Search Results (41)

Background/Objectives: In many parts of the world, pharmacists hold the primary responsibility for providing safe and effective pharmacotherapy. A key aspect is the availability of appropriate medicines for each individual patient. When industrially manufactured medicines are unsuitable or unavailable, pharmacists can prepare tailor-made medicines. While this principle applies globally, practices vary between countries. In the Netherlands, the preparation of medicines in pharmacies is well-established and integrated into routine healthcare. This narrative review explores the role and significance of extemporaneous compounding, pharmacy preparations and related product care in the Netherlands. Methods: Pharmacists involved in pharmacy preparations across various professional sectors, including community and hospital pharmacies, central compounding facilities, academia, and the professional pharmacists’ organisation, provided detailed and expert insights based on the literature and policy documents while also sharing their critical perspectives. Results: We present arguments supporting the need for pharmacy preparations and examine their position and role in community and hospital pharmacies in the Netherlands. Additional topics are discussed, including the regulatory and legal framework, outsourcing, quality assurance, standardisation, education, and international context. Specific pharmacy preparation topics, often with a research component and a strong focus on product care, are highlighted, including paediatric dosage forms, swallowing difficulties and feeding tubes, hospital-at-home care, reconstitution of oncolytic drugs and biologicals, total parenteral nutrition (TPN), advanced therapy medicinal products (ATMPs), radiopharmaceuticals and optical tracers, clinical trial medication, robotisation in reconstitution, and patient-centric solid oral dosage forms. Conclusions: The widespread acceptance of pharmacy preparations in the Netherlands is the result of a unique combination of strict adherence to tailored regulations that ensure quality and safety, and patient-oriented flexibility in design, formulation, and production. This approach is further reinforced by the standardisation of a broad range of formulations and procedures across primary, secondary and tertiary care, as well as by continuous research-driven innovation to develop new medicines, formulations, and production methods. Full article

Background: The incidence of external lymphatic fistula (ELF) represents a relatively rare complication after surgery for colorectal cancer, especially in Western countries. However, the rate of this complication is progressively increasing following the introduction of complete mesocolic excision and central vascular ligation with consequent extensive lymphadenectomy. There are no guidelines for the management of ELF, with therapeutic options varying from conservative procedures to more invasive surgeries. The aim of this study was to retrospectively quantify the rate of ELF after surgery for colorectal cancer, to describe its management, and to evaluate its clinical impact on early postoperative outcomes in a tertiary referral European centre. Methods: Data on all patients who underwent surgery for colorectal cancer at our institution between July 2022 and December 2024 were entered into a database. Preoperative, perioperative, and early (within 30 days) postoperative data were recorded. Results: A total of 279 patients underwent elective surgery for colorectal cancer (205 colon and 74 rectum). No postoperative deaths occurred within 30 days after surgery, and the rates of overall and major (grade ≥ 3) postoperative morbidity were 34.7% and 7.1%, respectively. The anastomotic leakage and reoperation rates were 2.8% and 5.3%, respectively. ELFs occurred in 15 patients (5.3%). In all patients, conservative treatment (based on fasting, total parenteral nutrition (TPN), and a prolonged medium-chain triglyceride (MCT) diet) was administered successfully. A recurrent ELF (after the first oral feeding resumption) occurred in four (26.6%) patients, but all were successfully treated with a conservative approach. The occurrence of an ELF prolonged the postoperative length of stay which was 12 days, a length higher than that recorded in patients without ELF. Conclusions: The occurrence of an ELF was found to be a relatively frequent complication after surgery for colorectal cancer and appears to negatively influence only the postoperative length of stay. Conservative management appeared to be a successful treatment. Full article

With advancements in medical technology, biochemistry, and clinical practices, the modern approach to total parenteral nutrition (TPN) has been focused on precision, safety, and the optimization of metabolic and nutritional parameters based on the patient’s needs. In the last decade, TPN mixtures have been transitioning from a lifesaving intervention for patients unable to receive enteral nutrition to a highly specialized therapy aimed at improving clinical outcomes, reducing complications, and personalizing care. Total parenteral nutrition has attracted great interest, and its adaptation to the patient’s needs is a topic of interest in the scientific community. However, there are problems related to shortages in the supply of the concentrates required to balance TPN mixtures and to infections linked to the venous access devices that are necessary for administering nutrition. Adjusting the TPN composition to meet specific patient needs requires specialist knowledge, as the ingredients available on the market differ in terms of excipients and this may increase the risk of physicochemical incompatibilities, particularly the destabilization of the lipid fraction. It is common clinical practice to inject drugs into the parenteral nutrition bag, and hence there is a high demand for confirmation of the compatibility of a given drug with the TPN composition. However, methods used in clinical practice still differ from the modern solutions proposed in scientific research. In order to ensure patient safety with the use of advanced therapy, continuous education and monitoring of the latest scientific research related to TPN is required. The integration of artificial intelligence (AI) into clinical nutrition represents a paradigm shift in the management of total parenteral nutrition (TPN). As TPN transitions from a standardized, one-size-fits-all approach to a highly personalized therapy, we must examine the challenges and future directions of AI-driven TPN to provide a comprehensive analysis of its impact on clinical practice. Full article

