The proportion of KT recipients with obesity was 9.8% . Adequate adherence to the Mediterranean diet (Medi-Lite score >9) was overall low . In participants with obesity the Medi-Lite score inversely correlated with BMI . Overall, 30.6% of participants had a low level of physical activity . The amount of energy expended walking was significantly lower among participants with obesity  vs. 1056  METs/week, p = 0.017). Conclusions: the burden of obesity among KT recipients is similar to that of the general population. Adherence to the Mediterranean diet was generally low, and nearly one-third of participants had a low level of physical activity. Building specialized multidisciplinary teams to manage obesity in KT recipients is urgently needed.Background: Obesity may negatively impact clinical outcomes in kidney transplant (KT) recipients. Limited information is available on the prevalence of obesity in this population, and on the lifestyle habits associated with obesity. Methods: we conducted an online, anonymous survey to assess of the proportion of KT recipients with obesity, adherence to the Mediterranean diet  using the MEDI-Lite questionnaire, and level of physical activity using the International Physical Activity Questionnaire (IPAQ) short form among KT recipients. Results: 255 KT recipients participated. Median (25th–75th quartile) age was 56.0  years, 43.9% female, median BMI 23.9  kg/m Obesity is a complex, chronic disease that impacts nearly all organs and systems, including the urinary system . The preSteroid therapy may contribute to post-transplant weight gain , but theGiven the impact of obesity on renal function and health status in KT recipients, and the potential benefits associated with a healthy lifestyle , providing information on the burden of obesity and the lifestyle habits of KT recipients is crucial to put the spotlight on an issue that is often overlooked both by healthcare professionals and patients, and to help design targeted strategies aimed at improving patient and graft outcomes. Therefore, the aim of this cross-sectional study was to investigate these aspects in a real-world population of KT recipients.We conducted an anonymous, open online survey among adult (age ≥ 18 years) individuals on renal replacement therapy . The survey was posted on a dedicated web page in Google Forms between 1 January 2022 and 31 March 2022, and was advertised through social media platforms by the main national associations of patients with polycystic kidney disease (PKD) or on renal replacement therapy. We collected self-reported height and weight to compute body mass index (BMI), age, sex, smoking status, region of residence, level of education, working status, cause of CKD, type, year and number of KT, use of steroid therapy, pre-KT dialysis duration and type. Participants were also asked about weight changes after starting dialysis or KT, and whether a physician had provided recommendations about their weight. The total number of questionnaire items was 45 over a single web page. Participants were required to provide an answer to each item in order to submit the questionnaire; therefore, only questionnaires with complete answers were available for analysis. As the two populations have different characteristics , data were analyzed separately. For the purpose of the present study, only KT recipients were included in the analysis.Adherence to the Mediterranean diet was assessed using the MEDI-LITE questionnaire, a validated questionnaire that assesses the consumption of nine food categories  ,21. The The level of physical activity was assessed using the International Physical Activity Questionnaire (IPAQ) short form, which estimates the level of physical activity  based on the subject-reported activities  relative to the 7 days prior to completion of the questionnaire and is validated for use in the Italian population .The study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee of IRCCS San Raffaele Roma . The voluntary questionnaire could be completed only by participants who provided their informed consent to be enrolled in the study. The questionnaire was anonymous; no information that could render the data subject identifiable was collected. The results are reported according to the Checklist for Reporting Results of Internet E-Surveys (CHERRIES) t-test or Mann–Whitney U-test were used for between-group comparisons, depending on variable distribution. The Fisher exact test or the χ2 test was used to assess the association between categorical variables and obesity status (BMI ≥ 30 kg/m2). The correlation between BMI and the Medi-Lite score was assessed using the Spearman’s rank correlation test. Logistic regression models were used to identify variables associated with obesity, adjusting for age and sex. All variables were screened for violations of the assumptions relevant to each of the statistical analysis performed. Statistical significance was set at p < 0.05. Statistical analysis was conducted using IBM SPSS Statistics .Descriptive statistics were obtained for all study variables. Normality was assessed with the Shapiro–Wilk test. Continuous variables are expressed as mean ± standard deviation or median (25th–75th percentile), depending on data distribution. Categorical variables were summarized as counts and percentages. Missing data were not imputed. The n = 67) were excluded. The characteristics of the 255 KT recipients included in the analysis are presented in A total of 333 potential participants accessed the informed consent page, of whom eleven (3.3%) did not consent to participate in the study. For the purpose of the present analysis, patients on dialysis , from Northern Italy, with an intermediate level of education and active workers. PKD was the most common CKD etiology. Nearly all participants received a KT alone, median time since transplant was 6.0 years, and most underwent dialysis prior to KT, for a median of 2.0 years. Hypertension was the most common comorbidity, followed by dyslipidemia, diabetes and vascular disease. Median BMI was 23.9 . The proportion of KT recipients with obesity was 9.8% (95% C.I. 6.4% to 14.1%) , with 19A comparison of patients with and without obesity is provided in p = 0.002). All participants living with obesity reported that their physician had addressed their weight and recommended weight loss.Participants were surveyed about weight changes following KT. Weight gain was reported by nearly half of the participants (47.8%), whereas 35.3% and 16.9% of participants reported either no change or weight loss after KT. The proportion of participants reporting weight gain after KT was significantly higher among those living with obesity  in participants with obesity, but not in the whole cohort nor in participants without obesity.The median Medi-Lite score in the whole cohort was nine . There were no significant differences in the Medi-Lite score nor in the proportion of participants with adequate adherence to the Mediterranean diet, which was overall low (44.7%), between participants with or without obesity . CorrelaAnalysis of the IPAQ-SF responses revealed that, overall, 30.6% of participants had a low level of physical activity. This proportion was numerically higher among participants with obesity, as compared to those without obesity . FurtherWe assessed the proportion of KT recipients with obesity and important lifestyle habits, including the adherence to Mediterranean diet and the level of physical activity, among KT recipients. We found that approximately 10% of KT recipients who participated in the survey were living with obesity. This figure is in line with recent data from the Italian National Institute of Health , which reports that 10.8% of Italians live with obesity , but is Most available data indicate that KT recipients with obesity are at risk of worse patient and graft outcomes, with the risk progressively increasing with increasing BMI . The risp < 0.025) in participants with obesity, which was very similar to that found by Dinu and colleagues in subjects with overweight/obesity  [We surveyed participants about their adherence to the Mediterranean diet using the validated Medi-Lite questionnaire. The median Medi-Lite score in our cohort was nine, which is three points lower than that found in a sample of nearly 2000 Italian adults by Dinu and colleagues , suggest 0.0001) . Efforts 0.0001) ,37, alth 0.0001) . More re 0.0001) . Finally 0.0001) .Physical activity, together with healthy eating, is a pillar of the management of obesity and associated cardiometabolic alterations. A recent analysis found that an active lifestyle is associated with slower decline of renal function in KT recipients . We founSome limitations of our study need to be acknowledged. To keep the survey completely anonymous, we did not collect information  that could be used to identify duplicate entries, therefore we cannot exclude that multiple entries from the same individual were included in the analysis. It is possible that the actual proportion of KT recipients with obesity is even higher than that we found, as self-reported height tends to be overestimated and weight to be underestimated when compared with measured values . FurtherIn conclusion, the burden of obesity among KT recipients is similar to that of the general Italian population. Adherence to the Mediterranean diet was generally low, and nearly one-third of participants had a low level of physical activity. Obesity in KT recipients may be associated with a lower adherence to the Mediterranean diet and reduced physical activity. Building specialized multidisciplinary teams to manage obesity in KT recipients is urgently needed.


