Use Of Total Parenteral Nutrition Research Articles

Use of Total Parenteral Nutrition (TPN) as a Vehicle for Drug Delivery.

Total Parenteral Nutrition (TPN) is a method of providing nutrients directly into the bloodstream for individuals who are unable to meet their nutritional needs through the normal digestive process or gastrointestinal system. It provides macronutrients and micronutrients in a single container, reducing handling and contamination risks and making it more cost-effective. TPN has the potential to be used as a drug delivery system, with applications in combination therapies, personalized medicine, and integrating advanced technologies. It can enhance drug dosage precision and provide nutritional assistance, potentially reducing hospitalization and improving patient outcomes. However, implementing new applications requires thorough testing and regulatory approval. TPN could be particularly useful in pediatric and geriatric care and could also contribute to global health by combating malnutrition in areas with limited medical resources. Healthcare professionals prepare a sterile solution tailored to each patient's nutritional needs, and administration involves a central venous catheter. However, the simultaneous administration of medications with PN admixtures can result in pharmacological incompatibility, which can impact the stability of the oil-in-water system. The European Society for Clinical Nutrition and Metabolism and the American Society for Parenteral and Enteral Nutrition recommendations advise against including non-nutrient drugs in PN admixtures due to safety concerns. This review focuses on the utilization of Total Parenteral Nutrition (TPN) as a method for delivering drugs. It discusses the benefits and difficulties associated with its commercial application and offers suggestions for future research endeavors.

Low Serum Creatinine as Well as High Serum Creatinine Is Associated with Prognosis of Patients with Cancer in End-of-Life.

The prognosis of end-of-life patients is challenging, and clinicians have attempted to predict survival more accurately. High serum creatinine (sCr) levels are associated with lower survival rates in patients with various cancers; however, low sCr levels are commonly expected in patients with terminal cancer because of muscle wasting and malnutrition. Therefore, we investigated the prevalence of low and high sCr levels and their association with survival duration in patients with terminal cancer in a palliative care unit. We analyzed the medical records of 280 patients admitted to a palliative care unit. Patients were divided into low (<0.5 mg/dL), normal (0.5-1.2 mg/dL), and high (>1.2 mg/dL) sCr groups. Kaplan-Meier survival curves using sCr levels were plotted and compared using the log-rank test. Using stepwise selection, a multivariable Cox proportional hazards model was used to identify the significant prognostic factors. The median survival durations in the high-, low-, and normal-sCr groups were 9.57 days, 22.26 days, and 27.51 days, respectively. Multivariable Cox proportional hazard model identified that males (hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.16-2.85), poor performance status (HR, 3.43; 95% CI, 1.12-10.54), total parenteral nutrition use (HR, 1.84; 95% CI, 1.09-3.1), high sCr (HR, 2.74; 95% CI, 1.52-4.94), and low sCr (HR, 1.22; 95% CI, 1.07-1.43) were significantly associated with a shorter survival time. Low and high serum creatinine levels were significantly associated with poor survival in patients with cancer at the end-of-life stage. Therefore, readily available and simple biomarkers may help plan advanced care in palliative care settings.

Analysis of risk factors for neonatal short bowel syndrome in two tertiary centers in Brazil

IntroductionShort bowel syndrome (SBS) is defined as a severe reduction in intestinal mucosal absorption secondary to reduced intestinal functional area. The main causative factor for SBS is the length of intestinal resection in the neonatal period. The prognosticating factors are age, length of remnant intestine, preserved ileocecal valve, and venous maintenance. ObjectiveTo evaluate the clinical and surgical aspects affecting survival outcomes in neonates with SBS at two tertiary care centers. Patients & methodsRetrospective cohort study involving two university tertiary care neonatal centers with diagnosed SBS. Neonates were allocated into two groups, SBS (<60 cm) and USBS (ultra-short bowel syndrome) (<25 cm) and demographically compared. ResultsIn total, 53 neonates met the inclusion criteria, with 31 and 22 in the SBS and USBS, respectively; 20 survived and 33 died (37 % survival rate). The remnant bowel length was greater in those with SBS (p < 0.001), with greater ability to acquire full adaptation (p = 0.047). Increased survival rate was associated with use of total parenteral nutrition (TPN) (p = 0.002) and enteral nutrition (p = 0.036), and the ability to acquire full intestinal adaptation (p = 0.047). Risk factors associated with mortality were the inability to tolerate enteral nutrition (p = 0.036) and acquire full intestinal adaptation (p < 0.001); Use of TPN proved to be protective against death (p = 0.002). ConclusionSBS has high mortality rates in neonatal period (57 %). We recommend caution with time taken to full intestinal adaptation, with continued TPN administration during this time, which can improve overall survival outcomes.