Background/Objectives: In recent years, strategies for improving outcomes in preterm neonates have been implemented in various aspects of neonatal care. This study aims to determine the prevalence, microbiology, and outcomes of late-onset sepsis (LOS) and the incidence of other morbidities in very preterm neonates following the implementation of specific infection control, enteral feeding, and ventilation strategies. Methods: This study retrospectively compared the morbidity and mortality of preterm neonates with a 23–32 weeks gestational age over two periods, period A (2010–2014),and period B (2018–2022). A series of changes were introduced between these periods, including restrictive use of antibiotics, aggressive enteral feeding, and wider use of non-invasive ventilation modalities. Results: A total of 310 neonates were included: 163 in period A and 147 in period B. The mean duration of antibiotic treatment was reduced from 4 ± 2 to 2 ± 1 days and from 5 ± 2 to 3 ± 1 days for suspected early-onset sepsis and LOS, respectively, and from 11.2 ± 4 to 16 ± 4 days for confirmed LOS between the two study periods. The incidence of LOS was 24% and 18%, while, for multiple LOS episodes, it was 26% and 11% in periods A and B, respectively. Total parenteral nutrition (TPN) duration and gestational age were independent predictors of LOS in both periods. The rate of Candida infections declined from 9.2% to 0.7%. The full enteral nutrition in period B was achieved after a median of 7.5 days compared with 10 days (p = 0.001), resulting in fewer days of TPN (p = 0.008). Episodes of feeding intolerance and necrotizing enterocolitis I (NEC I) were significantly reduced (p < 0.001). Incidence of intraventricular hemorrhage were significantly decreased. Conclusions: After changing antibiotic, ventilation, and nutrition protocols, Candida infections were almost completely eliminated. The incidence of LOS and multiple LOS episodes decreased. Early full enteral nutrition was achieved without adverse effects, and fewer episodes of food intolerance were observed. Candida elimination appears feasible when antibiotic stewardship is implemented in conjunction with other interventions in an NICU. Full article

Background: Patients with peritoneal carcinomatosis often experience intestinal failure throughout the course of their disease, and total parenteral nutrition (TPN) can be used as a temporary solution or as a bridge to definitive cytoreductive surgery. Guidelines for TPN are well established for inpatients and in 2014, guidelines were established for the initiation of TPN for outpatients in a home setting. However, the safety and efficacy of home start TPN in advanced oncology patients remain unknown. This study aims to explore the safety and efficacy of starting TPN in the home setting for patients with peritoneal carcinomatosis. Method: Health records of advanced cancer patients receiving TPN during 2009–2020 were retrospectively reviewed. Data pertaining to diagnosis, demographics, nutritional parameters, and outcomes including hospital readmission rates were collected. Safety was measured based on catheter-related complications and hospital admissions related to electrolyte or fluid imbalance due to TPN. Efficacy was determined by weight gain/stability and pre-albumin and albumin levels. The Fisher’s exact and Kruskal–Wallis tests were used to analyze the data. Results: Seventy TPN patients were identified, of which forty-two were home start (HS) and twenty-eight were in hospital (HP). The two groups were not significantly different in age, (HS: mean = 58.3 ± 13.9; HP: mean = 58.0 ± 13; p = 0.95), baseline body weight (p = 0.13), baseline albumin (p = 0.26) or pre-albumin (p = 0.48). At the end of treatment, the HS and HP groups had similar percentages of patients experiencing weight gain/stability (75% vs. 47%, p = 0.1), stable/increased pre-albumin (68% vs. 65%, p = 1), and stable/increased albumin levels (48% vs. 59%, p = 0.58). There was no difference in observed readmission between the groups (p = 0.79). At the end of treatment, 48% of the HS group and 36% of the HP group resumed an oral diet. Conclusions: This is the first study to present a comparison between home and hospital start TPN in advanced cancer patients, demonstrating that the initiation of outpatient TPN in the home setting is as safe and efficacious as TPN initiated in the hospital. Full article

