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The aim of this study was to evaluate the pharmacological modulation of these two pathways by pyrrolidine dithiocarbamate (PDTC), dimethyl sulfoxide (DMSO) and methylprednisolone (MP) on the expression of HSP70 and NF-kB after induction of hemorrhagic shock in rats. The results suggest that treatment with DMSO, PDTC and MP can modulate the expression of HSP70 and NF-kB after induction of hemorrhagic shock. This modulation may be beneficial for organ injury and dysfunction.

Background: The impact of home parenteral nutrition (HPN) on the quality of life (QoL) of cancer patients has been previously investigated. However, scarce data are available regarding near-death QoL in patients with cancer receiving HPN. This study aims to investigate the changes of QoL in these patients in the last two months before death. Methods: This is a secondary analysis of a previous, prospective, longitudinal, observational study. QoL was assessed using the EORTC QLQ-C30 questionnaire. Results: Eighty-four adult cancer patients who died on HPN and had filled out the questionnaire between 31 and 60 days (M2) and within 30 days prior (M1) to death were included in this analysis. The questionnaires filled out at M2 and M1 were compared with those filled out by the same patients at HPN start (T0). At M2, there was a significant improvement in both the global QoL and symptoms scales ( p < 0.001 and p < 0.033, respectively), while at M1, a significant improvement in the global QoL scale persisted ( p < 0.035) compared with T0. Conclusions: Our study first reports that HPN, if started early and according to European guidelines, is associated with an improvement in the QoL of patients with cancer even in the last two months before death.

Radical cystectomy (RC) with pelvic lymph node dissection is the standard treatment for patients with limited-stage muscle-invasive bladder cancer. RC is associated with a complication rate of approximately 50-88%. Immunonutrition (IMN) refers to the administration of substrates, such as omega-3 fatty acids, arginine, glutamine, and nucleotides, that modulate the immune response. IMN has been associated with improved outcomes following surgery for esophagogastric, colorectal and pancreatic cancer. In this paper, we describe a study protocol for a multicentre, randomised, open-label clinical trial to evaluate the effect of IMN in patients undergoing RC for bladder cancer. A 7-day preoperative course of IMN is compared with a standard high-calorie high-protein oral nutritional supplement. The primary outcome of this study is the rate of complications (infectious, wound-related, gastrointestinal, and urinary complications) in the first 30 days after RC. Secondary outcomes include time to recovery of bowel function and postoperative mobilisation, changes in muscle strength and body weight, biochemical modifications, need for blood transfusion, length of stay, readmission rate, and mortality. The results of this study may provide new insights into the impact of IMN on postoperative outcomes after RC and may help improve IMN prescribing based on patient nutritional status parameters.

Social and healthcare professionals often feel ill equipped to effectively engage in difficult conversations with patients, and poor proficiency negatively affects the quality of patient care. Printed educational resources (PERs) that provide guidance on sustaining complex clinical communication may be a source of support if thoughtfully designed. This study aimed to describe the key features of PERs in order to improve the quality of clinical communication according to the perspective of meaningful stakeholders. This was a descriptive secondary analysis of data collected by three remote focus group discussions that involved 15 stakeholders in the context of developing an educational booklet to support professionals in complex communication scenarios. Focus groups were audio-recorded and transcribed verbatim, and an inductive thematic analysis was performed. Three key features of PERs that aim toward quality improvement in clinical communication were identified: (1) having the potential to provide benefits in clinical practice; (2) facilitating, encouraging, and enticing reading; and (3) meeting the need of professionals to improve or update their knowledge. These findings suggest that PERs relevant to professionals' clinical priorities and learning needs may make their efforts to apply learning in practice more likely and consequently result in improved healthcare quality.

Health and social care professionals (HCPs) who work in nursing homes (NHs) are increasingly required to sustain serious illness conversations about care goals and preferences. Although these conversations may also be challenging for experienced HCPs and the literature recognizes high-quality communication as key to providing patient-centered care, so far, no specific educational program has been developed for the NH setting to improve HCPs' communication skills. Our study aims to test the feasibility and potential effectiveness of an innovative, blended communication skills training program ( Teach-to-Communicate ) targeting the HCPs who work in NHs. This program includes classroom-based theory, experiential learning, and e-learning, and relies on interdisciplinary contexts and several didactic methods. The study consists of two phases: phase I is the development of written resources that employ focus group discussion involving field experts and external feedback from key stakeholders. Phase II consists of a multicenter, pilot, pre-post study with nested qualitative study. The Teach-to-Communicate training program is expected to enhance the quality of communication in NH and HCPs' confidence in sustaining serious illness conversations, reduce family carers' psycho-emotional burden and improve their satisfaction with the care received, and increase advance care planning documentation. Our protocol will provide insight for future researchers, healthcare providers, and policymakers and pave the way for blended educational approaches in the field of communication skills training.

Background: Immune checkpoint inhibitors (ICIs) represent one of the most effective treatments for patients with cancer. As their activity relies on host immune system reactivity, the role of concomitant medications such as corticosteroids and antibiotics has been extensively evaluated. Preclinical data suggest that opioids may influence the immune system., Methods: a systematic literature revision was performed using specific keywords on the major search engines. Two authors analysed all the studies and provided a selection of the following inclusion and exclusion criteria, respectively: 1. data collection of patients older than 18 years old affected by solid tumours; 2. description of ICIs efficacy in terms of PFS, OS, TTF, and ORR; 3. concomitant ICIs-opioids treatment and 1. language different from English; 2. not pertinent analyses., Results: 523 studies were analysed, and 13 were selected and included in our series. A possible negative interaction between oral opioids and ICIs efficacy was observed. Most evidence was retrospective, and studies were heterogeneous., Conclusions: Even if oral opioids seem to impact negatively on ICIs efficacy in cancer patients, to date there is not sufficient evidence to avoid their prescription in this population.