The evidence that risks of morbidity and mortality are higher when very premature newborns are born during the on-call period is inconsistent. This study aimed to assess the impact of this situation among other determinants of outcomes, particularly newborn characteristics and care organization.Observational study including all infants born < 30 weeks’ gestation in a French tertiary perinatal center between 2007 and 2020. On-call period corresponded to weekdays between 6:30 p.m. and 8:30 a.m., weekends, and public holidays. The primary endpoint was survival without severe morbidity, including grade 3–4 intraventricular hemorrhage (IVH), cystic periventricular leukomalacia, necrotizing enterocolitis, severe bronchopulmonary dysplasia (BPD), and severe retinopathy of prematurity. The relationship between admission and outcome was assessed by an adjusted odds ratio (aOR) on the propensity of being born during on-call period and expressed vs. weekday. Secondary analyses were carried out in extremely preterm newborns (<27 weeks’ gestation), in cases of early death (within 7 days), and before  vs. after  the implementation of a pediatrician-nurse team dedicated to newborn care in the delivery room.A total of 1,064 infants  were included: 668 during the on-call period (63%) and 396 (37%) on weekdays. For infants born on weekdays, survival without severe morbidity was 54.5% and mortality 19.2%. During on-call, these rates were 57.3% [aOR 1.08 (0.84–1.40)] and 18.4% [aOR 0.93 (0.67–1.29)]. Comparable rates of survival without severe morbidity [aOR 1.42 (0.87–2.34)] or mortality [aOR 0.76 (0.47–1.22)] were observed in extremely preterm infants. The early death rate was 6.4% on weekdays vs. 8.2% during on-call [aOR 1.44 (0.84–2.48)]. Implementation of the dedicated team was associated with decreased rates of mortality [aOR 0.57 ] and grade 3–4 IVH [aOR 0.48 ], and an increased rate of severe BPD [aOR 2.16 ], for infants born during on-call.In this cohort, most births of very premature neonates occurred during the on-call period. A team dedicated to newborn care in the delivery room may have a favorable effect on the outcome of infants born in this situation. The quality of patient care depends on several factors, including the availability of caregivers. In many healthcare facilities, however, the caregiving workforce, especially physicians, is reduced at night and on holidays, although the activity may be comparable or even higher than in the daytime and on weekdays. Physical and mental fatigue may, under these conditions, be a pejorative factor in patient care. A study conducted among adult intensivists found that the cognitive abilities of physicians were significantly impaired following a nightshift in the intensive care unit, regardless of professional experience and the length of sleep while on call .In low-risk populations, birth during the on-call period has been associated with adverse perinatal outcomes, notably a lower Apgar score, more frequent admission to a neonatal intensive care unit (NICU), and increased neonatal mortality and morbidity –7. This The first objective of this study was to assess whether birth during the on-call period was associated with increased mortality or major morbidities in very preterm infants. Our second objective was to determine the impact of the team workforce and composition during these duty-hours on the occurrence of these adverse events.This observational study was carried out between 1 January 2007 and 31 December 2020, i.e., over 14 years. All live-born premature infants were included if they were born in our institution < 30 weeks’ gestational age (GA), actively managed in the delivery room (DR), and admitted to the department of neonatal medicine (in-born infants).The study was performed in a tertiary perinatal center located at a single site: Arnaud de Villeneuve Hospital, Montpellier University Hospital, France. The median (interquartile range) annual number of births in the center during the period was 3,551 , including 14.4 (14.1–14.8)% preterm deliveries.The DR is located on the ground floor, just below the department of neonatal medicine. Infants are transported in a mobile incubator  equipped with a ventilator , an infusion set , and a cardiorespiratory monitor  over an average distance of approximately 150 m. The elevator transport duration, from triggering of the call to the arrival on the first floor is 20–30 s.The department of neonatal medicine has a capacity of 47 beds, including 14 type 3 beds, corresponding to the NICU, 18 type 2b beds, and 15 type 2a beds. The medical team is composed of nine senior pediatricians, three fellows, and five residents. The number of nurses per neonate is framed by the French perinatal decrees of 1998, i.e., one nurse for two neonates for type 3 beds, one nurse for three neonates for type 2b beds, and one nurse for six neonates for type 2a beds.According to the perinatal protocol of our institution, the care was overwhelmingly palliative for live-born premature infants of 22–23 weeks’ GA, and intensive for infants of 24–29 weeks’ GA.Epoch 1 (January 2007 to December 2013): On weekdays, a pair composed of a senior pediatrician or a fellow and a resident was assigned to provide care for newborns in the DR. During on-call periods, a senior pediatrician or a fellow and a resident were present on site to provide care for infants hospitalized in the department, as well as for those in the DR. Another senior pediatrician could be mobilized for operational duty if necessary.Epoch 2 (January 2014 to December 2020): A nurse systematically participated in the care of newborns in the DR, on weekdays and during on-call periods. Operational duty was replaced by the on-site presence of a second senior pediatrician. Thus, medical organization was unchanged on weekdays; however, in the second epoch, one of the two pediatricians was fully available, along with the resident and the nurse, to provide care in the DR during on-call periods.–the systematic participation, on weekdays and on-call periods, of a nurse to provide care for newborns in the DR in Epoch 2, whereas this healthcare professional was not involved in Epoch 1;–the systematic participation, on weekdays and on-call periods, of a pediatrician to provide care for newborns in the DR in Epoch 2, whereas this healthcare professional was sometimes unavailable during on-call periods, and replaced by a resident, in Epoch 1.During the two epochs, midwives gave routine care to the newborns in the DR. However, when a newborn was considered vulnerable, following a premature birth, for example, they could urgently and even prenatally summon the resident and senior pediatrician by following a systematic appeal procedure. While waiting for their arrival, the midwives could initiate initial care, including warming, drying, stimulation, positioning of the upper airways, providing ventilatory assistance , and even resuscitating the newborn. Thereafter, they participated in the continuation of care under the direction of the pediatric team and ensured the communication of information between the parents and the obstetric team.Perinatal data for each premature infant were collected prospectively in a database created for neonates born before 33 weeks’ GA and/or with a birthweight less than 1,500 g and admitted to the department of neonatal medicine. The database uses a predetermined form, with detailed definitions of each item. More than 150 variables were assessed for each infant concerning antenatal history and the neonatal period.The on-call period corresponded to weekdays night, i.e., between 6:30 p.m. and 8:30 a.m., weekends and public holidays. Births during off-peak hours occurred between 12:00 a.m. and 6:59 a.m.  sevSevere cerebral lesion was defined by the presence of a grade 3–4 IVH and/or a cystic PVL on cranial ultrasonography.Early death was defined as occurring within 7 days , 7–11. TThe primary endpoint was survival without severe morbidity.The secondary endpoints included rates of mortality before hospital discharge and any of the major morbidities as defined above.Comparisons of infants born during vs. outside of an on-call period were made using the Fisher, chi-squared, Student, and Wilcoxon-Mann-Whitney tests, as appropriate.To limit confounding bias, the association between the birth period and the outcome was adjusted on a propensity score. The propensity score was defined as the infant’s probability of being born during the on-call period based on his/her individual observed covariates and estimated with a logistic regression model. In this model, the birth period was the dependent variable and was studied in relation to the baseline antenatal characteristics that were statistically associated with exposure to the following: multiple birth, antenatal glucocorticoid administration, delivery mode, gestational age, sex, intrauterine growth restriction, premature rupture of membranes, and preeclampsia. The relationship between birth during the on-call period and outcomes was expressed by the odds ratio (OR), weighted by the propensity score (aOR), and the 95% confidence interval (CI).Three subgroup analyses were carried out: in the group of infants born extremely preterm (< 27 weeks’ GA), in cases of early death (within 7 days), and to compare the outcomes in epochs 1 and 2.p < 0.05.Based on a survival rate without major morbidity of 50% reported in our country for this population , and witp < 0.05 was considered statistically significant.Statistical analysis was performed with SAS Version 9 software . Values are expressed as numbers (%) or medians ; Approval of this study was obtained from the institutional review board of Montpellier University Hospital (IRB-MTP-2021-07-202100891).During the study period, 1,064 infants < 30 weeks’ GA were admitted to the department: 668 during the on-call period (63%) and 396 (37%) on weekdays. The perinatal characteristics of these patients are summarized in The stay in the department of the infants born during the on-call period was characterized by more frequent use of an umbilical venous catheter for parenteral nutrition and cyclooxygenase inhibitor for patent ductus arteriosus. Their length of stay was comparable to that of infants born on weekdays, although with a slightly higher weight at discharge .For the infants born on weekdays, survival without severe morbidity was 54.5% (216/396). For the infants born during the on-call period, this rate was 57.3% (383/668), aOR (95% CI) 1.08 (0.84–1.40). No difference in either the unadjusted or adjusted analysis of the propensity score was observed for survival without severe morbidity for births in the different on-call subperiods. In addition, birth during off-peak hours, whether on weeknights or holidays, had no significant influence on the primary endpoint .No difference in mortality or any major morbidity was observed according to the period of birth in either the unadjusted or the adjusted analysis .In this cohort, 362 (34%) infants were born < 27 weeks’ GA, including 19 < 24 weeks’ GA. Their median GA and birthweight were, respectively, 25.6  weeks and 752  g. Survival without severe morbidity, mortality, and major morbidities were unaffected by birth occurring during the on-call period .Death occurred within 7 days in 71 (6.7%) infants, corresponding to 36% (71/199) of overall mortality. In infants born on weekdays, the early death rate was 6.4% (22/342). The occurrence of this event was unaffected by the birth period , includiPerinatal characteristics according to the two epochs are shown in For infants born on weekdays, the adjusted analyses revealed no significant change between the two epochs in rates of survival without severe morbidity, mortality, or severe morbidities .p = 0.03], grade 3–4 IVH , and severe brain lesions , as well as an increased rate of severe BPD   0.57 ,  = 0.03] .p = 0.009] and severe brain lesions . The mortality rate did not change significantly   0.50 ,  = 0.06] .Causes of death also differed; notably, mortality associated with severe cerebral lesions was reduced in the overall population in the second epoch .This study showed that most births of very preterm infants occurred during the on-call period. While these births differed in several perinatal characteristics from those occurring on weekdays, no impact was observed on survival or the occurrence of severe morbidities during hospitalization, including for