Gestational diabetes mellitus (GDM) may negatively affect offspring outcomes. A lifestyle intervention may therefore not only improve maternal, but also offspring outcomes. The effects of lifestyle interventions on birth, anthropometric, and psychobehavioral outcomes in offspring of women with GDM need further evidence.MySweetheart trial is a monocentric single-blind randomized controlled trial in 211 women with GDM. It tested the effect of a pre- and postpartum multidimensional interdisciplinary lifestyle and psychosocial intervention focusing on both the mothers and their infants and its effects on maternal (primary outcomes) and offspring (secondary outcomes) metabolic and psychobehavioral outcomes compared with guidelines-based usual-care. This paper focuses on offspring’s birth, anthropometric, and maternal report of psychobehavioral outcomes at singular timepoints.The Women with GDM aged ≥18 years, between 24-32 weeks of gestation, speaking French or English were included and randomly allocated to either the intervention or to an active guidelines-based usual-care group using a 1:1 allocation ratio. The intervention lasted from pregnancy until 1 year postpartum and focused on improving diet, physical activity, and mental health in the mother. For the offspring it focused on supporting breastfeeding, delaying the timing of introduction of solid foods, reducing the consumption of sweetened beverages, increasing physical activity of the family, and improving parental responsiveness to infant distress, hunger, satiety and sleeping cues, and difficult behavior.β:-0.64, CI:-1.27; -0.01, p: 0.05), i.e., offspring of mothers in the intervention group were born 0.64 cm shorter compared to those in the usual-care group.Adverse birth and neonatal outcomes rarely occurred overall. There were no differences between groups in offspring birth, neonatal, anthropometric, or psychobehavioral outcomes up to one year. After adjustments for maternal age and the offspring’s sex and age, there was a borderline significant between-group difference in birth length (This is the first pre- and postpartum multidimensional interdisciplinary lifestyle and psychosocial intervention in GDM focusing on both the mother and the offspring. It did not lead to a significant improvement in most birth, anthropometric, and psychobehavioral outcomes in offspring of women with GDM. ClinicalTrials.gov Identifier: NCT02890693 The preGDM is also associated with worsened maternal mental health, particularly with a higher risk of maternal depression –17. ThisMySweetheart trial, some lifestyle intervention studies mainly focusing on diet and physical activity in the mother had investigated the effect of these interventions on adverse birth and neonatal outcomes in offspring of mothers with GDM and mainly show there is low evidence for improvements in these outcomes for the intervention group  and offspring (secondary outcomes) metabolic and psychobehavioral outcomes.Previous studies in GDM investigating the impact of maternal lifestyle interventions on offspring health outcomes are scarce. Importantly, there are no published intervention trials intervening in the offspring of mothers with GDM . The MySThe aim of this paper was to focus on the secondary outcomes of the trial, i.e., on differences in the offspring’s birth, anthropometric or psychobehavioral outcomes up to one year of age between the intervention and an active guidelines-based usual-care group.22.1MySweetheart trial  was a monocentric single-blind randomized controlled trial (RCT) that tested the effect of a pre- and postpartum multidimensional interdisciplinary lifestyle and psychosocial intervention on metabolic and psychological outcomes in mothers with GDM and their offspring compared to an active guidelines-based control group. More details are provided in the study protocol , the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) and the Endocrine Society , 47, 48 2.4MySweetheart trial are characterized by several interacting components, several outcomes, a high degree of flexibility, and the possibility of tailoring the intervention. The Health Action Process Approach (HAPA) was chosen as the theoretical framework for this behavior change intervention , mothers received support for breastfeeding, recommendations regarding timing of solid food introduction, consumption of sweetened beverages, parental responsiveness to distress, hunger, satiety and sleeping cues and difficult behavior in the offspring, as well as his/her physical activity needs. Breastfeeding was additionally supported with the help of the midwife at birth and afterwards, as desired . MothersFollowing these visits, the lifestyle coach followed up with the goals by summarizing them through a text message sent to the mother. Questions and concerns were discussed during the bimonthly phone calls. Furthermore, co-parents were also invited to each session to reinforce a unified approach for both parents regarding the health goals of their offspring.2.5At the first visit, maternal anthropometric measures (height (cm), weight (kg)) were measured and pre-pregnancy weight was self-reported. Medical information, sociodemographic variables, and social support of the mother were also collected. HbA1c in pregnancy and the requirement for maternal medical treatment were recorded at the end of the pregnancy. In addition, the type of delivery was collected at the first postpartum visit. Breastfeeding presence (yes/no) was assessed by clinicians and self-reported at 6-8 weeks and 1 year. When clinician report of breastfeeding was missing, we retrieved the information from the participant’s report.At birth, the offspring’s baseline measures including birth and neonatal outcomes, gestational age, sex, weight, and height were assessed. At 6-8 weeks and at the one-year visits, the offspring’s weight, size, and skinfolds were measured and mothers completed additional self-report questionnaires at all visits. Data collection and outcomes were measured at the diabetes and pregnancy clinic at the Lausanne University Hospital at all time points. Data regarding birth and neonatal outcomes were extracted from medical charts and records. Secondary offspring outcomes also contained cardiometabolic laboratory outcomes in the cord blood of the offspring, but these are not presented here, as we have much fewer infants with this type of data  and thus the sample size would have been significantly reduced.2.62.6.1Adverse birth and neonatal outcomes including neonatal hospitalization to the neonatal intensive care unit, hyperbilirubinemia  ), hypogl2.6.2®). Macrosomia was defined as birthweight ≥4000 g. Large-for-gestational-age (LGA) and small-for-gestational-age (SGA) were defined as sex-and GA–specific birth weight >90th and <10th centile, respectively, according to the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) guidelines (Birth weight (g) and length (cm) were recorded at birth using calibrated electronic offspring scales . Of the2.8post hoc power analysis was conducted to see whether or not there was sufficient power to detect differences between the usual-care and intervention groups for our most important outcome: offspring weight. The post hoc power analysis revealed a power of 1, 0.99 and 1 to detect differences between groups for weight at birth, 6-8 weeks, and one year respectively, when using model 2. All statistical significance tests were accepted at p<0.05.All statistical analyses were performed with R . Descrip3Baseline maternal characteristics were similar between both groups Table 1,3.1The rate of adverse perinatal outcomes was 5% for neonatal hospitalizations, 2% for hyperbilirubinemia and hypoglycemia and 8% for prematurity for all offspring together Table 2.3.2The prevalence of LGA and SGA in the entire population were both 11%. The weight- and BMI z-scores were close to 0 in both the intervention and usual-care group at birth, 6-8 weeks and 1 year Table 2.3.3In the overall offspring population, the mean Parenting Stress Index was 22.38, the mean night-time sleep duration was 639 minutes/night with a mean of 1.22 awakenings/night and 5% of mothers perceived their child’s sleep as “a very serious problem” Table 2.4MySweetheart trial is the first randomized multidimensional lifestyle and psychosocial intervention trial during and after pregnancy in women with GDM also intervening on the offspring up to one year. The intervention did not lead to a significant improvement in most birth and neonatal outcomes, offspring anthropometry, or their psychobehavioral outcomes up to one year compared to an active lifestyle and guidelines-based usual-care comparator. However, adverse birth and neonatal outcomes, increased anthropometric measures , and psychobehavioral problems were very low in both groups. No between group differences were found for birth and neonatal outcomes. No between-group differences were observed in weight, BMI, BMI z-scores, sum of four skinfold, fat mass (BIA) at birth, 6-8 weeks or one year, except for birth length, which was -0.64 cm lower in the intervention compared to the usual-care group and was close to reaching statistical significance. Furthermore, there were no differences in maternal perception of self-regulation difficulty, the offspring’s total nighttime sleep duration, number of night waking, or the maternal perception of their child’s sleep as being “a very serious problem”.To our knowledge, the Regarding birth and neonatal outcomes, we had very low rates of neonatal hospitalization, hypoglycemia, hyperbilirubinemia, and prematurity in both groups. Prior intervention studies investigating the effect of lifestyle interventions on offspring birth and neonatal outcomes are scarce. A recent retrospective analysis of a cohort using a special program for women, infants, and children  in women recently diagnosed with GDM showed a reduction in the risk of prematurity in the group of women with GDM who had benefitted from this program . This lath and < 10th percentile, respectively