Malnutrition is an often-overlooked challenge for patients with cancer. It is associated with muscle mass reduction, poor compliance and response to cancer treatments, decreased quality of life, and reduced survival time. The nutritional assessment and intervention should be a vital part of any comprehensive cancer treatment plan. However, data on artificial nutrition supplied based on caloric needs during cancer care are scarce. In this review, we discuss the recommendations of the European and American societies for clinical nutrition on the use of nutritional interventions in malnourished patients with cancer in the context of current clinical practice. In particular, when enteral nutrition (oral or tube feeding) is not feasible or fails to meet the complete nutritional needs, supplemental parenteral nutrition (SPN) can bridge the gap. We report the available evidence on SPN in cancer patients and identify the perceived barriers to the wider application of this intervention. Finally, we suggest a 'permissive' role of SPN in cancer care but highlight the need for rigorous clinical studies to further evaluate the use of SPN in different populations of cancer patients., Competing Interests: Competing Interests: PC reported honoraria for speaking and teaching from Baxter. FB reported honoraria for speaking and teaching from Baxter. FG is a member of the board of experts for Baxter, Fresenius Kabi, and Nutricia and he reported honoraria for speaking and teaching for all three. PJF declares consulting/advisory role for Bristol, MSD, Mylan, Leo Pharma, HRA Pharma, all outside of the scope of this work. SRO reported honoraria for teaching for Baxter, received research grants from Baxter and Nutricia, participated in advisory role for Takeda. JWV has received travel grants from Ipsen, Novartis, and NuCana, Speakers’ Bureau support from Abbott, Celgene, Ipsen, Novartis, Pfizer, and Sirtex and has worked in a consulting or advisory role for Abbott, Agios, AstraZeneca, Baxalta, Baxter, Bioven, Celgene, Delcath, Genoscience Pharma, Incyte, Ipsen, Keocyt, Lilly, Merck, MidaTech, Mundipharma, Novartis, NuCana, PCI Biotech, Pfizer, Pieris Pharmaceuticals, and QED Pharmaceuticals., (© The Author(s), 2022.)

Malnutrition is a frequent problem in cancer patients, which leads to prolonged and repeated hospitalizations, increased treatment-related toxicity, reduced response to cancer treatment, impaired quality of life, a worse overall prognosis and the avoidable waste of health care resources. Despite being perceived as a limiting factor in oncologic treatments by both oncologists and patients, there is still a considerable gap between need and actual delivery of nutrition care, and attitudes still vary considerably among health care professionals. In the last 5 years, the Italian Intersociety Working Group for Nutritional Support in Cancer Patients (WG), has repeatedly revisited this issue and has concluded that some improvement in nutritional care in Italy has occurred, at least with regard to awareness and institutional activities. In the same period, new international guidelines for the management of malnutrition and cachexia have been released. Despite these valuable initiatives, effective structural strategies and concrete actions aimed at facing the challenging issues of nutritional care in oncology are still needed, requiring the active participation of scientific societies and health authorities. As a continuation of the WG's work, we have reviewed available data present in the literature from January 2016 to September 2021, together with the most recent guidelines issued by scientific societies and health authorities, thus providing an update of the 2016 WG practical recommendations, with suggestions for new areas/issues for possible improvement and implementation., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The prevalence of patients affected by end-stage diseases or advanced cancer is increasing due to an aging population and progression in medicine and public healthcare. The burden of symptoms these people suffer in the last months of life often forces them to seek aid in an emergency department. In developed countries, acute care hospital-based services are often better designed to treat acute clinical conditions than to manage the needs of patients with serious chronic diseases. Thus, the palliative care (PC) population poses very real clinical challenges to healthcare professionals who care for them in hospital settings. The authors have formulated four key questions (who, why, when, and how) to address in order to identify a model for providing the best care for these PC patients. The questions are related to: (1) defining people living with serious chronic diseases; (2) managing the challenge of unplanned hospital admission of these people; (3) identifying PC patients among people with serious chronic diseases; and (4) determining the appropriate work of caring for this inpatient PC population. Clinicians need the knowledge, tools, and services to care for these PC patients, and acute care hospitals should plan the work of caring for these inpatients.

