Parenteral nutrition in the critically ill patient

The metabolic alterations, nutritional and metabolic assessment, and nutritional requirements of critically ill patients are discussed, and parenteral nutrition support therapies are reviewed. Physiological alterations in the metabolism of the injured or septic patient are mediated through the interactions of neuroendocrine, cardiovascular, toxic, and starvation responses. These responses cause mobilization of nutritional substrates in an effort to maintain vital organ function and immune defenses. A patient's nutritional status can be determined from anthropometric measurements, creatinine excretion rate, and evaluations of protein stores and immune reserves and function; body weight is a poor indicator. Nitrogen-balance calculations are also useful for determining the adequacy of nutritional intake and the degree of metabolic stress. Early assessments of nutritional status may assist in identifying those patients for whom nutritional support interventions are needed. Nutritional requirements are altered by the metabolic responses to injury and sepsis. Studies suggest that use of nutrient solutions enriched for branched-chain amino acids may enhance nitrogen retention and that energy expenditures in injured or septic patients are only moderately elevated. Most nonprotein calories in parenteral nutrient solutions are provided as glucose, but lipids are an important source of energy in the critically ill patient who has high energy requirements or carbohydrate intolerance; however, clearance of lipids may be decreased. Fluid, electrolyte, and mineral status must be evaluated frequently. Critically ill patients have unique nutritional requirements, and parenteral nutrition support therapies for these patients are being investigated and refined.     

Pharmacological management of Kaposi's sarcoma

Introduction: Kaposi's sarcoma (KS) is an angioproliferative disease that occurs in four clinical-epidemiological forms sharing the same immunological and histopathological features, suggesting common etiological and pathogenic factors. Infection with the human herpesvirus 8, cytokine- and angiogenic factor-induced growth together with an immuno-dysregulated state represent fundamental conditions for the development of this tumor. Despite the recent improvements in KS management, it remains an incurable disease.

Areas covered: The growing knowledge of KS biology provides multiple opportunities for the development of rational, molecularly targeted therapies. The present review summarizes the current management of KS, including local and systemic conventional therapies, and thoroughly describes the results obtained with new pathogenesis-based anti-KS treatments.

Expert opinion: Kaposi's sarcoma represents a paradigm of how the elucidation of disease pathogenesis can drive the development of molecularly targeted treatments. The multifactorial pathogenesis of KS has led to the evaluation of many experimental agents targeting one or more specific factors or pathways involved in the development or progression of the disease. Although targeted therapy so far represents investigational treatment, clinical evaluation of several of these agents is yielding promising results.     

Pharmacological management of Kaposi's sarcoma

INTRODUCTION: Kaposi's sarcoma (KS) is an angioproliferative disease that occurs in four clinical-epidemiological forms sharing the same immunological and histopathological features, suggesting common etiological and pathogenic factors. Infection with the human herpesvirus 8, cytokine- and angiogenic factor-induced growth together with an immuno-dysregulated state represent fundamental conditions for the development of this tumor. Despite the recent improvements in KS management, it remains an incurable disease. AREAS COVERED: The growing knowledge of KS biology provides multiple opportunities for the development of rational, molecularly targeted therapies. The present review summarizes the current management of KS, including local and systemic conventional therapies, and thoroughly describes the results obtained with new pathogenesis-based anti-KS treatments. EXPERT OPINION: Kaposi's sarcoma represents a paradigm of how the elucidation of disease pathogenesis can drive the development of molecularly targeted treatments. The multifactorial pathogenesis of KS has led to the evaluation of many experimental agents targeting one or more specific factors or pathways involved in the development or progression of the disease. Although targeted therapy so far represents investigational treatment, clinical evaluation of several of these agents is yielding promising results.     

