HHb-AUC was highest for the 100 mmHg occlusion pressure compared with the 20 and 60 mmHg pressures (p < 0.01). These findings indicate that venous dilation may elicit a shift towards sympathetic dominance in the autonomic balance. Venous occlusion of the lower limbs, which simulates edema, can alter heart rate variability (HRV) by increasing feedback information from group III/IV sensory fibers. Our aim was to quantify this effect among healthy young men. The study group included 13 men . Venous occlusion of the lower limbs was induced using a pressure cuff around both thighs. The effect of occlusion on autonomic cardiac response was quantified under occlusion pressures of 20, 60, and 100 mmHg. Compression was applied for 5 min. HRV was evaluated from changes in the low-frequency (LF) and high-frequency (HF) power of the electrocardiogram and the resulting LF/HF balance. Near-infrared spectroscopy of the leg was used to quantify the effects of occlusion on deoxyhemoglobin, measured as the area under the curve (HHb-AUC). The occlusion pressure of 100 mmHg induced a significant increase in the LF/HF ratio, compared to the baseline ( The afferent information of the skeletal muscles plays a key role in physiological responses during exercise ,2. TheseSignals that ultimately trigger stimulation of venous dilation enter the cardiovascular center of the medulla oblongata through two pathways. One is through group III that stimulates the mechanoreceptor of connective tissue near the veins, and the other is through a fiber of group IV that stimulates the metaboreceptor of the venules and small lymphatic vessels ,11,12. EOveractivity of SNA may play an important role in developing hypertension and related cardiovascular diseases . FurtherConsequently, our aim in this study was to examine the effect of different subsystolic venous occlusion pressures on the ANS response. We applied thigh pressure in healthy young men to induce venous dilations of the lower extremities and used heart rate variability (HRV) as an index of the response. We hypothesized that venous occlusion would cause an increase in SNA-induced HRV and a widening of the area under the curve of HHb (HHb-AUC). The findings supporting this hypothesis could provide insight into the mechanisms that contribute to edema in the ANS.2. Participants were asked to avoid caffeine and intense exercise for 24 h before the test session and not to eat for 2 h before the session. The study group included 13 healthy men. The inclusion criteria for this study were as follows: (1) a minimum age of 20 years and (2) self-reported status as a non-smoker. The exclusion criteria for this study included any participants who had a diagnosis of a mental illness, neurological disorder, hypertension, or any other health condition affecting HR. Their mean (±standard deviation) age was 20.4 ± 0.5 years, height 172.2 ± 5.1 cm, weight 65.6 ± 6.2 kg, and body mass index (BMI) 22.1 ± 2.0 kg/mThe participants were fitted with a 9 cm compression tourniquet for the center of both thighs, which was connected to a rapid cuff inflation device . Before the testing session, the cuffs were inflated to ensure the absence of pain or other discomfort. The experimental protocol is presented in Electrocardiography (ECG) was performed using one lead in a standard CM5 configuration with three silver chloride monitoring electrodes placed on the chest A. ECG trSystolic (SBP) and diastolic (DBP) blood pressure and mean arterial pressure (MAP) were measured noninvasively from the right upper arm using an automated sphygmomanometer , with values obtained at 1 min intervals. NIRS , with different wavelengths, was used to measure HHb. The NIRS probe and detector were placed longitudinally over the maximum volume of the right triceps surae  muscle. An opaque wrapping was used to fix the NIRS sensors in place and eliminate the effects of direct light on measured values. The NIRS signal was sampled at 1 Hz using the Oxysoft system . To calculate the cumulative increase in HHb in the calf with venous occlusion, the mean value of HHb was calculated for 30 s before applying compressive force, and the HHb-AUC was calculated over a 5 min period after venous occlusion . AlthougData are presented as the mean ± standard error. Differences in measured outcomes  were evaluated using repeated measure linear mixed models with occlusive pressures as fixed factors. HHb-AUC was evaluated using a mixed linear model with the condition as a fixed factor. For the analyses, the participants were entered as random effects. The post hoc tests were multiple comparisons using the sequential Bonferroni correction to adjust for multiple comparisons, adjusted for BMI and age.All statistical analyses were performed with the SPSS version 26 statistical software package for Windows . None of the participants reported pain during venous occlusion. The measured cardiovascular variables and HRV parameters during all phases of the experiment are reported in p < 0.05). There was a significant mean change in increased LF and decreased HF at occlusion pressures of 60 mmHg  and 100 mmHg , all p < 0.05 (p < 0.05). The resulting effects of venous occlusion on HHb-AUC are shown in p > 0.05), the difference was significant between 20 and 100 mmHg (3018.5 ± 770.2 μL s) and between 60 and 100 mmHg (2595.7 ± 770.2 μL s), both p < 0.05. MAP decreased significantly at the three levels of venous occlusion pressures compared to baseline resting, with a mean decrease of 3.8 ± 1.1 mmHg at an occlusion pressure of 20 mmHg, 3.9 ± 1.1 mmHg at 60 mmHg, and 3.4 ± 1.2 mmHg at 100 mmHg (p < 0.05). This decrease in MAP appeared to be driven by a change in DBP, with a mean difference in DBP from baseline of 3.8 ± 1.2 mmHg at an occlusion pressure of 20 mmHg, 3.6 ± 1.2 mmHg at 60 mmHg, and 3.7 ± 1.2 mmHg at 100 mmHg (There was no difference in HR from baseline to occlusion (all p < 0.05 . At an o100 mmHg B. As a novel contribution, our findings identified an increase in the LF/HF ratio under a compressive pressure of 100 mmHg, with a resulting increase in HHb-AUC. These findings supported our hypothesis that increased afferent feedback through