Emerging therapies in metastatic bone pain

Introduction: Current treatment for metastatic bone pain is mainly palliative. Recent insights into the molecular mechanisms involved in bone metastases have led to the identification of promising therapeutic targets. This review offers an update of preclinical and clinical data on new drugs for metastatic bone pain. Areas covered: Biphosphonates are the gold standard of bone-targeted therapy in bone metastases, for their anti-resorptive and analgesic effects. New drugs aim at breaking the 'vicious cycle' of bone metastatic disease, due to the bidirectional interaction between cancer cells and bone microenvironment. Osteoprotegerin, RANK/RANKL interaction, cathepsin K, the Wnt/beta-catenin pathway and sclerostin are emerging targets for modulation of cancer-induced bone desorption. Other promising targets are those expressed in cancer cells that metastasize to bone, including Src, nerve growth factor, endothelin A, TGF-beta and CXCR4. Interesting therapeutic options include targets on nociceptors that innervate the bone, such as TPRV1, Trk and cannabinoid receptors. Expert opinion: Emerging therapies promise, in the next 10 years, a significant expansion in the array of therapeutic options for bone metastases. Most of these drugs are still in an early phase of development. Further clinical trials are needed to support the evidence of their efficacy and tolerability profile

Dolore cronico e comorbidità

La prevalenza del dolore cronico in Europa è di circa il 20%.Il dolore cronico è in grado di influire sulla vita quotidiana del soggetto, compromettendo sia la sua vita di relazione che la sua capacità lavorativa, determinando una perdita di reddito per il soggetto e per la società.Il dolore cronico si può ritrovare associato a molteplici patologie, tra le quali le più frequenti sono le patologie della colonna, la fibromialgia, l’osteoartrosi, la patologia neoplastica, ma anche ansia, disordini dell’umore e disordini del sonno. In questo lavoro vengono analizzati in particolare i rappor ti tra dolore cronico e due componenti cruciali nella qualità di vita di un paziente: il tono dell’umore ed il sonno

Non-analgesic effects of opioids: Opioid-induced nausea and vomiting: Mechanisms and strategies for their limitation

Nausea and vomiting are common gastrointestinal symptoms following opioid administration, for either chronic or acute pain management. As a consequence, patients' dissatisfaction has a negative impact on treatment efficacy. A number of mechanisms have been identified, involving both central and peripheral sites. This article will review the pathophysiology of opioid-induced nausea and vomiting and the various pharmacological treatments currently available for its management. Preventive strategies and therapeutic approaches are evaluated in the perioperative setting and in chronic pain. Newer drugs include second generation serotonin receptor antagonists (palonosetron) and neurokinin-1 (NK-1) antagonists (aprepitant). © 2012 Bentham Science Publishers

Bone Metastatic Disease: Taking Aim at New Therapeutic Targets

Conventional treatment for metastatic bone pain requires a multidisciplinary approach (medical therapy, surgery, and radiation), but is primarily palliative. Biphosphonates introduced the concept of disease-modifying therapy, by effectively reducing bone pain and skeletal related events in patients suffering from bone metastatic cancer. In the past decade, the growing knowledge of bone biology and our understanding of the molecular mechanisms at the basis of the interaction between cancer cells and bone matrix led to the identification of new therapeutic targets for innovative "smart drugs". The most investigated is the RANK/RANKL/OPG pathway, and denosumab, among novel targeted therapies, is the molecule that is in the most advanced development phase. Additional targets have been identified and potential novel therapeutic interventions, classified as inhibitors of bone resorption or stimulators of bone formation, are under preclinical and clinical evaluation. These promising targets include cathepsin K, the Src tyrosine kinases, integrins, chloride channels, the parathyroid hormone-related peptide, endotelin-1, sclerostin, and TGF-beta. Other pathways or molecules expressed by bone cells and cancer cells, such as CXCR4, GPNMB, EGF-family ligands, Wnt/DKK1, and MIP-1 alpha have recently emerged as potential targets. The aim of this review is to discuss the molecular mechanisms behind these emerging therapeutic targets in bone metastases and to give an overview of results from those in advanced clinical phases

Modificazioni dell’intake calorico e del comportamento alimentare dopo sleeve gastrectomy