Objective: The evidence base for home parenteral nutrition (HPN) in patients with advanced cancer is lacking. To compare the survival of malnourished patients with cancer undergoing palliative care who received HPN with a homogeneous group of patients, equally eligible for HPN, who did not receive HPN., Design: Prospective, cohort study; tertiary university hospital, home care, hospice., Methods: Patients were assessed for HPN eligibility according to the guidelines. In the eligible population, who received both HPN and chemotherapy was excluded, while who received only HPN was included in the HPN+ group and who received neither HPN nor chemotherapy but artificial hydration (AH) was included in the HPN- group., Results: 301 patients were assessed for HPN eligibility and 86 patients (28.6%) were excluded for having severe organ dysfunction or Karnofsky performance status <50. In outcome analysis, 90 patients (29.9%) were excluded for receiving both HPN and chemotherapy, while 125 (41.5%) were included, 89 in HPN+ group (29.5%) and 36 in HPN- group (12%). The survival of the two groups showed a significant difference favouring patients receiving HPN (median overall survival: 4.3 vs 1.5 months, p<0.001). The multivariate analysis of the risk factors for mortality showed that not receiving HPN accounted for the strongest one (HR 25.72, 95% CI 13·65 to 48.44)., Conclusions: Comparative survival associated with the use of HPN versus AH showed significantly longer survival in malnourished patients with advanced cancer receiving HPN. These data support the guideline recommendation that HPN should be considered when malnutrition represents the overriding threat for the survival of these patients., Competing Interests: Competing interests: PC reported grants (19700/27.001, 1837/27.001) from the Regional Public Healthcare Office and reported honoraria for speaking and teaching from Baxter. The other authors declare that they have no competing interests., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Whether peripherally inserted central catheters (PICCs) are appropriate as safe and durable venous access devices (VADs) is still controversial. The aim of this 7-year, prospective cohort study was to compare the incidence rate differences of catheter-related complications (CRCs) among 4 types of central VADs in cancer patients receiving home parenteral nutrition (HPN)., Methods: We enrolled all adult cancer outpatients who were candidates for HPN and who had a central VAD inserted during the study period, focusing on the incidence rate of CRCs., Results: We evaluated 854 central VADs (401 PICCs, 137 nontunneled centrally inserted central catheters [CICCs], 118 tunneled-cuffed CICCs, and 198 ports) in 761 patients, for a total of 169,116 catheter-days. Overall, the rate of total CRCs was 1.08/1000 catheter-days. The incidence of catheter-related bloodstream infections was low (0.29/1000), particularly for PICCs (0.08/1000; P < .001 vs tunneled-cuffed CICCs) and for ports (0.21/1000; P < .019 vs tunneled-cuffed CICCs). The rates of mechanical complications (0.58/1000) and of catheter-related symptomatic thrombosis (0.09/1000) were low and similar for PICCs, tunneled-cuffed CICCs, and ports. In terms of duration and removal rate due to complications, PICCs were like tunneled-cuffed CICCs and ports. Altogether, PICCs had fewer total complications than tunneled-cuffed CICCs (P < .001), there was no difference in total complications between PICCs and ports., Conclusion: PICCs had significantly better outcomes than tunneled-cuffed CICCs and were safe and durable as ports. Our extensive, long-term study suggests that PICCs can be successfully used as safe and long-lasting VADs for HPN in cancer patients., (© 2020 American Society for Parenteral and Enteral Nutrition.)

The role of nutritional support for cancer patients in palliative care is still a controversial topic, in part because there is no consensus on the definition of a palliative care patient because of ambiguity in the common medical use of the adjective palliative. Nonetheless, guidelines recommend assessing nutritional deficiencies in all such patients because, regardless of whether they are still on anticancer treatments or not, malnutrition leads to low performance status, impaired quality of life (QoL), unplanned hospitalizations, and reduced survival. Because nutritional interventions tailored to individual needs may be beneficial, guidelines recommend that if oral food intake remains inadequate despite counseling and oral nutritional supplements, home enteral nutrition or, if this is not sufficient or feasible, home parenteral nutrition (supplemental or total) should be considered in suitable patients. The purpose of this narrative review is to identify in these cancer patients the area of overlapping between the two therapeutic approaches consisting of nutritional support and palliative care in light of the variables that determine its identification (guidelines, evidence, ethics, and law). However, nutritional support for cancer patients in palliative care may be more likely to contribute to improving their QoL when part of a comprehensive early palliative care approach.

Malnutrition is common in surgical cancer patients and it is widely accepted that it can adversely affect their postoperative outcome. Assessing the nutritional status of every patient, in particular care of elderly and cancer patients, is a crucial feature of the therapeutic pathway in order to optimize every strategy. Evidence exists that the advantages of perioperative nutrition are more significant in malnourished patients submitted to major surgery. For patients recognized as malnourished, preoperative nutrition therapies are indicated; the choice between parenteral and enteral nutrition is still controversial in perioperative malnourished surgical cancer patients, although enteral nutrition seems to have the best risk-benefit ratio. Early oral nutrition after surgery is advisable, when feasible, and should be administered in all the patients undergoing elective major surgery, if compliant. In patients with high risk for postoperative infections, perioperative immunonutrition has been proved in some ways to be effective, even if operations including those for cancer have to be delayed.

Background: Robust data reporting the survival of cancer patients on home parenteral nutrition (HPN) are lacking. The aim of this prospective, cohort study was to investigate clinical characteristics, predictive factors, and overall survival (OS) of adult-malnourished cancer patients eligible for HPN according to the European guideline recommendations., Methods: During the study period, 1658 cancer patients were consecutively evaluated in a tertiary university hospital. Of these, 761 who received HPN were grouped into four cohorts according to the provision of supplemental PN (SPN) or total (TPN) and whether they received chemotherapy (CT + or CT - ): SPN/CT + (n = 376), TPN/CT + (n = 99), SPN/CT - (n = 191), and TPN/CT - (n = 95). Patient demographics, nutritional status, cancer-related characteristics, and prognostic scores assessed at HPN start. The primary outcome was OS., Results: Median OS was 8.9, 4.3, 5.7, and 2.2 months for the SPN/CT + , TPN/CT + , SPN/CT - , and TPN/CT - cohorts, respectively. In multivariable analysis, predictors showing significant association with decreased survival were patient cohorts, modified Glasgow Prognostic Score (1 and 2 scores), weight loss (>15%) in the 3 months before HPN start, and TNM IV stage while protective factors of survival were Karnofsky Performance Status (>50), albumin level (>3.5 g/dL), oral protein intake, BMI (>20.5), and weight at HPN start., Conclusion: For the first time, in four different cohorts of cancer patients on HPN, clinical characteristics and survival were compared. This large study showed that survival is significantly correlated with patient characteristics at HPN start and that the presence of favorable factors may determine even a fourfold increase in survival. These data are expected to assist physicians in the appropriate prescription of HPN., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Current guidelines recommend home parenteral nutrition (HPN) for cancer patients with chronic deficiencies of dietary intake or absorption when enteral nutrition is not adequate or feasible in suitable patients. HPN has been shown to slow down progressive weight loss and improve nutritional status, but limited information is available on the monitoring practice of cancer patients on HPN. Clinical management of these patients based only on nutritional status is incomplete. Moreover, some commonly used clinical parameters to monitor patients (weight loss, body weight, body mass index, and oral food intake) do not accurately reflect patient's body composition, while bioelectrical impedance analysis (BIA) is a validated tool to properly assess nutritional status on a regular basis. Therefore, patient's monitoring should rely on other affordable indicators such as Karnofsky Performance Status (KPS) and modified Glasgow Prognostic Score (mGPS) to also assess patient's functional status and prognosis. Finally, catheter-related complications and quality of life represent crucial issues to be monitored over time. The purpose of this narrative review is to describe the role and relevance of monitoring cancer patients on HPN, regardless of whether they are receiving anticancer treatments. These practical tips may be clinically useful to better guide healthcare providers in the nutritional care of these patients., Competing Interests: P.C. reports speakers’ honoraria from Baxter. R.C. reports speakers’ honoraria and research grants from Baxter. P.P. reports speakers’ honoraria from Baxter. F.B. reports speakers’ honoraria from Baxter. A.D.F. declares no conflict of interest.