in an international control population , as this would have increased the participant burden. However, the mothers were regularly followed up by the coach who reviewed the adherence with the participants. Moreover, the WHO recommends exclusive breastfeeding for at least 6 months. However, in accordance with the local pediatricians and the usual practice in Switzerland, we based ourselves on European and Swiss guidelines to introduce solid foods after at least 4 months of age. This could be considered as a potential limitation. Unfortunately, we did not formally check if women were still breastfeeding at 6 months. In addition, the psychobehavioral outcomes were solely assessed 6Knowledge regarding the importance of the transgenerational impact of metabolic diseases has increased in recent years. This is the first interdisciplinary lifestyle and psychosocial pre- and postpartum intervention in women with GDM that also focused on their offspring. It did not lead to a significant improvement in most birth and neonatal outcomes, offspring anthropometry or psychobehavioral outcomes in the offspring up to one year compared to an active lifestyle guidelines-based usual-care group, but the rates of adverse outcomes were very low in both groups and anthropometric and psychobehavioral outcomes were similar to healthy control populations. Prematurity tended to be lower in the intervention group and length at birth was reduced in the intervention group, although, these between-group difference were only close to reaching statistical significance. Also, the clinical significance of the reduction in length at birth remains to be elucidated. There were few adverse outcomes in both groups and no differences between the intervention and the guidelines-and lifestyle-based usual-care group. Thus, we could conclude that following the current guidelines in mental health and lifestyle recommendations in women with GDM stringently, following up and motivating patients regularly might be sufficient, although this should continue far beyond one year postpartum. A future trial to improve offspring outcomes in mothers with GDM might benefit from an intervention starting early in pregnancy, a stronger focus on the offspring behavior and health, as well as on novel, culturally adapted technologies and should continue far beyond one year postpartum.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Human Research Ethics Committee of the Canton de Vaud (study number 2016-00745). Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.JP and AH conceived the study, designed the trial, obtained grant funding, and oversaw management of the trial. LG, DQ, JG and SL helped in designing parts of the study and participated in the implementation of the study. LG performed the data analysis with the help of AL, BS and DQ. All authors  were involved in the interpretation of data. LG and DQ wrote the draft manuscript. Authors LG, DQ, SS, JG, AA, AH, AL, SL, BS and JP revised the manuscript for important intellectual content and gave final approval for the version to be published. JP and AH supervised all the work. All authors contributed to the article and approved the submitted version.


This study aimed to assess health care needs, electronic health literacy, mobile phone usage, and intention to use it for self-management purposes by informal caregivers of children with burn injuries.This cross-sectional research was carried out in 2021 with 112 informal caregivers of children with burns in a burn center in the north of Iran. The data collection tools were questionnaires that included the participants’ demographics, their E-Health Literacy, their current mobile phone usage, and their desires for mobile phone use for burn care services.Most informal caregivers had smartphones (83.0%) and Internet access (81.3%). Most participants occasionally used phone calls (63.4%), the Internet (45.5%), and social media (42.9) to receive information about psychosocial disorders, infection control, wound care, pain, itch, physical exercise, and feeding. Most participants have never used some of the mobile phone functionalities to receive burn-related information, such as applications/Software (99.1%) and e-mail (99.1%). Nevertheless, most informal caregivers desire to use mobile applications for self-management purposes in the future (88.4%). The mean eHealth literacy score was 25.01 (SD = 9.61). Informal caregivers who had higher education levels, access to the Internet, and lived in urban areas had higher eHealth literacy (P < 001).The current research delivers beneficial information about the healthcare needs of informal caregivers and their preference to use mobile functionality to receive burns-related healthcare and rehabilitation information post-discharge. This information can help design and implement mobile health  interventions to enhance the self-care skills of informal caregivers.The online version contains supplementary material available at 10.1186/s12911-023-02334-w. Burn injuries in children are distressing physical and emotional events with long-term outcomes . More thOne of the methods to improve the self-management abilities of patients with burns and their caregivers  is to use information technology tools  . With reAlthough there is insufficient research on the effects of mHealth tools on burn outcomes, two studies have shown that these interventions positively empower parents in caregiving for their children, improve their quality of life (QOL), and positively reduce unplanned hospital readmissions , 20. OneThe present cross-sectional study was conducted in 2021 in a burn center in the north of Iran. This center is the only burn center in Guilan province, with 55 beds in the burn department and ten beds in the ICU ward, and it has approximately 700 admissions per year, covering all burn patients in the region. This study surveyed health care needs, eHealth literacy, mobile phone usage, and intention to use for self-management purposes by informal caregivers of children with burns. In a similar study by Liang et al. , the meaThe research was conducted with the informal caregivers of discharged burn children under 18 who came for follow-up or wound dressing to the burn and plastic surgery clinic in the first month after discharge, between April and November 2021. Two researchers visited the burn and plastic surgery clinic daily during the study period to collect the data. Parents of children with burns who qualified were asked to participate in the study. If informal caregivers volunteered to participate in the study, they were given brief face-to-face explanations about the study objectives and how to complete the questionnaire in the waiting room. The paper questionnaires were delivered with an informed consent letter to the participants. Participants were informed that they could withdraw from the study at any moment and that their answers would remain private. The participants completed the questionnaires in the researcher’s presence so that the researchers could resolve any ambiguities. Participants identifying information was removed from the questionnaires to ensure confidentiality. Also, each questionnaire was given an identification code to collect clinical information (percentage and cause of burns) and match it with the completed questionnaires (ID code). The identification code of the informal caregivers was the medical record number of their children so that the researcher could access the patient’s clinical information using the hospital information system (HIS). A total of 153 informal caregivers of children with burns attending the burn and plastic surgery clinic were identified, of whom 114 were volunteers to complete the scale, with a response rate of 74.51%. The information related to two patients was deleted after the study was finished because of incompleteness and lack of access to the patients at the end of the study. A total of 112 participants were included in the study.Information collected included sex, age, marital status, education level, place of residence, socio-economic level, total body surface area (TBSA), and the primary cause of burns.The researchers developed the questionnaire based on the literature review to determine the healthcare needs of informal caregivers post-discharge , 23, 24.The questionnaire was prepared based on experts’ opinions about information relevant to burns and mobile phone usage. Two specialists in health information management and medical informatics reviewed and confirmed the face validity of the questionnaire. The content validity of the questionnaire was checked by a 12-member panel consisting of Faculty members of health information management, medical informatics, and burn specialists. Each item’s content validity was evaluated using the Content Validity Index (CVI), and if the CVI was less than 0.7, the item was revised. Also, the Content Validity Ratio (CVR) was determined based on Lawshe’s Table, and the items with values less than 0.56 were eliminated. The scale reliability was determined by Cronbach’s alpha which was 0.83. The final questionnaire, which contained 39 items , was divided into two main sections: (1) overall use of mobile phone functionalities (24 items) and (2) willingness to use mobile phone features (15 items). Five items had a “Yes” or “No” response, and six items had four options . Also, 20 items had seven options , and eight had six options .This study used the eight-item eHealth literacy scale (eHEALS) to measure perceived eHealth literacy . It is an 8-item scale designed to assess individuals’ knowledge, comfort, and perceived skills at using digital health technology to find, assess, and utilize electronic health information to solve a health problem  . The eHeA total of 114 informal caregivers participated in this study. However, at the study’s end, two participants were excluded because of incomplete information and a lack of access to them. A total of 112 participants were included in the study, and there was no missing data