extremely premature birth. Our study also suggested that organizational factors, such as the availability and composition of the team providing care in the DR, influenced the risk of death and some severe morbidities in cases of very premature birth.We defined the on-call period to include nights, weekends and public holidays because there are fewer physicians at these times and the team is less experienced compared with the traditional pair of a senior physician and a resident. In a conventional day/night segmentation , it is important to note that 70% of the time in a week corresponds to the on-call period (118 out of 168 h), and this ratio is even higher in weeks with public holidays. Therefore, it was unsurprising that most of the admissions in our sample occurred during this period. Few studies have adopted a comparable definition and have found birth occurrence or NICU admission rates ranging from 60 to 67% , 10.The ratio of births during the on-call period could not be explained only by the relative length of this period over a week. As observed , infantsStudies carried out in NICU networks in Canada and Australia have found contradictory results on the risk of early mortality among infants < 32 weeks’ gestation admitted at night. These differences may be related to organizational differences within units and within networks. Indeed, a network with the prerogative to regulate perinatal traffic may avoid excessive workloads in individual units, which can be a source of excessive mortality , 10, 22.A recent report from the Canadian Neonatal and Preterm Birth networks suggested a higher mortality in the event of evening birth (4:00 p.m. to 11:59 p.m.) in extremely premature infants of 22–27 weeks’ gestation . This fiEarly mortality, before 7 days, comprised only 34% of the mortality observed in our sample during hospitalization. This rate was identical to that observed in the French EPIPAGE-2 study, a prospective population-based cohort of very preterm births performed in 2011 . This tiThe composition and availability of the team caring for the patients during epoch 2 seemed clearly more appropriate, with a physician-nurse pair dedicated to this activity. The presence of a nurse trained in the department of neonatology ensured expertise for carrying out technical procedures in the DR, such as the placement of peripheral venous catheters; the initiation of intravenous fluids, caffeine and—if required—antibiotics or sedatives; the preparation and assistance for surfactant administration; and the set-up of non-invasive and invasive ventilation devices . MonitorSeveral factors may explain why improvements in death and severe brain lesion rates were observed only for on-call periods. Numerically, change in the organization of care in the DR was mainly applied to neonates born during the on-call period, since their rate increased significantly during the second epoch. In addition, this new organization also had several consequences for the dispensation of care by the pediatrician. First, the physician was more fully available, with the possibility of concentrating full attention on the infant in the DR, since a second pediatrician was present on site for the other patients hospitalized in the department. Second, the composition of the pair was more homogeneous, since it was always a senior pediatrician who provided care and no longer a resident, who could be called upon during the first period in the event of the senior’s unavailability. Third, the second senior on site could, if available, assist in the newborn’s care. In our experience, this process was sometimes easier to mobilize during on-call than on weekdays. Fourth, the presence of two seniors on site brought serenity and security and reduced the physicians’ stress. It also allowed each one to take a few minutes or hours of rest by alternating these rest times, which can restore mental capacities and performance .Our data found an increased rate of severe BPD in infants born on-call during epoch 2. Other prospective longitudinal registries have reported increased incidence of BPD, whereas in-hospital mortality had decreased over time among very preterm infants –36. PoteOur study has several limitations. The results of this retrospective, single-center study, which only considered patients born in a tertiary perinatal center and managed in a single NICU, may be difficult to extrapolate to other centers. Compared to population-based studies, however, it offers other advantages. Our data collection was homogeneous since it was carried out by only two investigators. The number of missing data items was very low, enabling us to present factual results with no imputed or projected data. Above all, we had in-depth knowledge of organizational factors, notably the resources and variations in staffing patterns, for both physicians and nurses, according to on-call or weekday periods, as well as the different epochs of the observational period.Maternal, obstetric and neonatal data were linked, which is not the case for all databases . We analAnother weakness is our limited number of patients. However, for the hypothesis tested, we greatly exceeded the number of subjects required. In addition, the result for the primary endpoint was very close to the rate observed in the national EPIPAGE-2 cohort, for infants of comparable gestational ages .It is also likely that active care was not provided for most of the births occurring at 22–23 weeks. Mortality in the DR despite intensive management of these newborns was not reliably documented over the study period. For this reason, we did not adjust our sample based on birth certificates from our institution, as some livebirths may have been misclassified and recorded as stillbirths since intensive care was not provided . We opteThis study showed that the births of the most vulnerable newborns occurred mainly during the on-call period, i.e., at moments when medical resources were suboptimal, both quantitatively and qualitatively. This finding suggests that each NICU should individually analyze the features of the population admitted during this period and adjust to ensure adequate organization. Our experience suggests that a physician-nurse pair specifically dedicated to the initial care in the DR may ease the situation in units with high patient volume and staff workload and prolonged workshifts during on-call periods. This might improve the prognosis for patients and enhance job satisfaction for caregivers and reduce the risk of burnout.The original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by the Institutional Review Board of Montpellier University Hospital (IRB-MTP-2021-07-202100891). Written informed consent from the participants’ legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.GC, BT, MB, PF, J-CP, and AG conceptualized and designed the study, contributed to the search for published works, carried out the data acquisition and interpretation, and drafted and finalized the report. CC performed the data analysis, contributed to the data interpretation, and critically revised the report. All authors have read and approved the final manuscript.


Background: Diabetes is a risk factor for chronic kidney disease because it induces nephropathy. Okra is a rich source of antioxidants, vitamins, minerals, and fibers, of which favorable effects in diabetes have been reported in many animal studies. The present trial aimed to investigate the effect of dried okra extract (DOE) supplementation on anthropometric measures, body composition, appetite, and dietary intake in diabetic nephropathy (DN) patients. Methods: In this triple-blind placebo-controlled randomized clinical trial, 64 DN patients were randomly allocated to receive a 125-mg capsule of DOE (n=32) or placebo (n=32) for 10 weeks. At baseline and endpoint of the trial, anthropometric variables, body composition indices, dietary intake, and appetite scores were evaluated. Results: The results showed that energy  and carbohydrate  intake as well as desire to eat salty food (P=0.023) were reduced in DOE group at the endpoint, compared to the baseline values. However, anthropometric measures, body composition, and appetite score were not significantly different between the two study groups. Conclusion: In conclusion, the present clinical trial showed that DOE could significantly decrease energy intake and carbohydrate consumption in the DN patients. Further clinical trials are needed to determine the effects of this supplement. In fact, increased blood glucose in diabetic patients impairs the vessels and various organs in the body.3 Diabetic nephropathy (DN) is one of the major microvascular complications of diabetes.4 DN occurs in nearly 20-30% of diabetic patients.5 DN is more common in patients with type 1 diabetes mellitus (T1DM), compared to type 2 diabetic patients. However, due to the higher prevalence of T2DM, the number of DN patients with this type of DM is higher.6 DN is characterized by reduced kidney function or glomerular filtration rate (GFR), 7 as well as increased creatinine in the serum and urinary albumin excretion.8 It is the major cause of end-stage renal disease (ESRD), as well as a financial burden on health system.9 Diabetes mellitus (DM) is one of the important public health issues in different societies.10 Also, obesity has a crucial role in the development of DN. In fact, in addition to diabetes, obesity also induces hypertension via increasing renal tubular reabsorption and creating a hypertensive change in renal pressure through several mechanisms, including sympathetic nervous system, renin-angiotensin-aldosterone system, and physical pressure on the kidney. Hypertension leads to increased GFR as well as renal injury induction.11 Previous evidence indicated that the storage of high-fat content in the body induces obesity consequently, triggering a low-grade inflammation in the body. It is already reported that the increment of inflammation in the body leads to an increase in blood glucose level and subsequent diabetes. Therefore, body weight (BW) is considered a major risk factor for diabetes.Abelmoschus esculentus (okra) is a yearly plant from Malvaceae family, which grows in tropical and subtropical regions.12 The main components of okra are dietary fibers, polysaccharides, vitamins, minerals, and antioxidant ingredients such as flavonoids and quercetin.13 The favorable effects of okra have been illustrated in various situations such as oxidative stress, inflammation, and tumor process.14 Recently, the desirable effects of okra on the management of BW has been cited in several studies.16 For instance, Dubey and Mishra reported that okra seed supplementation had desirable effects on BW and serum cholesterol level in hypercholesterolemic rats.17 Another study on diabetic rats showed that okra powder supplementation could significantly decline BW.18 Further, it was shown that antioxidants of okra prevented weight gain without any changes in food intake.19 In contrast, Wang et al illustrated that okra powder did not have any significant effect on BW of rats fed a hyperlipidemic diet plus okra powder compared to rats on a hyperlipidemic diet alone.20 Also, a clinical trial on diabetic patients did not find any significant effect on BW after 8 weeks of okra powder supplementation.2122 as well as concern over the relation between BW, hypertension, and kidney function, the present study was conducted to investigate the effects of okra extract supplementation on satiety, body weight, and body composition in DN patients. Due to the high global prevalence of DN, its huge costs on healthcare system, limited documents about the effects of okra on anthropometric measures in human samples,23 Preparing dried okra extract (DOE), 150-kg okra fruit was first prepared from Fruit and Vegetable Market of Tabriz in July 2019. The whole okra fruit was washed with water and tinily chopped for better and earlier drying. Then, the chopped okra was placed in the shade at 45°C to dry. Totally, 15 kilograms of okra powder was obtained from fresh okra fruits. After that, the okra powder was mixed with 50% alcohol in a ratio of 1 to 5 and placed in a percolator device at a temperature of 35 degrees centigrade, and the circulation operation was performed for 24 to 48 hours. After saturating the solvent and measuring the concentration of the solution, the mixture was filtered and transferred to a rotary device. Under