This retrospective observational study aimed to provide insights on the use of clinical nutrition (CN) (enteral and parenteral feeding) and outcomes in an Italian real-world setting. The data source comes from administrative databases of 10 Italian Local Health Units. Patients diagnosed with malignant neoplasms from 1 January 2010 to 31 December 2015 were included. Metastasis presence was ascertained by discharge diagnosis in the hospitalization database. CN was identified by specific codes from pharmaceutical and hospitalization databases. Two cohorts were created-one for metastatic patients ( N = 53,042), and one for non-metastatic patients ( N = 4379) receiving CN. Two survival analyses were set for the cohort of metastatic patients-one included patients receiving CN and the second included malnourished patients. Our findings show that (1) administration of CN is associated with positive survival outcomes in metastatic patients with gastrointestinal, respiratory, and genitourinary cancer; (2) CN in malnourished metastatic patients with gastrointestinal and genitourinary cancer was associated with significant improvement in survival; (3) early administration of CN was associated with improvement in survival in non-metastatic patients with gastrointestinal cancer (HR 95%CI: 0.5 (0.4-0.6), p -value < 0.05). This study highlights the need to improve the assessment of nutritional status in oncologic patients and suggests a potential survival benefit of CN treatment in metastatic disease.

The purpose of this paper is to update the oncologist on the correct approach to the nutritional care of the head and neck cancer patient. Recent scientific contributions on this issue, with a special emphasis on international guidelines and randomised clinical trials (RCTs), are reviewed. The following points are noteworthy: 1. Despite the advances in early diagnosis and modern treatment of head and neck cancer, this tumour still ranks first regarding frequency and severity of weight loss, both at the clinical presentation and during the therapy. 2. This is due to the combination of poor alimentation because of the tumour mass localization, as well as of the presence of an inflammatory response which furtherly drives catabolism. 3. Several studies have shown a very limited role for a dietary counselling unless it includes oral nutritional supplements which are protein or omega-3 fatty acid enriched. 4. A parental nutritional supplementation could represent an acceptable short-term alternative. 5. Long-term nutritional support relies on the use of percutaneous endoscopic gastrostomy (PEG), whereas the role of a prophylactic or "a la demande" PEG is still unsettled and requires further investigations. In conclusion, the nutritional approach using specific formulas and the appropriate route of administration should be part of the therapeutic armamentarium of the modern oncologist.