for these participants. The Statistical analysis was performed using the SPSS software package . Quantitative and qualitative variables were presented using mean (standard deviation) and number (percentage). The normality of the data was assessed using the Kolmogorov-Smirnov test. Due to the normal distribution of data, analysis of Variance and independent t-test were used to assess associations between eHealth literacy scores and sociodemographic characteristics. Also, Post hoc analysis using the Scheffé post hoc criterion was used to explore differences between specific groups. The significance level was considered less than 0.05.A total of 112 participants were included in the study. Of the informal caregivers, 93 (83.0%) were female. The mean age of participants was 34.79 (SD = 8.15) years. A total of 67 informal caregivers (59.8%) had a Diploma’s degree or lower, and 71 (63.4%) lived in the city. The average age of the children was 6.35 (SD = 5.11) years. The most frequent burn etiology was Hot liquid, steam, or gas, which occurred in 52.7% of the children. The mean TBSA was 23.96 (SD = 8.27).Table Table Table Informal caregivers had the most effective use of the Internet search to receive information about psychosocial disorders (53.6%), control of infection and wound care (52.7%), pain (50.9%), itch (44.6%), physical exercise (43.8%), and feeding (40.2%). Also, they used social media most to control infection and wound care (41.1%). The participants had made their greatest use of phone/voice call for psychosocial disorders (47.3%), pain (43.8%), and itch (42.0%). Meanwhile, the informal caregivers had a greater desire to use internet search, mobile applications, and social media  to receive information about infection control and wound care .Based on Table Among the eight questions related to the eHealth literacy scale, the statements “identifying high-quality health resources from low-quality health resources” (54.5%) and “evaluation skills of health resources on the Internet” (52.7%) had the highest level of disagreement .This is the first study investigating health care needs, eHealth literacy, use, and desire to use mobile phone functionalities in informal caregivers of children with burn injuries. In the present study, most informal caregivers of children with burns stated that after discharge, they face problems regarding how to perform physical activity, infection control, and wound care. The majority of the informal caregivers had smartphones and access to the Internet. Most participants occasionally used phone calls, social media, and the Internet to receive burn-related information. Participants used the Internet and social media the most to receive information about psychosocial disorders, infection control, wound care, pain, itch, physical exercise, and feeding. Most participants have never used some of the mobile phone functionalities to receive burn-related information, such as applications/Software, Email, and SMS. However, most informal caregivers desire to use mobile applications to receive reminders regarding medication use and warnings about the risks of not doing any burn-related rehabilitation programs.The present study showed that most informal caregivers of children with burn injuries require information and training in some areas, such as medication use, wound care, bathing, wearing clothes, physical exercise, feeding, itch, pain, and psychosocial concerns. However, participants’ most common health care needs included physical exercise, infection control, and wound care. A systematic review in 2019 found that informal caregivers need information and support through all stages of treatment and during periods of emotional distress . In a quEven among underserved communities, the use of digital technologies has grown gradually. The present study shows that many informal caregivers had access to smartphones and the Internet on their mobile phones, consistent with studies showing increasing access to digital technologies , 31, 32.The current study shows that most participants do not use E-mail communication and SMS to receive burn-related information. In contrast, a study in Michigan found that most patients used SMS and E-mails at least once a week . This diThe most common topics for which informal caregivers of children needed mobile services included learning how to do physical exercises, infection control, wound care, and warnings about non-completion rehabilitation programs. Other common areas include; medication reminders, pain control, itching control, psychological disorder, dressings, taking baths, and feeding advice. In the present study, more than two-thirds of informal caregivers occasionally used mobile phone calls and the Internet to receive burn-related information. A study in Portugal shows that about half of people search for health information on the Internet . In SpaiThe present findings showed that informal caregivers used mobile phone capabilities through an internet search, followed by social media, to get burn-related information about their children, which is consistent with the results of other studies , 37. TheStudies have shown that self-care applications developed for burn patients have promoted healthy behaviors, facilitated self-care management, and improved health outcomes –40. HoweA crucial part of health literacy is eHealth literacy. Identifying and evaluating patients’ eHealth literacy levels is the first step in developing strategies to improve patient health knowledge and empower them for positive actions. This is the first study to evaluate the eHealth literacy of informal caregivers of children with burns. Therefore, comparing our findings with other studies is difficult. In this study, the average eHealth literacy score of informal caregivers of children with burns was 25.01 (SD = 9.61). Similarly, a study in Australia reported that the average eHealth score of parents of children with complex CHD was 27.46 (5.47) . MoreoveIn this study, no significant differences were observed between sex and the eHealth literacy score, which was in line with previous studies –48. The Based on the literature review, the present study is the first study conducted in a developing country about mobile phone usage and the desire to use it by informal caregivers of children with burns to receive self-care services. These findings could provide a basis for future research on designing and developing mHealth interventions for burn patients. The current study had a sample of 112 informal caregivers of children with burns in a single center, which could be considered a limitation. Additionally, all the informal caregivers were chosen from one center because it was the only burn center in Guilan province. The findings cannot be generalized to all informal caregivers of children with burns after discharge because of the sample size and recruitment method. A limitation of this study is the presentation of associations in a univariate manner, acknowledging the inherent lack of independence among certain variables. Given the small sample size, we refrained from employing regression models to avoid potential instability. Therefore, our results should be interpreted with caution. Hence, for better generalizability, future research with larger samples and multivariate analyses is needed to delve deeper into these associations and identify independent predictors of eHealth and general health literacy.The current study specified the healthcare needs of children’s informal caregivers and their preferred types of mobile phone capabilities for acquiring burn self-care services. Designing prospective interventions based on these requirements seems crucial. However, the research findings can still guide clinical specialists to meet the healthcare needs of discharged burn patients and their informal caregivers using mhealth tools. Based on the data, most informal caregivers in this study did not use applications because of a lack of understanding and confidence about the information content of these tools. Therefore, the following activities are suggested: clinical specialists should assure informal caregivers about the quality of the information provided through mobile phones. In addition, specialists should encourage them to use these tools. Furthermore, practitioners should educate caregivers about the potential risks of cell phones, such as the transmission of pathogenic microorganisms.The present study showed that many informal caregivers of children with burns use the Internet, mainly through smartphones, to research health care information. Since informal caregivers of children with burns do not have access to their medical professionals after discharge, they need the proper education to learn how to manage their difficulties and find new ways to live with a chronic condition. Hence, it is essential to meet the educational needs of families by using alternative and efficient approaches. mHealth tools are critical to patient self-care and can potentially meet these purposes. To build helpful m-health tools for patients or their informal caregivers, physicians and nurses must focus on the needs and preferences of patients. Also, to encourage more m-health adoption, patients should be aware of the benefits of m-health tools and be actively involved in developing these technologies. Practical and user-friendly health promotion applications should be developed according to the e-health literacy level of patients.Below is the link to the electronic supplementary material.Additional file 1: Health Care Needs Questionnaire.Additional file 2: Use of mobile phone functionalities and intention to use for self-management purposes by caregivers of children with burns.Additional file 3: eHealth Literacy Questionnaire.Additional file 4: Use and desire to use mobile phone functionalities for receiving information, as reminders and warnings in caregivers of children with burns (N=112).Additional file 5: Distribution and frequency of eHealth Literacy Scale (eHEALS) scores.