Zinc (Zn) is a vital trace element that plays a pivotal role in protein synthesis, cellular growth, and differentiation and is involved as a cofactor of metalloenzymes, performing a wide variety of metabolic, immune, and synthesis roles. Zn is required at all stages of an infant’s and child’s development, and severe Zn deficiency has been reported to lead to slower physical, cognitive, and sexual growth. Preterm neonates are at a higher risk of developing zinc deficiency for a variety of reasons, including low Zn intake from enteral feeds containing breast milk, relative malabsorption due to immaturity of the gastrointestinal tract with limited absorptive capacity, increased urinary loss of zinc, and increased demand during the early developmental stages. Moreover, premature infants are at risk of gastrointestinal diseases like necrotizing enterocolitis (NEC), which can limit absorption capacity and potentially lead to malabsorption. TPN is frequently used in preterm infants to provide them with sufficient nutrients and calories. However, it has its own complications, including cholestasis, especially if used for prolonged periods. In this case report, we are presenting the case of a male preterm infant who was delivered by caesarean section at 26 weeks’ gestation. The baby developed an intestinal perforation due to NEC, for which he underwent surgery for resection of the necrotic bowel and the creation of a high ileal stoma and was put on prolonged total parenteral nutrition (TPN), which led to the development of zinc deficiency. Full article

Choline is an essential nutrient, with high requirements during fetal and postnatal growth. Tissue concentrations of total choline are tightly regulated, requiring an increase in its pool size proportional to growth. Phosphatidylcholine and sphingomyelin, containing a choline headgroup, are constitutive membrane phospholipids, accounting for >85% of total choline, indicating that choline requirements are particularly high during growth. Daily phosphatidylcholine secretion via bile for lipid digestion and very low-density lipoproteins for plasma transport of arachidonic and docosahexaenoic acid to other organs exceed 50% of its hepatic pool. Moreover, phosphatidylcholine is required for converting pro-apoptotic ceramides to sphingomyelin, while choline is the source of betaine as a methyl donor for creatine synthesis, DNA methylation/repair and kidney function. Interrupted choline supply, as during current total parenteral nutrition (TPN), causes a rapid drop in plasma choline concentration and accumulating deficit. The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) defined choline as critical to all infants requiring TPN, claiming its inclusion in parenteral feeding regimes. We performed a systematic literature search in Pubmed with the terms “choline” and “parenteral nutrition”, resulting in 47 relevant publications. Their results, together with cross-references, are discussed. While studies on parenteral choline administration in neonates and older children are lacking, preclinical and observational studies, as well as small randomized controlled trials in adults, suggest choline deficiency as a major contributor to acute and chronic TPN-associated liver disease, and the safety and efficacy of parenteral choline administration for its prevention. Hence, we call for choline formulations suitable to be added to TPN solutions and clinical trials to study their efficacy, particularly in growing children including preterm infants. Full article

Wickerhamomyces anomalus has been previously classified as Hansenula anomala, Pichia anomala, and Candida pelliculosa and was recently reclassified in the genus Wickerhamomyces after phylogenetic analysis of its genetic sequence. An increasing number of reports of human infections by W. anomalus have emerged, suggesting that this microorganism is an emerging pathogen. The present review aimed to provide data on the epidemiology, antifungal resistance, clinical characteristics, treatment, and outcomes of fungemia by W. anomalus by extracting all the available information from published original reports in the literature. PubMed/Medline, Cochrane Library, and Scopus databases were searched for eligible articles reporting data on patients with this disease. In total, 36 studies involving 170 patients were included. The age of patients with fungemia by W. anomalus ranged from 0 to 89 years; the mean age was 22.8 years, the median age was 2.2 years, with more than 37 patients being less than one month old, and 54% (88 out of 163 patients) were male. Regarding patients’ history, 70.4% had a central venous catheter use (CVC), 28.7% were on total parenteral nutrition (TPN), 97% of neonates were hospitalized in the neonatal ICU (NICU), and 39.4% of the rest of the patients were hospitalized in the intensive care unit (ICU). Previous antimicrobial use was noted in 65.9% of patients. The most common identification method was the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in 34.1%, VITEK and VITEK 2 in 20.6%, and ID32 C in 15.3%. W. anomalus had minimal antifungal resistance to fluconazole, echinocandins, and amphotericin B, the most commonly used antifungals for treatment. Fever and sepsis were the most common clinical presentation noted in 95.8% and 86%, respectively. Overall mortality was 20% and was slightly higher in patients older than one year. Due to the rarity of this disease, future multicenter studies should be performed to adequately characterize patients’ characteristics, treatment, and outcomes, which will increase our understanding and allow drawing safer conclusions regarding optimal management. Full article

