https://orcid.org/0000-0002-2333-9109
Figures
Abstract
Background
Predisposing factors for the development of pressure-related injuries (PRIs) include the presence of chronic diseases, polypharmacy, immobility and malnutrition. Nutrients such as arginine play an essential role in wound healing.
Methods and findings
A single-blind randomized controlled trial was carried out. Intervention group received a complete hyperproteic and hypercaloric oral nutritional supplement with a fiber mixture enriched in omega 3, L-arginine and nucleotides, providing vitamin C and Zinc, and the control group received a hyperproteic and hypercaloric oral nutritional supplement with fiber mixture.
Results
Descriptive analysis indicated a lower frequency of PRIs at 15 and 30 days in the Atémpero® group compared to the control group, although these differences did not reach statistical significance. However, both improved at the end of the study. In addition, the high risk decreased in both groups, with a higher decrease in the Atémpero® group (72.5% vs 40.9%), as well as the categorization and parameters of the PUSH scale, with a reduction of the same in the Atémpero® group.
Conclusions
While statistical significance was not achieved, the observed trends in PUSH scale scores and clinical observations within the Atémpero® group suggest areas for further investigation. These preliminary data highlight a potential avenue for the nutritional management of multi-pathological patients, establishing a solid foundation for future large-scale confirmatory trials to validate the efficacy of immunonutrient-enriched ONS in pressure injury care. Trial registration. ClinicalTrials.gov NCT06726486.
Citation: Sánchez-Sánchez E, Díaz-Jiménez J, García-García A, Úbeda-Iglesias A, Muñoz-Tejada B, Martínez-Diegues J, et al. (2026) Use of a hypercaloric and hyperprotein supplement enriched with immunonutrients in multi-pathological malnourished patients to improve the incidence and prevalence of pressure sores: A randomized controlled trial. PLoS One 21(7): e0353933. https://doi.org/10.1371/journal.pone.0353933
Editor: Johanna Pruller, PLOS: Public Library of Science, UNITED KINGDOM OF GREAT BRITAIN AND NORTHERN IRELAND
Received: August 19, 2025; Accepted: June 24, 2026; Published: July 29, 2026
Copyright: © 2026 Sánchez-Sánchez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: The database is registered in the Figshare repository and is available at https://figshare.com/s/094a9dff550c0ae9ea3f.
Funding: The study was supported by Vegenat Healthcare (Nutrisens Group) through funding for the recruitment of technical research staff and publication costs. The funder has not provided support in the form of my salary. Similarly, the funder did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. There was no additional external funding received for this study.
Competing interests: E.S.S. has collaborated as a scientific advisor to Vegenat Healthcare (Nutrisens Group) in developing research and training lines.
Introduction
Pressure-related injuries (PRIs) are included in dependence-related skin injuries (DRSI), along with moisture, friction/rubbing, and mixed or combined injuries [1]. PRIs are an essential health and clinical safety problem [2]. They are considered adverse effects of healthcare and have negative consequences for the health status of the population, the quality of life and the healthcare system in economic terms [3]. The prevention of PRIs remains a key priority area for healthcare professionals and a patient safety issue [4]. According to data reported by the 5th National Prevalence Study of PRIs in Spain, the crude prevalence of PRIs in hospitalized adults was 7.0% [5].
This type of injury is one of the most frequent events in hospitalized patients worldwide. They are associated with negative impacts on patients and healthcare systems, leading to increased risk of nosocomial infection, pain and disability, and prolonged hospitalization, resulting in increased morbidity, mortality and financial costs to healthcare systems [6,7]. Guest et al. estimated the cost of managing chronic wounds in the UK to be £3,000 million annually [8].
They are often highly prevalent in the frail adult population, especially in those with chronic diseases. Multimorbidity or comorbidity in this population negatively influences the occurrence of PRIs [9,10].
Clinical practice guidelines for preventing and treating PRIs recommend different strategies, among which is maintaining optimal nutritional status, especially in the at-risk population [11], since malnutrition is a risk factor for developing and worsening PRIs [12]. PRIs occur at bony prominences and where there is compression of the underlying skin or tissue with an external surface. Factors that increase the likelihood of these pressure ulcers are immobility, incontinence and, as discussed above, poor nutritional status. Therefore, new interventions should be created among which nutrition optimization appears [13].
Malnourished patients are more vulnerable to developing pressure injuries and infectious complications. Adequate energy intake and macro- and micronutrients can improve wound development and healing. Interventions that help prevent or treat pressure injuries reduce wound care costs and healthcare demand [14]. Optimal nutritional intervention improves the healing of PRIs [15]. Deficiencies of protein, calories, vitamins, and minerals are logically implicated as contributing to skin degradation. The importance of nutritional assessment for pressure ulcer prevention is evident, as reflected by its inclusion in several society guidelines and risk factor assessment tools [16].