group III/IV sensory fibers of the lower limb veins, induced by the venous occlusion technique, increases the cardiac response of SNA.The feedback to the circulatory system through group III/IV fibers helps maintain blood perfusion to exercising skeletal muscles by modulating cardiac output and vascular resistance during exercise ,21. In oStimulation of group III/IV afferent fibers by dilation of leg veins induced by thigh compression has previously been reported ,12. In pTo our knowledge, our study is the first to evaluate venous dilation using a venous occlusion technique and to quantify the resulting effect on HHb-AUC . HHb-AUCThese findings regarding the correlation between CVI and HHb provide support for our utilization of HHb-AUC as a method to evaluate the effects of venous dilation. Our use of the AUC, rather than the HHb level, allows for absolute comparisons between conditions. Our results showed that a 100 mmHg cuff occlusion increased the HHb-AUC compared with a 20 mmHg and 60 mmHg cuff occlusion. The venous pressure in the normal upright position at rest is 80 mmHg in the posterior tibial vein ; therefoWe noted a decrease in DBP and MAP for all occlusion pressures compared to the resting baseline B,C. ThisIn recent years, a correlation between CVI and cardiac risk factors has been established through the analysis of large cohort studies . HoweverThe strengths and limitations of our study should be considered in the interpretation of the findings. As a strength, HRV changes due to venous dilation were evaluated using a robust methodology. However, it should be acknowledged that there were certain limitations in the study. First, the sample size in this study was relatively small, which may limit the generalizability of our results. However, a linear mixed model was used to account for inter-individual variation by including random effects for participants. Second, the contribution of group III/IV afferent fibers to the cardiac response was inferred, as direct measurement of afference in group III/IV fibers is not feasible in participants. Additionally, we were unable to fully evaluate the ventilatory response to stimulation of group III fibers. This was due to the fact that the study only captured a limited portion of the physiological response to the stimulation of group III fibers, which simulates edema. This limitation was necessary in order to control respiration and allow for a more thorough examination of the cardiovascular effects. Third, the use of a venous cuff occlusion may have led to venous distension and activation of mechanosensitive afferents in skeletal muscle, which could not be fully explained as muscle metabolites were not monitored. Furthermore, it is possible that the metabolic reflex may have been activated, particularly at high cuff pressures where blood perfusion to the muscles may have been compromised. Fourth, the effect of the pressure of the occlusion cuff on changes in intravascular, interstitial, or intramuscular pressure, secondary to the induced venous occlusion, could not be differentiated.Our findings indicated that venous dilation, induced by the venous occlusion technique at a pressure of 100 mmHg, exacerbated the sympathetic HRV response. Therefore, induced lower limb edema can affect cardiovascular regulation in healthy male adults through feedback from group III/IV sensory fibers. These findings suggest that edema may elicit a shift towards sympathetic dominance in the autonomic balance. Thus far, there is no literature to support a correlation between edema and changes in HRV. Therefore, further investigation into patients with CVI is needed to obtain clinically meaningful findings.


Tissue hypoxia and insufficient energy delivery is one of the mechanisms behind the occurrence of several complications in acute brain injured patients. Several interventions can improve cerebral oxygenation; however, the effects of inotropic agents remain poorly characterized.2) catheter, in whom inotropic agents were administered according to the decision of the treating physician's decision; PbtO2 values were collected before, 1 and 2 h after the initiation of therapy from the patient data monitoring system. PbtO2 “responders” were patients with a relative increase in PbtO2 from baseline values of at least 20%.Retrospective analysis including patients suffering from acute brain injury and monitored with brain oxygen pressure (PbtO2 did not significantly increase over time . A total of 12/35 (34%) patients were PbtO2 “responders,” in particular if low PbtO2 was observed at baseline. A PbtO2 of 17 mmHg at baseline had a sensibility of 84% and a specificity of 91% to predict a PbtO2 responder. A significant direct correlation between changes in PbtO2 and cardiac output  and a significant negative correlation between changes in PbtO2 and cerebral perfusion pressure  were observed.A total of 35 patients were included in this study. Most of them  suffered from non-traumatic subarachnoid hemorrhage (SAH). Compared with baseline values [20 (14–24) mmHg], PbtOIn this study, inotropic administration significantly increased brain oxygenation in one third of brain injured patients, especially when tissue hypoxia was present at baseline. Future studies should highlight the role of inotropic agents in the management of tissue hypoxia in this setting. Indeepatients –12.2 values have been observed in different conditions, such as reduced cerebral blood flow (CBF) and/or cerebral perfusion pressure (CPP), intracranial hypertension (IH), hypoxemia, anemia, altered microcirculation or excessive cellular metabolism (2), temperature control and sedation  (Low PbtOtabolism . As suchumption) –18.2 values in those patients with poor clinical condition at presentation  with normovolemia; in patients suffering from SAH, this intervention can increase regional perfusion in the presence of cerebral vasospasm and neurological deterioration . Among Tentation , 22.1 agonist) and milrinone (a phosphodiesterase-3 inhibitor) on brain oxygenation remains unknown. These drugs have been proposed as “second-line” agents to improve CBF and CPP in acute brain injury patients  admitted