Effects of early supplemental parenteral nutrition on new-onset infection in adults with acute severe stroke: A single-center retrospective case-control study

Effects of early supplemental parenteral nutrition on new-onset infection in adults with acute severe stroke: A single-center retrospective case-control study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effects of early supplemental parenteral nutrition on new-onset infection in adults with acute severe stroke: A single-center retrospective case-control study Chen Ma, Zhirong Fan, Xuan Wang, Bian Li, Jingjing Zhao, Xiaogang Kang, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5132498/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 31 Jan, 2025 Read the published version in BMC Neurology → Version 1 posted 4 You are reading this latest preprint version Abstract Background : Early adequate feeding reduces the mortality in patients with acute severe stroke. Supplemental parenteral nutrition (SPN) may address enteral nutrition (EN) deficiency and mitigate the risk of nosocomial infection. The benefit of EN plus early SPN strategy over full EN strategy is unknown in acute severe stroke. Methods : We retrospectively enrolled 20 patients with acute severe stroke in SPN group who received EN plus early SPN (more than 50% of energy target within 72h after admission). Forty control cases in the EN group who received full EN were matched by age, sex and lesion site. Time to new-onset pneumonia or nosocomial infections were analyzed by Student’s t-test and Breslow generalized Wilcoxon test. Results : Baseline characteristics were major similar between matched groups, while patients in the SPN group had higher level of serum leukocyte, neutrophil and neutrophil to lymphocyte ratio (P<0.05). Compared to the EN group, the time to new-onset pneumonia was significantly delayed in the SPN group (7.6 days vs. 5.2 days; mean difference, 2.5 days; 95%CI, 0.65 to 4.31, P=0.009), as well as the time to new-onset nosocomial infections (7.1 days vs. 4.8 days; mean difference, 2.3 days; 95%CI, 0.46 to 4.07, P=0.015). Kaplan–Meier analysis showed similar cumulative probability of new-onset pneumonia or new-onset nosocomial infections in the two groups (P>0.05). The rate of digestive intolerance events between the two groups were similar (40% in the SPN group vs 52.5% in the EN group, P=0.361). Conclusions : In patients with acute severe stroke, the application of EN plus early SPN could delay the onset of pneumonia and nosocomial infections especially at early phase. Acute severe stroke Supplemental parenteral nutrition Enteral nutrition New-onset pneumonia New-onset nosocomial infections Case-control study Figures Figure 1 Figure 2 Figure 3 Introduction Severe stroke accounts for about 10% of all strokes, typically accompanies the presence of severe neurological disability and multiple system dysfunctions[1]. Post-stroke pneumonia (PSP) is a major early complication of acute severe stroke, which may prolongs hospitalization duration, increases medical costs, delays the time of rehabilitation, and is closely associated with poor prognosis and mortality[2]. Management of PSP has been proven to be of major significance for the overall improvement of long-term stroke prognosis[3, 4]. Early nutritional support with enteral nutrition (EN) approach for critical ill patients with stroke is part of standard care for patients with a decreased level of consciousness or prolonged severe dysphagia[5, 6]. However, dysphagia caused by consciousness disorders or aspiration in patients with EN support is one of major pathogenesis of PSP[7]. Besides, the EN approach may be interrupted due to various reasons and often fail to achieve targeted energy delivery[8]. In recent years, parenteral nutrition (PN) has been widely used in clinic for its advantage in reducing incidence of adverse events[9]. Some studies have shown that early optimized SPN nutrition can serve as an effective strategy for addressing EN deficiency in intensive care units and mitigating the risk of nosocomial infection[10], whereas some other studies suggest opposite conclusion and recommend that early PN not be used combined with EN for the increased complication rate[11, 12]. The benefit of early nutrition strategy of EN plus SPN is still controversial, and its advantage over full EN approach in acute severe stroke is unknown. In this study, we investigated the benefits of EN plus SPN strategy over full EN strategy on the occurrence of new-onset pneumonia and new-onset nosocomial infections in patients with severe stroke. Methods Study patients We conducted a retrospective case-control study in patients with acute severe stroke. From November 1, 2021 to May 1, 2024, a total of 297 consecutive patients with acute severe stroke were admitted to Xijing Hospital. Patients with acute severe stroke met the inclusion criteria if they were 18 years or older, received enteral nutrition or parenteral nutrition due to a water swallow test score ≥3 or a consciousness disorder. Severe stroke was defined as patients with an initial Glasgow Coma Scale (GCS) score ≤12 or with a National Institutes of Health Stroke Scale (NIHSS) score ≥11. Patients who received EN plus early SPN approach were included in the SPN group. For each case in the SPN group, two matched patients with full EN approach were included in the EN group. Baseline characteristics, including age differences (≤5 years), sex and lesion site, were matched to improve the balance of the two data set. According to physician preference, patients were permitted to initial nutritional support with EN plus early SPN approach if they had a high risk of aspiration or elevated markers of inflammation. Early SPN was initiated within 72h after admission and accounted for more than 50% of the daily energy target. Parenteral calories were delivered in a mixed way by ready-to-mix 3-chamber bag (Kabiven Glu 11%,) or by the physicians’ preparation containing glucose, lipids, amino acids, electrolytes, trace elements, minerals, and vitamins were added as clinically appropriate. EN was administered continuously according to routine protocols, by placement of nasogastric or nasointestinal feeding tubes, and the use of prokinetic agents if necessary (gastric residual volume ≥100 mL). EN formulation were selected according to the main patient's problem, and contained 0.81-1.26 kcal/mL of energy. Small amount of PN was allowed in the EN group. Patients were excluded if they were currently receiving total parenteral nutrition, had contraindications to enteral nutrition, had a history of gastrectomy or enterectomy, had severe systemic disease, had unstable vital signs, were documented to have pre-stroke dementia or disability, use steroids or immunosuppressants. A flow diagram of the included and excluded patients is provided in Fig.1 . The study was approved by the Ethics Committee of Xijing Hospital (KY20182024-F-1). Informed consent was obtained from the patients or their guardians. Data collection Demographics features, medical history, clinical scores of NIHSS, GCS and Nutrition Risk Screening 2002 (NRS-2002), data of laboratory test and vital signs, duration of ICU stay and mechanical ventilation were recorded. The daily nutritional data (total calories and protein), gastric residual volumes and blood glucose were checked four times (at 0800 h, 1200 h, 1600 h, and 2000 h) daily during the first 7 days. Clinical scores were assessed at ICU admission and discharge. During the entire period of hospitalization, adverse events, vital signs, and concomitant treatment data were collected. Modified Rankin Scale score (mRS) was assessed by an investigator who was unaware of group allocation by telephone at 90 days. Definition for some complication Gastric retention was defined as more than 200 mL of gastric residual volumes for two consecutive checks. The incidence and time to new-onset infection including pneumonia or other new-onset nosocomial infections were recorded. The diagnosis of new-onset pneumonia is defined by a professional respiratory physician based on the patient's symptoms, such as temperature higher than 38°C or lower than 36°C, cough, dyspnea, purulent tracheobronchial secretions, leukocytosis>12,000/mm 3 or leukopenia<4000/mm 3 , the presence of a new or progressive radiologic pulmonary infiltrate on the chest X-ray or CT, positive culture from respiratory secretions[13, 14]. Nosocomial infections included infection of urogenital tract, abdomen, blood-borne, skin, bone, soft tissue, ear, nose and throat, upper respiratory tract and chest[15]. Study outcomes The primary outcome was the time to new-onset pneumonia and the time to new-onset nosocomial infections. The secondary outcomes were the proportion of new-onset pneumonia and new-onset nosocomial infections within 7 days of hospitalization, the rate of digestive intolerance events, GCS, NIHSS, mRS at ICU discharge, duration of mechanical ventilation, length of ICU stay, mortality at ICU discharge, mortality at day 90 and poor outcome at day 90. Poor outcome at day 90 was defined as a mRS score of 3 or greater. Statistical analysis We used Stata 12.0 software for all statistical analyses. Normally distributed data were described as mean (standard deviation) and analyzed by Student’s t-test. Skewed data were described as median (interquartile range) and analyzed by Mann-Whitney U-test. Chi-square test or Fisher exact test was used for comparison between dichotomous data. To improve the balance of baseline characteristics, matching of baseline features including age, sex and lesion site were used to create a 1 to 2 matched data set. Student’s t-test were performed for between group comparisons in time to new-onset pneumonia or new-onset nosocomial infections. We constructed Kaplan-Meier curves and used the Breslow generalized Wilcoxon test to evaluate estimate the cumulative probability of new-onset pneumonia or new-onset nosocomial infections. P value < 0.05 was considered statistically significant. Results Study population We identified 20 pairs of patients in the SPN group and the EN group. The demographic characteristics are summarized in Table 1 . Baseline characteristics were similar between the SPN group and the EN group ( P >0.05), including age, sex, weight, body-mass index (BMI), previous disease, oxygenation index, stroke severity at baseline as reflected by score of NIHSS and GCS, nutritional status as reflected by albumin, prealbumin and