The relationship between malnutrition and PRIs is twofold: the response to injury can increase the metabolic needs of the area of injury, with large amounts of protein being lost through wound exudate. Thus, energy and protein needs in patients with chronic wounds may increase as cells involved in wound healing require protein for their formation and activity [2]. Moreover, malnutrition influences the immune response, decreases fibroblast activity, delays angiogenesis and reduces collagen formation [5]. Therefore, the European Pressure Ulcer Advisory Panel (EPUAP) states that sufficient calories and protein should be provided, promoting adequate vitamin and mineral intake. Individuals receiving medical care who are malnourished or at risk of malnutrition should receive expert nutritional assessment and intervention according to local practice [17].
Nutritional care of the multi-pathological population includes various techniques such as dietary counselling, meal fortification, increasing between-meal intake, oral nutritional supplements (ONS), enteral nutrition (EN) and parenteral nutrition (PN). During hospitalization, in malnourished patients or those at risk of malnutrition, ONS should be provided in order to improve dietary intake and decrease the risk of complications, such as PRIs and readmissions (grade of recommendation: A) [18]. In a multicenter study conducted in 2019, it was obtained that the most frequently performed nutritional interventions in patients with PRIs were assistance during intake (50.7%), an adaptation of the meal to the preferences of each patient (40.8%) and the performance of nutritional screening (39.4%). In other words, only 4 out of 10 patients underwent nutritional screening, and only 8.5% were prescribed oral enteral nutrition through nutritional supplements to meet their nutritional requirements [19]. In another study, the authors observed that between 22% and 38% of patients consumed < 50% of the food provided in the main meals, which increases the risk of malnutrition and the onset or delayed healing of PRIs [20].
On the other hand, patients with PRIs present a decrease in plasma arginine concentrations [21]. Among the amino acids, arginine plays an essential role in wound healing. It is a precursor of nitric oxide and proline, essential for the inflammatory process and collagen synthesis [22]. Arginine also stimulates growth hormone production and secretion, as well as T-cell activation [23]. Arginine enhances healing and modulates inflammation and immune response [18–20]. Evidence showed that arginine-enriched enteral nutrition led to a significant improvement in the healing of PRIs [24]. In Spain, the National Group for the Study and Advice on Pressure Ulcers and Chronic Wounds (GNEAUPP) published Technical Document No. XII, which states that the consumption of supplements that provide vitamins A, C, E, zinc and arginine improves the prevention (high level of evidence) and healing of PRIs (moderate level of evidence) [1].
Therefore, our study aims to evaluate whether using a hypercaloric and hyperproteic enteral formula enriched with immunonutrients reduces the incidence and prevalence of PRIs, improving their prevention and healing in hospitalized malnourished multipathological patients.
Materials and methods
This study was reported according to the Consolidated Standards of Reporting Trials (CONSORT) Statement [25] (S1 Text).
Design study
A single-blind parallel Randomized Controlled Clinical Trial (RCT) was conducted, where the investigator in charge of data analysis did not know the group to which each participant belonged. Data were collected from January 24, 2022, to April 12, 2024. The study was retrospectively registered in Clinical Trials with the code NCT06726486 (URL: https://clinicaltrials.gov/study/NCT06726486). The Ethics Committee for Drug Research of the Province of Cadiz approved the study on June 9, 2021, with registration number 84.21. All participants were informed of the study’s aims. Written informed consent was obtained from all participants and/or their legal representatives. Data confidentiality was guaranteed in accordance with the Helsinki Declaration and Spain’s Data Protection Act (Organic Act 3/2018).
Sample
The sample size was determined using the formula for finite populations, based on the initial screening of 955 patients assessed for eligibility. A baseline sample of 48 participants with a 95% confidence level and a precision of 6% was used to estimate PRI incidence. This initial result was subsequently adjusted to account for an anticipated attrition rate of 30%, a conservative estimate given the high complexity and frailty of this multipathological cohort. Using the adjustment formula N = n/(1 − R), the final required sample size was calculated to be 69 participants.
Randomization.
The random allocation sequence was generated using R software (version 4.2.0) employing a process of simple randomization. A table of random numbers, created via the random number generation function in R, was the primary tool. One member of the research team randomly selected a starting point and a direction of movement until an adequate sample size for this type of study was reached. The resulting numbers were interpreted to assign participants: Even numbers were assigned to the intervention group, and odd numbers were assigned to the control group.
To conceal the allocation sequence, the generation and assignment process was automated via R software, ensuring the sequence was unpredictable. The investigator responsible for data analysis was the only team member who had access to the group allocation key after data collection was complete and prior to analysis. The personnel who recruited participants and the two research team members who assessed patient eligibility did not have access to the random allocation sequence at any point. Allocation was revealed only after a participant met all eligibility criteria and was enrolled in the study.