to the Intensive Care Unit of Erasme hospital from January 2015 to February 2022, due to acute brain injury , who survived at least 24 h were eligible for inclusion. The study protocol was approved by the local ethics committees (SRB2022006). Data collection and analyses were carried out in accordance with relevant scientific and ethical guidelines and regulations.2 and who received inotropic treatment  during monitoring, according to the treating physician's decision. We excluded patients who had malfunctioning/unreliable PbtO2 readings or unavailable data.We included eligible patients who were monitored with intracranial pressure (ICP) and PbtO2, was included according to a recent consensus  or with demonstrated initial or delayed hypoperfusion on brain imaging for SAH.Current guidelines for the management of TBI , SAH 2727, and Ionsensus  and cons2, were measured in real-time and collected prospectively. Cerebral perfusion pressure (CPP) was calculated as the difference between mean arterial pressure (MAP) and ICP; MAP was zeroed at level of left atrium. Intracranial hypertension was defined by the observation of ICP values above 20 mmHg for at least 5 min at any time. Brain tissue hypoxia was defined as a PbtO2 <20 mmHg. At baseline (immediately before the start of inotropic therapy), 1 and 2 h after the start of inotropes, the 20-min mean value of the following variables was collected: PbtO2, MAP, heart rate (HR), ICP, CPP, body temperature, arterial oxygen saturation (SaO2), central venous oxygen saturation (SvcO2), cardiac output (CO), pH, PaCO2, PaO2, blood lactate and blood glucose levels. Vasopressors and inotropic doses were also recorded. We also calculated the ΔPbtO2 defined as the difference between PbtO2 values at 2 h and at baseline; similarly, the ΔCO, ΔICP, ΔCPP, and ΔPaCO2 were also computed.Physiological variables as well as ICP and PbtOWe also recorded demographics and the presence of comorbidities, the Sequential Organ Failure Assessment (SOFA)  and the Hospital mortality and the Glasgow Outcome Scale (GOS)  at 6 mon2 within 2 h after the initiation of inotropic therapy. PbtO2 increase was calculated as the difference between the highest mean PbtO2 values, measured at 1 or 2 h after the initiation of inotropic therapy, and the baseline PbtO2 value; PbtO2 “decrease” was identified as a difference value <0, “stable” PbtO2 as a difference = 0 and “increase” as a difference >0. A “significant” increase was defined as > 20% from the baseline. Patients that experienced a significant increase were defined as “responders.” Secondary outcomes included the identification of factors associated with a significant PbtO2 increase.The primary outcome of the study was the changes in PbtOt-test. Categorical variables were described as proportions (%) and compared using Chi square or Fisher's exact test. A logistic regression of physiological variables at baseline was conducted to assess factors associated with a significant PbtO2 increase after inotropic therapy. The independence of errors, presence of multicollinearity and of influential outlier assumptions were checked; none were violated. The area under the receiver operator characteristic (AUROC) was computed to identify the optimal cut-off value  of baseline PbtO2, baseline ICP and baseline CPP to predict a significant increase of PbtO2 after inotrope infusion. We performed a correlation analysis using Spearman's test between ΔPbtO2 and ΔCO, ΔICP, ΔCPP, and ΔPaCO2. The R coefficient and the 95% confidence interval were computed for all correlations. We also performed a linear regression analysis with ΔPbtO2 as the dependent variable and ΔCO, ΔICP, ΔCPP, and ΔPaCO2 as covariates. All statistical analyses were performed using SPSS 27.0 for MacIntosh. A p-value <0.05 was considered significant.Descriptive statistics were computed for all variables. Normality was assessed using the Kolmogorov-Smirnov test. Non-gaussian continuous variables were described as median and interquartile range [IQRs] and compared using Mann-Whitney test (independent variables) or Friedman/Wilcoxon test (repeated measures of related variables); normally distributed variables were expressed as mean (±SD) and compared using Student On a total of 157 patients monitored over the study period, 35 patients were eligible for our study. The characteristics of the study population are shown in 2 was observed in 22/35 patients (63%); of those, 12 (55% of patients with PbtO2 increase and 34% of the whole cohort) experienced a significant PbtO2 increase from baseline (responders). In 4 patients, PbtO2 did not change while it decreased in 9 patients (26%).An increase in PbtO2 after the initiation of the inotropic agents, as shown in p = 0.052). Also, a significant increase in heart rate and in cardiac output was observed after inotropic agents' administration; no changes in CPP values were observed. The doses of dobutamine are reported in *min.There was a non-significant change in PbtO2 and ΔCO  and a significant negative correlation between ΔPbtO2 and ΔCPP , as shown in 2 and ΔICP [r = 0.26 (95% CI −0.151 to 0.597)]. Linear regression analysis described the association of ΔPbtO2 and ΔCPP [beta coefficient −0.274 (95% CI −0.130 to 0.041)], adjusted for ΔICP [beta coefficient 0.018 (95% CI −0.139 to 0.148)], ΔPaCO2 [beta coefficient −0.038 (95% CI −0.026 to 0.021)] and ΔCO [beta coefficient 0.371 (95% CI −0.054 to 1.306)].There was a significant direct correlation between ΔPbtO2 and CPP were significantly lower, while ICP higher, than non-responders at baseline. No significant changes in measured variables over time were observed between groups, except a higher requirement in norepinephrine in the “responders” group when compared to the others (n = 15), responders [GOS 4 . The baseline PbtO2 cut-off that better discriminated between responders and non-responders was 17 mmHg, with a sensibility of 84% and a specificity of 91% to predict a significant PbtO2 increase. The AUROC for CPP and ICP and response to predict a significant PbtO2 increase were 0.72 (95% CIs 0.50–0.94—best cut-off of 99 mm Hg) and 0.76 (95% CIs 0.60–0.92—best cut-off of 14 