score of NRS-2002. Compared to patients in the EN group, patients in the SPN group had higher level of serum leukocyte (11.4 vs. 9.5, P =0.04), neutrophil (10.2 vs. 7.3, P =0.008) and neutrophil to lymphocyte ratio (15.97 vs. 7.12, P =0.001). Table 1 . Baseline demographic and clinical characteristics . SPN group, n=20 EN group, n=40 P -value Age, y, mean±SD 69.0±14.3 69.4±12,6 0.912 male, n (%) 10(50) 20(50) >0.99 Weight, kg, mean±SD 66.7±12.0 61.9±11.3 0.134 Body-mass index, kg/m², mean±SD 24.2±3.6 23.1±3.1 0.248 NIHSS, median (IQR) 20(17, 33.7) 17(14, 25.5) 0.116 GCS, median (IQR) 8(5.25, 10) 9(7, 11) 0.124 NRS 2002, median (IQR) 3(3, 4) 3 (3, 3) 0.746 Hypertension, n (%) 13(65) 28(70) 0.695 Previous stroke, n (%) 6(30) 11(27.5) 0.839 Diabetes, n (%) 5(25) 13(32.5) 0.55 Coronary artery disease, n (%) 8(40) 12(30) 0.439 Renal disease, n (%) 1(5) 3(7.5) >0.99 Temperature, ℃, median (IQR) 37.2(36.8, 37.7) 37.1(36.8, 37.4) 0.615 Oxygenation index, mean ±SD 253.7±96.5 272.8±119.0 0.537 Pneumonia, n (%) 6(30) 6(15) 0.304 Thrombolytic therapy, n (%) 2(10) 6(15) 0.893 Endovascular therapy, n (%) 11(55) 22(55) >0.99 Leukocyte, ×10 9 , median (IQR) 11.4(8.4, 15.0) 9.5(7.6, 10.8) 0.04 Neutrophil, ×10 9 , median (IQR) 10.2(6.9, 13.8) 7.3(5.9, 8.9) 0.008 Lymphocyte, ×10 9 , median (IQR) 0.63(0.48, 0.93) 0.95(0.82, 1.57) 0.001 Neutrophil/lymphocyte, median (IQR) 15.97(9.09, 21.89) 7.12(4.78, 10.21) 0.001 Procalcitonin, ng/ml, median (IQR) 0.14(0.03, 0.40) 0.06(0.04, 0.11) 0.075 Interleukin-6, pg/ml, median (IQR) 35.8(14.3, 77.9) 19.1(11.3, 57.5) 0.17 Albumin, g/L, median (IQR) 36.2(34.7, 42.6) 38.2(35.6, 40.8) 0.541 Prealbumin, g/L, median (IQR) 0.13(0.10,0.21) 0.18(0.13, 0.21) 0.237 Triglyceride, mmol/L, median (IQR) 0.69(0.53, 1.32) 1.01(0.75, 1.43) 0.115 Cholesterol, mmol/L, mean ±SD 4.07±1.04 3.99±1.17 0.824 HbA 1C , %, median (IQR) Creatinine, μmol/L, median (IQR) 6.05(5.72, 6.52) 64.5(50.7, 84.5) 5.9(5.45, 10.2) 66.0(56.2, 98.7) 0.522 0.342 NIHSS, National Institutes of Health Stroke Scale; GCS, Glasgow Coma Scale; NRS-2002, Nutrition Risk Screening 2002; IQR, interquartile range. Nutritional support during hospitalization The median caloric targets were 1587 kcal/day in the SPN group and 1500 kcal/day in the EN group. On the first day after admission, a low caloric intake about 40% of the estimated need was provided in both groups, and was increased gradually up to above 70% of estimated need within 3 days. The initial time of supplemental parenteral nutrition in the SPN group was 2.4±0.6 days. The average caloric intake was similar between the SPN group and the EN group during 7 days after admission ( P >0.05), and basically reached the target in both groups (Fig. 2). The median protein targets were similar in both groups (94.5g/day in the SPN group vs 93g/day in the EN group). Protein intake increased gradually to nearly 1.0g/kg/day at day 3 in both groups. A total of 1022 and 506 blood glucose data were collected in the EN group and the SPN group, respectively. Blood glucose concentrations between the both groups showed no significant difference within 7 days ( P =0.215) (Fig. S1) . New-onset infection and clinical outcomes Compared with patients in the EN group, the time to new-onset pneumonia was significantly delayed in the SPN group (7.6 days in the SPN group vs 5.2 days in the EN group; mean difference, 2.5 days; 95%CI, 0.65 to 4.31, P =0.009). The proportion of new-onset pneumonia within 7 days was lower in the SPN group than in the EN group (35% vs. 50%, P =0.271), but our study lacked power to show statistically significant differences. The time to new-onset nosocomial infections was significantly delayed in the SPN group (7.1 days in the SPN group vs. 4.8 days in the EN group; mean difference, 2.3 days; 95%CI, 0.46 to 4.07, P =0.015). There were no differences in the number of urogenital infection and other new-onset nosocomial infections within 7 days of hospitalization ( P >0.05) (Table 2 ) . Kaplan–Meier analysis showed similar cumulative probability of new-onset pneumonia (Fig. 3A) and of new-onset nosocomial infections (Fig. 3B) . There were no significant differences in median time to new-onset pneumonia (8.0 days, 95% CI [6.4 to 9.6] in the SPN group; 7.0 days, 95% CI [3.2 to 10.8] in the EN group; P = 0.173 for Breslow generalized Wilcoxon test), as well as in time to new-onset nosocomial infections (8.0 days, 95% CI [6.7 to 9.3] in the SPN group; 7.0 days, 95% CI [2.9 to 11.1] in the EN group; P = 0.282 for Breslow generalized Wilcoxon test). There were no significantly differences in disease severity at ICU discharge as reflected by GCS, NIHSS and mRS scores between the two groups ( P >0.05), as well as in mechanical ventilation duration during hospitalization, length of stay in ICU, ICU mortality, 90-day mortality, and poor outcome at day 90 ( Table 2 ) . Table 2 . Distribution of new-onset infections within 7 days of hospitalization and clinical outcomes in different nutrition strategies group. SPN group, n=20 EN group, n=40 P -value New-onset pneumonia within 7 days, n (%) 7(35) 20(50) 0.271 Time of new-onset pneumonia, days, mean±SD 7.6±2.1 5.2±3.0 0.009 Urogenital infection within 7 days, n (%) 2(10) 2(5) 0.855 Other infection within 7 days, n (%) * 1 0 0.721 New-onset nosocomial infections within 7 days, n (%) 9(45) 21(52.5) 0.584 Time of new-onset nosocomial infections, days, mean±SD 7.1±2.4 4.8±2.9 0.015 Hours on mechanical ventilation, days, median (IQR) 0(0, 3.5) 0(0, 0) 0.208 Glasgow Coma Scale at discharge, median (IQR) 11(9.25, 14) 12(10, 15) 0.668 NIHSS at discharge, median (IQR) 15(11.5, 19.2) 14.5(11, 22) 0.956 Modified Rankin Scale at discharge, median (IQR) 5(4, 5) 4(4, 5) 0.251 Days in ICU, days, median (IQR) 14.5(10, 19.2) 11(8, 14) 0.081 mortality in ICU, n (%) 0 2(5) 0.799 Death at day 90, n (%) 1(5) 5(12.5) 0.648 Poor outcome at day 90, n (%) 19(95) 38(95) >0.99 SPN, supplemental parenteral nutrition; EN, enteral nutrition; NIHSS, National Institutes of Health Stroke Scale. * Other infection included infections of abdominal, bloodstream, skin, bone, soft tissue, ear, nose, throat, upper respiratory, and non-pulmonary intrathoracic. Safety outcomes The rate of digestive intolerance events were similar in the SPN group compared to the EN group (40% vs. 52.5%, P =0.361). The incidence of cerebral herniation, heart failure, respiratory failure, renal failure, sepsis or septic shock were similar between both groups. The results were shown in Table S 1 . Discussion We found that the nutritional support with EN plus early SPN approach in patients with acute severe stroke could significantly delay the time to new-onset pneumonia or new-onset nosocomial infections compared to those with full EN approach. With the extension of hospital stay, the cumulative probability of infections became similarly between the two groups. Our result highlights the potential value of EN plus early SPN nutritional strategy for patients with acute severe stroke on mitigating infection at early phase after admission. Previously, the FOOD study has found that early feeding reduced mortality of stroke patients with dysphagia[16]. Meanwhile, results from the OPENS trial suggest that hypocaloric feeding during the acute phase of severe stroke might be associated with increased mortality[17]. Despite the benefits and widespread use of enteral tube feeding, some patients may experience complications leading to feeding interruption and calorie deficits, such as feeding intolerance, the performance of diagnostic or therapeutic procedures, tube displacement and clinical neglect[18, 19]. Therefore, it is a crucial clinical issue to find optimal feeding strategies and avoid inadequate energy supply. Pneumonia is a frequent clinical complication after stroke, which is closely related to the stroke severity[20]. A previous study showed that pneumonia complicated stroke in 47% of 55 critically ill patients[21], aged 33 to 91 (median 74) years, median baseline NHISS score was 18, while another study found that among stroke patients with a median baseline NIHSS score of 7.8, the incidence of pneumonia within 7 days of admission was 7.4%[22]. Patients enrolled in our study were similar in age and have similarly high baseline NIHSS score (median baseline NIHSS 17.5) comparing with the two studies, making a high overall incidence of pneumonia. So far, there is no uniform feeding regimen for PN feeding, and its effectiveness is controversial. Previous trials have provided that no difference between the patients receiving PN or EN in terms of 30-day mortality, number of infectious complications, or the rate of various adverse events[23]. The latest study proved that individually optimised energy supplementation with SPN starting 4 days after ICU admission could reduce nosocomial infections[10]. In this study, some patients developed fever, accompanying with increased inflammatory mediators within 48 hours after admission. Considering the combination of disturbance of consciousness and high aspiration risk, we chose the modified SPN nutritional approach. The time of parenteral nutrition initiation in the SPN group was 2.4 ± 0.6 days after admission. Similar to the above trials, PN was early-activated in our study. However, the population in our study were severe stroke adults and PN feeding was added obviously to reduce the risk of pneumonia in the SPN group in conjunction with the usage of EN. There were no significant differences in nutrient supply and blood glucose between the two groups, indicating that SPN is effective and feasible. Stroke severity and system condition in both groups were similar except for some laboratory baseline data. It has been well documented that post-stoke inflammation plays an important role in various stages of stroke. Neutrophil to Lymphocyte Ratio (NLR) as a newfound biomarker in systematic inflammation was proved to possess predictive capabilities in PSP recently[24]. The results showed that serum Leukocyte, Neutrophil (NEU) and NLR in the SPN group were significantly increased, suggesting that these patients may have a higher risk of pneumonia through clinical assessment by clinicians, and early SPN administration reflects a genuine clinical decision. Our results showed that the incidence of new-onset pneumonia was similar between the two groups within 7 days of hospitalization. Our findings are consistent with a randomised trial which included ICU critically ill patients [25], but are inconsistent with another study [10]. The following reasons could account for this inconsistency. The population in our study are severe stroke patients with a high incidence of pneumonia and respiratory failure, and they may benefit more through optimized feeding methods, but considering the small sample size, the difference cannot be reflected. Meanwhile, the mean age of the patients was nearly 70 years old, which was older than in previous studies (mean age was 60 years), and the patients all had serious clinical scores at admission. Advanced age and stroke severity were risk factors for PSP. In such patients, the overall incidence of pneumonia was increased, and the heterogeneity of critically ill patients was high, while it was difficult to show a significant difference consequently. Compared to the full EN strategy, the EN plus early SPN strategy had delayed onset of infection, while had similar cumulative incidence during hospitalization. It is rarely discussed in previous articles, and might be explained by that nutritional supply pathway may not a determining factor for pneumonia and infections in acute severe stroke patients. There were no differences in duration of mechanical ventilation, average length of stay in ICU, or ICU mortality between the two groups, which is consistent with a randomized controlled trial (ICU critically ill patients)[10] and a review[26]. It is suggested that SPN is safe for usage in these patients, although no efficacy for long-term prognosis has been found. Several potential limitations need to be taken into account. First, our study was designed as a retrospective study with a limited sample size and relatively low statistical power. With our strict inclusion criteria as well as the case-control 1:2 matching, it could represent the broader populations of patients with severe stroke. Therefore, our results deserve close clinical attention and needs to be further validation through a prospective, randomized controlled study. Second, the EN or PN regimens given to the patients were not the same specific formulations. Although, it could potentially confound the effects on inflammatory mediators, laboratory results, gastrointestinal tolerance and clinical outcomes, this approach was pragmatic in real-world medical practice. Finally, the clinical diagnosis of new-onset pneumonia and nosocomial infection is a comprehensive judgment made by physicians based on clinical manifestations and auxiliary examinations, which largely depends on the accuracy and integrity of medical documents. It may result in certain information bias, but the two groups remain homogenous. Conclusion The nutritional strategy with EN plus early SPN might be an alternative choice to full EN strategy for patients with acute severe stroke, especially for those with high risk of nosocomial infection. Further studies with larger sample sizes are needed to explore the effect of SPN on infection-related complications and functional outcome for patients with acute severe stroke. Abbreviations NICU, Neurology intensive care unit; EN, Enteral nutrition; PN, Parenteral nutrition; SPN, Supplemental parenteral nutrition; NIHSS, National Institutes of Health Stroke Scale; GCS, Glasgow Coma Scale; mRS, modified Rankin Scale score; NRS-2002, Nutrition Risk Screening 2002; PSP, Post-stroke pneumonia; BMI, Body mass index; IQR, interquartile range; NLR, Neutrophil to Lymphocyte Ratio; NEU, Neutrophil; LYM, Lymphocyte; PCT, Procalcitonin. Declarations Ethics approval statement The procedures of this study were approved by the ethics committee of Xijing Hospital (KY20182024-F-1) and adhered to the Helsinki Declaration. Patient consent statement Informed consent was obtained from the patients or their guardians. Consent for publication All authors agree to publication. Data availability statement The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Funding statement This study was supported by the Funding Key Research and Development Project of Shaanxi Province (No.2020SF-306) and the Xijing Hospital Clinical Application Research Program (No. JSYXM03). Conflict of interest disclosure The authors declare that they have no conflict of interest. Authors’ contributions F.Y. and W.J. designed the study. C.M., B.L, and X.K. collected the data. C.M., Z.F., and X.W. analyzed the data. J.Z. and X.K. revised the statistical analyses. C.M. and Z.F. wrote the manuscript. F.Y. and W.J. revised the manuscript. All authors have read and agreed to the published version of the manuscript. Acknowledgment Not applicable. References Luengo-Fernandez R, Paul NL, Gray AM, Pendlebury ST, Bull LM, Welch SJ, Cuthbertson FC, Rothwell PM. Population-based study of disability and institutionalization after transient ischemic attack and stroke: 10-year results of the Oxford Vascular Study. STROKE 2013, 44(10):2854-2861. Banda KJ, Chu H, Kang XL, Liu D, Pien LC, Jen HJ, Hsiao SS, Chou KR. Prevalence of dysphagia and risk of pneumonia and mortality in acute stroke patients: a meta-analysis. BMC GERIATR 2022, 22(1):420. Koennecke HC, Belz W, Berfelde D, Endres M, Fitzek S, Hamilton F, Kreitsch P, Mackert BM, Nabavi DG, Nolte CH et al . Factors influencing in-hospital mortality and morbidity in patients treated on a stroke unit. NEUROLOGY 2011, 77(10):965-972. Westendorp WF, Nederkoorn PJ, Vermeij JD, Dijkgraaf MG, van de Beek D. Post-stroke infection: a systematic review and meta-analysis. BMC NEUROL 2011, 11:110. Burgos R, Breton I, Cereda E, Desport JC, Dziewas R, Genton L, Gomes F, Jesus P, Leischker A, Muscaritoli M et al . ESPEN guideline clinical nutrition in neurology. CLIN NUTR 2018, 37(1):354-396. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B et al . Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. STROKE 2019, 50(12):e344-e418. Hannawi Y, Hannawi B, Rao CP, Suarez JI, Bershad EM. Stroke-associated pneumonia: major advances and obstacles. CEREBROVASC DIS 2013, 35(5):430-443. Uozumi M, Sanui M, Komuro T, Iizuka Y, Kamio T, Koyama H, Mouri H, Masuyama T, Ono K, Lefor AK. Interruption of enteral nutrition in the intensive care unit: a single-center survey. J Intensive Care 2017, 5:52. Doig GS, Simpson F, Sweetman EA, Finfer SR, Cooper DJ, Heighes PT, Davies AR, O'Leary M, Solano T, Peake S. Early parenteral nutrition in critically ill patients with short-term relative contraindications to early enteral nutrition: a randomized controlled trial. JAMA 2013, 309(20):2130-2138. Heidegger CP, Berger MM, Graf S, Zingg W, Darmon P, Costanza MC, Thibault R, Pichard C. Optimisation of energy provision with supplemental parenteral nutrition in critically ill patients: a randomised controlled clinical trial. LANCET 2013, 381(9864):385-393. Casaer MP, Mesotten D, Hermans G, Wouters PJ, Schetz M, Meyfroidt G, Van Cromphaut S, Ingels C, Meersseman P, Muller J et al . Early versus late parenteral nutrition in critically ill adults. N Engl J Med 2011, 365(6):506-517. Sena MJ, Utter GH, Cuschieri J, Maier RV, Tompkins RG, Harbrecht BG, Moore EE, O'Keefe GE. Early supplemental parenteral nutrition is associated with increased infectious complications in critically ill trauma patients. J Am Coll Surg 2008, 207(4):459-467. Badve MS, Zhou Z, van de Beek D, Anderson CS, Hackett ML. Frequency of post-stroke pneumonia: Systematic review and meta-analysis of observational studies. INT J STROKE 2019, 14(2):125-136. Kalil AC, Metersky ML, Klompas M, Muscedere J, Sweeney DA, Palmer LB, Napolitano LM, O'Grady NP, Bartlett JG, Carratala J et al . Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. CLIN INFECT DIS 2016, 63(5):e61-e111. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. AM J INFECT CONTROL 2008, 36(5):309-332. Dennis MS, Lewis SC, Warlow C. Effect of timing and method of enteral tube feeding for dysphagic stroke patients (FOOD): a multicentre randomised controlled trial. LANCET 2005, 365(9461):764-772. Zhao J, Yuan F, Song C, Yin R, Chang M, Zhang W, Zhang B, Yu L, Jia Y, Ma Y et al . Safety and efficacy of three enteral feeding strategies in patients with severe stroke in China (OPENS): a multicentre, prospective, randomised, open-label, blinded-endpoint trial. LANCET NEUROL 2022, 21(4):319-328. Blumenstein I, Shastri YM, Stein J. Gastroenteric tube feeding: techniques, problems and solutions. World J Gastroenterol 2014, 20(26):8505-8524. Heyland DK, Dhaliwal R, Wang M, Day AG. The prevalence of iatrogenic underfeeding in the nutritionally 'at-risk' critically ill patient: Results of an international, multicenter, prospective study. CLIN NUTR 2015, 34(4):659-666. Finlayson O, Kapral M, Hall R, Asllani E, Selchen D, Saposnik G. Risk factors, inpatient care, and outcomes of pneumonia after ischemic stroke. NEUROLOGY 2011, 77(14):1338-1345. Upadya A, Thorevska N, Sena KN, Manthous C, Amoateng-Adjepong Y. Predictors and consequences of pneumonia in critically ill patients with stroke. J CRIT CARE 2004, 19(1):16-22. Weimar C, Roth MP, Zillessen G, Glahn J, Wimmer ML, Busse O, Haberl RL, Diener HC. Complications following acute ischemic stroke. EUR NEUROL 2002, 48(3):133-140. Harvey SE, Segaran E, Leonard R. Trial of the route of early nutritional support in critically ill adults. N Engl J Med 2015, 372(5):488-489. Khanzadeh S, Lucke-Wold B, Eshghyar F, Rezaei K, Clark A. The Neutrophil to Lymphocyte Ratio in Poststroke Infection: A Systematic Review and Meta-Analysis. DIS MARKERS 2022, 2022:1983455. Bauer P, Charpentier C, Bouchet C, Nace L, Raffy F, Gaconnet N. Parenteral with enteral nutrition in the critically ill. Intensive Care Med 2000, 26(7):893-900. Sharma SK, Rani R, Thakur K. Effect of Early Versus Delayed Parenteral Nutrition on the Health Outcomes of Critically Ill Adults: A Systematic Review. J Crit Care Med (Targu Mures) 2021, 7(3):160-169. Additional Declarations No competing interests reported. Supplementary Files Supplementalmetarials.docx Cite Share Download PDF Status: Published Journal Publication published 31 Jan, 2025 Read the published version in BMC Neurology → Version 1 posted Editorial decision: Revision requested 23 Sep, 2024 Editor assigned by journal 23 Sep, 2024 Submission checks completed at journal 23 Sep, 2024 First submitted to journal 22 Sep, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5132498","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":357914910,"identity":"bdf84750-2c79-4ad3-8838-56c787fbbd4e","order_by":0,"name":"Chen Ma","email":"","orcid":"","institution":"Xijing Hospital, Air Force Medical