L’excess weight loss (%EWL) medio a 3-5 anni dopo Sleeve Gastrectomy Laparoscopica (LSG), è del 60%. La riduzione del volume gastrico ha un ruolo centrale nella perdita di peso post-operatoria,tuttavia diversi studi indicano che, anche il cambiamento delle abitudini alimentari nei pazienti, possa contribuire al calo ponderale. E’ stato dimostrato che diversi pazienti dopo intervento di chirurgia bariatrica, cambino le loro preferenze alimentari verso cibi a bassa densità calorica. La diminuzione nell’assunzione di cibi ad alto contenuto lipidico e di dolci, suggerisce che alcuni interventi bariatrici possano influenzare le scelte alimentari. Gli obiettivi di questo studio prospettico sono: valutare la riduzione quantitativa dell’introito calorico giornaliero e i cambiamenti nelle abitudini alimentari 1 anno dopo LSG utilizzando un Suter Questionnaire modificato. Si è inoltre analizzata la relazione tra la perdita di peso e il cambiamento del gusto e delle abitudini alimentari

Il ruolo del “gruppo psico-educazionale” quale strumento interattivo nel percorso del paziente candidato a chirurgia bariatrica. Valutazione prospettica di un programma sperimentale

La chirurgia bariatrica laparoscopica rappresenta il gold standard nel trattamento dell’obesità patologica. Tuttavia, nonostante i benefici intermini di calo ponderale e riduzione delle comorbidità obesità-correlate, il 20% - 30% dei pazienti non raggiunge la perdita di peso attesa e/o non mantiene il peso perso a lungo termine. I possibili fattori correlati possono essere scarsa adherence e l’acquisizione, o il persistere, di abitudini alimentari disfunzionali associate a disturbi psicopatologici. Il presente studio prospettico ha l’obiettivo di valutare l’efficacia di un gruppo psicologico di sostegno interattivo sugli outcome clinici (calo ponderale e sintomatologia psicopatologica a medio termine

Very low-carbohydrate ketogenic diet before bariatric surgery. Prospective evaluation of a sequential diet

Background We evaluated the effectiveness of a sequential diet regimen termed the obese preoperative diet (OPOD) in morbidly obese patients with and without type 2 diabetes mellitus (T2DM) scheduled for laparoscopic bariatric surgery. Methods Fifty patients (body mass index 53.5 ± 8.4 kg/m2) scheduled for bariatric surgery, including 14 with T2DM, were prospectively enrolled and followed the OPOD regimen: a very low-calorie ketogenic diet for 10 days, followed by a very low-calorie diet for 10 days, and then a low-calorie diet for 10 days. Patients were evaluated at baseline (T0) and after 10 days (T1), 20 days (T2), and 30 days (T3). Results Body weight, body mass index, waist circumference, and neck circumference were significantly lower at T1, T2, and T3 than at T0 in the 48 patients who completed the OPOD. Two patients discontinued the OPOD after 4-7 days. In patients with T2DM, fasting plasma glucose levels decreased significantly, enabling reduction of diabetic medications. Plasma and urine ketone levels increased at T1 but were all <1 mmol/L, and hunger decreased during the diet period. Conclusions OPOD, including 10 days of a VLCKD, was safe and effective in morbidly obese patients, and it seems to be promising in morbidly obese patients with and without T2DM scheduled for laparoscopic bariatric surgery. © 2014 Springer Science+Business Media New York.Background We evaluated the effectiveness of a sequential diet regimen termed the obese preoperative diet (OPOD) in morbidly obese patients with and without type 2 diabetes mellitus (T2DM) scheduled for laparoscopic bariatric surgery. Methods Fifty patients (body mass index 53.5 ± 8.4 kg/m2) scheduled for bariatric surgery, including 14 with T2DM, were prospectively enrolled and followed the OPOD regimen: a very low-calorie ketogenic diet for 10 days, followed by a very low-calorie diet for 10 days, and then a low-calorie diet for 10 days. Patients were evaluated at baseline (T0) and after 10 days (T1), 20 days (T2), and 30 days (T3). Results Body weight, body mass index, waist circumference, and neck circumference were significantly lower at T1, T2, and T3 than at T0 in the 48 patients who completed the OPOD. Two patients discontinued the OPOD after 4-7 days. In patients with T2DM, fasting plasma glucose levels decreased significantly, enabling reduction of diabetic medications. Plas