The study employed single-blinding, meaning the investigator responsible for data analysis was blinded to the intervention group assignments. Participants and care providers (medical and nursing staff) could not be blinded due to the distinctive nature of the Oral Nutritional Supplements (ONS) and the need to monitor their administration. However, outcome assessors (personnel who measured dependent variables such as the Braden scale and PUSH scale, as well as anthropometric and nutritional variables) were blinded to the intervention assignment.
Intervention.
Two groups of patients with non-equivalent ratios were created. The intervention group received the arginine-enriched ONS called Atémpero®. This ONS is a complete hyperproteic and hypercaloric diet with a mixture of fibers enriched in omega 3, L-arginine and nucleotides, which provides vitamin C and Zinc. This diet is specific for malnourished patients who present some wounds. There were no risks during the administration of this formula, and it is within the guidelines for approaching malnourished patients with some wounds. The control group is a complete high-protein, high-calorie diet with mixed fiber, indicated for malnourished patients with stress hyperglycemia and diabetes with increased protein and energy requirements. There were no methodological changes during the process. Both ONSs are suitable for diabetic patients and have very similar compositions, differing mainly in their composition of arginine and immunonutrients.
Participants
The study population consisted of all hospitalized patients followed by the Internal Medicine Department of a regional hospital who wished to participate in the study at the time of recruitment and who met the inclusion criteria: chronic patients with complex needs being; malnourished or at risk of malnutrition; moderate-high risk of developing Pressure Injuries (PIs) or presence of PIs. The exclusion criteria were limitations in oral intake (due to pathologies, health status, among others) or contraindications for the use of the oral route and digestive intolerance or allergy to any of the components of the products. Two members of the research team assessed patient eligibility.
Variables
The dependent variable under study was the presence of PRI, the risk of developing PRIs using the Braden scale as a measuring instrument, and the categorization of PRIs and PRIs healing using the PUSH scale (Pressure Ulcer Scale for Healing). The Braden Scale was selected as the primary instrument for risk assessment due to its high sensitivity and established predictive validity in acute care settings for multi-pathological patients. Complementarily, the Pressure Ulcer Scale for Healing (PUSH) was employed to monitor wound progression, as it provides a multidimensional evaluation—incorporating surface area, exudate amount, and tissue type—that is more sensitive to early physiological changes in wound bed preparation than simple staging. The 15 and 30-day time points were strategically chosen based on the metabolic window required for immunonutrients (for example: L-arginine and Zinc) to modulate the inflammatory phase and initiate collagen synthesis, which typically manifests clinically within the first two to four weeks of intensive nutritional support in malnourished individuals [26].
We collected sociodemographic variables (sex and age), clinical variables (degree of dependence using the Barthel test, chronic diseases, and others), anthropometric variables (weight, height, tricipital skin fold, subscapular skin fold, calf circumference, arm circumference, BMI, and body composition through electrical bioimpedance (model (50khz) Akern BIA 101), nutritional variables (nutritional status through the Mini-Nutritional Assessment (MNA), Global Leadership Initiative on Malnutrition (GLIM) criteria, % dietary intake and adherence to the ONS) and mortality.
Data were collected within 24 hours of hospital admission, at 15 and 30 days. Once the trial began, there were no variations in the variables or data collection.
Study monitoring.
Due to the nature of the study interventions, which consist of oral nutritional supplements with a well-established safety profile and for which no significant risks have been evidenced during their administration in similar populations, an independent Data Safety Monitoring Committee (DSMC/DMC) was not deemed necessary, as the intervention comprised commercially available oral nutritional supplements with an established safety profile.
Safety and data integrity monitoring were performed internally by the research team, particularly by the study coordinator, who continuously reviewed adverse events and data quality. Furthermore, ongoing ethical oversight was ensured by the Ethics Committee for Drug Research of the Province of Cadiz.
Data management.
Data collection was performed using standardized forms, ensuring consistency and accuracy. All collected data were entered into a secure electronic database hosted on the hospital server. Data entry was performed by a research technician and verified by a second research technician and the study coordinator to minimize transcription errors and ensure accuracy.
To ensure data quality, regular data cleaning procedures were implemented, including completeness checks, consistency checks, range checks, and detection of outliers. Any discrepancies or illogical values were queried with the study site for clarification and correction, in accordance with pre-established data management plans.
Participant confidentiality was maintained throughout the study. All participants were assigned a unique study identification number, and personal identifying information was stored separately from the research data in hard copy format under lock and key, with restricted access. Data were pseudonymized to protect participant privacy during analysis.
All relevant data underlying the findings of this study are fully available within the manuscript and its Supporting Information files (S1 Text), and the dataset can also be found in a public repository (Figshare). The authors confirm there are no ethical or legal restrictions on the public sharing of the de-identified participant data.
Data analysis
The data obtained from the variables are represented descriptively. Qualitative variables are shown by frequency and percentage, and quantitative variables by mean and standard deviation or median and interquartile range.