vacuum conditions and at a temperature of 40 to 45°C, the hydraulic solvent was separated; then, the okra solution was concentrated. Finally, the concentrated okra was transferred to a vacuum dryer device; then, it was dried and pulverized.2and under 40 kg/m2 were eligible to participate in the study. Having renal disorders, liver disease, cardiovascular disease, hypo- or hyperthyroidism, cancer, uncontrolled diabetes (HbA1c more than 8 mg/dL), consumers of anticoagulants and non-steroidal anti-inflammatory drugs, alcohol consumption, smoking, pregnancy or breast-feeding, following unusual diets in the last 6 months or consuming energy less than 800 kcal or more than 4200 kcal per day, routine consumption of okra in the last three months, and allergy to okra were considered exclusion criteria of the study. The estimated sample size for the present two-arm parallel study was 25 subjects for each group with a power of 80% and α = 0.05 to investigate a difference of 25 mg/dl in the mean value of fasting blood glucose with a pooled standard deviation obtained from the study of Saatchi et al.22 The present 10-week randomized, triple-blinded, placebo-controlled clinical trial was performed from June 2020 to September 2021 in Tabriz, Iran. Patients with DN were recruited from people who were referred to the diabetes clinic of Imam Reza hospital as well as public announcement. Diabetic patients aged between 40 and 70 years, diagnosed with DN, with proteinuria more than > 0.3 g/24 h, and BMI over 27 kg/m At baseline, the procedure of the study was explained for all eligible participants and written informed consent was obtained from all subjects. Patients were stratified by gender and randomly allocated either to the intervention (n = 32) or placebo (n = 32) group by block randomization method with block sizes of four . The intervention group received either one 125-mg capsule of DOE  or carboxymethyl cellulose (CMC) (containing 87 mg CMC) for 10 weeks. DOE and CMC capsules were similar in terms of shape, size, color, taste, and smell. The subjects and investigators were blinded until the end of the study and analysis of data, as the bottles of the supplements were coded with A or B before the study. Moreover, all patients in each group received a list of DN dietary recommendations. Every week, the investigators followed the participants by phone calls to ensure their supplement consumption and check for any possible side effects. The patients were given one bottle of the supplement every 24 days and requested to return their bottle in the next visit to check out the number of remaining capsules and degree of compliance with the supplement. Individuals with less than 90%-compliance were excluded from the final analysis.24 The physical activity level of the patients was classified as low, moderate, and high.25 At baseline and end of the study, a visual analogue scale was also completed to measure the appetite sensation of the patients.26 Systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the patients were measured twice in a seated position after ten minutes of rest, using a standard mercury sphygmomanometer. The average of the two measurements was entered to the final analysis. Dietary intake was assessed at the onsetof the study and the end of 10 weeks, using a 3-day  food record. The patients were trained how to record their dietary intake. The investigators interviewed the patients to check out their dietary records, according to the household measures for determination of the exact portion size. Afterward, the portion sizes were converted to grams and analyzed for energy and nutrient content, using Nutritionist IV software. The physical activity of the subjects were evaluated at the beginning and endpoint of the trial by the International Physical Activity Questionnaire short form (IPAQ-SF).2). In addition, waist circumference (WC) was determined by a non-elastic meter with 0.5 cm precision in the narrowest area between the rib cage and the umbilicus. Furthermore, hip circumference (HC), the largest circumference between the waist and knees, was measured by an inelastic meter with 0.5 cm precision. Waist to hip ratio (WHR) was calculated by the followed formula: WC/HC. Body composition indices were assessed using bioelectric impedance analysis (BIA) . The weight of the patients was measured while they were wearing light clothes, with 100-g precision, using a Seca digital scale . The height was measured barefoot to the nearest 0.1 cm, using a meter reader attached to the wall. Body mass index (BMI) was calculated by dividing weight (kg) by the square of height  for normally and non-normally distributed data, respectively. Also, qualitative variables were presented as frequency (percent). To check for between-group differences for quantitative data, independent samples t test or Mann-Whitney U test was applied, as appropriate. However, for qualitative variables, Fisher’s exact test or Sign test was performed. Paired samples t test and Wilcoxon signed-rank test were also used to evaluate intra-group differences, as appropriate. Analysis of covariance (ANCOVA) and quantile regression models  were conducted to control the effect of confounding factors for normally and non-normally distributed data, respectively. P values less than 0.05 were set as statistically significant level. All statistical analyses were performed using IBM SPSS Statistics software . Statistical analysis was conducted with per-protocol approach. As shown in P = 0.047) and carbohydrate consumption (P = 0.038) were decreased at the end of the trial only in DOE group, compared to the baseline levels. However, there were no significant differences in the intake of protein and fiber in neither groups. Between-group analyses revealed no significant changes in dietary intake, even after controlling the effects of confounders . Although the level of physical activity was reduced in DOE (P = 0.004) at the end of the study, no significant between-group was observed. The dietary intake and physical activity of the participants were presented in  Anthropometric variables including weight, BMI, WC, HC, and WHR of both groups are illustrated in P = 0.023) in DOE group and feeling to eat (P = 0.024) in placebo group, which reduced significantly at the end of the trial, compared to the baseline  to mice fed a high-fat diet (HFD) could significantly reduce their body weight in comparison with those receiving only HFD.15 It was also reported that supplementation with okra powder for 12 weeks inhibited weight gain caused by HFD.32 One in vivo study mentioned the effects of OP on decreasing the size of white adipose tissue (WAT) and the cells of WAT.15 In contrast, previous 33 Second, bioactive polysaccharides of okra and flavonoids involved in weight management via the regulation of nuclear transcription factors such as peroxisome proliferator-activated receptor-γ and liver X receptors.34 It was documented that weight loss needs the reduction of dietary intake as well as the increase in energy expenditure.35 Based on our results, although the energy intake of the patients in DOE group was significantly decreased, level of their physical activity was also reduced, in parallel, which could affect the results. Reduced levels of physical activity in patients may be due to the pandemic condition of the coronavirus in which people were encouraged to be quarantined. Although the results about the okra on body weight and body fat are inconsistent, some possible mechanisms have been proposed in previous studies. First, okra is reported to be a rich source of fibers that can delay gastric emptying and cause a full feeling.19 Another in vivo study indicated that supplementation with okra seed oil at 400 and 800 mg/kg for eight weeks did not have any effect on food intake of mice.36 According to the present clinical trial, okra had a significant effect neither on appetite score nor on food intake, compared to the placebo group. In line with our results, Fanet alreported that okra extract supplementation for 2 weeks did not affect dietary intake.37 The supplement used in the present study did not have any effect on satiety, it is not known whether the intervention was not of adequate dosage or the extraction procedure may reduced the amount of some ingredients such as fibers. Or, the supplement in the form of extract may really have no impact on appetite. The primary mechanism of okra on satiety is related to the fibers of okra which reduced the speed of gastric emptying and caused full feeling, although beneficial effects of okra on the regulation of adipokines such as leptin and adiponectin have also been reported in one study.in vitro and conducted on animal models. The bioavailability of okra in humans may differ from that in animals due to several factors, including intestinal absorption, intestinal microflora metabolism, hepatic and intestinal metabolism, cell uptake, and urinary and biliary excretion that can affect its efficiency. In addition, nearly all of the previous studies have been carried out on diabetes patients with milder disease conditions than those with DN state. In addition, inflammatory status is higher in DN due to increased oxidative stress,38 and this makes the comparison of our results with previous okra studies on diabetes difficult. Furthermore, the use of different types of okra products , as well as different preparation methods of supplements, cultivation area, cultivation condition, and harvest time, can all affect the results. Given that the finding of the present study decision about the effect of okra on weight and body composition still need further studies on the human sample at different circumstances, the obtined contradictory results against other studies may be due to the differences observed in the methodology and design of different studies; since many of the studies indicated the beneficial effect of okra are  The present clinical trial had several strengths. To best of our knowledge, this was the first clinical trial which examined the effects of okra extract on dietary intake, anthropometric measures, body composition, and appetite score in patients with DN. Second, all of the participants in both groups received a list of DN-related nutritional recommendations. Third, constant follow-up of the patients was performed by phone calls. However, there were some limitations, as below. First, the dietary intake of the patients seems to be underestimated due to self-reporting nature of food records. Second, the duration of the supplementation was a bit shorter due to budget deficit. It appears that better findings may have been achieved by longer durations of supplementation. However, a long-term study may increase the rate of drop-out of patients. The present study for the first time demonstrated that though supplementation of DOE for ten weeks resulted in decreased energy and carbohydrate intake as well as reduced tendency to salty food in DOE group, it did not have any significant effect on anthropometric variables, body composition, dietary intake, and appetite score, compared to the placebo. However, long-term trials with higher doses of okra are encouraged in future studies. The authors would like to thank all of the patients who agreed to participate voluntarily in this study, as well as the research team who collected the data. This research is based on the data obtained from the Ph.D. dissertation of Omid Nikpayam entitled ”The Effect of Okra Hydroalcoholic Extract supplemetation on Glycemic Control, Kidney Function, PPAR-α, PPARγ, TGF-β and Nrf-2 in Patients with Diabetic Nephropathy: A Triple-blinded Placebo-Controlled Clinical Trial” submitted to Tabriz University of Medical Sciences. MSA, ON conceptualized the study. Data collection was carried out by ON, NB, ES, VS, and MSA analyzed the data. The first draft was prepared by ON, with subsequent reviews and revisions completed by MSA. All authors reviewed the final draft and gave the approval to publish. This work was financially supported by the ‘Research Vice-Chancellor’ of Tabriz University of Medical Sciences (TBZMED), Tabriz, Iran, Grant agreement no:64859. The protocol of the present study was approved by the Ethics Committee of Tabriz University of Medical Sciences (IR.TBZMED.REC.1399.466) and registered at the Iranian registry of clinical trials (IRCT20110530006652N3). The authors report no declarations of interest.