临床药师参与1例肾移植术后患者合并人类免疫缺陷病毒感染、卡波西肉瘤的药学监护

临床药师通过专业特长,结合1例肾移植术后患者合并人类免疫缺陷病毒(HIV)感染、卡波西肉瘤的病例,分析该患者出现卡波西肉瘤的诱因,从药物相互作用、血药浓度监测、药物不良反应监测等方面提出个体化建议,并对患者进行用药教育,提高用药的科学性、合理性,同时提高患者的用药依从性。通过此病例的实践,临床药师梳理了工作模式,为保障临床安全合理用药积累了工作经验。     

Parenteral nutrition in pediatric patients

Protein, calorie, fluid, fat, and micronutrient requirements of pediatric patients are reviewed, as are methods of nutritional assessment and complications associated with the use of parenteral nutrition in these patients. In general, preterm infants and neonates require greater per-kilogram amounts of protein, calories, fluid, and micronutrients than older children. In addition, preterm infants and neonates have deficiencies in enzymes that metabolize certain amino acids, making otherwise nonessential amino acids essential. These unique protein needs have been addressed in amino acid formulations designed specifically for this group of patients. Supplying the neonate with the calcium and phosphorus needed for bone growth can be difficult because of solubility limitations in parenteral nutrient solutions. The use of intravenous fat emulsion in infants with hyperbilirubinemia or pulmonary complications is controversial. However, only rarely does fat emulsion have to be completely withheld. Complications associated with parenteral nutrition in pediatric patients include infection, metabolic disorders (cholestasis, bone demineralization), and mechanical problems. Cholestasis induced by parenteral nutrition has been shown to be more common in low-birth-weight infants; however, the precise etiology is unknown and may be multifactorial. Basic requirements necessary to promote growth while pediatric patients are receiving parenteral nutrition have been determined. However, current studies are challenging what were thought to be standards of pediatric parenteral nutrition therapy.     

Parenteral nutrition support in patients with cancer.

In the patient with cancer, malnutrition may result from the disease itself or from its treatment. Total parenteral nutrition (TPN) has been used for many years to treat or prevent malnutrition in the patient with cancer. There have been few studies, however, that demonstrate significant benefit from TPN therapy in these patients. Patients receiving high-dose chemotherapy (as in bone marrow transplantation), and patients with solid tumors who have documented malnutrition (cachexia, weight loss) prior to cancer surgery, may benefit from TPN. No other groups of patients with cancer appear to derive significant benefit from TPN, and some groups may actually be harmed by its use. Practical considerations in the use of TPN include periodic calorie-protein assessment, electrolyte management, and monitoring for drug-TPN interactions.     

Polyethylene glycol-liposomal doxorubicin: a review of its use in the management of solid and haematological malignancies and AIDS-related Kaposi's sarcoma

Polyethylene glycol (PEG)-liposomal doxorubicin is a formulation of the anthracycline doxorubicin in which the drug is encapsulated in PEG-coated liposomes. This alters the pharmacokinetic properties of doxorubicin, prolonging circulation time and enhancing localisation to tumours. In a large randomised trial, intravenous PEG-liposomal doxorubicin was at least as effective as topotecan in patients with ovarian cancer refractory or sensitive to first-line platinum-based chemotherapy. Overall response rates of patients with ovarian cancer refractory to platinum- and paclitaxel-based chemotherapy who received the drug ranged from 18.3 to 27.6% in noncomparative clinical trials. PEG-liposomal doxorubicin also has antitumour activity in patients with metastatic breast cancer pretreated with other chemotherapeutic agents. Overall response rates were similar in patients with pretreated metastatic breast cancer who had received PEG-liposomal doxorubicin or two comparator salvage chemotherapy regimens (vinorelbine or mitomycin C plus vinblastine) in an interim analysis of a large randomised study. In patients with advanced AIDS-related Kaposi's sarcoma, PEG-liposomal doxorubicin monotherapy produced overall response rates ranging from 46 to 77% in randomised trials. The drug was significantly more effective than bleomycin plus vincristine alone or in combination with standard doxorubicin, as measured by tumour response. As a replacement for standard doxorubicin in commonly used combination therapies, PEG-liposomal doxorubicin has shown activity in multiple myeloma and aggressive non-Hodgkin's lymphoma in small, preliminary trials. The most common adverse events associated with PEG-liposomal doxorubicin are myelosuppression, palmar-plantar erythrodysaesthesia, stomatitis and nausea. These can be managed by delaying or reducing dosages. Although preliminary trials are promising, the relative cardiotoxicity of PEG-liposomal doxorubicin compared with the standard formulation has not been clearly established. CONCLUSIONS: Monotherapy with PEG-liposomal doxorubicin is effective as a second-line chemotherapy in patients with platinum-refractory ovarian cancer and in patients with metastatic breast cancer. However, as with all chemotherapeutic agents, the benefits of treatment need to be weighed against the agent's tolerability profile. Strong comparative data have helped to establish PEG-liposomal doxorubicin as the first-line treatment option in patients with advanced Kaposi's sarcoma. Anticancer activity has also been observed in studies conducted in small numbers of patients with multiple myeloma or non-Hodgkin's lymphoma receiving PEG-liposomal doxorubicin instead of standard doxorubicin in combination regimens, although further data are needed to confirm the clinical relevance of these findings.     

