Most patients had a PSG of ≤3. A statistically significant number of patients achieved their PSG after starting palliative care. Patients with high intensity of ESAS items at admission achieved a more favorable PGI response. In the multivariate analysis, symptom intensity and PSG were the most frequent factors independently associated to a best PGI, whereas high levels of Karnofsky had a lower odd ratio. CONCLUSION: PSG and PGI seem to be relevant for patients' assessment and decision-making process, translating in terms of therapeutic intervention. Some factors may be implicated in determining the individual target and clinical response. IMPLICATIONS FOR PRACTICE: Personalized symptom goals and global impression of change are relevant for patients' assessment and decision-making process, translating in terms of therapeutic intervention. Some factors may be implicated in determining the individual target and clinical response.

Personalized Goal for Dyspnea and Clinical Response in Advanced Cancer Patients.

BACKGROUND: The clinical response after comprehensive symptom management is difficult to determine in terms of a clinically important difference. Moreover, therapies should try to reach the threshold perceived by the individual patient for the determination of a favorable response to a treatment. MEASURES: The Edmonton Symptom Assessment Score (ESAS) was measured at admission (T0), and seven days after starting palliative care (T7). Patient Global Impression and Goal Response after one week of palliative care and its relation with the Personalized Dyspnea Goal were measured at T7. INTERVENTION: Patients admitted to palliative care units underwent a comprehensive symptom assessment by a specialist palliative care team. At T0, patients were asked about their Personalized Dyspnea Intensity Goal on ESAS. One week later (T7), after a comprehensive palliative care treatment, Personalized Dyspnea Intensity Goals were measured again. Patients were considered to have achieved a Patient Dyspnea Goal Response if dyspnea intensity (measured at T7) was equal or less than their expected Personalized Dyspnea Intensity Goal. At the same interval (T7), Patient Global Impression (improvement or deterioration) was measured. OUTCOMES: 279 patients were analyzed in this study. The mean Personalized Dyspnea Intensity Goal at T0 and T7 were 0.97 (SD 1.3), and 0.71 (SD 2.1), respectively. 263 patients (94.2%) indicated a Personalized Dyspnea Intensity Goal of ≤3 as a target at T0. Patients perceived a bit better, a better improvement, and a much better improvement with a mean decrease in dyspnea intensity of -2.1, -3.5, and -4.3 points on the dyspnea intensity scale, respectively. In 60 patients (21.5%), dyspnea intensity did not change, and in 4.7%, dyspnea intensity worsened. Patients perceived a Minimal Clinically Important Difference (little worse) with a mean increase in dyspnea intensity of 0.10, and they perceived a worse with a mean increase of 1.7 points. Higher dyspnea intensity at T0 and lower dyspnea intensity at T7 were independently related to Patient Global Impression. At T7, 93 (33.3%) patients achieved their Personalized Goal Response, based on Personalized Dyspnea Intensity. Patient Dyspnea Goal Response was associated with Memorial Delirium Assessment Scale score and Personalized Dyspnea Intensity Goal at T0, and inversely associated with dyspnea intensity at T0 and T7, and lower Karnofsky level. For Patient Dyspnea Goal Response, no significant differences among categories of dyspnea intensity were found (P>0.05). CONCLUSION: Patient Dyspnea Goal Response and Patient Global Impression seem to be relevant for evaluating the effects of a comprehensive management of symptoms, including dyspnea, assisting decision making process. Some factors may be implicated in determining the individual target and clinical response. A personalized symptom goal may translate in terms of therapeutic intervention, according to the achievement of the patients' expectations. High values of dyspnea intensity, a lower Karnofsky level, as well as high level of Dyspnea Intensity Goal (that is less patients' expectations) favor the achievement of the target.

Symptom expression in advanced cancer patients admitted to hospice or home care with and without delirium.

The aim of this study is to investigate the relationship between delirium and symptom expression in advanced cancer patients admitted to palliative care services. This is a secondary analysis of a consecutive sample of advanced cancer patients who were admitted to home care and hospices, and prospectively assessed for a period of 10 months. The Edmonton Symptom Assessment Scale (ESAS) and the MDAS (Memorial Delirium Assessment Scale) were measured at admission (T0) and after seven days of home care or hospice care (T7). Of the eight hundred and forty-eight patients screened in the period, 585 were not considered in the analysis for various reasons. The mean age was 72.1 years (SD 13.7), and 146 patients were males (55.5%). The mean Karnofsky status recorded at T0 is 34.1 (SD = 6.69). The mean duration palliative care assistance is 38.4 days (SD = 48, range 2-220). Of 263 patients who had a MDAS available at T0, 110 patients (41.8%) had a diagnosis of delirium. Of them, 167 patients had complete data regarding MDAS measurement, either at T0 and T7. A larger number of patients (n 167, 63.5%) had delirium after a week of palliative care. Patients with delirium are likely to be older, to have a lower Karnofsky level at T0, and to be home care patients. At T0, weakness, nausea, drowsiness, lack of appetite, and well-being are associated with delirium. At T7, weakness, poor appetite, and poor well-being are significantly associated with delirium. 27% of patients who had a normal cognitive status at T0 developed delirium at T7. In patients with delirium, an improvement in the cognitive status corresponds to a significant improvement in weakness, depression, and appetite. Conversely, the occurrence of delirium in patients who had a normal cognitive status at admission significantly increases the level depression, while the level of weakness and appetite decrease. Symptom expression is amplified in patients with delirium admitted to home care or hospices, while patients without delirium can be more responsive to palliative treatments with a significant decrease in intensity of ESAS items.

Factors influencing the use of opioids for breakthrough cancer pain: A secondary analysis of the IOPS-MS study.

BACKGROUND: Controversies exist about the choice and the doses of opioid medication in breakthrough cancer pain (BTcP). METHODS: The aim was to assess factors influencing the use and the doses of opioids prescribed for BTcP. There was performed a secondary analysis of a national, multicentre study that involving 32 centres performed in patients having BTcP. Diagnosis of BTcP was based on a definite algorithm. Patients using opioids for background pain and for BTcP were selected. Average pain intensity and opioids used for background pain and BTcP, and adverse effects were assessed, as well as patient's satisfaction and the grade of mucositis. RESULTS: The analysis was performed in 2,771 patients. Opioid doses given for BTcP were significantly associated with those given for background pain. No relationship between adverse effects and the use and the doses of opioids used for BTcP was found. Drugs and doses were not correlated to the grade of oral mucositis. Nasal fentanyl preparations provided the fastest meaningful pain relief in comparison with other fentanyl transmucosal preparations or morphine preparations (P = 0.000). The majority of patients were satisfied with opioid medications given for BTcP. Only 2.8% of patients reported adverse effects related to opioid medication used for BTcP. Age and gender were independently associated with dosages of some fentanyl products. CONCLUSIONS: Opioids for BTcP were effective and safe in a large sample of cancer patients with different stages of disease. Doses of opioids proportional to doses used for background pain seem to guarantee both efficacy and safety. SIGNIFICANCE: The use of opioids for breakthough cancer pain was effective and safe in a large sample of advanced cancer patients recruited in different stages of disease and settings. Doses of opioids proportional to opioid doses used for background analgesia, seem to guarantee both effectiveness and safety.