One of the challenges during chemotherapy and radiotherapy is to complete the planned cycles and doses without dose-limiting toxicity. Growing evidence clearly demonstrates the relationship between dose-limiting toxicity and low muscle mass. Moreover, malnutrition leads to low performance status, impaired quality of life, unplanned hospital admissions, and reduced survival. In the past, the lack of clear and authoritative recommendations and guidelines has meant that oncologists have not always fully appreciated the importance of nutritional therapy in patients receiving anticancer treatments. Therefore, collaboration between oncologists and clinical nutrition specialists needs to be urgently improved. Recent guidelines from scientific societies and practical recommendations by inter-society consensus documents can be summarized as follows: 1) timely nutritional therapy should be carefully considered if patients undergoing anticancer treatments are malnourished or at risk of malnutrition due to inadequate oral intake; 2) if oral intake is inadequate despite counseling and oral nutritional supplements, supplemental enteral nutrition or, if this is not sufficient or feasible, parenteral nutrition should be considered; 3) home artificial nutrition should be prescribed and regularly monitored using defined protocols developed between oncologists and clinical nutrition specialists; 4) appropriate nutritional management in the context of simultaneous care should become a guaranteed right for all patients with cancer. The purpose of this review is to provide oncologists with an overview of the aims and current evidence about nutrition in oncology, together with updated practical and concise recommendations on the application of nutritional therapy in cancer patients receiving chemoradiotherapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Objectives: Cachexia is an important outcome-modulating parameter in patients with cancer. In the context of a randomized controlled trial on cachexia and nutritional therapy, the TiCaCONCO (Tight Caloric Control in the Cachectic Oncologic Patient) trial, the contacts between patients with cancer and health care practitioners and oncologists were screened. The aim of this retrospective study was to identify in the charts the input of data on body weight (necessary to identify cachexia stage), relevant nutritional data, and nutritional interventions triggered or implemented by oncologists and dietitians., Methods: In a tertiary, university oncology setting, over a time span of 8 mo (34 wk), the charts of patients admitted to an oncology, gastroenterology, or abdominal surgery unit were screened for the presence of information contributing to a cancer cachexia diagnosis. Data (patient characteristics, tumor type, and location) was gathered., Results: We analyzed 9694 files. Data on body weight was present for >90% of patients. Of the 9694 screening, 118 new diagnoses of cancer were present (1.22% of patient contacts). Information on weight evolution or nutritional status was absent for 54 patients (46%). In contacts between oncologists and patients with cancer, at the time of diagnosis, cachexia was present in 50 patients (42%). In 7 of these patients (14%), no nutritional information was present in the notes. Of the 50 patients with cachexia, only 8 (16%) had a nutritional intervention initiated by the physician. Nutritional interventions were documented in the medical note in 11 patients (9%) in the overall study population. Dietitians made notes regarding nutrition and weight for 49 patients (42%). We could not demonstrate a difference in mortality between cachectic and non-cachectic patients, although numbers are small for analysis., Conclusion: Patients newly diagnosed with cancer are not systematically identified as being cachectic and if they are, interventions in the field of nutrition therapy are largely lacking. Important barriers exist between oncologists and dietitians, the former being mandatory to the success of a nutrition trial in cancer., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aim: To investigate the incidence and risk factors for vancomycin concentrations less than 10 mg/L during cardiac surgery., Methods: In this prospective study, patients undergoing cardiac surgery received a single dose of 1000 mg of vancomycin. Multiple arterial samples were drawn during surgery. Exclusion criteria were hepatic dysfunction; renal dysfunction; ongoing infectious diseases; solid or hematologic tumors; severe insulin-dependent diabetes; body mass index of < 17 or > 40 kg/m 2 ; pregnancy or lactation; antibiotic, corticosteroid, or other immunosuppressive therapy; vancomycin or nonsteroidal anti-inflammatory drug therapy in the previous 2 wk; chemotherapy or radiation therapy in the previous 6 mo; allergy to vancomycin or cefazolin; drug abuse; cardiac surgery in the previous 6 mo; previous or scheduled organ transplantation; preoperative stay in the intensive care unit for more than 24 h; emergency procedure or lack of adequate preparation for surgery; and participation in another trial., Results: Over a 1-year period, 236 patients were enrolled, and a total of 1682 serum vancomycin concentrations (median 7/patient) were measured. No vancomycin levels under 10 mg/L were recorded in 122 out of 236 patients (52%), and 114 out of 236 patients (48%) were found to have at least 1 serum sample with a vancomycin level < 10 mg/L; 54 out of 236 patients (22.9%) had at least 5 serum samples with a vancomycin level lower than 10 mg/L. Vancomycin infusion was administered for 60 min in 97 out of 236 patients (41%). In 47 patients (20%), the duration of infusion was longer than 60 min, and in 92 patients (39%) the duration of infusion was shorter than 60 min. The maximum concentration and area under the concentration-time curve were significantly higher in patients with no vancomycin levels less than 10 mg/L ( P < 0.001). The multivariate analysis identified female gender, body mass index (BMI) > 25 kg/m 2 , and creatinine clearance above 70 mL/min as risk factors for vancomycin levels less than 10 mg/L., Conclusion: Results of this study identified female gender, BMI > 25 kg/m 2 , and creatinine clearance above 70 mL/min as risk factors for suboptimal vancomycin serum concentration during cardiac surgery; no relationship was found between infusion duration and vancomycin levels less than 10 mg/L. These findings call attention to the risk of facilitating the emergence of vancomycin-resistant methicillin-resistant Staphylococcus aureus strains., Competing Interests: Conflict-of-interest statement: All authors have no conflicts of interest to disclose.

Subcutaneous infusion, or hypodermoclysis, is a technique whereby fluids are infused into the subcutaneous space via small-gauge needles that are typically inserted into the thighs, abdomen, back, or arms. In this review, we provide an overview of the technique, summarize findings from studies that have examined the use of subcutaneous infusion of fluids for hydration or nutrition, and describe the indications, advantages, and disadvantages of subcutaneous infusion. Taken together, the available evidence suggests that, when indicated, subcutaneous infusion can be effective for administering fluids for hydration or nutrition, with minimal complications, and has similar effectiveness and safety to the intravenous route. Of note, subcutaneous infusion offers several advantages over intravenous infusion, including ease of application, low cost, and the lack of potential serious complications, particularly infections. Subcutaneous infusion may be particularly suited for patients with mild to moderate dehydration or malnutrition when oral/enteral intake is insufficient; when placement of an intravenous catheter is not possible, tolerated, or desirable; at risk of dehydration when oral intake is not tolerated; as a bridging technique in case of difficult intravenous access or catheter-related bloodstream infection while infection control treatment is being attempted; and in multiple settings (eg, emergency department, hospital, outpatient clinic, nursing home, long-term care, hospice, and home)., (© 2016 American Society for Parenteral and Enteral Nutrition.)

Traditionally, palliative care (PC) systems focused on the needs of advanced cancer patients, but most patients needing PC have end-stage organ diseases. Similarly, PC models focus on the needs of patients in hospices or at home; however, in most cases PC is provided in acute hospitals. Indeed, the symptom burden that these patients experience in the last year of life frequently forces them to seek care in emergency departments. The majority of them are admitted to the hospital and many die. This issue poses important concerns. Despite the efforts of attending healthcare professionals, in-hospital patients do not receive optimal care near the end-of-life. Also, evidence is emerging that delay in identifying patients needing PC have a detrimental impact on their quality of life (QoL). Therefore, there is an urgent need to identify, early and properly, these patients among those hospitalized. Several trials reported the efficacy of PC in improving the QoL in these patients. Each hospital should ensure that a multidisciplinary PC team is available to support attending physicians to achieve the best QoL for both PC patients and their families. This review discusses the role and the impact of in-hospital PC in patients with end-stage disease or advanced cancer., Competing Interests: The authors declare no conflict of interest.

