Gender differences in Nutritional Status, Food consumption and Oxidative Stress in Post-Stroke patients during Rehabilitation

doi:10.21203/rs.3.rs-3251950/v1

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Gender differences in Nutritional Status, Food consumption and Oxidative Stress in Post-Stroke patients during Rehabilitation

https://doi.org/10.21203/rs.3.rs-3251950/v1

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Objectives

This study aimed to clarify the gender differences in nutritional status, food consumption and oxidative stress and in post-stroke patients during rehabilitation treatment.

Design

A longitudinal observational study.

Methods

Patients with first stroke were sequentially enrolled, evaluated at admission (T0), and again after a 6-week rehabilitation program (T1). The rehabilitation regimen included traditional and robotic physical therapy. Functional independence in Activity of Daily Living (ADL) was evaluated with modified Barthel Index assesment (mBI T0 and mBI T1) and calculating its change after rehabilitation (∆BI= mBIT1- mBI T0). Patients were screened for malnutrition at admission, following the GLIM criteria, by the Mini Nutritional Assessment Short-form (MNA-SF®) and the assessment of the nutritional status during the study was performed by means of: i) anthropometric measurements ii) the Geriatric Nutritional Risk assessment (GNRI), and iii) daily estimation of food consumption (plate waste). An Analysis of blood parameters at T0 and at T1 was performed including: albumin, glucose, lipidic panel, calcium, magnesium and iron. Systemic Oxidative stress status was evaluated at T0 and at T1 measuring: hydroperoxides (dROMs), total antioxidants (BAP), thiols (-SHp) and calculating the antioxidant capacity (OSI index).

Results

We finally included 87 patients in this study (42 women, 45 men mean age 69 ± 12 years). The sample was homogeneous and the whole group was at highly risk of malnutrition at admission with 44 subjects clearly malnurished (score lower than 7). Women wasted 23% of total plate consumed respect to 17% wasted from men. Hydroperoxides levels were very high in the whole groupat T0 and T1, but men after rehabilitation had lower values of dROMs, while women did not. Men reached higher value of mBI T1 respect to women (67.1 ± 21.9 vs 55.3 ±26.1; p = 0.032), moreover only 36% of women ameliorated their mBI of at least ten point, respect to 64% of men. MNA-SF® correlated with mBI T0, mBI T1 and ∆BI, but in women this correlation was higher [mBI T0 (rho = 0.506 p<0.001); with mBI T1 (rho = 0.527; p<0.001); with ∆BI (rho = 0.394; p = 0.001)], suggesting a relationship between their nutritional status at admission and their performance in functional recovery.

Conclusions.

Among subacute post stroke patients hospitalized for rehabilitation treatment, women appeared to have lower rehabilitation outcome, to waste more food and to have higher oxidative stress even after six-week of hospitalization. So, especially in consideration of the advanced age, women should be carefully monitored forn nutritional status during hospitalization for rehabilitation; future studies should clarify if a better nutrition, which includes the right dose of antioxidants, can improve their recovery after stroke.

post-stroke

rehabilitation

malnutrition

gender

oxidative stress

Stroke is the leading cause of adult disability (1, 2) and the second leading cause of death worldwide, imposing significant burden on patients, their families, and healthcare systems. Approximately 75% of all strokes occur in persons aged ≥ 65 years. The incidence of strokes in older persons is expected to climb as the number of people aged 65 years grows, posing considerable difficulties for physicians and policymakers in the near future (3).

Each year, 53% of all strokes occur in women, and globally, women account for just over half (56%) of all persons who have experienced stroke; the incidence and prevalence of ischemic stroke is higher in women (55% and 57%, respectively) (3).

Gender differences have practical implication not only in stroke risk, due to different pathophysiology between two sex, but also in management of acute phase, in treatment and in post-acute care (4). Women are 5-years older, experiment more pre-stroke disability, and suffer more of atrial fibrillation; have stronger association with obesity, and have higher risk with hypertension after controlling for anti-hypertensives, have also higher risk with unique hormonal factors (4, 5).

Recent literature investigated with more interest gender differences in the rehabilitation outcome after stroke. A better recovery in men in terms of Activity of daily living performance was found (6–9); one interesting study, showed that, when each individual functional independence measure item is considered separately, females do as well or better than males on most items (10). Other studies showed no gender differences measuring disability (11, 12) while older women showed a better functional recovery (13).