mmHg), respectively. In SAH patients, a multivariable model adjusted for poor grade on admission (WFNS 4 or 5) and mFisher, lower baseline PbtO2 was associated with a higher chance of response to inotropes  , 50; how2 increase. Baseline tissue hypoxia could predict this significant PbtO2 increase after the initiation of therapy. The effects on brain oxygenation were proportional to changes in cardiac output. Further prospective studies are needed to explore the impact of inotropic therapy on brain oxygenation and outcome in this setting.In this study, the administration of inotropic agents could increase brain tissue oxygenation in nearly 65% of patients; however, only half of them had a significant PbtOThe original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by Erasme Hospital Ethics Committee. The Ethics Committee waived the requirement of written informed consent for participation.ED, GC, EG, and FT contributed to conception and design of the study and wrote the first draft of the manuscript. GC, AD, EM, and ED organized the database. EG performed the statistical analysis. SS, EM, AD, and JC revised the manuscript for intellectual content and English editing. All authors contributed to manuscript revision, read, 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.


There are few studies assessing the quality of life of patients with chronic and end stage kidney disease in sub-Saharan Africa. We aimed to describe the health-related quality of life (HRQOL) of patients undergoing in-centre maintenance hemodialysis in Rwanda using the KDQOL™-36 and determine sociodemographic and clinical factors associated with their quality of life.We conducted a multicenter, cross-sectional study between September 2020 and July 2021. Patients over the age of 18 receiving maintenance in-centre hemodialysis for at least three months at the Rwandan tertiary hospitals were administered the KDQOL™-36 questionnaire to assess physical and mental health functioning, the effect, burden and symptoms and problem of kidney disease. Sociodemographic and clinical information was collected for all eligible patients. Using mixed effects linear regression models, we explored factors associated with overall KDQOL and its domains, while accounting for clustering of patients within hemodialysis centres.Eighty-nine eligible patients were included in the study. The majority of participants were younger than 60 years old (69.7%), male (66.3%), had comorbidities (91%), and 71.6% were categorized as level 3 on a 4 tier in-country poverty scale. All participants had health insurance coverage, with 67.4% bearing no out of pocket payments for hemodialysis. The median (IQR) quality of life score was 45.1 (29.4) for overall HRQOL, 35.0 (17.9) for PCS and 41.7 (17.7) for MCS. Symptoms and problem of kidney disease, effect of kidney disease, and burden of kidney disease scored 58.3 (43.8), 56.3 (18.8) and 18.8 (37.5), respectively. A notable difference of KDQOL scores between hemodialysis centres was observed. Overall KDQOL was associated with male sex ; being employed ; dialysis vintage of 13–24 months , hemoglobin of 10-11 g/dl  and comorbidities  .Patients on in-centre hemodialysis in Rwanda have reduced KDQOL scores, particularly in the burden of kidney disease and physical composite summary domains. Higher overall KDQOL mean score was associated with male sex, being employed, and dialysis vintage of 13–24 months, hemoglobin of 10-11 g/dl and absence of comorbidities. The majority of patients receiving in-centre hemodialysis have higher socioeconomic status reflecting the social and financial constraints to access and maintain dialysis in resource limited settings. The burden of kidney disease worldwide is substantial and poses significant challenges for governments responding to the health of their populations, particularly in low and middle income countries (LMIC) . In middRwanda is one of the smallest central African countries with an approximately 13 million population and only about 17.6% living in urban areas. The groBased on estimates from the World Health Organization, noncommunicable diseases (NCDs) including renal diseases were the predominant cause of mortality in Rwanda, accounting for 58% of the mortality burden since 2016 . There aAccess to dialysis is limited by its cost, a shortage of specialized medical staff with training in nephrology and renal replacement therapy and geographic distribution of in-centre hemodialysis units , 11. TheSpecialized kidney care and dialysis centers are primarily located in urban areas in Rwanda, particularly Kigali City, however, the majority of Rwandans live in rural areas . CurrentBetween 2014 and 2017, approximately 47% of hemodialysis patients died within four months of initiation of dialysis at CHUK , 14. TheTo promote high-quality services in renal dialysis facilities, routine measurement of patient reported outcomes measures such health-related quality of life (HRQOL) is recommended. In the United States, these measurements are typically done four months after initiation of dialysis and at least every year , 23. TheIn this study, we aimed to determine the health-related quality of life of patients with ESKD undergoing in-centre maintenance hemodialysis in Rwanda, describe demographic and clinical features of those patients and establish factors associated with their quality of life. We hypothesized that sociodemographic factors affect the HRQOL of patients undergoing renal replacement via hemodialysis in Rwanda. This is the first study of HRQOL in patients living with kidney disease in Rwanda and will provide baseline data that can help inform improvement strategies for ESKD patients on hemodialysis in Rwanda and other settings with similar contexts.We conducted a multicenter, prospective, cross-sectional study on all patients with ESKD disease undergoing in-centre hemodialysis in Rwanda between September 2020 and July 2021. In-centre hemodialysis units are located at Kigali University Teaching Hospital (CHUK), Rwanda Military hospital (RMH), Butare University Teaching Hospital (CHUB) and at King Faisal Hospital (KFH). Of the 96 patients on in-centre hemodialysis during the study period, we enrolled 89 (92.3%) of the adult patients (18 years and above) with ESKD on chronic in-centre maintenance hemodialysis . Each item is scored from 0 to 100 representing the percentage of total possible score achieved. The higher score, the better the quality of life.  