The enhanced recovery after surgery program in elderly patients over 75 years of age undergoing elective colorectal cancer surgery

AbstractAimThe enhanced recovery after surgery (ERAS) program has been well established for patients undergoing colorectal surgery. However, there has been a lack of studies on its use for elderly patients. Our unit implemented the ERAS program in September 2018. The aim of this study is to evaluate the outcome of the ERAS program in patients over 75 years who are undergoing colorectal surgery.Patients and MethodsIn this retrospective study, we compared all patients aged 75 and above who were admitted to Queen Elizabeth Hospital for elective colorectal cancer surgery before the implementation of the ERAS program (1 January 2016 to 31 August 2018) with those treated after its implementation (1 April 2019 to March 2022). The primary end point was the post‐operative length of stay. The secondary end points were wound infection, retention of urine, pneumonia, deep vein thrombosis, pulmonary embolism, use of total parenteral nutrition, acute coronary syndrome, blood transfusion, reoperation, in‐hospital mortality, unplanned readmission within 28 days and Clinical Fragility Score.ResultsA total of 258 patients were included. The median length of stay was 8.4 days in the pre‐ERAS group vs 6.8 days in the ERAS group. In‐patient death (1.4% in the pre‐ERAS group vs 0.9% in the ERAS group) and readmission rate (7.7% in the pre‐ERAS group vs 12.2% in the ERAS group) were similar between the two groups. About 31.5% of patients in the pre‐ERAS group had higher Clinical Fragility Scale post‐operatively as compared with 7.8% in the ERAS group.ConclusionThe ERAS program shortened the length of hospital stay by 1.6 days, and patients had lower Clinical Fragility Scale post‐operatively. Adverse events were not increased. The ERAS program can be safely applied to elderly patients with colorectal cancer.

Post-operative Opioid Reduction Protocol Reduces Racial Disparity in Clinical Outcomes in Children

IntroductionRacial disparities in health outcomes continue to exist for children requiring surgery. Previous investigations suggest that clinical protocols may reduce racial disparities. A post-operative opioid reduction protocol was implemented in children undergoing abdominal surgery who were less than 1 years old at a tertiary level hospital. The purpose of this investigation was to determine if the clinical protocol was associated with a reduction in racial disparity in post-operative opioid prescribing patterns and associated clinical outcomes. MethodsA post-operative opioid reduction protocol based on standing intravenous acetaminophen, educational sessions with nursing staff, and standardized post-operative sign-out between the surgical and NICU teams was implemented in children under 1 year old in 2016. A time series and before and after analysis was conducted using a historical pre-intervention cohort (Jan 2011–Dec 2015) and prospectively collected post-intervention cohort (Jan 2016–Jan 2021). Primary outcomes included post-operative opioid use and post-operative pain scores stratified by race. Secondary outcomes included associated clinical outcomes also stratified by race. ResultsA total of 249 children were included in the investigation, 117 in the pre-intervention group and 132 in the post intervention group. The majority of patients in both cohorts were either White or Black. The two cohorts were equally matched in terms of pre-operative clinical variables. In the pre-intervention cohort, the median post-operative morphine equivalents in White children was 2.1 mg/kg (IQR 0.2, 11.1) while in Black children it was 13.1 mg/kg (IQR 2.4, 65.3), p-value = 0.0352. In the post-intervention cohort, the median value for White children and Black children was statistically identical (0.05 mg/kg (IQR 0, 0.5) and 0.0 mg/kg (IQR 0, 0.3), respectively, p-value = 0.237). This pattern was also demonstrated in clinical variables including length of stay, intubation length and total parenteral nutrition use. In the pre-intervention cohort, the total length of stay for white children was 16 days while for black children it was 45 days (p = 0.007). In the postintervention cohort the length of stay for both White and Black children were identical at 8 days (p = 0.748). ConclusionThe use of a clinical opioid reduction protocol implemented at a tertiary medical center was associated with a reduction in racial disparity in opioid prescribing habits in children. Prior to the protocol, there was a racial disparity in clinical variables associated with prolonged opioid use including length of stay, TPN use, and intubation length. The clinical protocol reduced variability in opioid prescribing patterns in all racial groups which was associated with a reduction in variability in associated clinical variables. Level of EvidenceLevel III.