There were more than 1 million new cases of stomach cancer concerning oesophageal cancer, there were more than 600,000 new cases of oesophageal cancer in 2020. After a successful resection in these cases, the role of early oral feeding (EOF) was questionable, due to the possibility of fatal anastomosis leakage. It is still debated whether EOF is more advantageous compared to late oral feeding. Our study aimed to compare the effect of early postoperative oral feeding and late oral feeding after upper gastrointestinal resections due to malignancy.Two authors performed an extensive search and selection of articles independently to identify randomized control trials (RCT) of the question of interest. Statistical analyses were performed including mean difference, odds ratio with 95% confidence intervals, statistical heterogeneity, and statistical publication bias, to identify potential significant differences. The Risk of Bias and the quality of evidence were estimated.p = 0.009), first defecation , and the length of hospitalization  favored the EOF group. Numerous binary outcomes were defined, but significant difference was not verified in the case of anastomosis insufficiency (p = 0.98), pneumonia (p = 0.88), wound infection (p = 0.48), bleeding (p = 0.52), rehospitalization (p = 0.23), rehospitalization to the intensive care unit (ICU) (p = 0.46), gastrointestinal paresis (p = 0.66), ascites (p = 0.45).We identified 6 relevant RCTs, which included 703 patients. The appearance of the first gas (MD = −1.16; Early postoperative oral feeding, compared to late oral feeding has no risk of several possible postoperative morbidities after upper GI surgeries, but has several advantageous effects on a patient's recovery.identifier, CRD 42022302594. Stomach cancer is the 5th most common cancer worldwide. It is the 4th most common cancer in men and the 7th most common cancer in women. There were more than 1 million new cases of stomach cancer in 2020. Concerning the stomach cancer, it causes 768,793/100,000 deaths worldwide. Esophageal cancer is the 8th most common cancer worldwide. It is the 7th most common cancer in men and the 13th most common cancer in women. There were more than 600,000 new cases of esophageal cancer in 2020. Esophageal cancer causes 544,076/100,000 deaths every year. Regarding tumors of the gastroesophageal junction, unfortunately we found little data. According to the latest 8th TNM classification, tumors of the gastroesophageal junction can be classified exactly as tumors of the stomach or stomach of the esophagus based on their location  protocol does not prove itself to be beneficial for the patient's nutritional state, while perioperative starvation provokes a severe catabolic state .Enhanced recovery protocols for perioperative care, such as Enhanced Recovery After Surgery (ERAS), have gained wide acceptance. The concept of ERAS is to facilitate postoperative recovery and improve the quality of life. The postoperative oral feeding process is a fundamental component of the ERAS . EOF is The aim is to compare the effect of early postoperative oral feeding and late oral feeding methods after upper gastrointestinal malignancy surgeries. For this express purpose, we performed a meta-analysis to compare the influence of the two diverse feeding strategies on postoperative recovery and to certify the safety and benefits of EOF.We assume that early oral feeding does not increase the anastomotic insufficiency rate, nor the morbidity rate, while it has several beneficial effects on the general state and on the recovery time.A meta-analysis was carried out using the population-intervention-control-outcomes (PICO) format. Those studies were selected where patients had surgery because of upper GI malignancy (P), and postoperative feeding methods were compared (I and C). Mortality, complications, length of hospitalization, first flatus, and defecation were compared, as the outcomes of different treatment groups (O). The meta-analysis was reported in accordance with the Preferred Reporting Items for Systematic Review (PRISMA) statement and it was registered in advance in the PROSPERO database. The registration number is CRD 42022302594.The selection was conducted on electronic databases, including PubMed and Embase, and Cochrane. Restrictions were not applied. We started the search on the date of 1st of February 2021.The search included the following keywords: AND ) OR (esophagectomy OR oesophagectomy OR gastrectomy)) AND  AND )) AND random*.We searched for studies, involving patients with upper GI cancers, including oesophageal and gastric tumors, and we excluded all the cases when the surgery was performed because of benign diseases.In our analysis, we compared the effect of early postoperative oral feeding, compared to late oral feeding, after upper gastrointestinal surgeries.Articles were included if they provided data on at least two feeding modalities on patients with either EOF or LOF or both reporting the outcomes mentioned above. Only randomized controlled trials were included. Non-English language studies, studies focusing on pediatric cases, and studies with combined interventions were excluded.The publications were processed by the EndNote X7.4 software . Duplications were removed, and the remaining records were screened first by title, second by abstract, and finally by full-text by two independent authors (DLS and DB).Data were collected by two independent authors (DLS and AC) using an Excel  data sheet, based on predetermined criteria. Numerous binary variables outcomes were defined such as anastomosis insufficiency, pneumonia, wound infection, bleeding, ascites, rehospitalization, gastrointestinal paresis, and laryngeal nerve paresis. The appearance of the first gas, first postoperative defecation, and length of hospitalization were the outcomes of continuous variables.The statistical analyses were made with R (R Core Team) Software . For calFor dichotomous outcomes the odds ratio (OR) with a 95% confidence interval (CI) was used for the effect measure; to calculate the OR, the total number of patients in each group and those with the event of interest were extracted from each study. Raw data from the selected studies were pooled using a random effect model with the Mantel-Haenszel method –13. For N), the mean, and the standard deviation (SD) in each group. If the mean and SD were not reported, the median and the upper and lower quartilee, the minimum and maximum values were extracted. If the mean value was not available, it was estimated from the sample size, median, and range using the method proposed by Luo et al.  with 95% CI were calculated as effect size. The extracted values to calculate the mean difference were the sample size  used the Risk of Bias Assessment Tool version 2 by Cochrane, and the GRADE approach was applied to assess the certainty of evidence.We found 3,147 articles from Embase, Cochrane, and PubMed databases. We did not identify any additional articles from other sources. After the filter of duplication, title, and abstract, 77 articles remained. During the full-text filtering, we excluded 71 articles because they were not RCTs. We also excluded trials, which did not include patients with esophageal or gastric tumors and pediatric or animal experiments. We identified 6 relevant RCTs by full-text, which included 703 patients. The detailed steps of the selection process can be seen on the PRISMA flowchart .The details of the characteristics of the studies were shown in the table below .p = 0.009; 95% CI: ). The between-study heterogeneity was significant   .p < 0.001; 95% CI: ). The between-study heterogeneity was not significant   .p = 0.008; 95% CI: ). The between-study heterogeneity was significant   .p = 0.25; 95% CI: ). The between-study heterogeneity was not significant .A total of 5 studies –29, 31 wp = 0.98; 95% CI: ). The between-study heterogeneity was not significant   .p = 0.88; 95% CI: ). The between-study heterogeneity was not significant .A total of 4 studies , 29, 31 p = 0.48; 95% CI: ). The between-study heterogeneity was not significant .A total of 4 studies , 30, 31 p = 0.52; 95% CI: ). The between-study heterogeneity was not significant .A total of 4 studies –28, 30 wp = 0.449; 95% CI: ). The between-study heterogeneity was not significant .A total of 3 studies , 27, 31 p = 0.43; 95% CI: ). The between-study heterogeneity was not significant .A total of 3 studies , 28, 30 p = 0.9; 95% CI: ). The between-study heterogeneity was not significant .A total of 3 studies , 29, 31 ROB was assessed as low in all outcomes –31. The The quality of the evidence was estimated as moderate in all outcomes –31 becauIn the case of operations performed for upper gastrointestinal tumors, the mortality and morbidity rates are very high, especially if the anastomosis is performed with the esophagus .For decades, anastomosis failure was one of the most dangerous complications leading to other morbidities. Li et al.  describeIn recent years, it has been proven that the ERAS protocol has a beneficial effect on the prehabilitation and rehabilitation of patients, which includes early oral feeding after surgery as part of the multimodal care protocol , therefoWe prepared a meta-analysis based on the PRISMA protocol, in which we included 6 studies with the participation of 703 patients. In these studies, early (EOF) and late (LOF), oral feeding methods were used after oesophageal and gastric cancer surgeries, and then the results of the 2 groups were compared. In the EOF group, they were allowed to consume liquid on the second post-operative day orally, and then from the postoperative day on, they started giving formula, which is how the feeding method is structured. In the control group, for 5–7 days after the operation, the patients were not allowed to consume food orally, it was provided enterally or by other parenteral means.As previously described, anastomotic leakage is one of the most common complications, associated with life-threatening infection and mortality, and influences the response of therapy, therefore, it is one of the most important outcomes. There was no significant difference between the EOF and LOF groups, based on our