The overing tool . All demDescriptive statistics were used to describe the study sample including demographic and clinical characteristics overall and by KDQOL. Mean and standard deviation or median with inter-quartile range (IQR) were used, as appropriate, for continuous variables and frequency with percentage for categorical variables. Mixed effects linear regression models were fitted to explore factors associated with overall KDQOL and its five domains, while accounting for clustering of patients within hemodialysis centers. First, unadjusted (crude) models were fitted to assess the association between each independent variable  and overall KDQOL (and its five domains) to check which variables pass an initial screening with α of 0.20 as model entry significance level. All potential factors associated with overall KDQOL (and its five domains) were retained for further exploration in multivariate (adjusted) models. Stepwise approach was used to select the most parsimonious models. Patients’ sex and age were retained in all models regardless of their α. Parameter estimates are reported as ß coefficients along with their 95% confidence interval (CI) and p values. All analyses were conducted using R version 4.0.2. Ethics approval was obtained through the University of Rwanda Institutional Review Board (IRB) Nº 053/CMHS IRB/2020 and the associated hospital sites.The majority of participants were young with a male to female ratio of nearly 2:1. Almost all participants (91%) had comorbidities and 79.8% were taking > 3 medications per day. More than half (59.5%) had been on hemodialysis for more than 12 months with 80.9% were prescribed three times weekly hemodialysis. Among our study participants, 53.9% were married or living with their partner, 68.5% were living in urban areas and 40.4% had completed post-secondary education. All participants had health insurance coverage, with 67.4% covered at 100% with no out-of pocket costs. All participants in Ubudehe category 1 and 77.8% in Ubudehe category 2 had full coverage of costs, whereas in category 3 full coverage accounted for 60.3%. The majority of patients in the study (71.6%) were categorized in Ubudehe level 3. . The physical composite summary (PCS) median score was 35.0  and mental composite summary (MCS) median score was 41.7 . Symptoms and problems of kidney disease (SPKD) scored 58.33 , whereas effect of kidney disease (EKD) and burden of kidney disease (BKD) had median (IQR) scores of 56.3 (18.8) and 18.8 (37.5) respectively . Similarly, participants with no comorbidities had higher HRQOL overall and in all five domains (Tables 3). Likewise, participants who had had hemodialysis for more than one year had on average greater HRQOL overall and in the domains of mental composite summary and the symptoms and problems of kidney disease. Participants with hemoglobin level between 10 and 11 g/dl had significantly greater overall kidney disease quality of life; whereas, those with fistula for hemodialysis access had significantly higher HRQOL in the burden of kidney disease domain.In adjusted models, on average male participants had significantly higher HRQOL overall and in the physical composite summary and the symptoms and problems of kidney disease domains Tables  and 3. PTables  and 3. Ss Tables  and 3. L(Table ) [In the current study, we found patients undergoing in-centre hemodialysis demonstrate low quality of life scores. HRQOL results were lower across all domains in comparison to studies that have used the KDQOL-36™ tool in high income countries. Similar scores in the physical and mental component summary were seen in comparison to studies conducted in other LMIC, however, the symptom and problem of kidney disease scores in Rwanda were much lower than those seen Kenya and Saudia Arabia Table  [28, 30–(Table ) . While o(Table )  and Baga(Table )  found an(Table ) –29. ThisSimilar to studies of hemodialysis patients conducted in LMICs, 69.7% of participants were younger than 60 years of age reflecting the epidemiology of kidney disease observed in LMICs, the lack of strategies for prevention and management of communicable and non-communicable diseases, poor socioeconomic status and the limited access to dialysis and transplantation , 33–35. Our results showed higher overall KDQOL score and in all five domains in patients on in-centre hemodialysis at King Faisal Hospital and lower scores at the CHUK-CHUB in-centre hemodialysis units. KFH is the most accredited hospital of the country, was the first hemodialysis unit in Kigali with more beds than other centers, specialized medical staff, greater human resources and materials. In addition, the national referral board office that transfers patients for kidney transplantation is located at KFH and patients access hemodialysis using health insurance coverage as in other in-centre dialysis units. While RRT care is covered by insurance similarly at all in-centre sites, additional care—consultations, investigations, admission to hospital—often is associated with additional out of pocket costs than would be borne at the public hospitals. The majority of patients managed at CHUK and CHUB are referred from rural areas with lower socioeconomic status with fewer patients on chronic maintenance hemodialysis at those units. The improved HRQOL of patients undergoing hemodialysis at KFH likely reflects the experience and resources available at KFH as well as the ability to access care at the in-centre site of patient preference.In our study, most patients were living in Kigali where three of four in-centre hemodialysis units are located. Patients and their family are required to travel long distances or relocate near dialysis centers to undergo dialysis and this in turn affects their daily activities and relationships with others, which likely contributed to reduced burden of kidney disease domain scores. Many