University","correspondingAuthor":false,"prefix":"","firstName":"Chen","middleName":"","lastName":"Ma","suffix":""},{"id":357914911,"identity":"d0b923cc-4488-4108-ad26-4c157ef4934a","order_by":1,"name":"Zhirong Fan","email":"","orcid":"","institution":"Xijing Hospital, Air Force Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zhirong","middleName":"","lastName":"Fan","suffix":""},{"id":357914912,"identity":"f848d6f8-4df5-43a2-b6c4-49819e046e3f","order_by":2,"name":"Xuan Wang","email":"","orcid":"","institution":"Xijing Hospital, Air Force Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xuan","middleName":"","lastName":"Wang","suffix":""},{"id":357914914,"identity":"2523f2a8-a079-413d-9752-05fc04ea369c","order_by":3,"name":"Bian Li","email":"","orcid":"","institution":"Air Force Medical University","correspondingAuthor":false,"prefix":"","firstName":"Bian","middleName":"","lastName":"Li","suffix":""},{"id":357914917,"identity":"5ada33c2-b7ef-4bef-a22a-a56566240c4e","order_by":4,"name":"Jingjing Zhao","email":"","orcid":"","institution":"Xijing Hospital, Air Force Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jingjing","middleName":"","lastName":"Zhao","suffix":""},{"id":357914923,"identity":"548bc8b1-2596-411a-bcb2-9c0a245b47a7","order_by":5,"name":"Xiaogang Kang","email":"","orcid":"","institution":"Xijing Hospital, Air Force Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xiaogang","middleName":"","lastName":"Kang","suffix":""},{"id":357914924,"identity":"11545ca3-9966-4c86-9cb5-bed972e5c9c2","order_by":6,"name":"Wen Jiang","email":"","orcid":"","institution":"Xijing Hospital, Air Force Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wen","middleName":"","lastName":"Jiang","suffix":""},{"id":357914925,"identity":"a7561f97-ead8-4acc-9ec3-dbe482d28c23","order_by":7,"name":"Fang Yang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAy0lEQVRIiWNgGAWjYBAC9gYwZcMP4bIRoYXnAJhKk2wgVcthUrRIJD97+LXtvITutDMGDB/KDjPwz24gpCXN3FjmzG0Js9s5Bowzzh1mkLhzAL8We4kEM2mJitt1IC3MvG2HGQwkEgjZkv5NWsLgHNgW5r/Eackxk/xQcQCihZEoLTxvyqQZziQDtaQVHOw5l84jcYOQFvb0bZI/2+yAWpI3PvhRZi3HP4OAFgaBBAZmHij7AMgMAuqBgP8AA+MPwspGwSgYBaNgJAMA1SRAYUJCOu8AAAAASUVORK5CYII=","orcid":"","institution":"Xijing Hospital, Air Force Medical University","correspondingAuthor":true,"prefix":"","firstName":"Fang","middleName":"","lastName":"Yang","suffix":""}],"badges":[],"createdAt":"2024-09-22 12:52:49","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5132498/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5132498/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12883-025-04050-6","type":"published","date":"2025-01-31T15:57:34+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":68653877,"identity":"6642c9e9-2d6a-4727-9485-be44eb8e34fe","added_by":"auto","created_at":"2024-11-10 13:49:31","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":33439,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlow diagram of the included and excluded patients\u003c/strong\u003e.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-5132498/v1/01fed432c6d04f3266556246.png"},{"id":68653874,"identity":"79af358b-a03b-4f97-a108-b982ae6a7436","added_by":"auto","created_at":"2024-11-10 13:49:31","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":137492,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eEnergy delivery. \u003c/strong\u003eEnergy is expressed in percentage (%) of energy target according to method of delivery: enteral route (A), parenteral route (B), or a combination of both routes (C) in patients. Horizontal lines within the boxes show the median, and the boxes show IQR. EN=enteral nutrition. SPN=supplemental parenteral nutrition. ICU=intensive-care unit.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-5132498/v1/3616f14d4f99597e631186bd.png"},{"id":68653875,"identity":"41417e5b-733b-4d87-b851-c3f6dfa39d65","added_by":"auto","created_at":"2024-11-10 13:49:31","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":114095,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan-Meier analysis of new-onset pneumonia\u003c/strong\u003e (A)\u003cstrong\u003eand new-onset nosocomial infections\u003c/strong\u003e(B)\u003cstrong\u003e. \u003c/strong\u003eSPN=supplemental parenteral nutrition. EN=enteral nutrition. \u003csup\u003ea\u003c/sup\u003eNumber of patients who were still in the study and did not achieve “new-onset pneumonia or nosocomial infections” at the end of specified time.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-5132498/v1/61a2eaf841ed058bc9b1484f.png"},{"id":75352078,"identity":"3bd07dab-82fd-4e77-9040-1d0fb28b383c","added_by":"auto","created_at":"2025-02-03 16:13:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1075668,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5132498/v1/f08e7ec8-a0ec-487d-a534-566ef1efea5f.pdf"},{"id":68654853,"identity":"406aaead-2620-4114-b2f9-558d486cbd6b","added_by":"auto","created_at":"2024-11-10 13:57:31","extension":"docx","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":90216,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementalmetarials.docx","url":"https://assets-eu.researchsquare.com/files/rs-5132498/v1/4e262b326d76546b58d76cd8.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effects of early supplemental parenteral nutrition on new-onset infection in adults with acute severe stroke: A single-center retrospective case-control study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSevere stroke accounts for about 10% of all strokes, typically accompanies the presence of severe neurological disability and multiple system dysfunctions[1].\u0026nbsp;Post-stroke pneumonia (PSP) is a major early complication of acute severe stroke,\u0026nbsp;which may\u0026nbsp;prolongs hospitalization duration, increases medical costs, delays the time of rehabilitation, and is closely associated with poor prognosis and mortality[2]. \u0026nbsp; Management of PSP\u0026nbsp;has been proven to be of major significance for the overall improvement of long-term stroke prognosis[3, 4].\u003c/p\u003e\n\u003cp\u003eEarly nutritional support with enteral nutrition (EN) approach for critical ill patients with stroke is part of standard care for patients with a decreased level of consciousness or prolonged severe dysphagia[5, 6]. However, dysphagia caused by consciousness disorders or aspiration in patients with EN support is one of major pathogenesis of PSP[7]. Besides, the EN approach may be interrupted due to various reasons and often fail to achieve targeted energy delivery[8]. In recent years, parenteral nutrition (PN) has been widely used in clinic for its advantage in reducing incidence of adverse events[9]. Some studies have shown that early optimized SPN nutrition can serve as an effective strategy for addressing EN deficiency in intensive care units and mitigating the risk of nosocomial infection[10], whereas some other studies suggest opposite conclusion and recommend that early PN not be used combined with EN for the increased complication rate[11, 12]. The benefit of early nutrition strategy of EN plus SPN is still controversial, and its advantage over full EN approach in acute severe stroke is unknown. In this study, we investigated the benefits of EN plus SPN strategy over full EN strategy on the occurrence of new-onset pneumonia and new-onset nosocomial infections in patients with severe stroke.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy patients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe conducted a retrospective case-control study in patients with acute severe stroke. From November 1, 2021 to May 1, 2024, a total of 297 consecutive patients with acute severe stroke were admitted to Xijing Hospital. Patients with acute severe stroke met the inclusion criteria if they were 18 years or older, received enteral nutrition or parenteral nutrition due to a water swallow test score \u0026ge;3 or a consciousness disorder. Severe stroke was defined as patients with an initial Glasgow Coma Scale (GCS) score \u0026le;12 or with a National Institutes of Health Stroke Scale (NIHSS) score \u0026ge;11. Patients who received EN plus early SPN approach were included in the SPN group. For each case in the SPN group, two matched patients with full EN approach were included in the EN group. Baseline characteristics, including age differences (\u0026le;5 years), sex and lesion site, were matched to improve the balance of the two data set. According to physician preference, patients were permitted to initial nutritional support with EN plus early SPN approach if they had a high risk of aspiration or elevated markers of inflammation. Early SPN was initiated within 72h after admission and accounted for more than 50% of the daily energy target. Parenteral calories were delivered in a mixed way by ready-to-mix 3-chamber bag (Kabiven Glu 11%,) or by the physicians\u0026rsquo; preparation containing glucose, lipids, amino acids, electrolytes, trace elements, minerals, and vitamins were added as clinically appropriate. EN was administered continuously according to routine protocols, by placement of nasogastric or nasointestinal feeding tubes, and the use of prokinetic agents if necessary (gastric residual volume \u0026ge;100 mL). EN formulation were selected according to the main patient\u0026apos;s problem, and contained 0.81-1.26 kcal/mL of energy. Small amount of PN was allowed in the EN group. Patients were excluded if they were currently receiving total parenteral nutrition, had contraindications to enteral nutrition, had a history of gastrectomy or enterectomy, had severe systemic disease, had unstable vital signs, were documented to have pre-stroke dementia or disability, use steroids or immunosuppressants. A flow diagram of the included and excluded patients is provided in \u003cstrong\u003eFig.1\u003c/strong\u003e. The study was approved by the Ethics Committee of Xijing Hospital (KY20182024-F-1). Informed consent was obtained from the patients or their guardians.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData collection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDemographics features, medical history, clinical scores of NIHSS, GCS and\u0026nbsp;Nutrition Risk Screening 2002 (NRS-2002), data of laboratory test and vital signs, duration of ICU stay and mechanical ventilation were recorded. The daily nutritional data (total calories and protein),\u0026nbsp;gastric residual volumes and blood glucose were checked four times (at 0800 h, 1200 h, 1600 h, and 2000 h) daily during the first 7 days. Clinical scores were assessed at ICU admission and discharge. During the entire period of hospitalization, adverse events, vital signs, and concomitant treatment data were collected. Modified Rankin Scale score\u0026nbsp;(mRS)\u0026nbsp;was assessed by an investigator who was unaware of group allocation by telephone at 90 days.