Trends in Management of Index Adhesive Small Bowel Obstruction in Children

IntroductionTo examine practice patterns and surgical outcomes of nonoperative versus operative management (OPM) of children presenting with an index adhesive small bowel obstruction (ASBO). MethodsA California statewide health discharge database was used to identify children (<18 y old) with an index ASBO from 2007 to 2020. The primary study outcome was evaluating initial management patterns (nonoperative versus OPM and early [≤3 d] versus late surgery [>3 d]) of ASBO. Secondary outcomes were hospital characteristics, patient demographics, and postoperative complications. ResultsOf the 2297 patients identified, 1948 (85%) underwent OPM for ASBO during the index admission. Of these, 14.7% underwent early surgery within 3 d. Teaching hospitals had higher operative intervention than nonteaching centers (87.1% versus 83.7%, P = 0.034). OPM was the highest in 0-5-year-olds compared to other ages (89% versus 82%, P < 0.001). In comparison to early surgery, late surgery was associated with longer length of stay (early 7[interquartile range 5-10], late 9[interquartile range 6-17], P < 0.001), increased infectious complications (16.4% versus 9.8%, P = 0.004), and greater use of total parenteral nutrition (28.0% versus 14.3%, P = 0.001); there was no difference in bowel resection (21% versus 18%, P = 0.102) or mortality (P = 0.423). ConclusionsOur pediatric study demonstrated a high rate of OPM for index ASBO, especially in newborns and toddlers. Although operative intervention, especially late surgery, was associated with increased length of stay, increased infectious complications, and increased total parenteral nutrition use, the rates of bowel resection and mortality did not differ by management strategy. These trends need to be further evaluated to optimize outcomes.

Total parenteral nutrition for patients with gastrointestinal cancers: a clinical practice review.

The use of total parenteral nutrition (TPN) in patients with gastrointestinal cancers is a well-established practice, yet there is substantial variability in its use across institutions. Decision-making around the initiation of TPN is complex. An interdisciplinary team can help identify patient factors and clinical situations that influence whether a patient is likely to benefit from parenteral nutrition. We present the case of a woman with a gastrointestinal cancer who benefited from the initiation of TPN as a bridge therapy to further cancer treatment. This case highlights the importance of establishing a plan for nutrition with specific goals in mind, such as optimizing patients for more cancer-directed therapy. Although patients with gastrointestinal cancers may be candidates for TPN, many patient-specific factors, such as functional status and opportunities for future treatments, must be considered prior to the initiation of parenteral nutrition. An interdisciplinary approach should be used to make recommendations based on patient goals, with a focus on patient and cancer characteristics that are associated with positive outcomes after initiation of TPN. These characteristics include functional status, nutritional status, degree of symptom control, and ability to safely administer nutrition. It is important to continually assess whether parenteral nutrition is beneficial in respect to a patient's preferences and prognosis.

Evaluation of infections associated with central venous catheters in ICU

Objective: Central venous catheter-related infections lead to an increase in widespread antibiotic use, prolonged hospital stays, increased costs, as well as morbidity and mortality. In this study, we aimed to evaluate the infections associated with central venous catheters used in our intensive care unit (ICU) and identify the possible contributing factors. Methods: The hospital records of patients aged 18 and above who were admitted to ICU and had central venous catheters (femoral, jugular, and subclavian catheters) were retrospectively evaluated. Patients’ demographic data and also reason for admission, APACHE II score, duration of ICU stay, and 28-day mortality were recorded. Additionally, data on the time of catheter insertion, catheter site, catheter type, administration of blood and total parenteral nutrition (TPN) through the catheter, presence of catheter-related infection, identified pathogens, time of infection development after catheter insertion, and concurrent blood culture results were recorded. Results: A total of 169 patients were included in the study, of whom 99 (58.6%) were male and 70 (41.4%) were female. The catheters were located in the femoral region in 56 (33.1%) cases, jugular region in 99 (58.6%) cases, and subclavian region in 14 (8.3%) cases. There was no significant difference in the development of catheter infection based on the site of application (p=0.929). The rates of infection were significantly higher in catheters used for TPN and blood transfusion (p=0.002 and p=0.005, respectively). The average duration of intensive care stay was significantly higher in patients who developed catheter infections. Conclusion: Catheter-related bacteremia is an important risk factor for morbidity and mortality, especially in critically ill patients. In our study, no significant differences were found in the rates of catheter-related infection based on the application sites. We observed that the use of TPN, blood transfusion, and longer catheter duration posed risks for infection.