Since there is little knowledge regarding the quality of life (QoL) of cancer patients on home parenteral nutrition (HPN), we planned a prospective, longitudinal, double-center study to investigate the changes of QoL in these patients. One hundred and eleven adult cancer patients who were candidates for HPN following the indications of the European guidelines were consecutively enrolled. For QoL analysis, EORTC QLQ-C30 questionnaires were filled at the HPN start and after 1, 2, 3, and 4 months, and scores changes over time were analyzed according to the univariate mixed-effects linear model for repeated measures. Most patients had gastrointestinal cancers, were severely malnourished, and were in stage IV; two-thirds were still receiving oncologic treatments. Median weight loss over 3 months and body mass index were 11.7% and 20.7, respectively. Median survival was 4.7 (1-42) months; 67 and 34% of patients survived 3 and 6 months, respectively. Global QoL, physical functioning, role functioning, emotional functioning, appetite loss, and fatigue scores had a statistically significant trend over time (P < 0.001, P < 0.001, P = 0.007, P < 0.001, P = 0.004, P = 0.022, respectively). At the univariate analyses, the determinants significantly associated with changes in trend over time for physical, role, and emotional functioning were oncologic treatments (P < 0.001, P = 0.014, P = 0.040, respectively) and for appetite loss they were weight loss and Karnofsky performance status (P = 0.003, P = 0.023, respectively). Global QoL, physical, role, and emotional functioning improved during HPN even in advanced cancer patients on oncologic treatments., (© 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: The aims of this study were to evaluate the feasibility of an Emergency Department (ED)-initiated screening to identify seriously ill patients in need of palliative care (PC) and to develop a simplified screening tool (SST)., Methods: Eligible patients with known diagnosis of chronic heart, lung, liver, and kidney failures, progressive neurological diseases or advanced cancer, awaiting to be hospitalized after an ED visit, were assessed with the screening tool from the Italian Society of Anesthesia, Analgesia, Resuscitation, and Intensive Care (SIAARTI)., Results: Out of 1497 patients with an ED visit, 485 were hospitalized, and 257 of them met the inclusion criteria. Of 257 enrolled patients, 91 (35%) were identified as in need of PC. Comparing patients with 4 positive criteria to those with <4, the general clinical indicators more frequently positive were: ≥1 admission within the last 12 months (P<0.001); hospital admission from or awaiting admission to health care services (HCS)/Hospice (P<0.001); cachexia (P<0.012); home oxygen use (P<0.001); dialysis (P<0.008). A SST was developed to identify patients in need of PC when a Palliative Performance Scale score <50 was present with at least one of the following indicators: ≥1 admission within the last 12 months; hospital admission from HCS; awaiting admission to HCS/Hospice; dialysis; home oxygen use; non-invasive ventilation. This SST showed a good agreement with the SIAARTI one as sensitivity (97.8%), specificity (92.8%), and accuracy (94.5%)., Conclusions: Our study estimated that over one-third of the people with chronic diseases awaiting to be hospitalized after an ED visit were in need of PC and can be identified with this easy-to-use, non-disease-specific SST.

Background: Intensivists and cardiothoracic surgeons are commonly worried about surgical site infections (SSIs) due to increasing length of stay (LOS), costs and mortality. The antimicrobial prophylaxis is one of the most important tools in the prevention of SSIs. The objective of this study was to investigate the relationship between the timing of antimicrobial prophylaxis administration and the rate of SSIs., Methods: A prospective cohort study was carried out over 1-year period in all consecutive adult patients undergoing elective cardiac surgery. The population was stratified in patients whose antimicrobial prophylaxis administration violated or not the vancomycin timing protocol (i.e., when the first skin incision was performed before the end of vancomycin infusion). To compare SSI rates, the cohort was further stratified in patients at low and high risk of developing SSIs., Results: Over the study period, 1020 consecutive adult patients underwent cardiac surgery and according to study inclusion criteria, 741 patients were prospectively enrolled. A total of 60 SSIs were identified for an overall infection rate of 8.1%. Vancomycin prophylaxis timing protocol was violated in 305 (41%) out of 741 enrolled patients. SSIs were observed in 3% of patients without violation of the antimicrobial prophylaxis protocol (13/436) compared with 15.4% of patients with a violation of the timing protocol (47/305) (P < 0.0001). Patients at low risk with protocol violation had a higher occurrence of SSIs (P = 0.004) and mortality (P = 0.03) versus patients at low risk without protocol violation. Similarly, patients at high risk with protocol violation had a higher occurrence of SSIs (P < 0.001) and mortality (P < 0.001) versus patients at high risk without protocol violation. The logistic regression analysis showed that internal mammary artery use (P = 0.025), surgical time (P < 0.001), intensive care unit (ICU) LOS (P = 0.002), high risk of developing SSIs (P < 0.001) and protocol violation (P < 0.001) were risk factors for SSI occurrence as well as age (P = 0.003), logistic EuroSCORE (P < 0.001), ICU LOS (P < 0.001), mechanical ventilation time (P < 0.001) and protocol violation (P < 0.001) were risk factors for mortality., Conclusions: This study showed that violation of the timing of prophylactic vancomycin administration significantly increased the probability of SSIs and mortality from infectious cause in cardiac surgery patients.

Artificial nutrition (AN) is necessary to meet the nutritional requirements of critically ill patients at nutrition risk because undernutrition determines a poorer prognosis in these patients. There is debate over which route of delivery of AN provides better outcomes and lesser complications. This review describes the management of parenteral nutrition (PN) in critically ill patients. The first aim is to discuss what should be done in order that the PN is safe. The second aim is to dispel "myths" about PN-related complications and show how prevention and monitoring are able to reach the goal of "near zero" PN complications. Finally, in this review is discussed the controversial issue of the route for delivering AN in critically ill patients. The fighting against PN complications should consider: (1) an appropriate blood glucose control; (2) the use of olive oil- and fish oil-based lipid emulsions alternative to soybean oil-based ones; (3) the adoption of insertion and care bundles for central venous access devices; and (4) the implementation of a policy of targeting "near zero" catheter-related bloodstream infections. Adopting all these strategies, the goal of "near zero" PN complications is achievable. If accurately managed, PN can be safely provided for most critically ill patients without expecting a relevant incidence of PN-related complications. Moreover, the use of protocols for the management of nutritional support and the presence of nutrition support teams may decrease PN-related complications. In conclusion, the key messages about the management of PN in critically ill patients are two. First, the dangers of PN-related complications have been exaggerated because complications are uncommon; moreover, infectious complications, as mechanical complications, are more properly catheter-related and not PN-related complications. Second, when enteral nutrition is not feasible or tolerated, PN is as effective and safe as enteral nutrition., Competing Interests: Conflict-of-interest statement: The author declares no conflict of interests for this article.