For comparisons, the Chi-square test was applied to qualitative variables if no more than 20% of the expected cell counts were less than 5; otherwise, Fisher’s exact test was used. In the case of quantitative variables, the Student’s t-test for independent samples was performed when the data distribution was normal, using the Mann-Whitney U test in the case of variables that did not have a normal distribution.
Regarding missing data, no imputation methods were used; all analyses were based on complete cases for each variable.
The level of significance or type I error to be used is 0.05. Given the multiple outcomes assessed, p-values were adjusted using the Benjamini-Hochberg procedure (False Discovery Rate) to control for multiple comparisons. For this purpose, we will use the R statistical program and SPSS 25 jointly and in a coordinated manner.
Results
Fig 1 shows the course of the procedure for both groups (January 2022 – April 2023). A total of 69 patients with a median age of 82 years were enrolled. Of the study participants, 55.1% were female and 44.9% were male.
Clinical categories and complexity criteria in multipathologic patients
Approximately 4 out of 10 participants (42.0%; n = 29) presented a single clinical category for chronic disease, with ischemic heart disease presenting the highest percentage of patients (30.4%; n = 21). One patient presented 7 clinical categories. A complexity criterion was present in 58.0% of the participants. Polymedication (10 or more chronic prescription active ingredients) was the most prevalent criterion with 53.6% (n = 37). In addition, 33.3% (n = 23) had two or more hospital admissions in the previous 12 months (Table 1).
Clinical, anthropometric and nutritional variables
Table 2 shows that the median age is higher in the Atémpero® group, although the percentage of patients with total dependence is lower (55.0% vs 72.4%). Arterial hypertension was the most prevalent previous pathology in both groups (68.9%; 67.5%), followed by diabetes mellitus (41.4%; 52.5%). Anthropometric variables did not show statistically significant differences between groups.
After 15 days, 7 participants in the control group and 14 patients in the Atémpero® group died (1 participant in the Atémpero® group revoked consent and left the study). Taking the phase angle value in the initial collection, patients who died in the first 15 days had a lower PA value than the initial one (4.4º vs 4.7º in the control group; 3.5º vs 4.1º in the Atémpero® group). The FA value for patients who completed the study was lower than or maintained the FA at 15 days (3.9º in the control group; 4.1º in the Atémpero® group) (Fig 2).
Table 3 shows the changes in the degree of dependence, weight, weight loss and dietary intake during the study period, adding adherence to the prescribed ONS. There were no statistically significant differences between the groups. There was an increase in participants who ingested 100% of the intake (36.4% vs 50.0% in the control group; 34.6% vs 54.4% in the Atémpero® group). Adherence to the ONS improved at visit 3 but did not reach 100% of the study population.
Risk and presence of PRI.
Table 4 shows that the presence of PRI in the Atémpero® group was higher than in the control group (47.5% vs 37.9%). In addition, they presented a higher prevalence of high risk of presenting PRI according to the Braden scale (72.5% vs 68.9%). They also obtained a higher value on the PUSH scale (12.0 vs 11.0), mainly due to the values according to the size of PRI and the amount of exudate.
A descriptive reduction in the absolute number of patients with PRIs was observed at 15 and 30 days within the Atémpero® group, whereas an increase was noted in the control group; however, both groups exhibited improvements by the study’s conclusion (n = 11 vs n = 5 vs n = 6 in the control group and n = 19 vs n = 12 vs n = 11 in the Atémpero® group) (Fig 3).
Another aspect studied was the score on the PUSH scale in those patients who presented PRI, which decreased at 15 days and increased or remained stable at 30 days, depending on the group under study (Fig 4).
Table 5 shows how the high risk of presenting a PRI, according to the Braden scale, decreased in both groups, with a greater decrease in the Atémpero® group (72.5% vs 40.9%), as well as the categorization and the parameters that form part of the PUSH scale.
Discussion
The prevention and management of PRIs play an essential role in health care, especially in elderly patients with multiple pathologies [27]. Age, chronic diseases, polypharmacy [28] and dependence [29] increase the risk of presenting PRI directly or indirectly through the reduction of food intake [30]. Our results show that polypharmacy is very present since 53.6% of the participants were prescribed ten or more active ingredients. The degree of total dependence in the initial population, according to the Barthel scale, was present in 6 out of 10 participants in the sample (62.3%), being higher in the control group (72.4%). This situation implies an increase in morbidity and hospital stays, which causes a high economic burden for the healthcare systems [31]. Of the participants, 33.3% had two or more admissions in the previous 12 months.
As previously mentioned, these patients’ food intake should be assessed [32]. 18% of the study participants ingested the entire prescribed diet, and 46.4% ingested less than 50% of the diet. Intake improved during the process, with the improvement in intake being similar in both groups (36.4% at 15 days and 50.0% at 30 days vs 34.6% and 54.6%). These data are opposed by Wong et al., who concluded that the prescription of an oral fortified enteral formula vs a standard diet did not modify nutritional intake [33] since there was an improvement in both groups during the study interval.