Nutritional impairment is a common risk for stroke survivors, and malnutrition has been identified as a recurrent complication, correlating with poor daily living function and scarce quality of life (14–16). Dysphagia, restricted upper limb movement, visuospatial impairment, increased catabolic processes, gastrointestinal dysfunction and depression are stroke-related conditions that may enhance malnutrition (17, 18).

Despite the significant frequency of malnutrition among post-stroke patients, very few studies have been carried out on the impact of nutrition on rehabilitation outcomes (19–23).

One particular aspect of nutritional status is the systemic oxidative stress which is a significant contributors to brain damage following stroke (24). High levels of peroxides, if not sufficiently counteracted by endogenous or exogenous -dietary- antioxidants can generate a condition of general cellular damage, and can be even responsible of other stroke events (25).

Oxidative stress levels has been found very elevated in post-stroke patients in the acute phase (26–28) and in the subacute phase(29, 30); another study showed that patients admitted to a rehabilitation centre showed very high levels of oxidative stress status with female group showing lower antioxidant reservoirs (31).

Malnutrition is frequently undiagnosed and untreated not only during hospitalization for acute treatment (32) but also throughout or after rehabilitation following a stroke (33). Oxidative distress could be strictly dependent from a not adequate nutrition. Moreover, rehabilitation outcomes depend on nutritional status and body composition, and could be influenced by the presence or not of sarcopenia (20, 21, 24, 34–40).

To our knowledge, there are no studies examining gender differences in nutritional status together with oxidative stress in relation to recovery in post-stroke subjects during rehabilitation. So, the aim of this study is to investigate this topic in a cohort of post-stroke patients during a 6-week rehabilitation treatment assessing: i) the nutritional status and systemic oxidative stress at admission and after rehabilitation treatment; ii) the food waste during the rehabilitation treatment iii) the rehabilitation outcome and its correlation with nutritional and systemic oxidative stress parameters.

2.1. Study Design and Participants

This longitudinal, prospective study analyzed a cohort of patients admitted to our rehabilitation department between September 2020 and April 2023 (NUTRISTROKE study, clinical trials identifier: NCT04923165).

Patients with first stroke were sequentially enrolled, evaluated at admission (T0), and again after a 6-week rehabilitation program (T1).

The following criteria were used to include the patients: i) first ischemic or hemorrhagic stroke, confirmed by magnetic resonance imaging (MRI) or computed tomography (CT); iii) age between 18 and 85; iii) less than six months since the stroke insult; iv) adequate cognitive and language abilities to comprehend the instructions for administering the assessment scales and to sign the informed consent.

Patients were excluded following these criteria: i) a previous stroke; ii) behavioral and cognitive disorders and/or reduced compliance interfering with active therapy or with understanding and signing informed consent.

The study design was approved by the Ethical Committee of Don Carlo Gnocchi Foundation, Milan, Italy on October 14, 2020 (FDG_6_14/10/20). All patients gave their written informed permission after being fully informed about the study's objectives and treatment procedures.

2.2. Rehabilitation treatment

Patients completed a rehabilitation regimen that included traditional physical therapy, which was carried out for 45 minutes each day, six days a week. The rehabilitation treatment consisted in: passive, active-assisted and active mobilizations, exercises for muscle strength recovery, stretching, functional and task-oriented training), proprioceptive exercises, postural passages and transfers, sitting and standing training, motor coordination and balance training, walking training and activities of daily living recovery training. Additionally, utilizing a set of robotic devices, each patient underwent robotic treatment of the upper limb five times each week for 45 minutes at a time. The following robotic devices were employed: Motore (Humanware Srl, Pisa, Italy), Amadeo, Diego, and Pablo (Tyromotion GmBH, Graz, Austria) as detailed in previous studies (Aprile et al. 2019; 2020). Patients through upper limb robotic therapy conducted both motor and cognitive tasks, with the aid of visual and audible input from the equipment.

2.3. Clinical assessment and Activity of daily living assessment

We recorded demographic, anamnestic, and clinical data at admission (T0). Disease Burden was measured with the 56-point Cumulative Illness Rating Scale (CIRS) (41).