study. Li et al.  also foup = 0.52), wound infection (p = 0.48), ascites (p = 0.45), and gastrointestinal paresis (p = 0.43). He et al. also found no significance in feeding intolerance (0.62)  .p < 0.0001), and prealbumin (p < 0.001) levels in case of gastrectomies. Xin et al. found a significant increment of immune indicators like CD3+ (p = 0.0009), CD4+ (p < 0.00001), CD4+/CD8+ (<0.00001), and NK cells (<0.00001) under the influence of EOF , which is confirmed by He .The appearance of the first flatus and gas is earlier in EOF, based on our investigation , and the meta-analyses by He (p < 0.001). Even though patients can be discharged earlier, the rate of rehospitalization does not increase (p = 0.25).The main advantage of applying the EOF is the shorter length of hospital stay, which our investigation  (p = 0.014)  . Altman , < 0.001= 0.014)  and Wang= 0.014) . An impo= 0.014) .Lower hospital costs can be achieved by reducing the length of stay in the intensive care unit. Roh et al. analyzed the length of hospital stay after a minimally invasive subtotal gastrectomy. In this study, the hospital length of stay in the early feeding group was significantly lower than that in the LOF group. However, the complication rate was not found to be higher in the EOF group .In our analysis, we did not examine mortality as an outcome due to the small amount of available data, despite the fact that we planned to examine it in advance. A short-term 30-day follow-up of mortality was performed by Jang et al.  who founQuality of life is a very important aspect in addition to postoperative morbidities, although we could not analyze it due to the small sample size and the high heterogeneity of the data, therefore it would be useful to measure QOL with one standard method, for example using the EORTC QLQC30 score system, in future studies.Patients who have undergone upper GI surgery are often malnourished, which is also contributed to by the surgical metabolic stress. Weight loss and the weakening of the patient's physical condition have been shown an increased the mortality rate . Pre- anAt the same time, this is also a factor, affecting the quality of life, which can be significantly improved by starting early oral feeding. Yang et al. investigated the effect of early oral feeding on the quality of life of patients who underwent minimally invasive oesophagectomy. They used Cancer-Quality of life Question-Core  and Oesophageal Cancer Module (QLQ-OES-18) questionnaires. They found that weight loss can be reduced and has a positive effect on early recovery, and can demonstrably improve the quality of life .In the future, it would be necessary to widely use quality-of-life questionnaires as part of the ERAS protocol for patients undergoing upper gastrointestinal surgery. For example, Sun et al. used the EORTC QLQC30 questionnaire to assess the quality of life, it can be said that the EOF group had significantly better results compared to the LOF group .We selected high-quality articles as there were only randomized controlled trials selected, therefore the risk of bias is low.The definition of outcomes is homogenous, thereby increasing the quality.The characteristic of patients was similar in the EOF and the LOF group.We were primarily interested in examining the EOF during oesophageal surgery, but unfortunately, due to the small number of RCTs, we had to combine it with gastrectomy, so in the end, we examined an integrated UGI group. Due to the rigorous criteria, a small number of cases were available. Another limitation is the averages had to be estimated in many places because it was not described precisely in the articles, and median values were not given in many places.Mostly Asian and American articles were included, therefore the population of the patients was overwhelmingly Asian, while European and American were represented by only one article each. Thus, these results are only applicable to the European and American populations in a limited manner.Due to the small number of cases and few studies, we did not separate the results of gastric tumor and oesophageal tumor patients during our meta-analysis but examined them in one group.Recently, more and more articles deal with the advantages of EOF, but the number of RCTs is still small. In our meta-analyses some limitations emerge, therefore further large sample size randomized controlled investigation is needed in the topic of the esophagus and gastric resection, especially in cases of minimally invasive UGI surgery. Trials should originate from distinct countries so that the results can be standardized. This is the reason why we are planning on conducting a multicentric clinical research project involving multiple Hungarian medical institutions that handle UGI surgeries.In our meta-analysis, we proved that the use of EOF has many advantages, but does not involve significant complications. It reduces the length of hospital stay and contributes to a better immune status, which in itself reduces the development of postoperative complications and contributes to a faster recovery time. Anastomotic leakage can be a dangerous complication in connection with EOF, but we could not prove this risk. All in all, we can say that EOF has negligible risk, however, it is a safe way to improve the recovery of patients.Our meta-analysis is more comprehensive and accurate than before, due to rigorous criteria. In conclusion, it can be said that oral feeding started early after surgery is safe even after upper gastrointestinal surgery. Based on our results EOF does not associate with higher morbidity especially anastomotic leakage, pneumonia, wound infection, bleeding, ascites, gastrointestinal paresis, and recurrent laryngeal nerve injury. The main advantages of the EOF are the appearance of the first flatus and defecation earlier, which means the recovery time of bowel function is more rapid. The risk of rehospitalization was similar in the investigated groups, and the time of hospital stay is also shortened in the EOF, which magnetifies lower cost. Even though many studies are still needed on this topic in the future, based on our results, we recommend the usage of EOF after upper GI surgery in practice, especially within the framework of the ERAS protocol, due to its many advantages and negligible complications.


Conclusions: The observed changes in BMI during social isolation were the result of lifestyle modifications including dietary behaviour and differed by gender.Background: Social isolation during the SARS-CoV-2 pandemic affected people’s body weight, therefore, this study was designed to evaluate the association between lifestyle elements and the change in BMI during lockdown. Methods: This retrospective observational study involved 290 questionnaires completed by adult participants divided into three groups according to BMI change during isolation. The structured questionnaire included a general description of the study objective and collected data regarding sociodemographics, anthropometrics, physical activity, sedentary behaviour, sleep duration, and food intake pre- and during COVID-19 lockdown. Results: A decrease or increase in BMI was found in 23.6% and 47.8% of women and 18.5% and 42.6% of men, respectively. Among those who lost weight, 46.5% of women and 40% of men followed a diet of their own choice, 30.2% of women and 25% of men changed their product mix and reduced their intake, 40% of men stopped eating outside the home. An increase in BMI was associated with increased food intake (32.2% of women and 28.3% of men), increased sleep duration on weekdays (49.2% of women and 43.5% of men) and, in more than 50% of subjects, decreased physical activity. In women, increased BMI was associated with the highest frequency of snacking ( The unprecedented social isolation in more than 100 years occurred due to restrictions imposed worldwide to protect against the spread of the SARS-CoV-2 in 2020 profoundly disrupted daily life, leading to changes in the habitual functioning of populations, and affected mental and physical health ,4,5, proHowever, interestingly, the lockdown caused by the COVID-19 pandemic has not only led to a consolidation of unfavourable eating habits but also a correction of previous inappropriate eating patterns and behaviors . COVID-1Studies in humans and animal models suggest that being in identical conditions of social isolation can lead to both weight gain and an inflammatory phenotype in adipocyte adipose tissue and weight loss ,29,30 anObesity was a huge global problem before the emergence of the SARS-CoV-2 pandemic . PandemiHabit in humans is a key determinant of behaviour maintenance . People The aim of this study was to identify which lifestyle factors  and sociodemographic characteristics influenced, and how they influenced, the change in BMI during COVID-19 closure. This will allow these factors and characteristics to be better controlled and enable the implementation of effective, gender-specific interventions to reduce the serious public health crisis associated with the increasing prevalence of obesity or malnutrition by shaping favourable health, dietary, physical activity habits, and choices. Well-formed habitual behaviours can be more easily reactivated in future outbreaks requiring isolation. Identifying the causes of changes in BMI will also help address the distant consequences of isolation caused by the SARS-CoV-2 pandemic.To assess lifestyle changes during the SARS-CoV-2 pandemic and their impacts on increasing or decreasing BMI, a retrospective observational study was conducted from 29 April to 19 May 2020 in healthy adults in Poland who did not become ill with COVID-19 before or during the study. The survey questionnaire included questions on the COVID-19 lockdown period, which covered the period of the introduced epidemic state from 20 March to 30 May 2020 and the period six months before the start of the COVID-19 lockdown (before the lockdown). For weight and height, we asked for measurements from the last three months before the start of the COVID-19 lockdown. The survey was completed during the COVID-19 lockdown. Inclusion criteria were age 18 to 65 years and the ability to give informed