patients had obtained a relatively higher level of education and were from a relatively higher socioeconomic status in ubudehe category 3, echoing other African studies that have highlighted that the majority of patients on hemodialysis are largely from a higher socioeconomic status , 35–37. ™ instrument has been validated in other contexts, it is yet to be validated in Rwanda and there is no validated translation into the local language (Kinyarwanda). Therefore, it is possible there could have been misinterpretations by study participants related to translation of the questionnaire and local validation of the KDQOL survey instrument in future studies is recommended. Second, being a cross-sectional study we are unable to infer causality of low HRQOL scores. Third, while the sample size appears relatively small, we included all eligible patients accessing in-centre hemodialysis. Fourth, our study did not include data from the three community dialysis units in the country, thus our results may not be generalizable to the overall hemodialysis population in Rwanda. Lastly, while our study does demonstrate the impact of socioeconomic status on HRQOL, our analysis could have been strengthened by the inclusion of additional variables. Future studies could include metrics exploring socioeconomic factors such as relocation or travel time to dialysis centres, out of pocket costs, yearly income or use of a validated poverty index to further evaluate the impact of poverty on quality of life.There are a number of limitations that need to be acknowledged. First, while the KDQOL-36Patients on in-centre hemodialysis in Rwanda have low HRQOL scores. The lowest score was found on burden of kidney disease and physical composite summary domains and there is a notable difference of HRQOL scores between hemodialysis units in Rwanda. Factors associated with overall HRQOL found were sex, employment status, number of comorbidities, dialysis vintage, and hemoglobin level, thus, optimizing medical and biomedical management of dialysis patients and finding ways to make dialysis less obstructive to maintain employment may assist in improving HRQOL. Further studies on HRQOL in both in-centre and community-based units as well as comparisons between using internationally accepted measures of dialysis adequacy (Kt/V) and QOL measures which are cheap and easy to administer in low income countries are recommended. Most patients in Rwanda on hemodialysis have higher socioeconomic status reflecting the financial constraints and the social impact to access and maintain renal replacement therapy in resource limited settings. As such, improving equitable access to RRT should remain a priority.


Metabolic syndrome (MetS) is a cluster of parameters encompassing the most dangerous heart attack risk factors, associated with increased morbidity and mortality. It is highly prevalent in recent-onset psychosis (ROP) patients. In this pilot study, we evaluated MetS parameters  cholesterol (HDL-c), fasting triglycerides, waist circumference, and systolic and diastolic blood pressure), clinical symptoms, pharmacological treatment, lifestyle, and inflammatory markers in 69 patients with ROP and 61 healthy controls (HCs). At baseline, waist circumference (p = 0.005) and fasting triglycerides (p = 0.007) were higher in patients with ROP than in HCs. At the 1-year follow-up, patients showed clinical improvement, with a reduction in the positive and negative syndrome scale (PANSS) score (p < 0.001), dietary intake (p = 0.001), and antipsychotic medication dose (p < 0.001); however, fasting glucose (p = 0.011), HDL-c (p = 0.013) and waist circumference worsened (p < 0.001). We identified sex, age, BMI, dietary intake, physical activity, daily tobacco use, daily cannabis use, and antipsychotic doses as risk factors contributing to baseline MetS parameters. After 1-year follow-up, those factors plus the PANSS and Calgary Depression Scale for Schizophrenia (CDSS) scores were associated with MetS parameters. Further studies are needed to understand the contributions of the studied risk factors in patients with ROP at onset and during disease progression. The prevalence of MetS in young adults is approximately 5–7%, with low HDL-c being the most prevalent MetS component (41.2%), followed by elevated blood pressure (26.6%) and abdominal obesity (23.6%)2. An increased prevalence of MetS of 13.2% has been recently identified in antipsychotic-naïve patients with first-episode psychosis (FEP)3. Similarly, blood pressure, waist circumference and fasting glucose have been reported to be slightly higher in antipsychotic-naïve subjects with a high risk of psychosis than in the general population4, and low HDL-c has been reported in drug-naïve adolescents with FEP5. Finally, a study of the evolution of MetS risk factors in patients with FEP revealed a progressive worsening of the MetS profile, specifically in abdominal circumference and HDL-c and triglyceride levels, with the most notable changes in the first year6. Sex, the presence of affective symptoms, early disease onset, antipsychotic polypharmacy, and the use of antidepressants or mood stabilizers were also identified as possible risk factors for the worsening of the metabolic profile6.Metabolic syndrome (MetS) is defined by the co-occurrence of several risk factors associated with increased morbidity and mortality, including high blood pressure, high blood glucose, excess fat around the waist, high triglycerides and low levels of high-density lipoprotein (HDL) cholesterol (HDL-c)8, mitochondrial dysfunction12, antipsychotic treatment16, clinical severity17, unhealthy lifestyle habits20 and a primary alteration of the innate immune system 22. Particularly, patients with FEP show an energy balance exceeding 26%23 and consumed more saturated fat and exercised less26. Poor dietary habits have been associated with increased BMI and abdominal obesity24 and cholesterol levels26. In addition, tobacco and alcohol consumption has been associated with some components of MetS in FEP patients28 and in the general population30. The relationship between cannabis use and the metabolic components of