Functional independence was assessed, both at admission and after 6 weeks of rehabilitation treatment (T1), in order to assess the effect of the rehabilitation treatment. The Modified Barthel Index (BI) was employed, which is an ordinal scale used to measure performance in Activity of Daily Living (ADL) (42). The presence of dysphagia was recorded at T0, without describing the severity; patients enrolled were able to feeding themselves.

2.4. Malnutritional risk screening, nutritional status and sarcopenia assesment

Patients were screened at T0 for risk of malnutrition, according to GLIM criteria (43) by the Mini Nutritional Assessment Short-form (MNA-SF®), a simple, quick and easy nutritional tool based on the full-Mini Nutritional Assessment (full MNA®). MNA-SF® includes six geriatric-specific assessment question related to nutritional and health condition. Patients were considered at “normal nutritional status” if MNA-SF® screening score’s values was from 12 to 14, at “risk of malnutrition” with values between 8 and 12, and “malnourished” with score less than 7.

The assessment of the nutritional status during the study was performed by means of: i) anthropometric measurements ii) the Geriatric Nutritional Risk (GNRI), and iii) daily estimation of food consumption (plate waste), as described in detail previously (20). The average percentage of plate waste was calculated for all meals consumed in a day, for Italian first dish, that consists essentially in carbohydrates and for Italian second dish, that consists of protein.

Diagnosis of sarcopenia was done on the basis of European Working Group on Sarcopenia in Older People revised guideline (EWGSOP2) (44) and following the procedure described in previously (20).

2.2 Biochemical analyses

The blood samples of patients were collected in the early morning (7:30–9:00 a.m.) after an overnight fast to standardize the assessment of those biochemical variables that are affected by the circadian cycle and food intake. Sera samples were separated by centrifugation (3,000 rpm, 10 min, and 4°C), divided into 0.5 mL aliquots and rapidly stored at -80°C. Subjects’ and reference samples were thawed just before the assays. All the analyses were performed in duplicate both at T0 and at T1 and tested on an integrated analytical photometer (Free Carpe Diem, Diacron, GR, Italy).

2.2.1 Hematochemical analysis

Albumin levels were measured by bromocresol colorimetric assay (Diacron, GR, Italy) (45); glucose was assessed by an oxidase/peroxidase system (46). Total cholesterol was measured by means of oxidation from a cholesteroxidase to cholest-4-en-3-one (47) while Direct HDL Cholesterol assessed by a transformation of the HDL portion into a quinone derivative, read at 600 nm (48); triglycerides was measured by a peroxidase-coupled method (49). Calcium was analyzed using a non-radioactive method based on the o-cresolpthalein complexone test (50) while Magnesium was assessed using a direct colorimetric assay based on the xylidyl Blue-I method (51). Serum Iron levels were measured by a colorimetric assay based on Ferene S (52).

2.2.1 Oxidative stress analysis

The colorimetric determination of Hydroperoxides content (ROOH, principally) was assessed by d-ROMs test (Diacron, GR, Italy). The values are expressed in arbitrary units (UCARR), 1 UCARR corresponding to 0.08 mg/100 mL of hydrogen peroxide (53). Reference values are between 250–300 UCARR, while 301–320 UCARR is considered border-line range, 321–340 UCARR low level oxidative stress, 341–400 UCARR middle level of oxidative stress, 401–500 UCARR high level of oxidative stress and > 500 UCARR very high level of oxidative stress (Diacron, GR, Italy).

The global antioxidant defenses, as for endogenous and exogenous molecules present in plasma, was measured by BAP test (Diacron, GR, Italy). Reference values in µmol/L of antioxidants is > 2200, 2200 − 2000 is a border line status, 2000 − 1800 is considered slight deficiency status, 1800 − 1600 deficiency status, 1600 − 1400 high deficiency status while < 1400 is a very high deficiency status condition (Diacron, GR, Italy).

The antioxidative/oxidative stress ratio was also calculated using the ratio equation: BAP/d-ROMs (54). The criterion value for the BAP/d-ROMs ratio was set at 7.3; a value lower than 7.3 was defined as an oxidized type and a higher or equal one as a reduced type (31).

Moreover, we tested a significant component of antioxidant plasma barrier, The thiol groups of plasma compounds with -SHp test (Diacron, GR, Italy), as for the Ellman method (55).