351 A Service Evaluation of Emergency Laparotomy and Total Parenteral Nutrition at a Single Teaching Hospital

Abstract Aim Malnourished patients undergoing emergency general surgery (EGS) have a greater risk of mortality than those not malnourished. There is often a need for nutritional support in EGS. This study investigated the risk factors for total parenteral nutrition (TPN) in patients undergoing emergency laparotomy, and whether there is an association with the NELA risk score. Method A five-year review (June 2016-2021) of the local NELA database and referrals to the Nutrition Support Team was performed. Pre-operative, operative and post-operative data for patients who received TPN and those who did not was collected. Associations between risk factors including NELA score and TPN use were examined using chi squared test and Mann Whitney U, as appropriate. Results There were 931 NELA patients, of which 22.8% (n = 173) received TPN. Intestinal obstruction was the commonest indication for surgery at 51.3% (n = 478) with no difference in age or sex. Despite patients receiving TPN being more likely to be frail (0.004), have higher ASA scores (0.001), lower albumin levels (&amp;lt;0.001), and worse pre- and post-operative NELA scores (both 0.002), stoma formation (0.002) and mortality (&amp;lt;0.001) was half that in patients without TPN. Sub-analysis reveals this was irrespective of when TPN was administered. Conclusions Two mutually exclusive explanations exist. TPN may be a predictor of disease severity and subsequent clinical intervention, or it may indeed improve the nutritional and clinical outcomes in this high risk EGS group. Further studies are needed to clarify this, in addition to the most appropriate method of identifying malnutrition in NELA-eligible patients.

WTP4.3 A Service Evaluation of Emergency Laparotomy and Total Parenteral Nutrition at a Single Teaching Hospital

Abstract Aims Malnourished patients undergoing emergency general surgery (EGS) have a greater risk of mortality than those not malnourished. There is often a need for nutritional support in EGS. This study investigated the risk factors for total parenteral nutrition (TPN) in patients undergoing emergency laparotomy, and whether there is an association with the NELA risk score. Methods A five-year review (June 2016-2021) of the local NELA database and referrals to the Nutrition Support Team was performed. Pre-operative, operative and post-operative data for patients who received TPN and those who did not was collected. Associations between risk factors including NELA score and TPN use were examined using chi squared test and Mann Whitney U, as appropriate. Results There were 931 NELA patients, of which 22.8% (n=173) received TPN. Intestinal obstruction was the commonest indication for surgery at 51.3% (n=478) with no difference in age or sex. Despite patients receiving TPN being more likely to be frail (0.004), have higher ASA scores (0.001), lower albumin levels (&amp;lt;0.001), and worse pre- and post-operative NELA scores (both 0.002), stoma formation (0.002) and mortality (&amp;lt;0.001) was half that in patients without TPN. Sub-analysis reveals this was irrespective of when TPN was administered. Conclusions Two mutually exclusive explanations exist. TPN may be a predictor of disease severity and subsequent clinical intervention, or it may indeed improve the nutritional and clinical outcomes in this high risk EGS group. Further studies are needed to clarify this, in addition to the most appropriate method of identifying malnutrition in NELA-eligible patients.

Extrauterine Growth Retardation—Incidence,Risk Factors, and Prediction Model in TertiaryCare Neonatal Intensive Care Unit in NorthIndia

Background With the increasing survival of preterm infants, their nutrition becomes an enormous challenge. Adequate nutrition plays an important role in good neurodevelopmental outcomes. Extrauterine growth retardation (EUGR) is defined as discharge weight below 10th percentile of the weight expected for that gestation after plotting on postnatal growth charts. Aims and Objective This study was conducted to assess the incidence of EUGR in preterm babies and its associated risk factors. Material and Methods This was a retrospective medical chart review of neonates admitted from January 2017 to November 2021 to a level III Neonatal Intensive Care Unit in Delhi, India. Eligible neonates were all preterm babies born at &lt;35 completed weeks’ gestation admitted in NICU within 24 hours of birth and survived for at least 7 days. Neonates who died during hospitalization or were born with a major congenital anomaly requiring surgery in immediate neonatal period or with any genetic syndrome were excluded. Results A total of 250 babies were enrolled in the study, out of which 45.2% neonates were EUGR. Factors significantly associated with EUGR status were long duration of hospital stay, lower birth weight, small for gestational age (SGA) at birth, male sex, persistent ductus arteriosus, sepsis, broncho-pulmonary dysplasia, use of total parenteral nutrition, long duration of mechanical ventilation, longer time to reach full feeds, and interruption of feeds. SGA was associated with highest odds of developing EUGR [OR-80.45 (16.96-1441.09), P&lt;0.001 followed by use of TPN [OR-2.86 (1.61-5.08), p&lt;0.001]. Risk of EUGR increased manifold as the number of risk factors increased. Future plans Strategies for prevention of EUGR should focus on prevention of various neonatal morbidities and risk factor reduction during the hospital stay.