Obesity is a pathology whose incidence is increasing throughout the world. There are many pathologies associated with obesity. In recent years, the influence of the microbiota on both health and pathological states has been known. There is growing information related to changes in the microbiome and obesity, as well as its associated pathologies. Changes associated with age, exercise, and weight changes have been described. In addition, metabolic changes associated with the microbiota, bariatric surgery, and fecal matter transplantation are described. In this review, we summarize the biology and physiology of microbiota in obese patients, its role in the pathophysiology of several disorders associated, and the emerging therapeutic applications of prebiotics, probiotics, and fecal microbiota transplantation. Obesity is often the initial pathophysiological mechanism of these pathologies and is currently defined for adults by the World Health Organization (WHO) as a body mass index (BMI) ≥30.0 kg/mor women , 2. Addinclusive , 2. Overnclusive . StudiesFirmicutes, accompanied by reduction of bacteria from phylum Bacteroidetes, was a characteristic of obese mice and human intestines , it has been possible to identify the profile of the intestinal microbiota and how its composition affects human metabolism, playing a fundamental role in the development of this disease –14. Sevetionship .Bacteroides in the third trimester; this condition doubles the risk of neonatal obesity due to changes in the microbial composition of the infant's intestine. This is demonstrated by the population in a cohort study of 935 mother-baby couples where 7.5% of newborns of obese mothers presented obesity at 1 year  and 3 years of age ; these children had a greater wealth of Firmicutes P < 0.05  and richness of bacterial species of these groups  . Ge. Ge16). P < 0.05 . AlthougFirmicutes (median 5.5 IQ 2.5–10.5) with respect to the other groups, without statistical significance (P = 0.384)  divided into three groups: eutrophic (EUT) with adequate body fat percentage (BF%), high EUT and BF%, and obese with high BF%, where the last group had a predominance of –19 yearsFirmicutes/Bacteroides (F/B) ratio (p = 0.002)  (F/B was significantly higher in obese people compared to non-obese (p = 0.55), family (p = 0.10) or gender (p = 0.12) and in all three Firmicutes and Bacteroidetes predominated (Firmicutes in the overweight group compared to low weight group (P = 0.002), and diversity was significantly lower in the group with the overweight (P = 0.007 for Shannon index and P = 0.009 for the Ace index) and low weight (p = 0.05 for the Shannon index and p = 0.08 for the Ace index) (P > 0.05); even in 1-month-old infants with normal weight there was a greater abundance of Lactobacillus and in the obese Rhomboutsia predominated and in the obese 6 months old, Clostridum sensu stricto  . The sam09–1.38) . Similaron-obese . These rominated . Althouge index) . Similar stricto .Firmicutes and Bacteroidetes, especially in the genera Clostridium clusters ; being a predictor in healthy subjects with high BMI  suggesting that the altered composition of BA may be involved in different metabolic states of obesity  and decreases the hepatic synthesis of BA; in addition, this BA activates the G protein-coupled plasma membrane bile acid receptor (TGR5) by increasing the production of GLP-1. This hormone modulates glucose homeostasis, energy metabolism , 24, and obesity .Clostridium scindens and Clostridium hylemonae in rodents prone to obesity. Due to their high capacity for bioconversion, these bacteria modify the metabolism of the BA and promote obesity. This conclusion was reaffirmed by findings in this same group of rodents of a decrease in secondary BA and an increase in primary ones  with an increase in Bacteroides (p =0.03) and a reduction in Blautia (P = 0.05) and Clostridium (P = 0.04) (2 (19 active and 21 sedentary) did not detect significant differences in alpha and beta diversity or the Firmicutes/Bacteroidetes relationship (p = 0.115) between the two groups. Nevertheless, there was more presence of Firmicutes (p = 0.085) and lower presence of Bacteroidetes (p = 0.076) in active women  . Similarve women .Obesity is a source of chronic low-level inflammation in various tissues, associated with metabolic defects , such asOn the other hand, the gut microbiota can influence glucose metabolism and host hormone regulation by producing various metabolites, such as short-chain fatty acids and BA –43. FurtA matter of great importance is that bacterial LPS has been reported not to be necessary for impaired glucose or insulin tolerance . The assClostridium and Clostridiaceae, lower LDL cholesterol and Lachnospiraceae, Gemellaceae, Turicibacter, higher metabolic syndrome risk, and the presence of Coriobacteriaceae meanwhile Faecalibacterium prausnitzii, Parabacterodes, Bacteroides caccae, Oscillospira, Parabacteroides distasonis, Coprococcus, and Haemophilus parainfluenzae were associated lower metabolic syndrome score, fasting glucose, and HOMA_IR , cardiovascular disease (CVD), and cancer , 58. ThiLactobacillus rhamnosus and Bifidobacterium animalis subspecies lactis) did not prevent gestational diabetes mellitus (GDM) (Lactobacillus plantarum K50 (LPK) supplementation for 12 weeks significantly reduced the total cholesterol and triglyceride levels with an increase in L. plantarum and a decrease in Actinobacteria, both correlated with changes in visceral adiposity ” at the hepatic level; however, more research is required . Researcus (GDM) . On the diposity . In postdiposity .Lactobacillus abundance with a symbiotic supplement. However, the decrease in BMI, waist circumstance, and body fat mass was associated with a decrease in Bifidobacterium abundance over time, supporting the idea that the synbiotic supplement used in this clinical trial modulates human gut microbiota by increasing the abundance of potentially beneficial microbial species (2) according to the Asia-Pacific criteria, aged 18–65 years (P < 0.05) were observed in body weight, BMI, body fat, waist circumference, waist/hip ratio, HDL-C, LDL-C, IL-6, IL-10, IL-1β, TNF-α, IgA, LPS, and zonulin values compared to the baseline values, meanwhile in placebo group no significant changes were obtained  and Streptococcus (P < 0.01) compared to the placebo  with prebiotic (refined ultra polydextrose or LU) in overweight and obese adult patients compared to B420, LU, demonstrated that the gut microbiota was modified for all groups compared to placebo . The 6-m placebo . The intnstrated .Currently, bariatric surgery is considered the only sustainable, efficient treatment for obesity . SurgicaPrevotellaceae, Bacteroidales, and Peptococcaceae taxa; the increase in iron is associated with an increase in Pasteurellaceae; the decrease in HbA1c is associated with a decrease in Coriobacteriacea and the increase in Clostridiales taxa. The most pronounced positive association is described between Lachnospiraceae and Coriobacteriaceae taxa in the reduction of cholesterol levels; however, the associations described correspond to the sequential impact of a crash diet followed by RYGB and SG, in which progressive weight loss and changes in the composition of the microbiota of patients with morbid obesity have been demonstrated  . The incnstrated . The chaeriaceae .The crash diet causes changes in the diversity and composition of the microbiota, while surgical procedures  prevent early changes in the composition and restoration of the microbial diversity that probably contributes to weight loss . The eleFirmicutes  surgery improves plasma glucose with a long-lasting effect in patients withT2D. Although the mechanism is unclear, RYGB increases the secretion of GLP-1 and improves insulin resistance . Obese prmicutes  and an ibenefits .Prevotella enterotypes exhibit a significant weight reduction compared to individuals enterotype Bacteroides  advised for patients with metabolic alterations and healthy adults imply a reduction of 40% of the daily recommendation and allows for the observation of changes in the microbial composition, patients with teroides . CR can teroides . A studyteroides . In additeroides . Despiteteroides . This coteroides . In additeroides . A studyteroides .Another current hypothesis about the usefulness of the gut microbiota in weight loss is the one that refers to the possible regulation of glycemia and body weight through the manipulation of the intestinal microbiota . Previouvia FMT and suggest a therapeutic potential for treating individuals with obesity. FMT has also shown efficacy in the treatment of ulcerative colitis (UC). It has been described that after 1 week of treatment with anaerobic FMT from a donor, it results in a high probability of remission at 8 weeks  has shown significant improvement in insulin sensitivity after 6 weeks with FMT from a lean donor  vs. FMT autologous or aFMT . In addi 8 weeks . Still,  8 weeks .Some GM processes have been better studied through intensive research that associates GM with obesogenic mechanisms. One is related to its participation in the BA's metabolism that finally contributes, in different ways, to increase the GLP-1 production, leading to more efficient glucose homeostasis, decreased insulin resistance, reduced fat absorption, and weight gain risk.Another way that GM may affect bodyweight control is through its effects depending on modifications to other metabolic processes related to immune function, mainly due to elevated levels of bacterial LPS, which have been found among subjects with obesity induced by a high-fat diet. These changes might cause an immune response of the mucosa and, consequently, an increase in intestinal permeability, even though it is not LPS dependent. Otherwise, hyperglycemia may also increase intestinal permeability, causing the translocation of LPS to the systemic circulation, which contributes to chronic inflammation of the liver and adipose tissue associated with the development of impaired glucose or insulin resistance, as well as metabolic syndrome.Bacteroidetes proportion in GM.Studies have been conducted about the influence of physical activity (PA) on GM to improve body weight control. PA improves the metabolic profile and immune response, at least temporarily, probably by incrementing Firmicutes/Bacteroides is higher in the obese gut, other researchers indicate the opposite or no association with this ratio.Nevertheless, there are still many gaps in the underlying mechanisms that GM exerts around body weight control. One poorly understood mechanism is related to how specific GM composition and function are associated with body weight dysregulation and related pathologies. Even though most of the research indicates that the ratio of On the other hand, there is still much controversy regarding the benefits, dosage, ideal