2.6. Statistical analysis

Descriptive statistics were used to express demographic and clinical characteristics of patients, with numerical data expressed as mean (SD), and categorical data presented as counts and percentages. To compare demographic and clinical characteristics in women and man as well as the nutritional status variables, and the biochemical and oxidative stress variables, both at T0 and at T1 we used the Mann-Whitney U test, or the chi-squared test, as appropriate. The difference between ADL value (mBI) between admission and discharge were investigated with the Wilcoxon signed rank test, in the whole group, in women and in men. After treatment, patients were classified as responders if the change from baseline of the modified Barthel Index (ΔBI = BIT1 − BIT0) was higher than 10 points; otherwise, they were classified as non-responders. This threshold was detected in our sample, using the approach previously described (56). Chi-squared test was employed to analyze the distribution of patients with better recovery between two sexes

The correlation of nutritional status parameters, as well as oxidative stress parameters with the functional status, as measured by the mBI both at T0, at T1 and change from baseline of the modified Barthel Index (ΔBI) was investigated using the Spearman’s rank correlation coefficients.

For all the statistical analysis, a p value lower than 0.05 was deemed significant. Statistical analysis was performed using IBM SPSS Statistics for Windows (Version 28.0. Armonk, NY: IBM Corp).

3.1. Participants and baseline characteristics

We screened 140 patients and 91 met the inclusion criteria and were enrolled in the study; 4 patients did not complete the follow up due to clinical adverse conditions. Finally, 87 patients (42 women, 45 men mean age 69 ± 12 years); were evaluated both at baseline (T0) and after a six-weeks rehabilitation treatment (T1).

Baseline characteristics (demographic and clinical features, disability assessment) are reported for the whole group, for women and for men in Table 1. The sample was homogeneous, a part for a difference in distribution of prior heart attack and thyroid disease between two sex.

Table 1

Baseline characteristics of the whole sample (n = 87) and distinguished for women (n = 42) and men (n = 45). Data are reported in mean ± standard deviation or number and percentage (%). P values refer to Mann-Whitney U-test dividing sample by gender.
Baseline Characteristics	Whole group (n = 87)	Women (n = 42)	Men (n = 45)	P value
Age (years)	69 ± 12	71 ± 9	66 ± 13	0.110
Index stroke type
Ischemic	66 (76%)	33 (79%)	33 (73%)	0.568
Hemorrhagic	21 (24%)	9 (21%)	12 (27%)
Affected side
Right	43 (49%)	21 (49%)	22 (51%)	0.918
Days from stroke onset to enrollment	105 ± 52	114 ± 57	96 ± 47	0.136
Neglect	16 (19%)	11 (27%)	5 (27%)	0.061
Aphasia global	6 (7%)	5 (12%)	1 (2%)	0.129
Smokers and former smokers	45 (54%)	18 (46%)	27 (61%)	0.165
Dysphagia	29 (33%)	16 (38%)	16 (30%)	0.363
Comorbidities
Hypertension	74 (85%)	35 (83%)	39 (87%)	0.663
Type 2 Diabetes	26 (30%)	11 (26%)	15 (33%)	0.467
Dyslipidemia	37 (43%)	18 (42%)	19 (42%)	0.952
Prior heart attack	4 (5%)	0 (0%)	4 (9%)	0.048^*
Congestive heart failure	10 (12%)	3 (7%)	7 (16%)	0.219
Atrial fibrillation	12 (14%)	7 (17%)	5 (11%)	0.453
Prior Cancers	8 (9%)	4 (10%)	4 (9%)	0.918
Peripheral vascular disease (PVD)	24 (28%)	11 (26%)	13 (29%)	0.778
Chronic Obstructive Pulmonary Disease (COPD)	10 (12%)	5 (12%)	5 (11%)	0.908
Thyroid Disease	19 (22%)	13 (91%)	6 (13%)	0.047^*
More than 2 comorbidities	86 (98%)	41 (98%)	45 (100%)	0.298
Cumulative Illness Rating Scale (CIRS)
CIRS severity	2.3 ± 0.4	2.3 ± 0.3	2.3 ± 0.4	0.309
CIRS comorbidity	5.7 ± 1.7	5.7 ± 1.7	5.6 ± 1.8	0.570
Sarcopenia	24 (28%)	14 (33%)	10 (44%)	0.247
Activities of daily living (ADL) Assessment
Modified Barthel Index (0–100)	45 ± 20	49 ± 21	41 ± 17	0.144
* p-value < 0.05;

3.2. Nutritional and oxidative stress status

All subjects were found to be at highly risk of malnutrition, as assessed by the MNA-SF® questionnaire (Table 2). In particular 44 subjects were clearly malnourished (score lower than 7), with women that showed a higher tendency even if not significant (55% of malnourished women, respect to a 47% of men).