Total pancreatectomy with islet autotransplantation reduces opioid use and improves nutritional support in children with debilitating pancreatitis.

Chronic pancreatitis (CP) can result in opioid dependence and nutritional challenges in children. Total pancreatectomy with islet autotransplantation (TPIAT) is a viable surgical option in appropriately selected patients. We examined differences between children who met criteria for TPIAT versus those who did not and continued with non-operative management. Retrospective observational cohort study of patients evaluated for TPIAT between August 2014 and July 2020 was performed. Cohort-based analyses between TPIAT and non-TPIAT groups were performed. Analyses included 121 patients, 69 of whom underwent TPIAT. Demographics, genetic risk factors, and anatomic variants did not differ between groups. TPIAT patients were more likely to have CP (88% vs 71%; p = 0.02), had higher median number of endoscopic retrograde cholangiopancreatography procedures (2.0 vs 1.0; p = 0.0001), and had higher likelihood of opioid use (61% vs 42%; p = 0.04) and nutritional supplementation (23% vs 4%; p = 0.004), compared to non-TPIAT. At 6 months post-TPIAT, patients had lower use of any analgesic pain medications (39% vs 73%; p = 0.0002) and lower use of opioids (9% vs 39%; p = 0.0006), compared to non-TPIAT patients at 6 months after evaluation. At 6 months post-TPIAT, rate of exclusively oral nutrition increased from 77% to 86%, and total parenteral nutrition use decreased from 13% to 0% (p = 0.02). In children referred for TPIAT evaluation, there is greater burden of disease in those selected for operation, compared to patients who do not undergo operation. TPIAT achieves lower analgesic pain medication use compared to continuation with non-TPIAT management and achieves freedom from nutritional supplementation. Level of evidence: Retrospective comparative study, Level III.

Opioid and Methadone Use for Infants With Surgically Treated Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) requiring surgical intervention is the most common reason for surgical procedures in preterm neonates. Opioids are used to manage postoperative pain, with some infants requiring methadone to treat physiologic opioid dependence or wean from nonmethadone opioid treatment during recovery. To describe postoperative opioid use and methadone treatment for infants with surgically treated NEC and evaluate postoperative outcomes. A cohort study of infants with surgically treated NEC admitted from January 1, 2013, to December 31, 2022, to 48 Children's Hospital Association hospitals contributing data to the Pediatric Health Information System (PHIS) was performed. Infants who received methadone preoperatively, were aged 14 days or less at the time of the operation, had a congenital heart disease-related operation, or died within 90 days of the operation were excluded. Mixed-effects multivariable logistic regression was used to evaluate thresholds for duration of opioid use after the operation associated with methadone treatment and clinical outcomes associated with methadone use were enumerated. Postoperative administration of nonmethadone opioids. Methadone use and postoperative length of stay, ventilator days, and total parenteral nutrition (TPN) days. Of the 2037 infants with surgically treated NEC identified, the median birth weight was 920 (IQR, 700.0-1479.5) g; 1204 were male (59.1%), 911 were White (44.7%), and 343 were Hispanic (16.8%). Infants received nonmethadone opioids for a median of 15 (IQR, 6-30) days after the operation and 231 received methadone (11.3%). The median first day of methadone use was postoperative day 18 (IQR, days 9-64) and continued for 28 days (IQR, 14-73). Compared with infants who received nonmethadone opioids for 1 to 5 days, infants receiving 16 to 21 days of opioids were most likely to receive methadone treatment (odds ratio, 11.45; 95% CI, 6.31-20.77). Methadone use was associated with 21.41 (95% CI, 10.81-32.02) more days of postoperative length of stay, 10.80 (95% CI, 3.63-17.98) more ventilator days, and 16.21 (95% CI, 6.34-26.10) more TPN days. In this cohort study of infants with surgically treated NEC, prolonged use of nonmethadone opioids after the operation was associated with an increased likelihood of methadone treatment and increased postoperative length of stay, ventilation, and TPN use. Optimizing postoperative pain management for infants requiring an operation may decrease the need for methadone treatment and improve health care use.