MetS is not well understood32. Finally, inflammation may also play a role in the pathogenesis of psychoses, with an elevation of specific cytokines and inflammatory mediators such as fibrinogen and C-reactive protein (CRP)36. The baseline levels of interleukin-6, CRP and leptin predicted incident MetS in schizophrenia patients, and it has been suggested that patients at increased risk of suffering the cardiometabolic adverse effects of antipsychotics could be identified before treatment initiation37.In individuals with psychotic disorders, MetS has been associated with genetic variation38. Nonetheless, the progression of MetS parameters is of great interest in the context of psychotic disorders, and preventive strategies based on improving lifestyle might not be sufficient to prevent future cardiometabolic alterations39. Our study evaluated the progression of MetS parameters at the initial stages of psychosis in patients seen in an early intervention unit. Specifically, we aimed (1) to compare the MetS components between patients with recent-onset psychosis (ROP) at the beginning of the intervention and healthy controls (HCs); (2) to assess the evolution of MetS components in patients with ROP after a 1-year follow-up; and (3) to identify the contributions of demographic factors, lifestyle, clinical factors and antipsychotic medication to MetS components at the two time points.Few prospective studies have investigated the relationships between lifestyle habits and metabolic parameters in the early stages of psychosis. One study reported a worsening of MetS components after 1 year of treatment, with antipsychotic treatment and low aerobic fitness identified as significant contributing risk factorsU = 1525; p = 0.007) and waist circumference  in ROP patients and lower systolic blood pressure . In the sex-stratified sample, we found significant differences in waist circumference  and systolic  and diastolic blood pressure  in the male group. The prevalences of MetS components in male patients were as follows: high triglycerides 17.3%, low HDL-c 13.5%, high systolic blood pressure 13.4%, high diastolic blood pressure 9.6%, high waist circumference 9.6% and high fasting glucose 1.9%. In female patients, the prevalence rates were as follows: high triglycerides 11.8%, low HDL-c 29.4%, and high waist circumference 47.0%. No women presented alterations in fasting glucose or systolic and diastolic blood pressure. In addition, BMI was higher in ROP patients , but in the sex-stratified analysis, only females showed statistically significant differences between ROP and HC groups . At baseline, the overall prevalence of MetS was 2.9% and 4.9% in ROP patients and HCs, respectively.Patients and controls were age matched but differed in sex distribution, ethnic makeup, civil status and working status. Table U = 1077; p < 0.001) and lower physical activity levels . Greater proportions of ROP individuals showed daily consumption of tobacco , cannabis  and alcohol . When the sample was stratified by sex, these differences were maintained for all variables in the two groups.Patients showed higher calorie intake  and waist circumference , but fibrinogen was not correlated with any MetS component. The prevalence of patients with MetS increased from 3.2% at baseline to 7.9% after 1 year.Differences in inflammatory markers (CRP and fibrinogen) between patients and the control group were not observed in either the whole sample or the sex-stratified analysis. Notably, CRP showed a partial correlation (controlling for sex) with triglyceride levels . No differences in MetS parameters were observed between patients with or without pharmacological treatment with antidepressants, benzodiazepines, or mood stabilizers. Inflammatory markers and lifestyle habits also did not differ between patients with and without neuroleptic treatment.At baseline, 79.4% of the patients were treated with antipsychotics, 17.5% with antidepressants, 14.3% with mood stabilizers and 30.2% with benzodiazepines. The most common antipsychotic was risperidone (38.9%), the most common antidepressant was venlafaxine (33.3%), and the most common mood stabilizer was valproic acid (63.6%). The median [IQR] dose of antipsychotics in chlorpromazine equivalents (eCPZ) was 360 [206] mg/day. HDL-c was the only MetS parameter that differed between patients with neuroleptic treatment and treatment-naïve patients , general PANSS score (PANSS-G) , total PANSS score (PANSS-T) , and the State Trait Anxiety Inventory (STAI-S)  score significantly improved. Depressive symptoms of the CDS also improved, without reaching statistical significance (p = 0.326). These improvements in clinical symptoms were observed along with a decrease in the dose of antipsychotic medication after the 1-year follow-up .Psychopathological evaluation with the positive and negative syndrome scale (PANSS) after 1 year of follow-up revealed that the positive PANSS score (PANSS-P)  and waist circumference  and a decrease in HDL-c . They also showed a significant increase in BMI . In the sex-stratified analysis, the differences in MetS components were significant only in men. The prevalence of MetS components in males at the 1-year follow-up was as follows: high fasting glucose 7.7%, high waist circumference 33.3%, low HDL-c levels 21.3%, high triglycerides 19.2%, high systolic blood pressure 7.7%, and high diastolic blood pressure 5.8%. The prevalence of MetS components in female patients was as follows: high waist circumference 64.7%, low HDL-c 17.6%, high triglycerides 11.8% and high diastolic pressure 5.8%. Women did not present alterations in fasting glucose or systolic blood pressure.The comparison of MetS parameters between baseline and 1-year follow-up in patients with ROP is shown in Table t = 3.497; p = 0.001) and, in the sex-stratified analysis, only in men ; however, physical activity did not . The number of individuals showing daily consumption of tobacco, cannabis and alcohol also improved, although the differences were not statistically significant. Patients had no differences between baseline and 1 year in the CRP or fibrinogen level, but their values increased after 