Table 2

Nutritional risk screening, nutritional assessment, plate waste estimation and hematochemical parameters of the whole group, and distinguished for women and men: at admission (T0) and after the rehabilitation treatment (T1). P values refer to Mann-Whitney U-test dividing sample by gender.
	Whole group (n = 87)	Women (n = 42)	Men (n = 45)	P value
Mini Nutritional Assessment Short-Form (MNA-SF®) MNA-SF® ≤7	7 ± 2 44 (51%)	7 ± 2 23 (55%)	8 ± 2 21(47%)	0.592 0.450
Plate Waste of all meal (average %)	20 ± 15	23 ± 13	17 ± 17	0.011*
Plate Waste of italian first dish (carbohidrates) (average %)	22 ± 20	26 ± 19	17 ± 19	0.005**
Plate Wasteof italian second dish (protein) (average %)	20 ± 17	24 ± 15	15 ± 17	0.003**
Anthropometric measure
Height (m)	1.66 ± 0.11	1.61 ± 0.07	1.71 ± 0.11	< 0.001***
Weight T0 (kg)	69.6 ± 17.3	62.8 ± 13.9	75.9 ± 10.8	< 0.001***
Weight T1 (kg)	69.2 ± 16.8	62.5 ± 13.5	75.5 ± 17.3	< 0.001***
Body Mass Index (BMI) T0 (kg/m²)	24.9 ± 4.9	24.3 ± 5.4	25.6 ± 4.4	0.058
Body Mass Index (BMI) T1 (kg/m²)	24.8 ± 4.7	24.2 ± 5.2	25.4 ± 4.1	0.080
Biochemical parameters
Geriatric Nutritional Risk Index (GNRI) T0	105.2 ± 12.8	103.8 ± 14.2	106.5 ± 11.4	0.248
Geriatric Nutritional Risk Index (GNRI) T1	107.6 ± 12.7	107.9 ± 14.9	107.4 ± 10.6	0.889
Albumine T0 (g/dL)	3.9 ± 0.5	3.8 ± 0.5	3.9 ± 0.5	0.332
Albumine T1 (g/dL)	4.1 ± 0.5	4.1 ± 0.6	4.0 ± 0.4	0.871
Glucose T0 (mg/dL)	107.1 ± 37.6	113.1 ± 43.4	101.6 ± 30.7	0.315
Glucose T1 (mg/dL)	103.3 ± 41.7	102.2 ± 41.4	104.3 ± 42.3	0.959
Total Cholesterol T0 (mg/dL)	123.6 ± 37.6	131.6 ± 41.4	116.2 ± 32.4	0.198
Total Cholesterol T1 (mg/dL)	127.9 ± 62.4	143.0 ± 53.2	113.9 ± 37.8	0.013*
HDL cholesterol T0 (mg/dL)	54.5 ± 17.0	58.6 ± 14.3	50.7 ± 18.5	0.006**
HDL cholesterol T1 (mg/dL)	54.6 ± 16.1	61.5 ± 17.1	48.1 ± 12.1	< 0.001***
Triglycerides T0 (mg/dL)	124.0 ± 62.4	120.3 ± 65.2	127.5 ± 60.2	0.415
Triglycerides T1 (mg/dL)	121.9 ± 59.0	129.4 ± 50.9	114.9 ± 65.5	0.051
Calcium T0 (mg/dL)	8.8 ± 1.1	8.9 ± 1.2	8.8 ± 1.0	0.424
Calcium T1 (mg/dL)	8.8 ± 1.0	9.0 ± 1.1	8.7 ± 0.9	0.062
Magnesium T0 (mg/dL)	1.8 ± 0.3	1.8 ± 0.3	1.7 ± 0.3	0.068
Magnesium T1 (mg/dL)	1.7 ± 0.4	1.7 ± 0.3	1.6 ± 0.4	0.685
Iron T0 (µg/dL)	64.2 ± 19.7	67.3 ± 16.8	61.8 ± 21.8	0.263
Iron T1 (µg/dL)	60.9 ± 18.5	63.0 ± 22.0	59.1 ± 14.8	0.671
* p-value < 0.05; p-value < 0.01; * p-value < 0.001.