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDefinition for some complication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGastric retention was defined as more than 200 mL of gastric residual volumes for two consecutive checks. The incidence and time to new-onset infection including pneumonia or other new-onset nosocomial infections were recorded. The diagnosis of new-onset pneumonia is defined by a professional respiratory physician based on the patient\u0026apos;s symptoms, such as temperature higher than 38\u0026deg;C or lower than 36\u0026deg;C, cough, dyspnea, purulent tracheobronchial secretions, leukocytosis\u0026gt;12,000/mm\u003csup\u003e3\u003c/sup\u003e or leukopenia\u0026lt;4000/mm\u003csup\u003e3\u003c/sup\u003e,\u0026nbsp;the presence of a new or progressive radiologic pulmonary infiltrate on the chest X-ray or CT, positive culture from respiratory secretions[13, 14]. Nosocomial infections included infection of urogenital tract, abdomen, blood-borne, skin, bone, soft tissue, ear, nose and throat, upper respiratory tract and chest[15].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary outcome was the time to new-onset pneumonia\u0026nbsp;and the\u0026nbsp;time to new-onset nosocomial infections. The secondary outcomes\u0026nbsp;were the proportion of new-onset pneumonia\u0026nbsp;and\u0026nbsp;new-onset nosocomial infections within 7 days of hospitalization, the\u0026nbsp;rate of\u0026nbsp;digestive intolerance\u0026nbsp;events,\u0026nbsp;GCS, NIHSS, mRS\u0026nbsp;at ICU discharge, duration of mechanical ventilation, length of ICU stay, mortality at ICU discharge, mortality at day 90 and poor outcome at day 90. Poor outcome at day 90 was defined as a mRS score of 3 or greater.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe used Stata 12.0 software for all statistical analyses. Normally distributed data were described as mean (standard deviation) and analyzed by Student\u0026rsquo;s t-test. Skewed data were described as median (interquartile range) and analyzed by Mann-Whitney U-test. Chi-square test or Fisher exact test was used for comparison between dichotomous data. To improve the balance of baseline characteristics, matching of baseline features including age, sex and lesion site were used to create a 1 to\u0026nbsp;2\u0026nbsp;matched data set. Student\u0026rsquo;s t-test were performed for between group comparisons in time to new-onset pneumonia or new-onset nosocomial infections. We constructed Kaplan-Meier curves and used the Breslow generalized Wilcoxon test to evaluate estimate the cumulative probability of new-onset pneumonia or new-onset nosocomial infections.\u0026nbsp;\u003cem\u003eP\u003c/em\u003e value \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eStudy population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe identified 20 pairs of patients in the SPN group and the EN group. The demographic characteristics are summarized in \u003cstrong\u003eTable 1\u003c/strong\u003e. Baseline characteristics were similar between the SPN group and the EN group\u0026nbsp;(\u003cem\u003eP\u003c/em\u003e\u0026gt;0.05), including age, sex, weight, body-mass index (BMI), previous disease, oxygenation index, stroke severity at baseline as reflected by score of NIHSS and GCS, nutritional status as reflected by albumin, prealbumin and score of NRS-2002. Compared to patients in the EN group, patients in the SPN group had higher level of serum leukocyte (11.4 vs. 9.5, \u003cem\u003eP\u003c/em\u003e=0.04), neutrophil (10.2 vs. 7.3, \u003cem\u003eP\u003c/em\u003e=0.008) and neutrophil to lymphocyte ratio (15.97 vs. 7.12, \u003cem\u003eP\u003c/em\u003e=0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003cstrong\u003e. Baseline demographic and clinical characteristics\u003c/strong\u003e.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"562\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003eSPN group, n=20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003eEN group, n=40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003eAge, y, mean\u0026plusmn;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e69.0\u0026plusmn;14.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e69.4\u0026plusmn;12,6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e0.912\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003emale, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e10(50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e20(50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e\u0026gt;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003eWeight, kg, mean\u0026plusmn;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e66.7\u0026plusmn;12.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e61.9\u0026plusmn;11.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e0.134\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003eBody-mass index, kg/m\u0026sup2;, mean\u0026plusmn;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e24.2\u0026plusmn;3.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e23.1\u0026plusmn;3.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e0.248\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003eNIHSS, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e20(17, 33.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e17(14, 25.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e0.116\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003eGCS, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e8(5.25, 10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e9(7, 11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e0.124\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003eNRS 2002, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e3(3, 4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e3 (3, 3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e0.746\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003eHypertension, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e13(65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e28(70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e0.695\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003ePrevious stroke, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e6(30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e11(27.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e0.839\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003eDiabetes, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e5(25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e13(32.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003eCoronary artery disease, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e8(40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e12(30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e0.439\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003eRenal disease, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e1(5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e3(7.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e\u0026gt;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003eTemperature, ℃, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e37.2(36.8, 37.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e37.1(36.8, 37.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e0.615\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003eOxygenation index, mean\u0026nbsp;\u0026plusmn;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e253.7\u0026plusmn;96.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e272.8\u0026plusmn;119.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e0.537\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003ePneumonia, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e6(30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e6(15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e0.304\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003eThrombolytic therapy, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e2(10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e6(15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e0.893\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003eEndovascular therapy, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e11(55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e22(55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e\u0026gt;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003eLeukocyte, \u0026times;10\u003csup\u003e9\u003c/sup\u003e, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e11.4(8.4, 15.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e9.5(7.6, 10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003eNeutrophil, \u0026times;10\u003csup\u003e9\u003c/sup\u003e, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e10.2(6.9, 13.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e7.3(5.9, 8.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003eLymphocyte, \u0026times;10\u003csup\u003e9\u003c/sup\u003e, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e0.63(0.48, 0.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e0.95(0.82, 1.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003eNeutrophil/lymphocyte, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e15.97(9.09, 21.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e7.12(4.78, 10.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003eProcalcitonin, ng/ml, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e0.14(0.03, 0.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e0.06(0.04, 0.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e0.075\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003eInterleukin-6, pg/ml, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e35.8(14.3, 77.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e19.1(11.3, 57.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003eAlbumin, g/L, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e36.2(34.7, 42.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e38.2(35.6, 40.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e0.541\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003ePrealbumin, g/L, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e0.13(0.10,0.