Nutritional screening and correct diagnosis of malnutrition are essential since, as mentioned, the risk of malnutrition or malnutrition already in place plays a fundamental role in skin integrity [34,35]. Body composition at the beginning of the study was similar in both groups. However, there were statistically significant differences (p = 0.038) in fat-free mass, taking the average values for each age as a reference. The control group presented a higher percentage of patients below the normal range (41.4% vs 12.5%). In both groups, almost 9 out of 10 participants had presented weight loss in the previous six months. Both ONSs formulas decreased weight loss at 15 days (22.7% control group; 19.2% Atémpero® group) with an increase in patients with weight loss at 30 days (30.0% control group; 22.7% Atémpero® group), although this was lower than that presented at the beginning of the study.
Of the sample, 100.0% were moderately or severely malnourished, although only 7.2% of the patients were classified as malnourished within the complexity criteria. The nutritional management of patients at risk or with PRI is the most influential factor for its prevention and healing [36]. Within this management is the use of enteral nutrition if the patient cannot meet his nutritional requirements. Our results showed that only 3 out of 10 participants received some EN, and none received individualized nutritional counselling. The lack of oral nutritional supplementation in patients with low intake increases the risk of developing PRI [37].
According to the data obtained, the high risk of developing PRI according to the Braden scale was higher in the Atémpero® group (72.5% vs 68.9%). The 91.3% presented a moderate or high risk of presenting PRI. This risk decreased during the study in both groups. 43.5% presented PRI at the start of the study, being higher in the Atémpero® group (19 = 47.5%; 11 = 37.9%). The presence of PRI in absolute numbers (number of patients) was reduced at 15 and 30 days in the Atémpero® group and increased in the control group, although both improved at the end of the study (n = 11 vs n = 6 in the control group and n = 19 vs n = 11 in the Atémpero® group). The categorization of PRIs in the Atémpero® group improved by decreasing the percentages in higher categories. These data coincide with those reported by other researchers, such as Cereda et al., where they obtained that patient who received a hyperproteic oral formula enriched with arginine, zinc and vitamin C presented a higher cure rate [2,38]. This conclusion was also reinforced by Bauer et al., concluding that using nutritional supplements enriched with nutrients improves healing in relation to using a standard formula [39]. Other authors concluded that using nutrients such as arginine in Atémpero® improves wound healing [22,40].
Scores on the PUSH scale decreased at 15 days and increased or remained stable at 30 days depending on the study group (control 11 vs 7 vs 10 and Atémpero® 12 vs 11 vs 11). These data show that the use of a nutrient-enriched hypercaloric and hyperprotein formula (Fig 5) reduced PUSH scores to a lesser extent than a standard hyperprotein and hypercaloric formula at 15 days, but showed descriptively lower PUSH scores at 30 days. Among the parameters studied for obtaining the PUSH score was the area of the PRI. Cereda et al. found that participants taking a hypercaloric and hyperprotein diet enriched with immunonutrients reduced the PRI area after eight weeks (60.9% vs 45.2%) [41]. After four weeks of supplementation, the PRI area was reduced in both groups.
Although statistical significance was not reached—potentially due to the limited sample size—the observed reduction in PUSH scores and the downward shift in Braden risk categories within the Atémpero® group represent descriptive trends that warrant further evaluation in larger cohorts. In geriatric, multi-pathological populations, even incremental improvements in skin integrity and risk reduction can significantly decrease the probability of infection and associated mortality, which are critical outcomes for patient safety [42–44].
These findings align with the principles outlined by various national and international organizations regarding nutritional support. According to the NICE (National Institute for Health and Care Excellence) and Wound Healing Society guidelines, the prescription of nutritional supplementation is only recommended when the patient has an inadequate intake or in the presence of a nutritional deficit [45]. The ESPEN guideline recommends (grade B) offering nutritional interventions to older patients at risk of PRI to prevent development. Nutritional interventions should be offered to malnourished older people with PRI to improve healing [18]. Although the findings lack statistical significance, the observed trends align with the clinical principles outlined by the National Group for the Study and Advice on Pressure Ulcers and Chronic Wounds (GNEAUPP) in Spain, published in Technical Document No. XII, which states that the consumption of supplements that provide vitamins A, C, E, zinc and arginine improves the prevention (high level of evidence) and healing of PRI (moderate level of evidence) [1]. Overall, future studies should also analyse biomarkers related to immunity in this type of oral supplementation.