Women wasted on average 23% of total plate respect to 17% of men, 26% of Italian first dish respect to 17% of men and 24% of italian second dish respect to 15% of men. As expected anthropometric measurements were different between gender.

The values of GNRI in both the timepoints (T0 and T1) were similar in both sexes; in the whole group both GNRI at T0 and at T1correlates with MNA-SF® (rho = 0.345; p = 0.001 and rho = 0.345; p = 0.001). In women MNA-SF® correlated positively with GNRI both at T0 and at T1 (rho = 0.391; p = 0.011 and rho = 0.354; p = 0.022). Among hematochemical parameters, total cholesterol was higher in women at T1, and HDL cholesterol values were higher in women both at T0 and at T1.

Table 3 shows the oxidative stress systemic parameters measured at T0 and at T1. Women tend to have higher values od hydroperoxides (dROMs) and lower values of total antioxidants (BAP), but data are not statistically significant. Men, after rehabilitation treatment, showed lower levels of hydroperoxides respect to women (491 ± 121 vs 549 ± 143 UCARR; p = 0.041). However, both women and men had very high levels of oxidative stress (> 500 UCARR), and low levels of OSI (< 7.3), showing an insufficient antioxidant power respect to circulating hydroperoxides, even if total levels of antioxidant (BAP) were in the normal range.

Table 3

Systemic Oxidative stress variables measured in the whole group, in women and men at admission (T0) and after rehabilitation program (T1). Hydroperoxides measured with dROMs test; total antioxidant defences (endogenous *plus* exogenous) measured with BAP; Thiol groups measured with SHp test; the index of potential antioxidant capacity OSI was calculated from the ratio between BAP and dROMS. P values refer to Mann-Whitney U-test dividing sample by gender.
	Whole group (n = 87)	Women (n = 42)	Men (n = 45)	P value
dROMs T0 (UCaRR)	544 ± 125	556 ± 145	532 ± 102	0.764
dROMs T1 (UCaRR)	520 ± 135	549 ± 143	491 ± 121	0.041*
BAP T0 (µmol/L)	2284 ± 458	2301 ± 512	2268 ± 406	0.796
BAP T1 (µmol/L)	2345 ± 479	2364 ± 515	2328 ± 448	0.797
SHp T0 (µmol/L)	626 ± 125	693 ± 141	613 ± 106	0.643
SHp T1 (µmol/L)	640 ± 126	643 ± 132	637 ± 120	1.000
OSI (BAP/dROMs) T0	4.4 ± 1.3	4.4 ± 1.5	4.4 ± 1.2	0.773
OSI (BAP/dROMs) T1	4.8 ± 1.5	4.6 ± 1.5	4.6 ± 1.5	0.154
* p-value < 0.05;

3.3. Functional preformance in Activity of daily living

The whole group, and man and women separately showed an enhancement in ADL after rehabilitation treatment (Table 4). The mBI at T0 was not different between gender; but man had a higher mBI value at discharge (67.1 ± 21.9 vs 55.3 ± 26.1; p = 0.032) (Fig. 1).

Table 4

Performance in Activity of Daily Living (ADL) at admission (mBI T0) and after rehabilitation (mBI T1) in the whole group, and disaggregated by gender. P values refer to Wilcoxon signed rank test.
	mBI T0	mBI T1	P value
Whole group (n = 87)	45.3 ± 19.5	61.3 ± 24.6	< 0.001***
Women (n = 42)	41.2 ± 17.3	55.3 ± 26.1	< 0.001***
Men (n = 45)	49.5 ± 20.8	67.1 ± 21.9	< 0.001***
*** p-value < 0.001.