composition, time of administration, side effects, and feasibility studies concerning pre-pro and symbiotic use in humans, as well as the real benefits of FMT in the prevention and management of obesity. Nonetheless, most research has found a more significant benefit in using symbiotics than prebiotics or probiotics administered individually. Besides, the aFMT has been associated with attenuation in weight regain and administration of aFMT capsules with long-term weight maintenance, but assessment and focus on individual response to intervention are needed.Therefore, despite the evidence supporting that GM induces favorable changes in the intestine of the subject with obesity, research on maintaining the long-term effects of therapeutics for the prevention and treatment of metabolic disorders associated with obesity is still lacking.RS, YS-A, BQ, and KG wrote the paper. SC conceived the draft, supervised the writing, and corrected the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Introduction: Axial spondyloarthritis (axSpA) is characterized by damage to the axial skeleton and entheses, and is often associated with extra-articular manifestations, in the presence of the human leukocyte antigen (HLA) B27. The aim of our study is to assess the performance of rheumatologists in interpreting the inflammatory and structural damage to sacroiliac joints, in comparison to radiologists. Material and Methods: The present study included a total of 34 patients diagnosed with axSpA, according to the Assessment of SpondyloArthritis International Society (ASAS) criteria for axSpA, examined from January 2021 to November 2021 in the Departments of Rheumatology and Radiology and Medical Imaging of the University of Medicine and Pharmacy of Craiova. All patients underwent physical examination, laboratory tests, and magnetic resonance imaging (MRI) of the sacroiliac joints. The images were interpreted by a senior radiologist (SR), a junior radiologist (JR), a senior rheumatologist (SRh), and a junior rheumatologist (JRh), who were blinded to the clinical and paraclinical data. Results: The overall κ was 0.7 for the JR , 0.707 for the SRh , and 0.601 for the JRh (moderate agreement), in comparison with the SR. Regarding the overall inflammatory changes, the SRh and JR were proven to have substantial agreement  with the SR, while the JRh was proven to have moderate agreement (κ = 0.607). The structural damage observed by the JR showed substantial agreement (κ = 0.676) with the SR, while the SRh and JRh had substantial and moderate agreement  with the SR. Conclusions: Our study showed substantial agreement between the senior radiologist, senior rheumatologist, and junior radiologist, and moderate agreement with the junior rheumatologist. Axial spondyloarthritis (axSpA) is characterized by damage to the axial skeleton (spine and sacroiliac joints) and entheses, and is often associated with extra-articular manifestations, such as ocular, cardiac, pulmonary, or renal involvement, in the presence of the human leukocyte antigen (HLA) B27 ,2,3.The term axial spondyloarthritis includes both the radiographic and non-radiographic forms, in which case sacroiliitis can be objectified by magnetic resonance imaging (MRI) only, and not by conventional radiographs. This form of the disease is called non-radiographic axial spondyloarthritis (nr-axSpA), and may or may not progress to ankylosing spondylitis (AS) ,5.The hallmark of sacroiliitis, from a clinical point of view, is represented by sacroiliac joint pain. Furthermore, while sacroiliac discomfort is often restricted to the buttocks and lower lumbar areas, some patients experience pain radiating to the groin, lower abdomen, trochanter, and even lower leg. Joint palpation and provocation tests, aimed at inducing pain while straining the sacroiliac joints, are part of the physical evaluation of the sacroiliac joint ,7.However, at least in the early stages of sacroiliitis, alterations in the sacroiliac joints, detected on radiographs, are not sensitive or specific enough. In many individuals with axSpA, it may take years of clinically obvious illness before clear abnormalities of the sacroiliac joints become detectable on standard radiographs ,9.MRI can identify joint inflammation in its early stages, before structural damage develops, thanks to its good contrast resolution. With potentially successful therapy, applicable to a limited window of opportunity for disease control, MRI has become a dominating diagnostic technology, and, at the same time, was incorporated in the axSpA classification criteria, thus becoming the cornerstone of SpA diagnosis ,11.Sacroiliitis is usually bilateral and symmetrical. Initially, it involves the lower two-thirds of the sacroiliac joint space. The progression of the erosive process results in pseudo-enlargement of the sacroiliac joint space with bone sclerosis, followed by complete fusion of the sacroiliac joints.In daily practice, MRI images are interpreted by radiologists, and the readings are presented to the primary care physician or to the rheumatologist. However, a rheumatologist with special training should be able to interpret musculoskeletal MRI examinations. The interobserver agreement, defined as the difference in the measurements between radiologists and rheumatologists, should be further tested. It is not clear whether the assessment criteria for sacroiliitis are reproducible among rheumatologists and radiologists with different levels of experience ,13.The aim of our study is to assess the performance of rheumatologists in interpreting the inflammatory and structural damage to sacroiliac joints, in comparison to radiologists.The present study included a total of 34 patients diagnosed with axSpA according to the Assessment of SpondyloArthritis International Society (ASAS) criteria for axSpA, examined from January 2021 to November 2021 in the Departments of Rheumatology and Radiology and Medical Imaging of the University of Medicine and Pharmacy of Craiova. The inclusion criteria were as follows: age >16 years, diagnosis of AS, and symptoms of sacroiliac joint pain lasting for more than 6 months. The exclusion criteria included the presence of any other rheumatic disease, infection, or trauma to the pelvic region. All patients expressed their agreement to be a part of this study. The study was approved by the local ethics committee of the University of Medicine and Pharmacy of Craiova (Registration no. 210/08.12.2021), according to the European Union Guidelines (Declaration of Helsinki).All patients underwent physical examination, laboratory tests, and MRI of the sacroiliac joints.The clinical assessment included specific maneuvers for the sacroiliac joints, such as Patrick’s maneuver. Patrick’s maneuver, or the FABER test, was performed by having the leg flexed, while the thigh was abducted and externally rotated. If pain was perceived anteriorly on the ipsilateral side, it suggested hip joint dysfunction on that side. If pain was evoked posteriorly, on the contralateral side around the sacroiliac joint, it was likely caused by sacroiliac joint dysfunction. The patient’s pain and severity were assessed with a visual analog scale (VAS) of 100 mm. Standardized scores, such as the Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Functionality Score (BASFI), were used in order to assess disease activity in the group of patients.The evaluated biological parameters consisted of complete blood count (CBC), liver enzymes, serum creatinine, erythrocyte sedimentation rate (ESR), with a normal range <10 mm/h, and C-reactive protein (CRP), with a normal range <5 mg/L.All MRI examinations of the sacroiliac joints were performed on a Philips Ingenia 3 Tesla device available in the Department of Radiology and Medical Imaging of the University of Medicine and Pharmacy of Craiova. The MRI protocol for evaluating the sacroiliac joints consisted of coronal oblique T1, T2 (without fat suppression), short tau inversion recovery (STIR) sequences oriented parallel to the sacrum, and axial oblique T2 spectral attenuated inversion recovery (SPAIR) positioned perpendicularly to the sacrum. We evaluated the presence of inflammatory changes  and structural damage .The images were interpreted by a senior radiologist (SR), a junior radiologist (JR), a senior rheumatologist (SRh), and a junior rheumatologist (JRh), scored independently without knowledge of the other interpretations. In addition, the scans were anonymized, with no clinical and paraclinical patient data. The SR and SRh have 15 years of experience in radiology and rheumatology, respectively. They both have a particular interest in musculoskeletal imaging, specifically in rheumatic diseases, having attended multiple European Alliance of Associations for Rheumatology (EULAR) and ASAS courses on SpA imaging. The JR and JRh are trainees of the seniors, with 5 years of experience in their chosen specialties.Statistical analyses of the data were performed using SPSS Software version 20 for Windows. The relationship between the variables was analyzed using the unpaired t-test and the Pearson/Spearman’s coefficient for evaluating correlations. Values less than 0.05 for p were considered to be statistically significant. The summary statistics of the mean ± standard deviation (SD) are presented for continuous variables. The agreement between observers was calculated using cross-tabulation expressed in Cohen’s kappa (κ). The value of kappa was interpreted according to Landis and Koch as follows: <0—poor agreement; 0.0–0.20—slight agreement; 0.21–0.40—fair agreement; 0.41–0.60—moderate agreement; 0.61–0.80—substantial agreement; 0.81–1.00—almost perfect agreement .The study included 34 patients diagnosed with axSpA , with a mean age of 39.14 ± 10.31 years.The patients had either only axial involvement, as in 32.25% of the cases, or both axial and peripheral joint involvement, as in 67.75% of the cases. The genetic mark of axSpA, HLA-B27, was positive in 76.47% of the patients.The disease activity, according to ASDAS-CRP, was low in 8.83% of the cases, and high and very high in 2.94% and 88.23% of the cases, respectively. Regarding BASDAI, the inactive and active disease was described in 5.88% and 94.11% of the patients, respectively.The descriptive parameters of the patients enrolled in the study are presented in We evaluated 68 sacroiliac joints. The prevalence of MRI-detected abnormalities is presented in The MRI findings on the total number of sacroiliac joints, as well as the interobserver agreement results, are depicted in Moderate to substantial agreement (0.489–0.766) was encountered between the observers regarding the inflammatory changes, whereas poor to almost perfect agreement (0.396–0.813) was noted in the case of structural damage. The overall κ was 0.7 for the JR , 0.707 for the SRh , and 0.601 for