Efficacy of Systemic Chemotherapy in Patients With Low-grade Mucinous Appendiceal Adenocarcinoma

Appendiceal adenocarcinoma is a rare tumor, and given the inherent difficulties in performing prospective trials in such a rare disease, there are currently minimal high-quality data to guide treatment decisions, highlighting the need for more preclinical and clinical investigation for this disease. To prospectively evaluate the effectiveness of fluoropyrimidine-based systemic chemotherapy in patients with inoperable low-grade mucinous appendiceal adenocarcinoma. This open-label randomized crossover trial recruited patients at a single tertiary care comprehensive cancer center from September 2013 to January 2021. The data collection cutoff was May 2022. Enrollment of up to 30 patients was planned. Eligible patients had histological evidence of a metastatic low-grade mucinous appendiceal adenocarcinoma, with radiographic imaging demonstrating the presence of mucinous peritoneal carcinomatosis and were not considered candidates for complete cytoreductive surgery. Key exclusion criteria were concurrent or recent investigational therapy, evidence of bowel obstruction, and use of total parenteral nutrition. Data were analyzed from November 2021 to May 2022. Patients were randomized to either 6 months observation followed by 6 months of chemotherapy, or initial chemotherapy followed by observation. The primary end point was the percentage difference in tumor growth in treatment and observation groups. Key secondary end points included patient-reported outcomes in the chemotherapy and observation periods, objective response rate, rate of bowel complications, and differences in overall survival (OS). A total of 24 patients were enrolled, with median (range) age of 63 (38 to 82) years, and equal proportion of men and women (eg, 12 men [50%]); all patients had ECOG performance status of 0 or 1. A total of 11 patients were randomized to receive chemotherapy first, and 13 patients were randomized to receive observation first. Most patients (15 patients [63%]) were treated with either fluorouracil or capecitabine as single agent; 3 patients (13%) received doublet chemotherapy (leucovorin calcium [folinic acid], fluorouracil, and oxaliplatin or folinic acid, fluorouracil, and irinotecan hydrochloride), and bevacizumab was added to cytotoxic chemotherapy for 5 patients (21%). Fifteen patients were available to evaluate the primary end point of difference in tumor growth during treatment and observation periods. Tumor growth while receiving chemotherapy increased 8.4% (95% CI, 1.5% to 15.3%) from baseline but was not significantly different than tumor growth during observation (4.0%; 95% CI, -0.1% to 8.0%; P = .26). Of 18 patients who received any chemotherapy, none had an objective response (14 patients [77.8%] had stable disease; 4 patients [22.2%] had progressive disease). Median (range) OS was 53.2 (8.1 to 95.5) months, and there was no significant difference in OS between the observation-first group (76.0 [8.6 to 95.5] months) and the treatment-first group (53.2 [8.1 to 64.1] months; hazard ratio, 0.64; 95% CI, 0.16-2.55; P = .48). Patient-reported quality-of-life metrics identified that during treatment, patients experienced significantly worse fatigue (mean [SD] score, 18.5 [18.6] vs 28.9 [21.3]; P = .02), peripheral neuropathy (mean [SD] score, 6.67 [12.28] vs 38.89 [34.88]; P = .01), and financial difficulty (mean [SD] score, 8.9 [15.2] vs 28.9 [33.0]; P = .001) compared with during observation. In this prospective randomized crossover trial of systemic chemotherapy in patients with low-grade mucinous appendiceal adenocarcinoma, patients did not derive clinical benefit from fluorouracil-based chemotherapy, given there were no objective responses, no difference in OS when treatment was delayed 6 months, and no difference in the rate of tumor growth while receiving chemotherapy. ClinicalTrials.gov Identifier: NCT01946854.

Intensity at the end of life in pediatric neuro-oncology patients: The case for pediatric palliative care.