The study has limitations that make it difficult to generalize its results, but it should be noted that the results obtained are a starting point for future, more specific research. One limitation is the insufficient sample size due to the difficulty in recruiting participants given their clinical characteristics and the setting in which the study was conducted, which may lead to a risk of type II error. Although comparatively, it presents more participants than similar studies [37–39]. The mean age between the two groups differs, with the Atémpero® group having a higher mean age, which suggests a higher degree of baseline frailty in this group. Another limitation is the high mortality rate of our participants, which could be a consequence of the diseases present, malnutrition and the presence of PRI, all of which aggravate morbidity and mortality [46]. Our data show that 6 participants died in the control group, of whom 4 (66.6%) had PRI. In the Atémpero® group, 14 patients died, 7 of whom had PRI (50.0%). At 30 days, 2 participants died in the control group, 0 (0.0%) of whom had pre-PRI. In the Atémpero® group, there were 4, of which 1 had PRI (25.0%). Future studies should take special care to recruit a sufficient number of participants to ensure that the analysis can be carried out, taking into account the losses that may arise from the process due to the clinical conditions of this type of participant. In addition, adherence to the ONS was low since not all patients took 100% of the regimen due to clinical conditions, although most took 50% or more. Another possible factor hindering significant results is the clinical approach to wounds and the interprofessional variability in this approach. Another aspect to be taken into account is that all the malnourished patients were prescribed ONS on an individualized basis, which makes it difficult to compare with other studies in which the control group did not take ONS or took a normoprotein and isocaloric formula or did not undergo a prior nutritional assessment for a correct diagnosis of malnutrition.
Conclusions
Patients with multiple pathologies present factors that increase the risk of presenting PRI: chronic diseases, polypharmacy, dependence and alterations in nutritional status. Therefore, carrying out a correct nutritional assessment and early intervention is crucial. While the administration of the intervention ONS was associated with descriptive variations in PRI risk and healing, the lack of statistical significance requires these results to be interpreted strictly as exploratory trends. Due to the lack of statistical significance, these findings provide a basis for future confirmatory trials with larger sample sizes to validate the definitive efficacy of this specific immunonutrient profile in multi-pathological populations.
Acknowledgments
We thank all the participants in the study, the Internal Medicine Unit of the Hospital Universitario Punta de Europa, for their help in recruiting participants, the Nursing Department and the Management Department of the Campo de Gibraltar West Health Management Area. We also thank University Research Institute for Sustainable Social Development (INDESS) for their support in the translation and grammatical editing of the manuscript.
References
- 1. García Fernández FP, Soldevilla Agreda JJ, Pancorbo Hidalgo PL, Verdú Soriano J, López Casanova P, Rodríguez Palma M. Classification-categorization of dependency-related injuries [Clasificación-categorización de las lesiones relacionadas con la dependencia]. Grupo Nacional para el Estudio y Asesoramiento en Úlceras por Presión y Heridas Crónicas. Spain; 2014. Available at: https://gneaupp.info/wp-content/uploads/2014/12/59_pdf1.pdf
- 2. Cereda E, Neyens JCL, Caccialanza R, Rondanelli M, Schols JMGA. Efficacy of a Disease-Specific Nutritional Support for Pressure Ulcer Healing: A Systematic Review and Meta-Analysis. J Nutr Health Aging. 2017;21(6):655–61. pmid:28537329
- 3. Cichosz SL, Voelsang A-B, Tarnow L, Hasenkam JM, Fleischer J. Prediction of In-Hospital Pressure Ulcer Development. Adv Wound Care (New Rochelle). 2019;8(1):1–6. pmid:30705784
- 4. Ledger L, Worsley P, Hope J, Schoonhoven L. Patient involvement in pressure ulcer prevention and adherence to prevention strategies: An integrative review. Int J Nurs Stud. 2020;101:103449. pmid:31706155
- 5. Pancorbo-Hidalgo PL, García-Fernández FP, Pérez-López C, Soldevilla-Agreda JS. Prevalence of pressure sores and other dependency-related skin lesions in adult population in Spanish hospitals: results of the 5th National Study 2017. Gerokomos. 2019;30(2):76–86.