Objectives: The attitude toward malnutrition varies considerably among oncologists and many malnourished cancer patients receive inadequate nutritional support. The aim of this brief report was to report the results of the exploratory national survey conducted by the Italian Society of Medical Oncology (AIOM) and the Italian Society of Artificial Nutrition and Metabolism (SINPE) before publication of a consensus document aimed at evaluating current attitudes toward malnutrition and management of nutrition, among Italian medical oncologists., Methods: Between January and July 2015, the AIOM and the SINPE conducted a national web-based exploratory survey to investigate the attitude of oncologists toward malnutrition, and the management of nutritional support, before publication of an intersociety consensus document., Results: Of the 2375 AIOM members, 135 (5.7%) participated in the survey, with a satisfactory distribution across all Italian regions. Nutritional assessment and support were routinely integrated into patient care for 38 (28%) responders. According to 66 (49%) participants, nutritional assessment was carried out only at the patients' request (n = 62), or not at all (n = 4). Availability of clinical nutritionists was reported by 88 (65%) participants. For 131 responders (97%), nutritional status was decisive (n = 63) or often crucial (n = 68) in assessing whether anticancer treatment was practicable or would be tolerated., Conclusions: The low response rate may reflect the lack of awareness and consideration of nutritional issues among Italian oncologists. Although malnutrition and nutritional support seemed to be perceived by the responders as relevant factors for the efficacy of oncologic treatments, it seems that nutritional care practices may well be inappropriate. The lack of collaboration between oncologists and clinical nutritionists may be the first obstacle to overcome. Educational intersociety initiatives aimed at improving nutritional support management for cancer patients in Italy appear urgently needed., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The debate over the use of enteral nutrition (EN) and parenteral nutrition (PN) is an old but evergreen and hot topic. Since many years, studies comparing EN and PN have been a pivotal 'leitmotif' in the published literature on artificial nutrition (AN). Actually, there is a background misunderstanding in this debate; specifically, that EN and PN are competitors in the choice of the route for delivering nutrition support in cancer patients. Conversely, EN and PN have specific indications and contraindications. This review has the purpose to discuss the indications and complications as well as pros and cons of EN and PN in cancer patients, the crucial role of nutrition support in oncology patients during anticancer treatments and throughout the course of disease, and, finally, the role of AN in advanced cancer patients. In summary, we have no evidence-based data able to definitively indicate the optimal method for delivering AN in cancer patients. EN and PN have to be considered equally effective in maintaining or improving nutritional status in cancer patients. Besides, this review strongly supports the recommendation that a baseline nutritional assessment should be carried out by a healthcare professional expert in AN for all cancer patients at the time of diagnosis or anticancer treatment plan, taking the nutritional status, estimated duration of AN, AN-related potential benefits and possible complications into consideration on an individual basis. Moreover, the patient symptoms, performance status, estimated life expectancy, and mainly, will or preferences have to be evaluated and incorporated into the nutrition support plan before the definitive choice of the route for delivering nutrients is decided. Finally, applying a decision-making process tailored to patient needs-regardless of whether receiving or not anticancer treatment-allows to choose reasonably the optimal nutritional support strategy.

Despite many advances in prevention and perioperative care, deep sternal wound infection (DSWI) remains a pressing concern in cardiac surgery, with a still relevant incidence and with a considerable impact on in-hospital mortality and also on mid- and long-term survival. The permanent high impact of this complication is partially related to the increasing proportion of patients at high-risk for infection, as well as to the many patient and surgical risk factors involved in the pathogenesis of DSWI. The prophylactic antibiotic therapy is one of the most important tools in the prevention of DSWI. However, the choice of antibiotic, the dose, the duration, the adequate levels in serum and tissue, and the timing of antimicrobial prophylaxis are still controversial. The treatment of DSWI ranges from surgical revision with primary closure to surgical revision with open dressings or closed irrigation, from reconstruction with soft tissue flaps to negative pressure wound therapy (NPWT). However, to date, there have been no accepted recommendations regarding the best management of DSWI. Emerging evidence in the literature has validated the efficacy and safety of NPWT either as a single-line therapy, or as a "bridge" prior to final surgical closure. In conclusion, the careful control of patient and surgical risk factors - when possible, the proper antimicrobial prophylaxis, and the choice of validated techniques of treatment could contribute to keep DSWIs at a minimal rate.