Background: Catheter line infection is a common complication within clinical environments, and there is a pressing need for technological options to aid in reducing the possibility of sepsis. The early identification of contamination could be pivotal in reducing cases and improving outcomes. Method: A sensing rationale based on a riboflavin-modified electrode system integrated within a modified 3D-printed catheter needle-free connector is proposed, which can monitor changes in pH brought about by bacterial contamination. Results: Riboflavin, vitamin B2, is a biocompatible chemical that possesses a redox-active flavin core that is pH dependent. The oxidation peak potential of the adsorbed riboflavin responds linearly to changes in pH with a near-Nernstian behavior of 63 mV/pH unit and is capable of accurately monitoring the pH of an authentic IV infusate. Conclusions: The proof of principle is demonstrated with an electrode-printed hub design offering a valuable foundation from which to explore bacterial interactions within the catheter lumen with the potential of providing an early warning of contamination. Full article

Parenteral nutrition (PN), a vital therapy for patients with intestinal failure, can lead to the development of parenteral nutrition-associated liver disease (PNALD). In this study, we aimed to investigate the role of Lactobacillus johnsonii (L. johnsonii) in a rat model of PNALD. Total parenteral nutrition (TPN)-fed rats were used to assess the role of L. johnsonii in liver steatosis, bile acid metabolism, gut microbiota, and hepatocyte apoptosis. We observed a depletion of L. johnsonii that was negatively correlated with the accumulation of glycochenodeoxycholic acid (GCDCA), a known apoptosis inducer, in rats subjected to TPN. L. johnsonii attenuated TPN-induced liver steatosis by inhibiting fatty acid synthesis and promoting fatty acid oxidation. TPN resulted in a decrease in bile acid synthesis and biliary bile secretion, which were partially restored by L. johnsonii treatment. The gut microbial profile revealed depletion of pathogenic bacteria in L. johnsonii-treated rats. L. johnsonii treatment reduced both hepatic GCDCA levels and hepatocyte apoptosis compared with the TPN group. In vitro, L. johnsonii treatment inhibited GCDCA-induced hepatocyte apoptosis via its bile salt hydrolase (BSH) activity. Our findings suggest that L. johnsonii protects against liver steatosis, bile acid dysregulation, and hepatocyte apoptosis in TPN-fed rats. Full article

Gender-based medicine is attracting increasing interest every day, but studies on pediatric populations are still limited. In this setting, sex differences among patients undergoing total parenteral nutrition (TPN) have not been previously reported. This study investigated the presence of sex differences in parenteral nutrition composition and outcomes among a cohort of pediatric patients admitted at the Oncohematology and Bone Marrow Transplant Unit of the Institute for Maternal and Child Health “Burlo Garofolo” of Trieste, Italy. For all 145 recruited patients (87 males, 58 females), the following data were collected: age, sex, volume and duration of TPN, macro- and micronutrient composition of TPN bags, electrolytic or blood gases imbalance, glycolipid alterations, liver damage during TPN, and the incidence of sepsis and thrombosis. The analysis showed that females required higher daily phosphate intake (p = 0.054) and essential amino acid supplementation (p = 0.07), while males had a higher incidence of hypertriglyceridemia (p < 0.05) and cholestasis. A higher incidence of sepsis was found in the non-transplanted male population (p < 0.05). No significant differences were appreciable in other analyzed variables. This study aims to create a basis for future gender-based nutritional recommendations in the pediatric field. Full article

Total Parenteral Nutrition (TPN), which uses intravenous administration of nutrients, minerals and vitamins, is essential for sustaining premature infants until they transition to enteral feeds, but there is limited information on metabolomic differences between infants on TPN and enteral feeds. We performed untargeted global metabolomics on urine samples collected between 23–30 days of life from 314 infants born <29 weeks gestational age from the TOLSURF and PROP cohorts. Principal component analysis across all metabolites showed a separation of infants solely on TPN compared to infants who had transitioned to enteral feeds, indicating global metabolomic differences between infants based on feeding status. Among 913 metabolites that passed quality control filters, 609 varied in abundance between infants on TPN vs. enteral feeds at p < 0.05. Of these, 88% were in the direction of higher abundance in the urine of infants on enteral feeds. In a subset of infants in a longitudinal analysis, both concurrent and delayed changes in metabolite levels were observed with the initiation of enteral feeds. These infants had higher concentrations of essential amino acids, lipids, and vitamins, which are necessary for growth and development, suggesting the nutritional benefit of an enteral feeding regimen. Full article