- 6. Saghaleini SH, Dehghan K, Shadvar K, Sanaie S, Mahmoodpoor A, Ostadi Z. Pressure Ulcer and Nutrition. Indian J Crit Care Med. 2018;22(4):283–9. pmid:29743767
- 7. Li Z, Lin F, Thalib L, Chaboyer W. Global prevalence and incidence of pressure injuries in hospitalised adult patients: A systematic review and meta-analysis. Int J Nurs Stud. 2020;105:103546. pmid:32113142
- 8. Guest JF, Ayoub N, McIlwraith T, Uchegbu I, Gerrish A, Weidlich D, et al. Health economic burden that different wound types impose on the UK’s National Health Service. Int Wound J. 2017;14(2):322–30. pmid:27229943
- 9. Jaul E, Menczel J. A comparative, descriptive study of systemic factors and survival in elderly patients with sacral pressure ulcers. Ostomy Wound Manage. 2015;61(3):20–6. pmid:25751847
- 10. Jaul E, Barron J, Rosenzweig JP, Menczel J. An overview of co-morbidities and the development of pressure ulcers among older adults. BMC Geriatr. 2018;18(1):305. pmid:30537947
- 11. Wung Buh A, Mahmoud H, Chen W, McInnes MDF, Fergusson DA. Effects of implementing Pressure Ulcer Prevention Practice Guidelines (PUPPG) in the prevention of pressure ulcers among hospitalised elderly patients: a systematic review protocol. BMJ Open. 2021;11(3):e043042. pmid:33712523
- 12. Stracci G, Scarpellini E, Rinninella E, Mignini EV, Clementi N, Boni MV, et al. Effects of enteral nutrition on patients with pressure lesions: a single center, pilot study. Eur Rev Med Pharmacol Sci. 2020;24(3):1563–70. pmid:32096205
- 13. Wood J, Brown B, Bartley A, Margarida Batista Custódio Cavaco A, Roberts AP, Santon K, et al. Reducing pressure ulcers across multiple care settings using a collaborative approach. BMJ Open Qual. 2019;8(3):e000409. pmid:31523723
- 14. Clark RK, Stampas A, Kerr KW, Nelson JL, Sulo S, Leon-Novelo L, et al. Evaluating the impact of using a wound-specific oral nutritional supplement to support wound healing in a rehabilitation setting. Int Wound J. 2023;20(1):145–54. pmid:35684975
- 15. Banks MD, Ross LJ, Webster J, Mudge A, Stankiewicz M, Dwyer K, et al. Pressure ulcer healing with an intensive nutrition intervention in an acute setting: a pilot randomised controlled trial. J Wound Care. 2016;25(7):384–92. pmid:27410392
- 16. Mervis JS, Phillips TJ. Pressure ulcers: Prevention and management. J Am Acad Dermatol. 2019;81(4):893–902. pmid:30664906
- 17. Langer G, Fink A. Nutritional interventions for preventing and treating pressure ulcers. Cochrane Database Syst Rev. 2014;2014(6):CD003216. pmid:24919719
- 18. Volkert D, Beck AM, Cederholm T, Cruz-Jentoft A, Goisser S, Hooper L, et al. ESPEN guideline on clinical nutrition and hydration in geriatrics. Clin Nutr. 2019;38(1):10–47. pmid:30005900
- 19. Eglseer D, Hödl M, Lohrmann C. Nutritional management of older hospitalised patients with pressure injuries. Int Wound J. 2019;16(1):226–32. pmid:30440105
- 20. Roberts S, Chaboyer W, Desbrow B. Nutrition care-related practices and factors affecting nutritional intakes in hospital patients at risk of pressure ulcers. J Hum Nutr Diet. 2015;28(4):357–65. pmid:24974729
- 21. Yatabe J, Saito F, Ishida I, Sato A, Hoshi M, Suzuki K, et al. Lower plasma arginine in enteral tube-fed patients with pressure ulcer and improved pressure ulcer healing after arginine supplementation by Arginaid Water. J Nutr Health Aging. 2011;15(4):282–6. pmid:21437560
- 22. Cheshmeh S, Hojati N, Mohammadi A, Rahmani N, Moradi S, Pasdar Y, et al. The use of oral and enteral tube-fed arginine supplementation in pressure injury care: A systematic review and meta-analysis. Nurs Open. 2022;9(6):2552–61. pmid:34170617
- 23. Barchitta M, Maugeri A, Favara G, Magnano San Lio R, Evola G, Agodi A, et al. Nutrition and Wound Healing: An Overview Focusing on the Beneficial Effects of Curcumin. Int J Mol Sci. 2019;20(5):1119. pmid:30841550
- 24. Liu P, Shen W-Q, Chen H-L. Efficacy of arginine-enriched enteral formulas for the healing of pressure ulcers: a systematic review. J Wound Care. 2017;26(6):319–23. pmid:28598762
- 25. Hopewell S, Chan A-W, Collins GS, Hróbjartsson A, Moher D, Schulz KF, et al. CONSORT 2025 statement: updated guideline for reporting randomised trials. BMJ. 2025;389:e081123. pmid:40228833
- 26. Fukui Y, Takahashi T, Kunimitsu M, Muta M, Shimada S, Nakagami G. Prognostic factors of pressure injury: a scoping review. J Tissue Viability. 2026;35(1):100984. pmid:41605124