Reactive oxygen species (ROS) are crucial in long-term diabetes complications, including peripheral artery disease (PAD). In this study, we have investigated the potential clinical impact of unacylated ghrelin (UnAG) in a glucose intolerance and PAD mouse model. We demonstrate that UnAG is able to protect skeletal muscle and endothelial cells (ECs) from ROS imbalance in hind limb ischemia-subjected ob/ob mice. This effect translates into reductions in hind limb functional impairment. We show that UnAG rescues sirtuin 1 (SIRT1) activity and superoxide dismutase-2 (SOD-2) expression in ECs. This leads to SIRT1-mediated p53 and histone 3 lysate 56 deacetylation and results in reduced EC senescence in vivo. We demonstrate, using small interfering RNA technology, that SIRT1 is also crucial for SOD-2 expression. UnAG also renews micro-RNA (miR)-126 expression, resulting in the posttranscriptional regulation of vascular cell adhesion molecule 1 expression and a reduced number of infiltrating inflammatory cells in vivo. Loss-of-function experiments that target miR-126 demonstrate that miR-126 also controls SIRT1 and SOD-2 expression, thus confirming its role in driving UnAG-mediated EC protection against ROS imbalance. These results indicate that UnAG protects vessels from ROS imbalance in ob/ob mice by rescuing miR-126 expression, thus emphasizing its potential clinical impact in avoiding limb loss in PAD., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Background: This study investigated whether the 1 : 2 ω-3/ω-6 ratio may reduce proinflammatory response in human alveolar cells (A549) exposed to an ex vivo inflammatory stimulus (bronchoalveolar lavage fluid (BALF) of acute respiratory distress syndrome (ARDS) patients). Methods. We exposed A549 cells to the BALF collected from 12 ARDS patients. After 18 hours, fatty acids (FA) were added as docosahexaenoic acid (DHA, ω-3) and arachidonic acid (AA, ω-6) in two ratios (1 : 2 or 1 : 7). 24 hours later, in culture supernatants were evaluated cytokines (TNF-α, IL-6, IL-8, and IL-10) and prostaglandins (PGE2 and PGE3) release. The FA percentage content in A549 membrane phospholipids, content of COX-2, level of PPARγ, and NF-κB binding activity were determined., Results: The 1 : 2 DHA/AA ratio reversed the baseline predominance of ω-6 over ω-3 in the cell membranes (P < 0.001). The proinflammatory cytokine release was reduced by the 1 : 2 ratio (P < 0.01 to <0.001) but was increased by the 1 : 7 ratio (P < 0.01). The 1 : 2 ratio reduced COX-2 and PGE2 (P < 0.001) as well as NF-κB translocation into the nucleus (P < 0.01), while it increased activation of PPARγ and IL-10 release (P < 0.001). Conclusion. This study demonstrated that shifting the FA supply from ω-6 to ω-3 decreased proinflammatory mediator release in human alveolar cells exposed to BALF of ARDS patients.

Venous access devices are of pivotal importance for an increasing number of critically ill patients in a variety of disease states and in a variety of clinical settings (emergency, intensive care, surgery) and for different purposes (fluids or drugs infusions, parenteral nutrition, antibiotic therapy, hemodynamic monitoring, procedures of dialysis/apheresis). However, healthcare professionals are commonly worried about the possible consequences that may result using a central venous access device (CVAD) (mainly, bloodstream infections and thrombosis), both peripherally inserted central catheters (PICCs) and centrally inserted central catheters (CICCs). This review aims to discuss indications, insertion techniques, and care of PICCs in critically ill patients. PICCs have many advantages over standard CICCs. First of all, their insertion is easy and safe -due to their placement into peripheral veins of the arm- and the advantage of a central location of catheter tip suitable for all osmolarity and pH solutions. Using the ultrasound-guidance for the PICC insertion, the risk of hemothorax and pneumothorax can be avoided, as well as the possibility of primary malposition is very low. PICC placement is also appropriate to avoid post-procedural hemorrhage in patients with an abnormal coagulative state who need a CVAD. Some limits previously ascribed to PICCs (i.e., low flow rates, difficult central venous pressure monitoring, lack of safety for radio-diagnostic procedures, single-lumen) have delayed their start up in the intensive care units as common practice. Though, the recent development of power-injectable PICCs overcomes these technical limitations and PICCs have started to spread in critical care settings. Two important take-home messages may be drawn from this review. First, the incidence of complications varies depending on venous accesses and healthcare professionals should be aware of the different clinical performance as well as of the different risks associated with each type of CVAD (CICCs or PICCs). Second, an inappropriate CVAD choice and, particularly, an inadequate insertion technique are relevant-and often not recognized-potential risk factors for complications in critically ill patients. We strongly believe that all healthcare professionals involved in the choice, insertion or management of CVADs in critically ill patients should know all potential risk factors of complications. This knowledge may minimize complications and guarantee longevity to the CVAD optimizing the risk/benefit ratio of CVAD insertion and use. Proper management of CVADs in critical care saves lines and lives. Much evidence from the medical literature and from the clinical practice supports our belief that, compared to CICCs, the so-called power-injectable peripherally inserted central catheters are a good alternative choice in critical care.

Background: Surgical treatment of peripheral artery disease, even if successful, does not prevent reoccurrence. Under these conditions, increased oxidative stress is a crucial determinant of tissue damage. Given its reported antioxidant effects, we investigated the potential of unacylated-ghrelin (UnAG) to reduce ischemia-induced tissue damage in a mouse model of peripheral artery disease., Methods and Results: We show that UnAG but not acylated ghrelin (AG) induces skeletal muscle regeneration in response to ischemia via canonical p38/mitogen-actived protein kinase signaling UnAG protected against reactive oxygen species-induced cell injuries by inducing the expression of superoxide dismutase-2 (SOD-2) in satellite cells. This led to a reduced number of infiltrating CD68(+) cells and was followed by induction of the myogenic process and a reduction in functional impairment. Moreover, we found that miR-221/222, previously linked to muscle regeneration processes, was up-regulated and negatively correlated with p57(Kip2) expression in UnAG-treated mice. UnAG, unlike AG, promoted cell-cycle entry in satellite cells of mice lacking the genes for ghrelin and its receptor (GHSR1a). UnAG-induced p38/mitogen-actived protein kinase phosphorylation, leading to activation of the myogenic process, was prevented in SOD-2-depleted SCs. By siRNA technology, we also demonstrated that SOD-2 is the antioxidant enzyme involved in the control of miR-221/222-driven posttranscriptional p57(Kip2) regulation. Loss-of-function experiments targeting miR-221/222 and local pre-miR-221/222 injection in vivo confirmed a role for miR-221/222 in driving skeletal muscle regeneration after ischemia., Conclusions: These results indicate that UnAG-induced skeletal muscle regeneration after ischemia depends on SOD-2-induced miR-221/222 expression and highlight its clinical potential for the treatment of reactive oxygen species-mediated skeletal muscle damage.