Investigational agents for treatment of AIDS-related Kaposi's sarcoma

AIDS-related Kaposi's sarcoma (KS) is a neoplasm that results from the co-infection of HIV and KS herpesvirus/human herpesvirus-8 (KSHV/HHV8). Targeting HIV with highly active antiretroviral therapy has attenuated the natural history of this disease. Recent discoveries have elucidated the role of multiple signaling pathways in the pathogenesis of AIDS-related KS. In particular, KSHV/HHV8-specific gene products, including a G-protein-coupled receptor (vGPCR) and a homolog of human IL-6 (vIL-6), have been implicated in the development of tumorigenesis and angiogenesis. In addition, KSHV/HHV8 can modulate cellular growth and angiogenic pathways to augment malignant transformation and potentiate growth. This article discusses the main signaling pathways that are implicated in the pathogenesis of AIDS-related KS, reviews recently completed clinical trials and anticipates the future direction of molecularly targeted agents in this disease.     

Novel pharmacological therapies for the treatment of AIDS-related Kaposi's sarcoma

Kaposi's sarcoma (KS) is the most common cancer associated with AIDS. KS aetiology and pathogenesis are still poorly defined and no definitive treatment has yet been identified. However, the introduction in 1996 of highly active antiretroviral therapy as a standard of care for those infected with HIV-1 determined a strong protection against the development of opportunistic infections, as well as a remission of pre-existing complications, including KS. Under highly active antiretroviral therapy, KS in particular has shown the highest clinical response rate reported to date among AIDS patients. Furthermore, recent insights into the pathogenetic mechanisms involved in KS development have provided new hope for a response and improved survival in patients with AIDS-related KS. This paper presents an overview of the current knowledge concerning pharmacological approaches to treating this disease. Newer treatments such as PEGylated liposomal anthracyclin, paclitaxel and pathogenesis-based strategies are also discussed.     

肠外营养在胃肠肿瘤患者中应用进展

目的探讨胃肠肿瘤患者中最适肠外营养支持应用的方法、剂量与疗效。方法研究方法采用文献调研的方式,以肠外营养、肿瘤等关键词,在CNKI和万方数据库中检索相关文献。以parenteral nutrition、tumor、cancer等在Elsevier数据库中检索国外相关文献。结论以非蛋白热量15～20kcal·kg-1·d-1,含氮量0.1～0.2g·kg-·1d-1的低氮低热量的肠外营养支持较传统的PN具有优势。添加适宜剂量的特殊营养素如谷氨酰胺、精氨酸、1,6-二磷酸果糖的肠外营养在调节机体代谢、增强免疫功能等方面可发挥更大作用。