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e0.18(0.13, 0.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e0.237\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003eTriglyceride, mmol/L, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e0.69(0.53, 1.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e1.01(0.75, 1.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e0.115\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003eCholesterol, mmol/L, mean\u0026nbsp;\u0026plusmn;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e4.07\u0026plusmn;1.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e3.99\u0026plusmn;1.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e0.824\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 40.0356%;\"\u003e\n \u003cp\u003eHbA\u003csub\u003e1C\u003c/sub\u003e, %,\u0026nbsp;median (IQR)\u003c/p\u003e\n \u003cp\u003eCreatinine,\u0026nbsp;\u0026mu;mol/L, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e6.05(5.72, 6.52)\u003c/p\u003e\n \u003cp\u003e64.5(50.7, 84.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23.4875%;\"\u003e\n \u003cp\u003e5.9(5.45, 10.2)\u003c/p\u003e\n \u003cp\u003e66.0(56.2, 98.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.9893%;\"\u003e\n \u003cp\u003e0.522\u003c/p\u003e\n \u003cp\u003e0.342\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNIHSS, National Institutes of Health Stroke Scale; GCS, Glasgow Coma Scale; NRS-2002, Nutrition Risk Screening 2002; IQR, interquartile range.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNutritional support during hospitalization\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe median caloric targets were\u0026nbsp;1587\u0026nbsp;kcal/day in the SPN group and\u0026nbsp;1500\u0026nbsp;kcal/day in the EN group. On the first day after admission, a low caloric intake about\u0026nbsp;40% of the estimated need was provided in both groups, and was increased gradually up to above 70% of estimated need within 3 days. The initial time of supplemental parenteral nutrition\u0026nbsp;in the SPN\u0026nbsp;group was\u0026nbsp;2.4\u0026plusmn;0.6\u0026nbsp;days. The average caloric intake was similar between the SPN group and the EN group\u0026nbsp;during 7 days\u0026nbsp;after admission\u0026nbsp;(\u003cem\u003eP\u003c/em\u003e\u0026gt;0.05), and basically reached the target in both groups \u003cstrong\u003e(Fig. 2).\u0026nbsp;\u003c/strong\u003eThe median protein targets were similar in both groups (94.5g/day\u0026nbsp;in the SPN\u0026nbsp;group vs\u0026nbsp;93g/day\u0026nbsp;in the EN\u0026nbsp;group). Protein intake increased gradually to\u0026nbsp;nearly\u0026nbsp;1.0g/kg/day at day 3 in both groups.\u0026nbsp;A total of 1022 and 506 blood glucose data were collected\u0026nbsp;in the EN group and the SPN group, respectively.\u0026nbsp;Blood glucose concentrations between the both groups showed no significant difference within 7 days (\u003cem\u003eP\u003c/em\u003e=0.215) \u003cstrong\u003e(Fig. S1)\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNew-onset infection and clinical outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCompared with patients in the EN group, the time to new-onset pneumonia was significantly delayed in the SPN group (7.6 days in the SPN group vs 5.2 days in the EN group; mean difference, 2.5 days; 95%CI, 0.65 to 4.31, \u003cem\u003eP\u003c/em\u003e=0.009). The proportion of new-onset pneumonia within 7 days was lower in the SPN group than in the EN group (35% vs. 50%, \u003cem\u003eP\u003c/em\u003e=0.271), but our study lacked power to show statistically significant differences. The time to new-onset nosocomial infections was significantly delayed in the SPN group (7.1 days in the SPN group vs. 4.8 days in the EN group; mean difference, 2.3 days; 95%CI, 0.46 to 4.07, \u003cem\u003eP\u003c/em\u003e=0.015). There were no differences in the number of urogenital infection and other new-onset nosocomial infections within 7 days of hospitalization (\u003cem\u003eP\u003c/em\u003e\u0026gt;0.05)\u003cstrong\u003e\u0026nbsp;(Table\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eKaplan\u0026ndash;Meier analysis showed similar cumulative probability of new-onset pneumonia \u003cstrong\u003e(Fig. 3A)\u003c/strong\u003e and of new-onset nosocomial infections\u003cstrong\u003e\u0026nbsp;(Fig. 3B)\u003c/strong\u003e. There were no significant differences in median time to new-onset pneumonia (8.0 days, 95% CI [6.4 to 9.6] in the SPN group; 7.0 days, 95% CI [3.2 to 10.8] in the EN group; \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.173 for Breslow generalized Wilcoxon test), as well as in time to new-onset nosocomial infections (8.0 days, 95% CI [6.7 to 9.3] in the SPN group; 7.0 days, 95% CI [2.9 to 11.1] in the EN group; \u003cem\u003eP\u0026nbsp;\u003c/em\u003e=\u0026nbsp;0.282\u0026nbsp;for Breslow generalized Wilcoxon test). There were no significantly differences in disease severity at ICU discharge as reflected by GCS, NIHSS and mRS scores between the two groups (\u003cem\u003eP\u003c/em\u003e\u0026gt;0.05), as well as in mechanical ventilation duration during hospitalization, length of stay in ICU, ICU mortality, 90-day mortality, and poor outcome at day 90 (\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003cstrong\u003e)\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003cstrong\u003e. Distribution of new-onset infections within 7 days of hospitalization and clinical outcomes in different nutrition strategies group.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"555\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50.722%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.1336%;\"\u003e\n \u003cp\u003eSPN group, n=20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.0361%;\"\u003e\n \u003cp\u003eEN group, n=40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.1083%;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50.722%;\"\u003e\n \u003cp\u003eNew-onset pneumonia within 7 days, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.1336%;\"\u003e\n \u003cp\u003e7(35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.0361%;\"\u003e\n \u003cp\u003e20(50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.1083%;\"\u003e\n \u003cp\u003e0.271\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50.722%;\"\u003e\n \u003cp\u003eTime of new-onset pneumonia, days, mean\u0026plusmn;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.1336%;\"\u003e\n \u003cp\u003e7.6\u0026plusmn;2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.0361%;\"\u003e\n \u003cp\u003e5.2\u0026plusmn;3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.1083%;\"\u003e\n \u003cp\u003e0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50.722%;\"\u003e\n \u003cp\u003eUrogenital infection within 7 days, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.1336%;\"\u003e\n \u003cp\u003e2(10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.0361%;\"\u003e\n \u003cp\u003e2(5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.1083%;\"\u003e\n \u003cp\u003e0.855\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50.722%;\"\u003e\n \u003cp\u003eOther infection within 7 days, n (%) \u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.1336%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.0361%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.1083%;\"\u003e\n \u003cp\u003e0.721\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50.722%;\"\u003e\n \u003cp\u003eNew-onset\u0026nbsp;nosocomial infections within 7 days, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.1336%;\"\u003e\n \u003cp\u003e9(45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.0361%;\"\u003e\n \u003cp\u003e21(52.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.1083%;\"\u003e\n \u003cp\u003e0.584\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50.722%;\"\u003e\n \u003cp\u003eTime of\u0026nbsp;new-onset\u0026nbsp;nosocomial infections, days, mean\u0026plusmn;SD\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.1336%;\"\u003e\n \u003cp\u003e7.1\u0026plusmn;2.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.0361%;\"\u003e\n \u003cp\u003e4.8\u0026plusmn;2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.1083%;\"\u003e\n \u003cp\u003e0.015\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50.722%;\"\u003e\n \u003cp\u003eHours on mechanical ventilation,\u0026nbsp;days, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.1336%;\"\u003e\n \u003cp\u003e0(0, 3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.0361%;\"\u003e\n \u003cp\u003e0(0, 0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.1083%;\"\u003e\n \u003cp\u003e0.208\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50.722%;\"\u003e\n \u003cp\u003eGlasgow Coma Scale at discharge, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.1336%;\"\u003e\n \u003cp\u003e11(9.25, 14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.0361%;\"\u003e\n \u003cp\u003e12(10, 15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.1083%;\"\u003e\n \u003cp\u003e0.668\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50.722%;\"\u003e\n \u003cp\u003eNIHSS at discharge, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.1336%;\"\u003e\n \u003cp\u003e15(11.5, 19.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.0361%;\"\u003e\n \u003cp\u003e14.5(11, 22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.1083%;\"\u003e\n \u003cp\u003e0.956\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50.722%;\"\u003e\n \u003cp\u003eModified Rankin Scale at discharge, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.1336%;\"\u003e\n \u003cp\u003e5(4, 5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.0361%;\"\u003e\n \u003cp\u003e4(4, 5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.1083%;\"\u003e\n \u003cp\u003e0.251\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50.722%;\"\u003e\n \u003cp\u003eDays in ICU, days, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.1336%;\"\u003e\n \u003cp\u003e14.5(10, 19.