- 27. Collier M, Jones S, Glendewar G. Pressure ulcer prevention, patient positioning and protective equipment. Br J Nurs. 2023;32(3):108–16. pmid:36763473
- 28. Fluck D, Lisk R, Yeong K, Robin J, Fry CH, Han TS. Association of Polypharmacy and Anticholinergic Burden with Length of Stay in Hospital Amongst Older Adults Admitted with Hip Fractures: A Retrospective Observational Study. Calcif Tissue Int. 2023;112(5):584–91. pmid:36899089
- 29. Schneider KL, Yahia N. Effectiveness of Arginine Supplementation on Wound Healing in Older Adults in Acute and Chronic Settings: A Systematic Review. Adv Skin Wound Care. 2019;32(10):457–62. pmid:31498170
- 30. Arai K, Yamamoto K, Suzuki T, Shiko Y, Kawasaki Y, Mitsukawa N, et al. Factors affecting severity of pressure ulcers: Impact of number of medications. Wound Repair Regen. 2023;31(5):671–8. pmid:37516924
- 31. Hill JE, Edney S, Hamer O, Williams A, Harris C. Interventions for the treatment and prevention of pressure ulcers. Br J Community Nurs. 2022;27(Sup6):S28–36. pmid:35671199
- 32. Cereda E, Veronese N, Caccialanza R. Nutritional therapy in chronic wound management for older adults. Curr Opin Clin Nutr Metab Care. 2024;27(1):3–8. pmid:37921900
- 33. Wong A, Chew A, Wang CM, Ong L, Zhang SH, Young S. The use of a specialised amino acid mixture for pressure ulcers: a placebo-controlled trial. J Wound Care. 2014;23(5):259–69. pmid:24810310
- 34. Alhaug J, Gay CL, Henriksen C, Lerdal A. Pressure ulcer is associated with malnutrition as assessed by Nutritional Risk Screening (NRS 2002) in a mixed hospital population. Food Nutr Res. 2017;61(1):1324230. pmid:28659732
- 35. Citty SW, Cowan LJ, Wingfield Z, Stechmiller J. Optimizing Nutrition Care for Pressure Injuries in Hospitalized Patients. Adv Wound Care (New Rochelle). 2019;8(7):309–22. pmid:31832278
- 36. Woo HY, Oh S-Y, Lim L, Im H, Lee H, Ryu HG. Efficacy of nutritional support protocol for patients with pressure ulcer: comparison of before and after the protocol. Nutrition. 2022;99–100:111638. pmid:35576874
- 37. Papier I, Sagi-Dain L, Chermesh I, Mashiach T, Banasiewicz T. Absence of oral nutritional support in low food intake inpatients is associated with an increased risk of hospital-acquired pressure injury. Clin Nutr ESPEN. 2022;51:190–8. pmid:36184204
- 38. Cereda E, Gini A, Pedrolli C, Vanotti A. Disease-specific, versus standard, nutritional support for the treatment of pressure ulcers in institutionalized older adults: a randomized controlled trial. J Am Geriatr Soc. 2009;57(8):1395–402. pmid:19563522
- 39. Bauer JD, Isenring E, Waterhouse M. The effectiveness of a specialised oral nutrition supplement on outcomes in patients with chronic wounds: a pragmatic randomised study. J Hum Nutr Diet. 2013;26(5):452–8. pmid:23627791
- 40. Yamanaka H, Okada S, Sanada H. A multicenter, randomized, controlled study of the use of nutritional supplements containing collagen peptides to facilitate the healing of pressure ulcers. J Nutr Intermed Metab. 2017;8:51–9.
- 41. Cereda E, Klersy C, Serioli M, Crespi A, D’Andrea F, OligoElement Sore Trial Study Group. A nutritional formula enriched with arginine, zinc, and antioxidants for the healing of pressure ulcers: a randomized trial. Ann Intern Med. 2015;162(3):167–74. pmid:25643304
- 42. Heybeli C, Uzun O, Smith L, Veronese N, Rahmati M, Hajek A, et al. Associations between malnutrition and dehydration among older adults: A cross-sectional observational study. Nutr Clin Pract. 2025;40(3):630–42. pmid:39601408
- 43. Völzer B, El Genedy-Kalyoncu M, Fastner A, Tomova-Simitchieva T, Neumann K, Hillmann K, et al. Enhancing skin health and safety in aged care (SKINCARE trial): A cluster-randomised pragmatic trial. Int J Nurs Stud. 2024;149:104627. pmid:37956524
- 44. Al-Qudimat AR, Maabreh AH, Shtayat H, Khaleel MA, Allatayfeh JM, Iblasi AS. Prevention of Pressure Injuries and Nursing Interventions in Critical Care Settings: a Synthesis Without Meta-Analysis (SWiM). Chronic Wound Care Manage Res. 2024;Volume 11:13–30.
- 45. Kreindl C, Basfi-fer K, Rojas P, Carrasco G. Nutritional treatment for pressure ulcers and venous ulcers. Rev Chil Nutr. 2019;46(2):197–204.
- 46. Munoz N, Litchford M, Cox J, Nelson JL, Nie AM, Delmore B. Malnutrition and Pressure Injury Risk in Vulnerable Populations: Application of the 2019 International Clinical Practice Guideline. Adv Skin Wound Care. 2022;35(3):156–65. pmid:35188483