the JRh (moderate agreement), in comparison with the SR. Regarding the overall inflammatory changes, the SRh and JR showed substantial agreement  with the SR, while the JRh showed moderate agreement (κ = 0.607). The structural damage observed by the JR showed substantial agreement (κ = 0.676) with the SR, while the SRh and JRh had substantial and moderate agreement  with the SR.p = 0.019), while a positive Patrick’s maneuver on the left was associated with the presence of bone marrow edema interpreted by the SR (p = 0.019). None of the other parameters tested, such as enthesitis, subchondral sclerosis, erosions, backfill, fat metaplasia, and joint narrowing, reflected an association with Patrick’s maneuver.A positive Patrick’s maneuver on the right was associated with the presence of synovitis on the MRI interpreted by the SR (p = 0.012) and on the left (p = 0.034) sacroiliac joints, and also with joint space narrowing of the right (p = 0.007) and left (p = 0.007) sacroiliac joints. None of the other MRI parameters tested, such as bone marrow edema, synovitis, enthesitis, subchondral sclerosis, erosions, and backfill, showed associations with the disease activity score.The disease activity score ASDAS-CRP showed an association with fat metaplasia, both on the right  in interpreting the MRI of the sacroiliac joints, in concordance with a study conducted by Rueda et al. Their study included an expert radiologist, a local radiologist, and a rheumatologist as observers, showing substantial agreement between the expert radiologist and the rheumatologist. In our case, the senior radiologist and rheumatologist had special training in interpreting MRIs in SpA .A study by Arnbak et al., regarding the back pain cohort in Denmark, showed moderate to almost perfect interobserver agreement, with the almost perfect agreement being found for bone marrow edema. In our study, the interobserver reliability between the senior radiologist, senior rheumatologist, and junior radiologist was substantial, while moderate agreement was found between the senior radiologist and junior rheumatologist .In a study by Geijer et al., regarding findings of sacroiliitis on computed tomography (CT) scans, the authors showed substantial agreement between the interpretations of two expert radiologists; whereas, in our study, the SR and JR had substantial agreement in reading the scans .A study by Berg et al. evaluated the patients included in the DESIR cohort. The images were interpreted by local rheumatologists or radiologists, versus central trained readers. In the case of recent-onset inflammatory back pain, the trained readers and local rheumatologists/radiologists showed substantial agreement, in concordance with our study, in which the SR, SRh, and JR showed substantial agreement. Compared with this study, our readers were blinded to the diagnosis .Overall, our study demonstrated that the senior radiologist, senior rheumatologist, and junior radiologist trained by the senior were in substantial agreement regarding inflammatory changes (κ = 0.708—SRh and κ = 0.748—JR), structural damage (κ = 0.676—SRh and κ = 0.705—JR), and overall findings (κ = 0.707—SRh and κ = 0.70—JR). The junior rheumatologist demonstrated moderate agreement with the senior radiologist regarding inflammatory, structural, and overall changes . The findings may prove that, with special training, the results between radiologists and rheumatologists are comparable.Even if there was substantial agreement between the SR, SRh, and JR, regarding inflammatory, structural, and overall sacroiliac joint abnormalities, there were certain differences between the interpretations. One reason for these discrepancies is related to the fact that the interpretation of an MRI is subjective, dependent on the interpreter. Another reason may be that the SR and JR have more experience in interpreting MRIs in general, having opportunities to describe MRI lesions on a daily basis. Due to the fact that the SRh underwent special training in spondyloarthritis imaging, the interobserver agreement was substantial. Regarding the moderate agreement with the JRh, it only proves that the better the training, the better the agreement between interpreters.p = 0.019) between bone marrow edema and clinical maneuvers, regarding the pain of the sacroiliac joints (Patrick’s maneuver); these findings were compatible with a study conducted by Yang et al., which proved that bone marrow edema correlated with pain in the sacroiliac joints [In our study, we also encountered a positive association (c joints .p = 0.019), with both bone marrow edema and synovitis being inflammatory changes that can trigger positive provocation maneuvers of the sacroiliac joints.In addition, the presence of synovitis was associated with a positive Patrick’s maneuver  showed greater likelihood ratios to identify sacroiliac joint inflammation, in concordance with our findings. In our case, active/inflammatory changes had a positive correlation with Patrick’s maneuver .p = 0.017—right; p = 0.017—left) and the sacroiliac joint space narrowing on both sides . The evidence in the literature is contrasting, with MRI scores showing either no association with ASDAS-CRP or a positive association. We believe that these discrepancies may be due to the fact that inflammation parameters, such as CRP, are not frequently high in spondyloarthritis, even if the patients are proven to have high disease activity from a clinical point of view [In our study, we showed a positive association between fat metaplasia on both sacroiliac joints ( of view ,25,26.The limitations of our study were the small sample size and the fact that the interpreters were aware of the overall diagnosis of the patients, but not of the clinical and paraclinical data.Our study showed substantial agreement between the senior radiologist, senior rheumatologist, and junior radiologist, and moderate agreement with the junior rheumatologist; these findings are in concordance with other studies in the literature. However, the interobserver reliability in the MRI assessment of sacroiliac joints is not a very well-studied domain, so further studies on larger numbers of patients have to be conducted in order to establish the level of agreement.


Risk stratification of elderly patients with ischemic stroke (IS) who are admitted to the intensive care unit (ICU) remains a challenging task. This study aims to establish and validate predictive models that are based on novel machine learning (ML) algorithms for 28-day in-hospital mortality in elderly patients with IS who were admitted to the ICU.Data of elderly patients with IS were extracted from the electronic intensive care unit (eICU) Collaborative Research Database (eICU-CRD) records of those elderly patients admitted between 2014 and 2015. All selected participants were randomly divided into two sets: a training set and a validation set in the ratio of 8:2. ML algorithms, such as Naïve Bayes (NB), eXtreme Gradient Boosting (xgboost), and logistic regression (LR), were applied for model construction utilizing 10-fold cross-validation. The performance of models was measured by the area under the receiver operating characteristic curve (AUC) analysis and accuracy. The present study uses interpretable ML methods to provide insight into the model's prediction and outcome using the SHapley Additive exPlanations (SHAP) method.As regards the population demographics and clinical characteristics, the analysis in the present study included 1,236 elderly patients with IS in the ICU, of whom 164 (13.3%) died during hospitalization. As regards feature selection, a total of eight features were selected for model construction. In the training set, both the xgboost and NB models showed specificity values of 0.989 and 0.767, respectively. In the internal validation set, the xgboost model identified patients who died with an AUC value of 0.733 better than the LR model which identified patients who died with an AUC value of 0.627 or the NB model 0.672.The xgboost model shows the best predictive performance that predicts mortality in elderly patients with IS in the ICU. By making the ML model explainable, physicians would be able to understand better the reasoning behind the outcome. Ischemic stroke (IS) approximately accounts for 80% of strokes in elderly patients, which has become the second most serious cause of death in the world . PatientSome models have also been developed to predict in-hospital mortality in cases of acute ischemic stroke. Mittal and Goel  reportedHowever, these models were not applicable to the elderly population in the ICU, and the performance of the model predicting the mortality among the elderly admitted to the ICU was unknown. The elderly patients should be given more attention because the majority of ischemic stroke cases occur in these elderly patients, while young patients who suffer from IS have a low mortality rate. In addition, with prolonged life expectancy, the aging population experiences a significant increase in stroke incidence. Additionally, elderly patients exhibit physiological changes including neuronal plasticity and decreased repair ability, as well as changes in the structure of the vascular system and complications, which increase the complexity of prediction. Limited data regarding short-term mortality predictors for elderly patients with IS are available. A model based on the LR method was constructed with 469 older patients . FurtherSeveral factors were found to be associated with the increased short-term mortality, including age , sex 5)5), strokIn this study, we aimed to develop prediction models for 28-day in-hospital mortality in elderly patients with IS using ML algorithms. The model was based on variables collected at admission. This will improve clinical decision-making and healthcare quality through early risk stratification after acute IS in elderly patients.https://eicu-crd.mit.edu/) (certification ID: 42039823). The eICU-CRD database is a publicly available multi-center critical care database made available by Philips Healthcare in partnership with the MIT Laboratory for Computational Physiology and contains de-identified clinical data of over 200,000 patients admitted in the ICU from 2014 to 2015. Individuals were selected if their hospital discharge records contained at least one of the following: International Classification of Diseases (ICD)-9-Clinical Modification (CM) (ICD-9-CM) diagnoses of IS: 434.91  and IS: I63.50 . The inclusion criteria for the present study were as follows: (1) first-ever ICU admission and (2) age ≥ 65 years. The exclusion criteria for the present study were as follows: (1) ICU stay < 24 h or more than 28 days; (2) individuals with severe liver disease; (3) individuals with heart failure; (4) individuals with metastatic solid tumor; and (5) individuals with more than 30% of