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.0361%;\"\u003e\n \u003cp\u003e11(8, 14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.1083%;\"\u003e\n \u003cp\u003e0.081\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50.722%;\"\u003e\n \u003cp\u003emortality in ICU, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.1336%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.0361%;\"\u003e\n \u003cp\u003e2(5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.1083%;\"\u003e\n \u003cp\u003e0.799\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50.722%;\"\u003e\n \u003cp\u003eDeath at day 90, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.1336%;\"\u003e\n \u003cp\u003e1(5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.0361%;\"\u003e\n \u003cp\u003e5(12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.1083%;\"\u003e\n \u003cp\u003e0.648\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 50.722%;\"\u003e\n \u003cp\u003ePoor outcome at day 90, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 19.1336%;\"\u003e\n \u003cp\u003e19(95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20.0361%;\"\u003e\n \u003cp\u003e38(95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.1083%;\"\u003e\n \u003cp\u003e\u0026gt;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eSPN, supplemental parenteral nutrition; EN, enteral nutrition; NIHSS, National Institutes of Health Stroke Scale. \u003csup\u003e*\u003c/sup\u003e Other infection included infections of abdominal, bloodstream, skin, bone, soft tissue, ear, nose, throat, upper respiratory, and non-pulmonary intrathoracic.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSafety outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe rate of\u0026nbsp;digestive intolerance\u0026nbsp;events\u0026nbsp;were\u0026nbsp;similar in the SPN group compared to the EN group (40% vs.\u0026nbsp;52.5%, \u003cem\u003eP\u003c/em\u003e=0.361). The incidence of cerebral herniation, heart failure, respiratory failure, renal failure, sepsis or septic shock were similar between both groups. The results were shown in \u003cstrong\u003eTable S\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe found that the nutritional support with EN plus early SPN approach in patients with acute severe stroke could significantly delay the time to new-onset pneumonia or new-onset nosocomial infections compared to those with full EN approach. With the extension of hospital stay, the cumulative probability of infections became similarly between the two groups. Our result highlights the potential value of EN plus early SPN nutritional strategy for patients with acute severe stroke on mitigating infection at early phase after admission.\u003c/p\u003e \u003cp\u003ePreviously, the FOOD study has found that early feeding reduced mortality of stroke patients with dysphagia[16]. Meanwhile, results from the OPENS trial suggest that hypocaloric feeding during the acute phase of severe stroke might be associated with increased mortality[17]. Despite the benefits and widespread use of enteral tube feeding, some patients may experience complications leading to feeding interruption and calorie deficits, such as feeding intolerance, the performance of diagnostic or therapeutic procedures, tube displacement and clinical neglect[18, 19]. Therefore, it is a crucial clinical issue to find optimal feeding strategies and avoid inadequate energy supply.\u003c/p\u003e \u003cp\u003ePneumonia is a frequent clinical complication after stroke, which is closely related to the stroke severity[20]. A previous study showed that pneumonia complicated stroke in 47% of 55 critically ill patients[21], aged 33 to 91 (median 74) years, median baseline NHISS score was 18, while another study found that among stroke patients with a median baseline NIHSS score of 7.8, the incidence of pneumonia within 7 days of admission was 7.4%[22]. Patients enrolled in our study were similar in age and have similarly high baseline NIHSS score (median baseline NIHSS 17.5) comparing with the two studies, making a high overall incidence of pneumonia.\u003c/p\u003e \u003cp\u003eSo far, there is no uniform feeding regimen for PN feeding, and its effectiveness is controversial. Previous trials have provided that no difference between the patients receiving PN or EN in terms of 30-day mortality, number of infectious complications, or the rate of various adverse events[23]. The latest study proved that individually optimised energy supplementation with SPN starting 4 days after ICU admission could reduce nosocomial infections[10]. In this study, some patients developed fever, accompanying with increased inflammatory mediators within 48 hours after admission. Considering the combination of disturbance of consciousness and high aspiration risk, we chose the modified SPN nutritional approach. The time of parenteral nutrition initiation in the SPN group was 2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6 days after admission. Similar to the above trials, PN was early-activated in our study. However, the population in our study were severe stroke adults and PN feeding was added obviously to reduce the risk of pneumonia in the SPN group in conjunction with the usage of EN. There were no significant differences in nutrient supply and blood glucose between the two groups, indicating that SPN is effective and feasible.\u003c/p\u003e \u003cp\u003eStroke severity and system condition in both groups were similar except for some laboratory baseline data. It has been well documented that post-stoke inflammation plays an important role in various stages of stroke. Neutrophil to Lymphocyte Ratio (NLR) as a newfound biomarker in systematic inflammation was proved to possess predictive capabilities in PSP recently[24]. The results showed that serum Leukocyte, Neutrophil (NEU) and NLR in the SPN group were significantly increased, suggesting that these patients may have a higher risk of pneumonia through clinical assessment by clinicians, and early SPN administration reflects a genuine clinical decision. Our results showed that the incidence of new-onset pneumonia was similar between the two groups within 7 days of hospitalization. Our findings are consistent with a randomised trial which included ICU critically ill patients [25], but are inconsistent with another study [10]. The following reasons could account for this inconsistency. The population in our study are severe stroke patients with a high incidence of pneumonia and respiratory failure, and they may benefit more through optimized feeding methods, but considering the small sample size, the difference cannot be reflected. Meanwhile, the mean age of the patients was nearly 70 years old, which was older than in previous studies (mean age was 60 years), and the patients all had serious clinical scores at admission. Advanced age and stroke severity were risk factors for PSP. In such patients, the overall incidence of pneumonia was increased, and the heterogeneity of critically ill patients was high, while it was difficult to show a significant difference consequently. Compared to the full EN strategy, the EN plus early SPN strategy had delayed onset of infection, while had similar cumulative incidence during hospitalization. It is rarely discussed in previous articles, and might be explained by that nutritional supply pathway may not a determining factor for pneumonia and infections in acute severe stroke patients. There were no differences in duration of mechanical ventilation, average length of stay in ICU, or ICU mortality between the two groups, which is consistent with a randomized controlled trial (ICU critically ill patients)[10] and a review[26]. It is suggested that SPN is safe for usage in these patients, although no efficacy for long-term prognosis has been found.\u003c/p\u003e \u003cp\u003eSeveral potential limitations need to be taken into account. First, our study was designed as a retrospective study with a limited sample size and relatively low statistical power. With our strict inclusion criteria as well as the case-control 1:2 matching, it could represent the broader populations of patients with severe stroke. Therefore, our results deserve close clinical attention and needs to be further validation through a prospective, randomized controlled study. Second, the EN or PN regimens given to the patients were not the same specific formulations. Although, it could potentially confound the effects on inflammatory mediators, laboratory results, gastrointestinal tolerance and clinical outcomes, this approach was pragmatic in real-world medical practice. Finally, the clinical diagnosis of new-onset pneumonia and nosocomial infection is a comprehensive judgment made by physicians based on clinical manifestations and auxiliary examinations, which largely depends on the accuracy and integrity of medical documents. It may result in certain information bias, but the two groups remain homogenous.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe nutritional strategy with EN plus early SPN might be an alternative choice to full EN strategy for patients with acute severe stroke, especially for those with high risk of nosocomial infection. Further studies with larger sample sizes are needed to explore the effect of SPN on infection-related complications and functional outcome for patients with acute severe stroke.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eNICU, Neurology intensive care unit; EN, Enteral nutrition; PN, Parenteral nutrition; SPN, Supplemental parenteral nutrition; NIHSS, National Institutes of Health Stroke Scale; GCS, Glasgow Coma Scale; mRS, modified Rankin Scale score; NRS-2002, Nutrition Risk Screening 2002; PSP, Post-stroke pneumonia; BMI, Body mass index; IQR, interquartile range; NLR, Neutrophil to Lymphocyte Ratio; NEU, Neutrophil; LYM, Lymphocyte; PCT, Procalcitonin.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe procedures of this study were approved by the ethics committee of Xijing Hospital (KY20182024-F-1) and adhered to the Helsinki Declaration.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient consent statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from the patients or their guardians.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors agree to publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the Funding Key Research and Development Project of Shaanxi Province (No.2020SF-306) and the Xijing Hospital Clinical Application Research Program\u0026nbsp;(No. JSYXM03).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest disclosure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eF.Y. and W.J. designed the study. C.M., B.L, and X.K. collected the data. C.M., Z.F., and X.W. analyzed the data. J.Z. and X.K. revised the statistical analyses. C.M. and Z.F. wrote the manuscript. F.Y. and W.J. revised the manuscript. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLuengo-Fernandez R, Paul NL, Gray AM, Pendlebury ST, Bull LM, Welch SJ, Cuthbertson FC, Rothwell PM. Population-based study of disability and institutionalization after transient ischemic attack and stroke: 10-year results of the Oxford Vascular Study. \u003cem\u003eSTROKE\u003c/em\u003e 2013, 44(10):2854-2861.\u003c/li\u003e\n\u003cli\u003eBanda KJ, Chu H, Kang XL, Liu D, Pien LC, Jen HJ, Hsiao SS, Chou KR. Prevalence of dysphagia and risk of pneumonia and mortality in acute stroke patients: a meta-analysis. \u003cem\u003eBMC GERIATR\u003c/em\u003e 2022, 22(1):420.\u003c/li\u003e\n\u003cli\u003eKoennecke HC, Belz W, Berfelde D, Endres M, Fitzek S, Hamilton F, Kreitsch P, Mackert BM, Nabavi DG, Nolte CH\u003cem\u003e et al\u003c/em\u003e. Factors influencing in-hospital mortality and morbidity in patients treated on a stroke unit. \u003cem\u003eNEUROLOGY\u003c/em\u003e 2011, 77(10):965-972.\u003c/li\u003e\n\u003cli\u003eWestendorp WF, Nederkoorn PJ, Vermeij JD, Dijkgraaf MG, van de Beek D. Post-stroke infection: a systematic review and meta-analysis. \u003cem\u003eBMC NEUROL\u003c/em\u003e 2011, 11:110.\u003c/li\u003e\n\u003cli\u003eBurgos R, Breton I, Cereda E, Desport JC, Dziewas R, Genton L, Gomes F, Jesus P, Leischker A, Muscaritoli M\u003cem\u003e et al\u003c/em\u003e. ESPEN guideline clinical nutrition in neurology. \u003cem\u003eCLIN NUTR\u003c/em\u003e 2018, 37(1):354-396.\u003c/li\u003e\n\u003cli\u003ePowers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B\u003cem\u003e et al\u003c/em\u003e. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. \u003cem\u003eSTROKE\u003c/em\u003e 2019, 50(12):e344-e418.\u003c/li\u003e\n\u003cli\u003eHannawi Y, Hannawi B, Rao CP, Suarez JI, Bershad EM. Stroke-associated pneumonia: major advances and obstacles. \u003cem\u003eCEREBROVASC DIS\u003c/em\u003e 2013, 35(5):430-443.\u003c/li\u003e\n\u003cli\u003eUozumi M, Sanui M, Komuro T, Iizuka Y, Kamio T, Koyama H, Mouri H, Masuyama T, Ono K, Lefor AK. Interruption of enteral nutrition in the intensive care unit: a single-center survey. \u003cem\u003eJ Intensive Care\u003c/em\u003e 2017, 5:52.\u003c/li\u003e\n\u003cli\u003eDoig GS, Simpson F, Sweetman EA, Finfer SR, Cooper DJ, Heighes PT, Davies AR, O\u0026apos;Leary M, Solano T, Peake S. Early parenteral nutrition in critically ill patients with short-term relative contraindications to early enteral nutrition: a randomized controlled trial. \u003cem\u003eJAMA\u003c/em\u003e 2013, 309(20):2130-2138.\u003c/li\u003e\n\u003cli\u003eHeidegger CP, Berger MM, Graf S, Zingg W, Darmon P, Costanza MC, Thibault R, Pichard C. Optimisation of energy provision with supplemental parenteral nutrition in critically ill patients: a randomised controlled clinical trial. \u003cem\u003eLANCET\u003c/em\u003e 2013, 381(9864):385-393.\u003c/li\u003e\n\u003cli\u003eCasaer MP, Mesotten D, Hermans G, Wouters PJ, Schetz M, Meyfroidt G, Van Cromphaut S, Ingels C, Meersseman P, Muller J\u003cem\u003e et al\u003c/em\u003e. Early versus late parenteral nutrition in critically ill adults. \u003cem\u003eN Engl J Med\u003c/em\u003e 2011, 365(6):506-517.\u003c/li\u003e\n\u003cli\u003eSena MJ, Utter GH, Cuschieri J, Maier RV, Tompkins RG, Harbrecht BG, Moore EE, O\u0026apos;Keefe GE. Early supplemental parenteral nutrition is associated with increased infectious complications in critically ill trauma patients. \u003cem\u003eJ Am Coll Surg\u003c/em\u003e 2008, 207(4):459-467.\u003c/li\u003e\n\u003cli\u003eBadve MS, Zhou Z, van de Beek D, Anderson CS, Hackett ML. Frequency of post-stroke pneumonia: Systematic review and meta-analysis of observational studies. \u003cem\u003eINT J STROKE\u003c/em\u003e 2019, 14(2):125-136.\u003c/li\u003e\n\u003cli\u003eKalil AC, Metersky ML, Klompas M, Muscedere J, Sweeney DA, Palmer LB, Napolitano LM, O\u0026apos;Grady NP, Bartlett JG, Carratala J\u003cem\u003e et al\u003c/em\u003e. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. \u003cem\u003eCLIN INFECT DIS\u003c/em\u003e 2016, 63(5):e61-e111.\u003c/li\u003e\n\u003cli\u003eHoran TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. \u003cem\u003eAM J INFECT CONTROL\u003c/em\u003e 2008, 36(5):309-332.\u003c/li\u003e\n\u003cli\u003eDennis MS, Lewis SC, Warlow C. Effect of timing and method of enteral tube feeding for dysphagic stroke patients (FOOD): a multicentre randomised controlled trial. \u003cem\u003eLANCET\u003c/em\u003e 2005, 365(9461):764-772.\u003c/li\u003e\n\u003cli\u003eZhao J, Yuan F, Song C, Yin R, Chang M, Zhang W, Zhang B, Yu L, Jia Y, Ma Y\u003cem\u003e et al\u003c/em\u003e. Safety and efficacy of three enteral feeding strategies in patients with severe stroke in China (OPENS): a multicentre, prospective, randomised, open-label, blinded-endpoint trial. \u003cem\u003eLANCET NEUROL\u003c/em\u003e 2022, 21(4):319-328.\u003c/li\u003e\n\u003cli\u003eBlumenstein I, Shastri YM, Stein J. Gastroenteric tube feeding: techniques, problems and solutions. \u003cem\u003eWorld J Gastroenterol\u003c/em\u003e 2014, 20(26):8505-8524.\u003c/li\u003e\n\u003cli\u003eHeyland DK, Dhaliwal R, Wang M, Day AG. The prevalence of iatrogenic underfeeding in the nutritionally \u0026apos;at-risk\u0026apos; critically ill patient: Results of an international, multicenter, prospective study. \u003cem\u003eCLIN NUTR\u003c/em\u003e 2015, 34(4):659-666.\u003c/li\u003e\n\u003cli\u003eFinlayson O, Kapral M, Hall R, Asllani E, Selchen D, Saposnik G. Risk factors, inpatient care, and outcomes of pneumonia after ischemic stroke. \u003cem\u003eNEUROLOGY\u003c/em\u003e 2011, 77(14):1338-1345.\u003c/li\u003e\n\u003cli\u003eUpadya A, Thorevska N, Sena KN, Manthous C, Amoateng-Adjepong Y. Predictors and consequences of pneumonia in critically ill patients with stroke. \u003cem\u003eJ CRIT CARE\u003c/em\u003e 2004, 19(1):16-22.\u003c/li\u003e\n\u003cli\u003eWeimar C, Roth MP, Zillessen G, Glahn J, Wimmer ML, Busse O, Haberl RL, Diener HC. Complications following acute ischemic stroke. \u003cem\u003eEUR NEUROL\u003c/em\u003e 2002, 48(3):133-140.\u003c/li\u003e\n\u003cli\u003eHarvey SE, Segaran E, Leonard R. Trial of the route of early nutritional support in critically ill adults. \u003cem\u003eN Engl J Med\u003c/em\u003e 2015, 372(5):488-489.\u003c/li\u003e\n\u003cli\u003eKhanzadeh S, Lucke-Wold B, Eshghyar F, Rezaei K, Clark A. The Neutrophil to Lymphocyte Ratio in Poststroke Infection: A Systematic Review and Meta-Analysis. \u003cem\u003eDIS MARKERS\u003c/em\u003e 2022, 2022:1983455.\u003c/li\u003e\n\u003cli\u003eBauer P, Charpentier C, Bouchet C, Nace L, Raffy F, Gaconnet N. Parenteral with enteral nutrition in the critically ill.\u003cem\u003e Intensive Care Med\u003c/em\u003e 2000, 26(7):893-900.\u003c/li\u003e\n\u003cli\u003eSharma SK, Rani R, Thakur K. Effect of Early Versus Delayed Parenteral Nutrition on the Health Outcomes of Critically Ill Adults: A Systematic Review. \u003cem\u003eJ Crit Care Med (Targu Mures)\u003c/em\u003e 2021, 7(3):160-169.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Acute severe stroke, Supplemental parenteral nutrition, Enteral nutrition, New-onset pneumonia, New-onset nosocomial infections, Case-control study","lastPublishedDoi":"10.21203/rs.3.rs-5132498/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5132498/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Early adequate feeding reduces the mortality in patients with acute severe stroke. Supplemental parenteral nutrition (SPN) may address enteral nutrition (EN) deficiency and mitigate the risk of nosocomial infection. The benefit of EN plus early SPN strategy over full EN strategy is unknown in acute severe stroke.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: We retrospectively enrolled 20 patients with acute severe stroke in SPN group who received EN plus early SPN (more than 50% of energy target within 72h after admission). Forty control cases in the EN group who received full EN were matched by age, sex and lesion site. Time to new-onset pneumonia or nosocomial infections were analyzed by Student’s t-test and Breslow generalized Wilcoxon test.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Baseline characteristics were major similar between matched groups, while patients in the SPN group had higher level of serum leukocyte, neutrophil and neutrophil to lymphocyte ratio (P\u0026lt;0.05). Compared to the EN group, the time to new-onset pneumonia was significantly delayed in the SPN group (7.6 days vs. 5.2 days; mean difference, 2.5 days; 95%CI, 0.65 to 4.31, P=0.009), as well as the time to new-onset nosocomial infections (7.1 days vs. 4.8 days; mean difference, 2.3 days; 95%CI, 0.46 to 4.07, P=0.015). Kaplan–Meier analysis showed similar cumulative probability of new-onset pneumonia or new-onset nosocomial infections in the two groups (P\u0026gt;0.05). The rate of digestive intolerance events between the two groups were similar (40% in the SPN group vs 52.5% in the EN group, P=0.361).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: In patients with acute severe stroke, the application of EN plus early SPN could delay the onset of pneumonia and nosocomial infections especially at early phase.\u003c/p\u003e","manuscriptTitle":"Effects of early supplemental parenteral nutrition on new-onset infection in adults with acute severe stroke: A single-center retrospective case-control study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-10 13:49:26","doi":"10.21203/rs.3.rs-5132498/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-09-23T11:57:55+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-09-23T11:17:56+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-09-23T11:16:49+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2024-09-22T12:51:19+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"21e9a830-5030-45a5-8462-60de8e3b8df3","owner":[],"postedDate":"November 10th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-02-03T16:09:28+00:00","versionOfRecord":{"articleIdentity":"rs-5132498","link":"https://doi.org/10.1186/s12883-025-04050-6","journal":{"identity":"bmc-neurology","isVorOnly":false,"title":"BMC Neurology"},"publishedOn":"2025-01-31 15:57:34","publishedOnDateReadable":"January 31st, 2025"},"versionCreatedAt":"2024-11-10 13:49:26","video":"","vorDoi":"10.1186/s12883-025-04050-6","vorDoiUrl":"https://doi.org/10.1186/s12883-025-04050-6","workflowStages":[]},"version":"v1","identity":"rs-5132498","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5132498","identity":"rs-5132498","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}