consent to participate in the study. Subjects under 18 years of age and over 65 years of age, those with COVID-19, those on a therapeutic or alternative diet, and pregnant women were excluded. The survey questionnaire was posted and made available on Google’s online survey platform. The link to the electronic survey was disseminated through various methods to reach a wide range of respondents: posting on the official profile of the Institute of Public Health, on the accounts of the researchers taking part in the survey, via email, and sharing on social media sites Facebook, WhatsApp, and Instagram.Study participation was voluntary and participants could withdraw from the study at any stage. Participants were informed that anonymity and the purposes and scope of the study would be maintained, and they provided informed consent to participate. The study was conducted in accordance with the principles of medical research ethics contained in the Declaration of Helsinki and was approved by the local ethics committee of the Warsaw Medical University (no. AKBE/122/2020).The study included 290 participants from 15 provinces in Poland, of whom, 62.8% were women and 37.2% were men. The response rate was 48.1% (number of surveys completed and sent divided by number of surveys started × 100%). The questionnaire was started by 603 participants (they answered the first question). Of these, 285 participants did not complete the questionnaire, 23 did not complete the anthropometric section, and 5 did not qualify due to not meeting the inclusion criteria . Complete questionnaires were obtained from 290 participants for analysis and the flow of participants is shown based on the STROBE guidelines  in FigurThe minimum sample size was calculated before the start of the study using Surveymonkey.com sample-size-calculator , assuminThe research tool was a web-based questionnaire containing 96 questions designed to collect information regarding the respondents’ sociodemographic data , selected dietary behaviour, sleep duration, sedentary behaviour, and physical activity, as well as weight measurements before and during the SARS-CoV-2 pandemic. The questions were developed based on the validated and recommended standards for research in the Polish population Questionnaire of Eating Habits and Food Beliefs for Persons Aged 15–65 Years (KomPAN) developed by the Behavioral Nutrition Team of the Committee on Human Nutrition at the Polish Academy of Sciences . CompletQuestions on age, body height, gender, education, and place of residence were asked once. The questionnaire also asked participants about their employment, with the options to answer: (a) I am retired, or on a pension, (b) I am on maternity leave, unemployed, or other, (c) I have a part-time job, (d) I have a permanent job, and (e) I am in education or studying. The section regarding dietary habits included questions on the use of diet with possible answers: (a) no, (b) yes, on doctor’s orders for health reasons, and (c) yes, of my own choice; the number of meals eaten per day with the possibility of recording the number of meals consumed; frequency of snacking with answers and scores: (a) never—1, (b) 1–3 times a month—2, (c) once a week—3, (d) several times a week—4, (e) once a day—5, and (f) several times a day—6; frequency of consumption of fast food, fried foods, sweets, alcohol, sweetened beverages, vegetables, and fruit with the options to answer: (a) never, (b) 1–3 times a month, (c) once a week, (d) several times a week, (e) once a day, and (f) several times a day, and frequency of eating out (including home delivery), e.g., in bars, restaurants, cafés, and canteens, with the options to answer: (a) never, (b) 1–3 times a month, (c) once a week, (d) several times a week, and (e) once a day.There was also a question not included in the KomPAN questionnaire regarding the change in the form of work during isolation caused by COVID-19 compared to before with the options to answer: (a) yes, I work as before, (b) yes, I work remotely from home, (c) no, (d) no, I am on unpaid/paid leave looking after a child/children under 8 years old, and (e) not applicable, and changes in diet due to social isolation with possible answers: (a) no change, (b) eat the same products in larger quantities, (c) eat the same products in smaller quantities, (d) changed the range of products without changing the quantities, (e) changed the range of products and increased the quantities, and (f) changed the range of products and decreased the quantities.The questionnaire also included questions on the number of hours of sleep on weekdays and weekends, with responses and scores: (a) 6 h or less/day—1, (b) more than 6 but less than 9 h/day—2, and (c) 9 h or more/day; sedentary behavior: (a) <2 h, (b) 2–4 h, (c) 4–6 h, (d) 6–8 h, (e) 8–10 h, and (f) >than 10 h; and a question on physical activity during work or school time, with three possible levels with scores—low: more than 70% of the time is sitting—1, moderate: about 50% of the time is sitting and 50% activity—2, and high: about 70% of the time is high-intensity activity or physical work—3; and physical activity in leisure time, with responses and scores, respectively—low: mainly sedentary lifestyle, watching TV, reading newspapers/books, light housework, or walking for 1–2 h/week—1, moderate: walking, cycling, exercising, gardening, or other light physical activity for 2–3 h/week—2, and high: cycling, running, gardening, and other sports/recreational activities requiring physical activity for more than 3 h/week—3. Respondents were asked the same questions twice regarding the time before and during lockdown due to the SARS-CoV-2 pandemic.The questionnaire was supplemented with questions on anthropometric parameters.2) as the quotient of the weight of a body to its height in meters squared was calculated for each participant at two time points. The interpretation of nutritional status based on BMI was based on the World Health Organization (WHO) guidelines for adults [Participants reported their weight (kg) measurements before and during the lockdown based on measurements taken on household scales. Body height was given only once, based on measurements with a height meter. Based on the declared measurements, body mass index , weight gain and BMI , or no change in weight and BMI . Based on the subgroups thus formed, we analyzed the effect of individual factors on BMI during the COVID-19 lockdown. For physical activity, the subgroups with increase/decrease/no change in BMI were separated within the entire study group with no division between men and women.In order to separate the study participants into groups with an increase/decrease or no change in BMI, we relied on the following scheme: a BMI was calculated for each respondent on the basis of body weight and height obtained. Those for whom the difference between BMI during lockdown and before the SARS-CoV-2 pandemic was <0.00 were classified in the group with a decrease in BMI, and those for whom the difference in BMI was >0.00 were classified in the group of people who had gained weight. If there was no change in BMI—they were assigned to the group with no change. For men and women, we made an identical allocation and it was as follows: women and men who experienced a decrease in weight and BMI  assuming a statistical significance of  <0.05.p = 0.0072), age (p = 0.0004), and body height (p = 0.0252), while there were no differences in terms of place of residence, education, and employment. The mean BMI in these groups of women was also similar both before and during lockdown. The group of women who had a reduced BMI during isolation had the highest mean body weight before the SARS-CoV-2 pandemic. Among these women, almost half followed a diet of their own choice (46.5%), which may explain the observed weight loss. This was also the youngest group of women (mean age 34.5 ± 10.0 years).A decrease in BMI was reported by 23.6% of women and 18.5% of men, while 47.8% of women and 42.6% of men reported an increase. The subgroups of women who had a decrease/increase or no change in BMI differed significantly in terms of weight before isolation due to the SARS-CoV-2 pandemic  and the weight of sweets consumed per day (p = 0.0021), whereas it was the quantity of alcoholic beverage consumption (p = 0.0017) for men  between the subgroups of women (p = 0.0454) but no longer during isolation (p = 0.2636). Of the men who reported a reduction in BMI, up to 40% stopped consuming food outside the home.No significant difference was observed in the frequency of meals eaten outside the home before and during lockdown  in a similar number of women with an observed decrease in BMI. There were no significant changes in sleep length on weekends between the subgroups of men (p > 0.05).Increased sleep duration on weekdays was reported by almost half of the women and 43.5% of the men in whom BMI increased during lockdown, as well as in 40% of men in whom BMI decreased . Only subjects who reported a decrease in BMI during lockdown maintained a similar amount of physical activity during work (p = 0.3978) and leisure time compared to the previous period  . The per% . The pThere were no differences between the subgroups of women and men regarding their place of residence, education, or type of employment. Interestingly, men were also characterized by similar age regardless of BMI changes. Several studies have shown that older age is associated with weight gain during the COVID-19 lockdown . The oldEnergy deficit is the most important factor influencing weight loss and BMI reduction , hence, For effective weight maintenance or weight reduction, it is also important to maintain appropriate meal times, eat meals with higher energy value earlier in the day, and maintain consistent periods of overnight fasting. In several cross-sectional studies in free-living populations, a higher eating frequency was associated with a lower risk of obesity . In the Snack consumption does not necessarily result in increased body weight. The inclusion of 1–2 snacks per day alleviates potential gastrointestinal and metabolic overload caused by fewer heavier meals and may contribute to meeting recommendations for