10021 Background: Although pediatric cancer is rare, it is the leading cause of death by disease after infancy for children and adolescents in the United States. Children exist in the context of a family; hence, excellent care for a child must also include attention to the needs of the family. Palliative care aims to enhance quality-of-life for these children living with life threatening illnesses and their families. Among pediatric cancers, brain tumors have high disease-related mortality rates; therefore, early introduction of palliative care to these patients is critical. This study aims to evaluate the association of palliative care during the terminal admissions of pediatric neuro-oncology patients and intensity of care provided at the end of life. Methods: Pediatric patients with brain tumors were identified using the Pediatric Health Information System (PHIS). Inclusion criteria were age &lt;18, diagnosis of brain tumor as defined by ICD-10 codes, discharged as deceased, and hospital admission between 1/1/2017 and 12/31/2021. Intensity of care measures included: pediatric intensive care unit (PICU) admission, mechanical ventilation, total parenteral nutrition (TPN), and extracorporeal membrane oxygenation (ECMO). Results: 567 patients met the inclusion criteria. 359/567 (63%) patients had an inpatient palliative care consultation during their terminal hospital stay. Patients receiving a palliative care consultation had a lower percentage of PICU admission (64.9 vs 83.2, p=&lt;0.001), mechanical ventilation use (51.0 vs 76.0, p=&lt;0.001), and TPN use (18.1 vs 25.5, p=0.027). There were no significant differences in length of stay (22.07 vs 22.25 days, p=0.181) and ECMO use (0.28% vs 1.92%, p=0.450). Conclusions: Pediatric patients receiving palliative care consultations during their terminal admission received less intense care while having comparable lengths of stay. Palliative care should be offered to all families, even with aggressive goals, to help incorporate quality of life and comfort in the treatment plan and to ensure bereavement support is available if needed. Similar to data in the adult palliative care literature, this data demonstrates reduced resource utilization among pediatric patients receiving palliative care. Palliative care has been shown to be a supportive service that has the potential to improve the quality of life of patients. The first step toward equitable healthcare is to ensure that all children with a potentially terminal cancer diagnosis have access to full supportive services, including palliative care.

Metabolic Complications Associated With Total Parenteral Nutrition

Total parenteral nutrition (TPN) is a very important means of providing nutrients to patients who have no access to receiving nutrients by enteral route. It consists of all the essential components like lipids, protein, dextrose, electrolytes, vitamins, minerals and trace elements. The concentration of all these components can be adjusted according to the requirement of the patients. They are also available as fixed solutions. Administration of TPN requires careful monitoring as small change in concentration of nutrients in the solution may cause serious, life-threatening complications. Metabolic complications like electrolyte abnormalities, refeeding syndrome, hyperglycemia, hypertriglyceridemia and many hepatobiliary dysfunctions like steatosis, cholestasis, hepatic dysfunction and gallbladder dysfunction are all associated with the use of total parenteral nutrition.&#x0D;  

Clinical impacts of the concomitant use of L-asparaginase and total parenteral nutrition containing L-aspartic acid in patients with acute lymphoblastic leukemia.

L-asparaginase (ASNase) depletes L-asparagine and causes the death of leukemic cells, making it a mainstay for the treatment of acute lymphoblastic leukemia (ALL). However, ASNase's activity can be inhibited by L-aspartic acid (Asp), which competes for the same substrate and reduces the drug's efficacy. While many commercially used total parenteral nutrition (TPN) products contain Asp, it is unclear how the concomitant use of TPNs containing Asp (Asp-TPN) affects ALL patients treated with ASNase. This propensity-matched retrospective cohort study evaluated the clinical effects of the interaction between ASNase and Asp-TPN. The study population included newly diagnosed adult Korean ALL patients who received VPDL induction therapy consisting of vincristine, prednisolone, daunorubicin, and Escherichia coli L-asparaginase between 2004 and 2021. Patients were divided into two groups based on their exposure to Asp-TPN: (1) Asp-TPN group and (2) control group. Data, including baseline characteristics, disease information, medication information, and laboratory data, were collected retrospectively. The primary outcomes for the effectiveness were overall and complete response rates. Relapse-free survival at six months and one year of treatment were also evaluated. The safety of both TPN and ASNase was evaluated by comparing liver function test levels between groups. A 1:1 propensity score matching analysis was conducted to minimize potential selection bias. The analysis included a total of 112 ALL patients, and 34 of whom received Asp-TPN and ASNase concomitantly. After propensity score matching, 30 patients remained in each group. The concomitant use of Asp-TPN and ASNase did not affect the overall response rate (odds ratio [OR] 0.53; 95% confidence interval [CI] = 0.17-1.62) or the complete response rate (OR 0.86; 95% CI = 0.29-2.59) of the ASNase-including induction therapy. The concomitant use of Asp-TPN and ASNase also did not impact relapse-free survival (RFS) at six months and one year of treatment (OR 1.00; 95% CI = 0.36-2.78 and OR 1.24; 95% CI, 0.50-3.12, respectively). The peak levels of each liver function test (LFT) and the frequency of LFT elevations were evaluated during induction therapy and showed no difference between the two groups. There is no clear rationale for avoiding Asp-TPN in ASNase-treated patients.