Food intake and changes in eating behavior after laparoscopic sleeve gastrectomy

Abstract Background Laparoscopic sleeve gastrectomy (LSG) results in reduced calorie intake and weight loss. Whether patients consume the same types of food before and after surgery or whether they reduce the volume and calorie density of the foods they consume remains unknown. Objectives The aim of this prospective study was to evaluate the changes in daily caloric and macronutrient intake after LSG and the relation between changes of taste and food tolerance over 2 years. Methods Thirty morbidly obese patients with median body mass index (BMI) of 43.9 kg/m2 (39.5–57.3) were prospectively enrolled prior to LSG. Weight, BMI, %EWL, weight loss percentage (%WL), and daily intake were evaluated preoperatively at 1, 3, 6, 12, and 24 months after surgery along with a questionnaire evaluating food choices, quality of eating, tolerance of certain types of food, frequency of vomiting, and changes in taste. Results The median %EWL and %WL at 12 and 24 months was 65 % (33.9–93.6 %), 27.3 % (14.2–45.5 %) and 71.5 % (39.6–101.1%),31%(19.1–50.3%)respectively.Sixmonths after surgery, the dailycaloric intakereduced by68% and the reduction was maintained until 24 months. The median score of the eating questionnaire was 18 (10–27) at 6 months, 22 (16–26) at 12 months, and 23 (10–27) at 24 months, suggesting that the quality of nutrition improved over time. At 6, 12, and 24 months, 75 % of the patients reported changes in taste with reduced interest in sweets, high fat food, and alcoholic drinks. However, at 24 months, 20 % of patients reported a heightened interest in sweets compared to 12 months previously. Conclusions LSG reduced calorie intake both through volume of food and the calorie density of the food consumed. The mechanisms for the changes in food preferences may involve both unconditioned and conditioned effects. The influence of dietary counseling on learning which foods are consumed still requires further exploration. Keywords Foodintake .Eatingbehavior .Sleeve gastrectomy Introduction Bariatric surgery is the most effective long-term treatmen

Low-Calorie Ketogenic Diet with Continuous Positive Airway Pressure to Alleviate Severe Obstructive Sleep Apnea Syndrome in Patients with Obesity Scheduled for Bariatric/Metabolic Surgery: a Pilot, Prospective, Randomized Multicenter Comparative Study

: Obstructive sleep apnea syndrome (OSAS) and obesity are frequently associated with hypertension (HTN), dyslipidemia (DLP), and insulin resistance (IR). In patients with obesity and OSAS scheduled for bariatric surgery (BS), guidelines recommend at least 4 weeks of preoperative continuous positive airway pressure (CPAP). Low-calorie ketogenic diets (LCKDs) promote pre-BS weight loss (WL) and improve HTN, DLP, and IR. However, it is unclear whether pre-BS LCKD with CPAP improves OSAS more than CPAP alone. We assessed the clinical advantage of pre-BS CPAP and LCKD in patients with obesity and OSAS. Seventy patients with obesity and OSAS were randomly assigned to CPAP or CPAP+LCKD groups for 4 weeks. The effect of each intervention on the apnea-hypopnea index (AHI) was the primary endpoint. WL, C-reactive protein (CRP) levels, HTN, DLP, and IR were secondary endpoints. AHI scores improved significantly in both groups (CPAP, p=0.0231; CPAP+LCKD, p=0.0272). However, combining CPAP and LCKD registered no advantage on the AHI score (p=0.863). Furthermore, body weight, CRP levels, and systolic/diastolic blood pressure were significantly reduced in the CPAP+LCKD group after 4 weeks (p=0.0052, p=0.0161, p=0.0008, and p=0.0007 vs baseline, respectively), and CPAP+LCKD had a greater impact on CRP levels than CPAP alone (p=0.0329). The CPAP+LCKD group also registered a significant reduction in serum cholesterol, LDL, and triglyceride levels (p=0.0183, p=0.0198, and p<0.001, respectively). Combined with CPAP, LCKD-induced WL seems to not have a significant incremental effect on AHI, HTN, DLP, and IR but lower CRP levels demonstrated a positive impact on chronic inflammatory status