food groups  and nutrients, such as fibre and vitamins . HoweverThe association between high sugar intake and weight gain is not in doubt . Also, t2, respectively. Thus, a reduced intake of such meals significantly contributes to weight reduction and lower BMI in this subgroup of men.The increased consumption of alcoholic beverages observed in a group of men with increased BMI was also an independent predictor of weight gain in studies by other authors dating back to the COVID-19 lockdown  and was A change in the type of work from stationary to remote also lead to weight gain during the lockdown caused by the SARS-CoV-2 pandemic . AccordiThe observations on sleep duration were interesting. Although the causal relationship between sleep duration and obesity is not clear ,94, epidThe lockdown to curb the spread of the SARS-CoV-2 pandemic also resulted in decreased physical activity and increased sedentary behaviour ,26, whicSeveral studies suggest that negative changes in physical activity have a particularly negative impact among those with higher BMI ,55,73, aIncreased sedentary behaviour may impede the maintenance of normal body weight and BMI during lockdown ,26. HoweIn this study, we attempted to capture as accurately as possible the potential lifestyle factors responsible for the change in BMI in men and women during the SARS-CoV-2 lockdown. The speed with which the surveys were implemented ensured that the population response to the relevant government-mandated mitigation strategies was captured at similar levels. Despite the large amount of data, we are aware of some study limitations that need to be highlighted, particularly in terms of survey methodology. First, this was a retrospective study assessing lifestyle behaviours before the COVID-19 lockdown. The study was conducted at the start of the pandemic. In addition, the change in body weight was self-reported and not measured by the researchers which may reduce the sensitivity of the study. Also, whether participants were infected with COVID-19 was not assessed, and, therefore, data on a possible bidirectional effect of weight change with COVID-19 infection could not be obtained. The questionnaire was completed online and not in the presence of a dietician due to COVID-19 restrictions so there may have been measurement errors, especially for anthropometric measurements. Finally, the completion rate of the questionnaire was low, possibly because the respondents could halt the survey at any time and/or not answer all questions or complete all sections, especially regarding the anthropometric parameters. However, although this may introduce significant errors when interpreting the results, many estimates based on telephone surveys with fairly low response rates overlap with estimates from surveys with higher response rates ,106. AlsThe very high proportion of people who experienced a change in BMI during the lockdown caused by the SARS-CoV-2 pandemic indicates an urgent need to identify the factors responsible for these changes. The present study provides insight into the impact of the lockdown caused by the SARS-CoV-2 pandemic on selected lifestyle components responsible for the increase or decrease in BMI according to gender. All the more so, as the impact of the lockdown caused by the SARS-CoV-2 pandemic on BMI is observed long after its end.The increase in BMI is associated with increased food intake and sleep duration, decreased physical activity, and increased frequency of snacking and number of sweets consumed by women and alcoholic beverages by men, while a decrease in BMI with the range of products consumed and reduced intake and, in men, additionally a reduction in eating out and low alcohol intake will allow effective gender-specific interventions to be achieved in the future. Increasing physical activity by promoting exercise that can be done at home and improving sleep duration should be considered for future risks. Strategies to achieve and maintain a healthy body weight and BMI should be prioritised at the population level, which could help to reduce the burden of COVID-19, as well as potential future pandemics and other reasons requiring isolation, however, taking into account complex gender-dependent factors.


Patients with UC had increased overall odds of having MM (odds ratio (OR), 1.26). Males with UC had higher prevalence of MM  than females. Patients with UC and MM were more likely to be African American than White . Patients with UC age >64 had a higher prevalence of MM than those aged below 65 . Patients with UC who were obese (BMI > 30) had a higher prevalence of MM than those who were non-obese (12.6% vs. 8.3%). Conclusions: Overall, UC appears to be associated with MM. This association can be particularly observed in specific demographic groups, such as obese, African American males, or patients >64 years of age. Thus, a high degree of clinical suspicion for MM is warranted, even with minimal symptomatology, in patients with UC, in particular among elder, obese, and African American males.Background and Aims: Multiple myeloma (MM) is a plasma cell dyscrasia that is common among patients with autoimmune diseases. However, the association between ulcerative colitis (UC) and multiple myeloma (MM) is yet to be established. We aimed to evaluate the prevalence of MM among patients with UC in the United States. Methods: This cross-sectional cohort analysis used the National Inpatient Sample from 2015–2018 to assess the overall MM prevalence among patients with and without UC, and within specific demographic subgroups. Prevalences were compared using a logistic regression model controlling for sex and age. Results: The crude prevalence of MM among patients with UC ( Multiple myeloma is a rare malignancy caused by plasma cell proliferation leading to a monoclonal expansion of immunoglobulin in the bone marrow. MM represents approximately 2% of all cancers and about 17% of all hematologic malignancies . SymptomTo make a diagnosis of MM, laboratory exams, and radiologic and pathologic findings are needed. Serum protein electrophoresis can detect the colony of monoclonal antibody (M protein), which is secreted by most MM patients. Immunofixation or mass spectrometry help identify the different components of the M protein, in heavy and light chains . Bence Jones proteins, which are free light chains, can be detected in the urine using previously mentioned techniques; more recently, Bence Jones proteins have been detected in the serum using highly sensitive free light chain tests ,2,3. MM Inflammatory bowel disease (IBD) is a chronic, autoimmune, inflammatory, intestinal condition—primarily affecting patients in their third or fourth decades of life. Ulcerative colitis presentation consists of weeks to months of bouts of bloody bowel movements. Recurring symptoms are observed during treatment, with long periods of compete subsidence of symptoms. It is estimated that up to 67% of patients will have a relapse in the 10 years following diagnosis, with age at diagnosis being a key indicator of relapse ,5. OwingIn IBD, there is a compromise of the first line of mucosal defense, leading to a systemic response of antigens crossing the intestinal mucosal barrier. As a result, B-lymphocytes and plasma cells are activated, which could explain the causal relationship between MM and IBD . FurtherAlthough ulcerative colitis (UC) and multiple myeloma (MM) are reported to coexist, albeit in the form of small case-series, the association between MM and UC is yet to be established, nor has it been systematically evaluated ,5. WhileTo fill in the gap in the literature, using a large United States (US) population-based dataset, we aimed to evaluate the prevalence of MM among patients with UC and to determine the strength of association between these two medical conditions.https://hcup-us.ahrq.gov/nisoverview.jsp, accessed on 16 March 2021), which is the largest publicly available inpatient database in the United States, containing data on more than seven million hospital stays [The study used the standardized electronic health record information of the National Inpatient Sample (NIS)  and ulcerative colitis (K51) were used to identify cohorts. The use of electronic health data to identify UC and MM cohorts has been performed in prior studies evaluating the associations between other conditions ,10.Exclusion criteria:We excluded patients younger than 18 years, with an unknown ethnicity, BMI, or sex.Variables included in our study are age, sex, ethnicity, and BMI.p value < 0.05. Software STATA 16.1. was used to perform all of the statistical tests.A logistic regression model that controlled for sex and age was used to compare prevalences. Two-tailed hypothesis tests were used, and a threshold of statistical significance was considered with a The NIS dataset is a public-use dataset, for which informed consent is waived.This study does not require institutional board review as it contains deidentified, publicly available data.n = 1750) compared with patients without UC  were 0.44% vs. 0.37%, as seen in From a total of 98,355,141 patients hospitalized between 2015–2018, we identified 393,630 patients with UC and 367,415 with MM. The crude prevalence of MM among patients with UC (p  =  0.03).Males with UC had a higher prevalence of MM compared with females with UC (53.7% vs. 46.3%). Significant effect modification was observed in the association between UC and MM across sex subgroups as the ORs for the association between UC and MM were higher in males  than in females  (p  =  0.001).Regarding ethnic groups, African Americans had a higher prevalence of MM among patients with UC compared with White patients (15.6% vs. 9.2%). Significant effect modification was observed in the association between UC and MM across ethnic subgroups as the ORs for the association between UC and MM were higher in African American patients  than in White patients  (p  < 0.001 for the interaction of MM with age).Patients with UC aged 65 years or older had a higher prevalence of MM than those aged below 65 . Age was a significant effect modifier in the association between UC and MM. Patients with UC aged greater than or equal to 65 years had 2.7  times