[Status of fungal sepsis among preterm infants in 25 neonatal intensive care units of tertiary hospitals in China].

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34+0 weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.

Novel lipid emulsion for total parenteral nutrition based on 18-carbon n–3 fatty acids elicits a superior immunometabolic phenotype in a murine model compared with standard lipid emulsions

While lipid emulsions in modern formulations for total parenteral nutrition (TPN) provide essential fatty acids and dense calories, they also promote inflammation and immunometabolic disruptions. We aimed to develop a novel lipid emulsion for TPN use with superior immunometabolic actions compared with available standard lipid emulsions. A novel lipid emulsion [Vegaven (VV)] containing 30% of 18-carbon n-3 fatty acids (α-linolenic acid and stearidonic acid) was developed for TPN (VV-TPN) and compared with TPN containing soybean oil-based lipid emulsion (IL-TPN) and fish-oil-based lipid emulsion (OV-TPN). In vivo studies were performed in instrumented male C57BL/6 mice subjected to 7-d TPN prior to analysis of cytokines, indices of whole-body and hepatic glucose metabolism, immune cells, lipid mediators, and mucosal bowel microbiome. IL-6 to IL-10 ratios were significantly lower in liver and skeletal muscle of VV-TPN mice when compared with IL-TPN or OV-TPN mice. VV-TPN and OV-TPN each increased hepatic insulin receptor abundance and resulted in similar HOMA-IR values, whereas only VV-TPN increased hepatic insulin receptor substrate 2 and maintained normal hepatic glycogen content, effects that were IL-10-dependent and mediated by glucokinase activation. The percentages of IFN-γ- and IL-17-expressing CD4+ T cells were increased in livers of VV-TPN mice, and liver macrophages exhibited primed phenotypes when compared with IL-TPN. This immunomodulation was associated with successful elimination of the microinvasive bacterium Akkermansia muciniphila from the bowel mucosa by VV-TPN as opposed to standard lipid emulsions. Assay of hepatic lipid mediators revealed a distinct profile with VV-TPN, including increases in 9(S)-hydroxy-octadecatrienoic acid. When co-administered with IL-TPN, hydroxy-octadecatrienoic acids mimicked the VV-TPN immunometabolic phenotype. We here report the unique anti-inflammatory, insulin-sensitizing, and immunity-enhancing properties of a newly developed lipid emulsion designed for TPN use based on 18-carbon n-3 fatty acids.

Recurrent Candidemia: Trends and Risk Factors Among Persons Residing in 4 US States, 2011-2018.

Candidemia is a common healthcare-associated infection with high mortality. Estimates of recurrence range from 1% to 17%. Few studies have focused on those with recurrent candidemia, who often experience more severe illness and greater treatment failure. We describe recurrent candidemia trends and risk factors. We analyzed population-based candidemia surveillance data collected during 2011-2018. Persons with >1 episode (defined as the 30-day period after a positive Candida species) were classified as having recurrent candidemia. We compared factors during the initial episode between those who developed recurrent candidemia and those who did not. Of the 5428 persons identified with candidemia, 326 (6%) had recurrent infection. Recurrent episodes occurred 1.0 month to 7.6 years after any previous episode. In multivariable logistic regression controlling for surveillance site and year, recurrent candidemia was associated with being 19-44 years old (vs ≥65 years; adjusted odds ratio [aOR], 3.05 [95% confidence interval {CI}, 2.10-4.44]), being discharged to a private residence (vs medical facility; aOR, 1.53 [95% CI, 1.12-2.08]), hospitalization in the 90 days prior to initial episode (aOR, 1.66 [95% CI, 1.27-2.18]), receipt of total parenteral nutrition (aOR, 2.08 [95% CI, 1.58-2.73]), and hepatitis C infection (aOR, 1.65 [95% CI, 1.12-2.43]). Candidemia recurrence >30 days after initial infection occurred in >1 in 20 persons with candidemia. Associations with younger age and hepatitis C suggest injection drug use may play a modifiable role. Prevention efforts targeting central line care and total parenteral nutrition use may help reduce the risk of recurrent candidemia.