Total parenteral nutrition (TPN) is a life-saving therapy for patients with intestinal failure, but it carries the risk of complications, including an increase in liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) after long-term use. Patients receiving chronic TPN are also exposed to metabolic stress from both the underlying disease and parenteral nutrition. The aim of this study was to compare the concentration of liver transaminases AST and ALT in relation to the rate of oxygen consumption in platelet mitochondria in patients receiving long-term TPN with the degree of oxidative stress induced by lipid emulsions, and to explain their role in cellular energy metabolism and changes in the liver based on the percentage of genomic DNA damage. The study group consisted of 86 TPN patients, while the control group consisted of 86 healthy volunteers who were fed only orally. The results of the study showed that the percentage of molecular oxygen depended on the type of lipid emulsion supplied. Analyzing time on TPN as a factor, we observed a decrease in percentage genomic DNA damage and an increase in percentage molecular oxygen in cells. It remains unclear whether TPN has a direct effect on genomic DNA damage and the level of molecular oxygen in cells during the course of treatment. In conclusion, this study provides important insights into the potential effects of TPN on liver enzymes and cellular metabolism. Further research is needed to better understand the underlying mechanisms and to develop strategies to minimize the risk of complications associated with TPN. Full article

Total parenteral nutrition (TPN) is life-saving therapy for the pediatric patients with intestinal failure (IF) who cannot tolerate enteral nutrition (EN). However, TPN-induced metabolic alterations are also a critical issue for the maintenance of intestinal homeostasis, and thus the global metabolomic signatures need to be addressed. In this study, ileal mucosal biopsies were collected from 12 neonatal Bama piglets receiving either EN or TPN for 14 days, and changes in the intestinal metabolism were examined by multi-omics (HM350 Metabolomics + Tandem Mass Tag (TMT)-based proteomics). As a result, a total of 240 compounds were identified by metabolomics, including 56 down-regulated and 9 up-regulated metabolites. Notably, tissue levels of fatty acyl-carnitines (decreased by 35–85%) and succinate (decreased by 89%) dramatically decreased in the TPN group, suggestive of disrupted processes of fatty acid oxidation (FAO) and the citrate cycle, respectively. Interestingly, however, no differences were found in the production of adenosine 5′-triphosphate (ATP) between groups, suggesting that these dysregulated metabolites may have mainly led to the loss of bioactive compounds rather than energy deficit. Additionally, 4813 proteins were identified by proteomics in total, including 179 down-regulated and 329 up-regulated proteins. The analysis of protein–protein interactions (PPI) indicated that most of the differentially expressed proteins were clustered into “lipid metabolism” and “innate immune responses”. In summary, this work provided new findings in TPN-induced intestinal metabolic alterations, which would be useful to the improvement of nutritional management for IF patients. Full article

Recent findings implicate brain vulnerability following long-gap esophageal atresia (LGEA) repair. We explored the relationship between easily quantifiable clinical measures and previously reported brain findings in a pilot cohort of infants following LGEA repair. MRI measures (number of qualitative brain findings; normalized brain and corpus callosum volumes) were previously reported in term-born and early-to-late premature infants (n = 13/group) <1 year following LGEA repair with the Foker process. The severity of underlying disease was classified by an (1) American Society of Anesthesiologist (ASA) physical status and (2) Pediatric Risk Assessment (PRAm) scores. Additional clinical end-point measures included: anesthesia exposure (number of events; cumulative minimal alveolar concentration (MAC) exposure in hours), length (in days) of postoperative intubated sedation, paralysis, antibiotic, steroid, and total parenteral nutrition (TPN) treatment. Associations between clinical end-point measures and brain MRI data were tested using Spearman rho and multivariable linear regression. Premature infants were more critically ill per ASA scores, which showed a positive association with the number of cranial MRI findings. Clinical end-point measures together significantly predicted the number of cranial MRI findings for both term-born and premature infant groups, but none of the individual clinical measures did on their own. Listed easily quantifiable clinical end-point measures could be used together as indirect markers in assessing the risk of brain abnormalities following LGEA repair. Full article