the odds of MM compared with patients without UC who were under 65 (p  < 0.001 for the interaction of MM with obesity).Patients with UC who were obese (BMI > 30) had a higher prevalence of MM than those who were non-obese (12.6% vs. 8.3% respectively). Obesity was a significant effect modifier in the association between UC and MM. Patients with UC who were obese had 2.2  times the odds of MM compared with patients without UC who were non-obese , have been shown to be at increased risk for extra intestinal malignancies . While mChronic inflammation similar to what is observed in UC can lead to the stimulation of B lymphocytes, which in turn will promote the expansion of plasma cells in a monoclonal fashion. As a result, monoclonal gammopathy of undetermined significance (MGUS) may arise. Regarding MGUS, being a precursor of MM, one can conclude that there is an association between MM and IBD . HoweverSeveral cases of IBD associated with MM have been reported in the literature. Fadem et al. reported a case of plasmacytoma in a patient with UC . In the The era of newer treatments in IBD, including biologics, has helped unveil a new mechanism through which IBD can be associated with MM. Liu et al. reported two cases of UC and MM associated with biologics. In the first case, the patient was diagnosed with MM shortly after the initiation of daclizumab. The patient’s UC remained silent after MM treatment. In the second case, the patient developed MM one year after the initiation of infliximab for the management of UC. The patient was found to have thrombocytopenia, anemia, and fatigue, and was eventually diagnosed with MM; however, given the delay of diagnosis, the patient passed away shortly after diagnosis . SimilarThe results herein are important for several reasons. Clinicians should place a high degree of suspicion for MM in patients with UC, especially in the patient population that is historically known to be at risk for MM. UC patients with multiple cytopenias, including anemia, should be further evaluated as well . ProlongDespite these robust findings, several limitations of our study must be acknowledged. First, the dataset used relies on administrative (ICD) codes, which carry the potential for misclassification. Second, while the accuracy of ICD-10 codes used herein has not been prospectively validated, we reviewed previously published manuscripts on the topic to confidently include the most appropriate codes ,8. ThirdIn conclusion, by way of this large, nationally representative cross-sectional analysis, a significant association was identified between MM and UC. Moreover, we highlighted specific demographic subgroups of patients with UC that are at high risk of developing MM. Hence, a high degree of clinical suspicion of MM is warranted in patients with UC—especially in the demographic subgroups found to be at higher risk. In this era of precision medicine and increasing use of biologics for treatment of UC, future prospective data are needed to evaluate the impact of immunosuppressive therapy on the development of hematologic malignancies in patients with UC. Furthermore, we hope to encourage clinicians to keep MM in the differential diagnosis of UC patients with unexplained blood derangements, especially in the demographic subgroups at higher risk, as evidenced in this study. Further studies on the subject may lead to an update of guidelines that could implement systematic screening for MM in UC patients at higher risk.


As a commonly used physical intervention, electrical stimulation (ES) has been demonstrated to be effective in the treatment of central nervous system disorders. Currently, researchers are studying the effects of electrical stimulation on individual neurons and neural networks, which are dependent on factors such as stimulation intensity, duration, location, and neuronal properties. However, the exact mechanism of action of electrical stimulation remains unclear. In some cases, repeated or prolonged electrical stimulation can lead to changes in the morphology or function of the neuron. In this study, immunofluorescence staining and Sholl analysis are used to assess changes in the neurite number and axon length to determine the optimal pattern and stimulation parameters of ES for neurons. Neuronal death and plasticity are detected by TUNEL staining and microelectrode array assays, respectively. mRNA sequencing and bioinformatics analysis are applied to predict the key targets of the action of ES on neurons, and the identified targets are validated by western blot analysis and qRT-PCR. The effects of alternating current stimulation (ACS) on neurons are more significant than those of direct current stimulation (DCS), and the optimal parameters are 3 μA and 20 min. ACS stimulation significantly increases the number of neurites, the length of axons and the spontaneous electrical activity of neurons, significantly elevates the expression of growth-associated protein-43 (GAP-43) without significant changes in the expression of neurotrophic factors. Furthermore, application of PI3K/AKT-specific inhibitors significantly abolishes the beneficial effects of ACS on neurons, confirming that the PI3K/AKT pathway is an important potential signaling pathway in the action of ACS. The economic impact of central nervous system-related diseases on patients is substantial because permanent disability leads to a high estimated lifetime cost of treatment per patient ,2 . AltIn vitro, ES also influences several types of cell behavior, including proliferation, differentiation, and migration ) was used to calculate the expression levels of mRNAs. The mRNAs with a fold change >2 or <0.5 and aP value<0.05 from a parametric F test comparing nested linear models were selected as differentially expressed mRNAs using the R package edgeR (https://bioconductor.org/packages/release/bioc/html/edgeR.html). The sequencing data have been uploaded onto the Gene Expression Omnibus with the accession no. GSE207117.Fastp software was used to remove reads containing adaptor contamination, low-quality bases and undetermined bases with default parameters. Afterward, the sequence quality was also verified using fastp. HISAT2 (http://powerandsamplesize.com/). The group sizes were calculated to provide at least 80% power. Each dot represents the number (N) of samples per group. The data normality was evaluated with the Kolmogorov–Smirnov test, and the variance homogeneity was evaluated using Levene’s test. To compare two groups of data, unpairedt tests were used. If the data were normally distributed and the variance was homogeneous, one-way ANOVA followed by the post hoc Bonferroni′s test was performed. If the data were not normally distributed or variance homogeneity was not met, the Kruskal–Wallis test was performed followed by the post hoc Mann–Whitney U test. The nonparametric data are displayed as the medians and interquartile ranges, and the other data are displayed as the means±standard deviations (SDs).P<0.05 was considered to indicate a significant difference. All the samples were assayed in a randomized manner. All analyses were conducted blinded to the experimental or control group.The data were analyzed using SPSS (version 23.0) and GraphPad Prism (version 8.0.2). Fiji was used to quantitatively analyze the images. Sample size calculation was performed to determine the appropriate sample size  but not in the control group (P<0.01vs. the control)  E. Therefontrol) F‒H. Moreontrol) I,J.In the present study, we directly compared the effects of ACS and DCS on primary cortical neurons. Given the intrinsic electrical characteristics of neurons, we selected primary cortical neurons. Both ACS and DCS enhance the dendritic complexity of cortical neurons, and ACS exhibited a better effect than DCS. Additionally, we investigated the formation of the neuron network after ES by evaluating the firing spikes depicted in the raster plots, which reflect the activity, synchrony, and oscillation of the neuron network. We confirmed that the neurite growth effects of ACS might be associated with the PI3K/Akt/GAP43 signaling pathway.et al.et al.Neurotrauma, neurodegenerative diseases, and other central nervous system-related diseases threaten the lives of millions of people worldwide. ES plays an important role in neural regeneration and is widely used for the treatment of nervous system disorders caused by SCIet al.At present, we recognize two primary forms of ES: ACS and DCS. Numerous preclinical studies at the cell molecular level have been conducted to probe the possible mechanisms of action. Previous studies have reported that PC12 cell lines exposed to ACS exhibit enhanced neurite elongationHowever, despite the growing evidence showing the effectiveness of ES, the differences between the effects of ACS and DCS on cells are unclear. Most types of ES used in published studies were ACS. The underlying mechanism of the cellular response to ACS and DCS remains unclear. ACS might prevent the buildup of charge in the cellular environment. Therefore, a direct comparison between ACS and DCS is needed.2+ channels, transmembrane potentials, and ion flowPrevious investigations of the mechanisms of ES have focused on voltage-gated CaThe membrane-associated protein GAP43, a marker of axonal and synaptic growth, is involved in axonal elongation, regeneration, and neurotransmitter release ,42 . WeIn summary, we explored the influence of ACS and DCS on the electrophysiological characteristics of cultured primary cortical neurons. We established a simple, safe, and effective electrostimulation culture platform that is amenable to further research and translation. It is particularly important to study the mechanism through which ES affects cells and to formulate effective clinical therapy parameters. Moreover, neuronal electrophysiological properties and axonal morphology after ACS and DCS were compared. Transcriptome sequencing showed changes in the neuronal cytoskeleton and associated pathways, such as axonogenesis, the shape of axons, the growth of neurites, and the branching of axons after ACS. Based on these findings, we further determined the association of ACS with the PI3K/AKT/GAP43 pathway.Supplementary