Dividing the sample for the ΔBI cutoff, we observed that 64% percentage of men had a better recovery, enhancing more than ten-point of mBI at the end of treatment, while only 36% of women ameliorated their mBI (p = 0.010) (Fig. 2)

Analyzing correlation between nutritional parameters and ADL we found that MNA-SF® correlated respectively with mBI T0, (rho = 0.327; p = 0.002); with mBI T1 (rho = 0.400 p < 0.001) and with ∆BI (rho = 0.232; p = 0.032). Disaggregating data by gender we found that in women the correlations were even higher between MNA-SF® with mBI T0 (rho = 0.506 p < 0.001); with mBI T1 (rho = 0.527; p < 0.001); with ∆BI (rho = 0.394; p = 0.001). Men showed correlation only between MNA-SF® and mBI T1 (rho = 0.298; p = 0.049).

Looking at oxidative stress parameters we found that dROMsT0 correlated weakly and negatively with mBI T0 (rho = − 0.214; p = 0.047) and dROMsT1 correlated negatively with mBI T1 (rho = − 0.232; p = 0.032); men maintained a weak correlation between dROMsT0 and mBI T0 (rho = − 0.351; p = 0.018).

The data from this study show that, under the same initial condition, subacute stroke women showed a greater tendency to be malnourished during rehabilitation treatment, discarded more food and have higher levels of hydroperoxides even at the end of rehabilitation.

Furthermore, the level of performance in ADL achieved after rehabilitation is lower, as well as a higher percentage of women failed to exceed the ten-point cutoff of recovery scale. In addition, women showed a high correlation between MNA-SF® score values measured on admission and mBI values both on admission and discharge and with recovery values measured in terms of ∆BI.

Malnutrition has a significant impact on numerous clinical outcomes in hospitalized patients, affecting up to 90% of the older population. Even if malnutrition prevalence rises with age, comorbidities, and the degree of care, it is commonly misdiagnosed and undertreated in hospitals (32).

Nutritional status in hospitalized patients is highly dependent on the environment of treatment, with malnutrition becoming more prevalent as care intensity increases, reaching 29% (Volkert et al. 2019). In fact, aging is associated with an increased risk of malnutrition due to numerous age-related changes that might affect nutritional statuses, such as a lack of physical activity, a low appetite, a sense of unwantedness, or a sense of neglect. Female sex is also related with a higher risk of malnutrition due to a variety of factors such as longer life expectancies than men or a greater likelihood of experiencing unfavourable economic and social situations in old age (57).

In our sample, that was not different for age, nor for initial level of disability or comorbidity, nor for pharmaceutical treatment, women showed a more fragile profile. During hospitalization they discharged an average of 23% of all meals. Even if this was an expected data, considering that plates were equally portioned, and men tend to eat more than women, an average of almost one-quarter of plate is an important food waste. Fortunately, they did not lost weight during hospitalization and their GNRI levels were within normal ranges, as well as the other hematochemical parameters.

However, the malnutrition assessment and evaluation is a very complex and critical issue, and several definitions of malnutrition have been offered in recent years, influencing the true prevalence of nutritional diseases as well as the timeliness of intervention (32). A full nutritional assessment would be required for the diagnosis of malnutrition, which is often difficult to accomplish throughout all the hospital stay.

There are not standardized procedures to assess malnutrition in post stroke patients during rehabilitation, as recently highlighted (19, 33). Reliable and easy screening/biomarkers to identify post stroke patients at risk of malnutrition or malnourishment should be defined for developing a personalized nutritional intervention.

In our opinion, from data of this study, women nutritional condition should be considered with more attention. From our data, not only women showed a worsen nutritional panel, but also showed a worsen rehabilitation outcome. After the six-week rehabilitation treatment, men had a higher score of ADL performance, assessed with mBI, and 64% of men achieved at least 10 point of score in ∆BI cutoff. Moreover, during hospitalization they wasted less food. On the contrary, a lower percentage of women has a recovery in terms of ∆BI cutoff after rehabilitation treatment, and they reach a lower mBI with respect to men. Moreover, in women there are higher correlations between score of MNA-SF® at admission and both mBI T1 and recovery measured measured as ∆BI.

Another important point is the level of very high systemic hydroperoxides and the very low relative antioxidant capacity measured by OSI index. After six-week rehabilitation men showed lower levels of dROMS, while women did not.