missing values. With the clinical information from patients de-identified, the database's official ethics committee has approved the public release of these clinical data. A consent waiver was also given because of anonymized retrospective patient data.Data of elderly patients with IS were extracted from the eICU Collaborative Research Database (eICU-CRD) version 2.0 . All datThe primary outcome event was in-hospital death within 28 days in elderly ICU patients with IS. The clinical data were collected within 24 h of admission. To identify candidate predictor variables, a review of literature was done and the present study selected variables that were available in the eICU. The finally selected 51 variables, including vital signs, demographics, laboratory tests, and comorbidities, are listed in The database was randomly divided into two sets: the training set and the validation set in the ratio of 8:2. The recursive feature elimination (RFE) algorithm was used to filter features until the model's AUC value was >0.7.The present study applied four common machine learning (ML) algorithms to predict the 28-day in-hospital mortality among ICU elderly patients with IS, including Naïve Bayes (NB), eXtreme Gradient Boosting (xgboost), and logistic regression (LR). A validation set of 241 patients who never participated in the model training was used to evaluate all of those ML metrics. To improve the stability of the prediction model, all continuous features are rescaled to a distribution with a mean of 0 and standard deviation of 1, and the scale conversion is performed. After 10-fold cross-validation, the performances of the three prediction models were compared with each other using areas under the curve, specificity, sensitivity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and F1 score. The best model was selected by the area under the receiver operating characteristic curve (AUC) values of the testing set.P < 0.05 is considered statistically significant.Normally distributed continuous data were expressed as the mean with standard errors. To analyze all non-normal homogeneous distributions' continuous characteristics, the Wilcoxon rank sum test was used, which is expressed as the median and interquartile range (IQR). Chi-square analysis or Fisher's exact tests were used to analyze categorical features expressed in frequencies (percentages). Outliers for features will be removed. The imbalance in the distribution of data structures is solved by the SMOTE (synthetic minority oversampling technique) method. The R packages “Nortest” and “CBCgrps” were used for univariate analysis. The RFE function was used for the filtering feature . Receiver operating characteristic (ROC) mapping and AUC calculation are performed by the “pROC” package, and the interpretability analysis is performed by the “shapviz” package in R (version 4.2.0), data visualization is carried out with the ggplot2 package, and a value of A total of 2,435 patients were diagnosed with IS at admission. Finally, a total of 1,518 patients with IS were enrolled in this study according to the inclusion criteria and exclusion criteria , includiP < 0.05). However, the levels of bilirubin, alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), BUN, creatinine, potassium, glucose, WBC, the international standardization percentage ratio (INR), prothrombin time (PT), pulse oximetry (SpO2), Acute Physiology Score III (APSIII), Acute Physiology And Chronic Health Evaluation II Score (APACHE II) score, and Oxford Acute Severity of Illness Score (OASIS) were higher in the death group. The death group also had more patients with mild liver disease (P < 0.05).The levels of albumin, blood calcium, bicarbonate, percentage of lymphocytes, percentage of monocytes, percentage of eosinophils, percentage of polymorphonuclear granulocytes (Polys), and Glasgow Coma Scale (GCS) score were much higher in the survival group compared to the death group , heart rate, WBC, and creatinine could be used as predictors of the prediction model.After feature selection using the recursive feature elimination (RFE) algorithm, eight features remained . FeatureWe attempted to use several widely applied machine learning (ML) algorithms  for the construction of the prediction models.We used a receiver operating characteristic (ROC) curve, specificity, sensitivity, accuracy, PPV, NPV, and F1 score to evaluate the prediction model in both training and validation data. Before evaluation, optimal cutoffs were determined by maximizing the Youden index  by the ROC curve in the validation set. In the validation set, ROC curves revealed that xgboost had the best predictive performances, with an area under the curve of 0.733, better than that of the area under the curves of NB (0.672) and LR (0.627) .In the training set, the accuracy of the xgboost model (0.994) was higher than the accuracies of the other models. All details about the parameters of the models developed with different algorithms are shown in 2, BUN, percentage of lymphocytes, AST, Polys, heart rate, WBC, and creatinine.As shown in Using the SHAP force plot, the Shapley value for each feature, which increases  or decreases  the prediction from its baseline, was visualized . A ShaplThis is an elderly patient who was admitted to the ICU for IS. The patient died on the 28th day. The predicted probability for mortality is high at 72.4%, compared with the baseline of 53.4% . The features detected by the model for predicting a higher mortality in this patient include Polys, WBC, BUN, AST, and creatinine. In Patient 1, all characteristics, except creatinine, supported the occurrence of the outcome. It was predicted by the ML model that this patient would die, and it truly occurred during admission (true positive).From a physician's point of view, the ICU observation for this IS patient is reasonable, considering the higher BUN, AST, and creatinine levels in the ICU.This is an elderly patient who was admitted to the ICU for IS. The patient survived on the 28th day. The predicted probability for mortality by the model was 52.0% compared with the baseline of 53.4%. The features detected by the model for predicting mortality were all normal. In Patient 2, all features, except creatinine and AST, did not support the occurrence of the outcome. It was predicted by the ML model that this patient would survive, and it occurred during admission (true negative) .From a physician's perspective, the ICU observation for this IS patient is reasonable, considering the normal values in the ICU.The novelty of this study is the use of machine learning (ML) to come up with a model that is superior to the traditional LR model. We used this machine learning (ML)-based model that was built on objective indicators to predict the short-term in-hospital mortality risk of elderly people. The model can be used as an automatic warning system to indicate the risk of death of patients. Previous studies proved that the C statistic can improve by 0.12 with the NIHSS score added to the model . The C sIschemic stroke is the most common type of stroke, which predominantly affects older adults and has a high short-term mortality rate after admission to the ICU. Therefore, establishing a death prediction model is essential for the risk stratification of these elderly patients with IS.The present study is the first to use machine learning (ML) models to predict the short-term prognosis of elderly patients with IS admitted to the ICU, which provides a basis for identifying those critically ill older IS patients early. The present study compares the performance of multiple supervised machine learning (ML) algorithms with that of traditional LR methods to explore the best model for predicting short-term death in elderly patients with IS. Each model's prediction performance on the test set resembles that on the training set, indicating that the model has good robustness. In particular, xgboost model based on machine learning shows the best short-term death prediction accuracy compared with those of the traditional LR method and another common machine learning algorithm.The existing scores for 30-day mortality prediction are PLAN   and IScoIn addition, the present study provides a simpler prediction tool that displays clinically useful discrimination of in-hospital risk of mortality for elderly patients with IS in the ICU. Our model is based on readily available variables of the eICU-CRD database, including patient demographics, history, and examination information. The database did not include variables about disease severity such as the Canadian Neurological Scale (CNS) and the National Institutes of Health Stroke Scale (NIHSS). A more widespread use of stroke severity assessments is probably held back by the time needed to complete even a short assessment. NIHSS strongly influences mortality and improvement. When the NIHSS score was added to the model, the C statistic can improve by 0.12 . The C sSome ML models for IS patients  have limWe found elevated oxygen saturation, AST, Polys, heart rate, WBC, and creatinine levels and decreased BUN level, and the percentage of lymphocytes could be used as predictors of the prediction model for 28-day in-hospital mortality in elderly patients with IS admitted to the ICU. Bhatia et al.  found imWe conceived and developed an observational study that is known to increase the risk of selection bias. Additionally, in the eICU-CRD database, data are collected from electronic health records of 208 hospitals across the country; however, each hospital populates the data differently, which results in significant missing data. Our statistical models did not include variables with more than 30% missing data, which was a major limitation. In addition, the predicting models were built with the US elderly population as a reference; therefore, its application to different ethnic groups and non-elderly people requires further investigation and validation.Predicting mortality helps physicians make better decisions and judgments, as well as coordinate services, communicate with patients, and adjust care plans. Moreover, it provides a reference for assessing stroke mortality and hospital performance.https://eicu-crd.mit.edu/.Publicly available datasets were analyzed in this study. This data can be found at: The data analyzed in this study is available at The eICU-CRD databases were approved by the Massachusetts Institute of Technology  and the Beth Israel Deaconess Medical Center . The data used for this study are publicly available and de-identified.JH, ZL, and XL were responsible for conceiving the study. XD, JD, and HC collected data. WJ, YJ, and TS were responsible for writing the manuscript and for revision of the manuscript. ZL was responsible for designing the study and article processing charge (APC). All authors have approved the submitted version.