Inflammation and oxidative stress are highly related, as well explained in a recent review (24). Acute illnesses, such as stroke itself may trigger inflammatory responses within body that can, in turn, potentially disrupt dietary behaviours in patients beside to physical impairment such as dysphagia (24). Moreover, a very recent multicentre European study showed that inflammation was the principal risk factor for low food intake and malnutrition is greater than factors such as age, gender, infection, and comorbidity (58).

This connection between malnutrition, oxidative stress and inflammation deserve more detailed study, especially to clarify how long oxidative stress levels remain elevated in stroke patients. Oxidative stress is a potential contributor to the pathophysiological consequences of stroke. Studies following the changes in the level of oxidative stress indicators in patients in the chronic phase after stroke are scarce, and showed that persistent oxidative stress and inflammation is present in the blood after 6 months from insul (59).

So, antioxidant therapy could be a strategy to lower oxidative stress and studies were carried out to explore the more suitable molecules or supplies (59, 60). There is urgent to set clinical trial that evaluated the antioxidant administration and /or a balanced or mediterranean diet, in post stroke patients; these studies should be carried out with a punctual monitoring of oxidative stress, measuring both systemic hydroperoxides, inflammation and total antioxidant status months after acute events. This could improve the knowledge of the interconnection between inflammation and oxidative stress, and should clarify if an antioxidant diet and/or supplies can ameliorate the oxidative imbalance. Moreover, more specific gender-disaggregated studies, should clarify gender-related needs and intervention.

This study has the strength to show the existence of gender differences in post stroke patients not only assessing nutritional status by means of nutritional risk screening, anthropometric measurements, visual estimation of plate consumption, and by assessment of general hematochemical parameters, and oxidative stress status parameters. On the other hand, this study has two principal limitations: the first is that we did not measure inflammation biomarkers in blood, but we planning to do so in the near future; the second is that these results were obtained only in one center; but we are about to complete the analysis of data that will also include subjects from another rehabilitation center.

Among subacute post stroke patients hospitalized for rehabilitation treatment, women appeared to have a lower rehabilitation outcome, wasted more food and had higher oxidative stress even after six-week of hospitalization. So, especially in consideration of the advanced age, women should be carefully monitored for nutritional status during hospitalization for rehabilitation; future studies should clarify if a better nutrition, which includes the right dose of antioxidants, can improve their recovery after stroke.

Author Contributions: Conceptualization, M.S., C.C., A.G. and I.A.; methodology, M.S., C.C., A.G.; software, M.G.; validation, M.S., M.G., and; formal analysis, M.S.; investigation, M.S., C.C., A.G., M.G., R.C., V.C., L.C., A.P., S.L., S.I. and E.R..; data curation, M.S., C.C, A.G. and M.G.; writing—original draft preparation, M.S. ; writing-review and editing, M.S., C.C. ,A.G. , M.K., and I.A.; visualization, C.C., A.G., M.G., R.C., V.C., L.C., A.P., S.L., S.I., E.R M-K. and I.A.; supervision: I.A. All authors have read and agreed to the published version of the manuscript.

Funding: This study was partially supported and funded by the Italian Ministry of Health - Ricerca Corrente.

Institutional Review Board Statement: The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board (or Ethics Committee) of FONDAZIONE DON CARLO GNOCCHI, Milan on October 14, 2020 (FDG_6_14/10/20).

Informed Consent Statement: Informed consent was obtained from all subjects involved in the study, after a detailed explanation of the study’s aims and rehabilitation protocols.

Data Availability Statement: The data supporting the findings of this study are available from the corresponding author upon reasonable request.

Conflicts of Interest: “The authors declare no conflict of interest.”

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Gender differences in Nutritional Status, Food consumption and Oxidative Stress in Post-Stroke patients during Rehabilitation

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Abstract

Figures

1. Introduction

2. Materials and Methods

2.1. Study Design and Participants

2.2. Rehabilitation treatment

2.3. Clinical assessment and Activity of daily living assessment

2.4. Malnutritional risk screening, nutritional status and sarcopenia assesment

2.2 Biochemical analyses

2.2.1 Hematochemical analysis

2.2.1 Oxidative stress analysis

2.6. Statistical analysis

3. Results

3.1. Participants and baseline characteristics

3.2. Nutritional and oxidative stress status

3.3. Functional preformance in Activity of daily living

4. Discussion

5. Conclusion

Declarations

References

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