1 year of follow-up. Similar to the findings at baseline, CRP 1 year later also showed a partial correlation with triglycerides , waist circumference , systolic pressure  and diastolic pressure , while fibrinogen was correlated with fasting glucose .Calorie intake improved after 1 year of follow-up , fasting triglycerides , waist circumference , systolic pressure  and diastolic pressure  and almost significant for HDL-c . Age and eCPZ contributed to fasting glucose; tobacco contributed to triglyceride levels; BMI contributed to waist circumference; sex and diet intake contributed to systolic pressure; and finally, physical activity, tobacco use and cannabis use contributed to diastolic pressure.We conducted hierarchical multiple regression analysis with backward elimination to identify the best predictive model for the MetS components at baseline and after the 1-year follow-up. We included sex, age, BMI, calorie intake, physical activity, daily tobacco use, daily cannabis use, PANSS-T, CDSS score and eCPZ in the analysis as covariates. We did not include inflammatory markers because they did not show significant differences between patients with ROP and HCs. Table 2 = 0.436; p = 0.004), waist circumference , systolic pressure  and diastolic pressure . Sex, age, PANSS-T and CDSS score contributed to fasting glucose; sex and PANSS-T contributed to waist circumference; sex, physical activity and tobacco and cannabis daily consumption contributed to systolic pressure; and finally, sex, age, and tobacco and cannabis daily consumption contributed to diastolic pressure. No significant models were obtained for HDL-c  or triglyceride levels .After the 1-year follow-up, we conducted the same models to predict MetS components considering the risk factors at baseline Table , panel A2 = 0.849; p < 0.001), fasting triglycerides , waist circumference , and systolic pressure  but not for fasting glucose  or diastolic pressure , which showed better predictive values at baseline. Age and PANSS contributed to fasting glucose; sex, tobacco and cannabis daily consumption, PANSS-T and CDSS score contributed to HDL-c; sex, BMI, diet intake and CDSS score contributed to triglyceride levels; BMI, physical activity and PANSS-T contributed to waist circumference; sex, age, physical activity, tobacco and cannabis daily use, PANSS-T and eCPZ doses contributed to systolic pressure; and finally, age, BMI, diet intake and eCPZ contributed to diastolic pressure.When considering the values of risk factors obtained after the 1-year follow-up, we observed better and more significant models for HDL-c  are in place. At the beginning of the intervention, we identified two MetS parameters that were higher in ROP patients than HCs: fasting triglycerides and waist circumference. After the 1-year follow-up, HDL-c decreased, and fasting glucose and waist circumference increased, indicating that these three MetS parameters worsened as the psychotic illness progressed. It is worth mentioning that fasting glucose levels were similar between ROP patients and HCs at baseline but worsened in patients at the 1-year follow-up. Additionally, both systolic and diastolic blood pressure presented lower or equal values in ROP patients than in HCs and did not change after 1 year of patient follow-up. Our results are in accordance with previous studies that identified higher waist circumference and lipid abnormalities regardless of FEP treatment40. HDL-c has been highlighted by some authors as an early-onset indicator of cardiometabolic risk in drug-naïve patients5, and low HDL-c levels have also been described as the most prevalent MetS component in healthy young people and might be a target in the primary prevention of MetS2. In our study, waist circumference and both systolic and diastolic blood pressure were significantly worse in males, while no differences were observed in females. However, studies with larger samples found that male FEP patients showed higher systolic blood pressure and lower HDL-c, while female patients showed higher waist circumference and lower HDL-c levels6.The increased rates of MetS recently reported in antipsychotic naïve FEP patients41, and furthermore, CRP has been identified as a predictor of future sequelae of MetS, such as atherosclerotic cardiovascular disease42. CRP and fibrinogen increased at the 1-year follow-up, but not significantly. CRP has been suggested as a biomarker for onset risk, as well as a risk factor for cardiovascular disease, MetS and increased nicotine dependence in smokers with schizophrenia. For these reasons, the use of anti-inflammatory strategies in those patients showing increased CRP levels at baseline has been proposed22.We did not find differences between ROP patients and HCs in the two inflammatory markers investigated, CRP and fibrinogen, though CRP showed significant correlations with triglyceride level and waist circumference. This finding suggests a possible relationship between the circulating inflammatory marker CRP and metabolic alterations related to MetS, as has been suggested in subjects exhibiting MetS in the general population26. Some remarkable results of the present study were the changes at the 1-year follow-up in patients with ROP. After attending the early intervention unit for 1 year, patients significantly reduced their calorie intake. Additionally, the number of subjects consuming cannabis daily significantly decreased, as did the number of those consuming tobacco and alcohol, but not significantly. In addition, they showed a significant clinical improvement, as the scores of the clinical scales PANSS and STAI-S significantly decreased, and their antipsychotic doses were reduced. Conversely, fasting glucose, HDL-c and waist circumference were significantly worse. The patients’ BMI also increased. Of note, after one year of attending the early intervention unit, patients had not improved in the performance of physical exercise, and an intervention to improve this aspect could be beneficial to improve, or at least not worsen, the parameters of MetS. This aspect should be further investigated in future studies. Our results are difficult to compare with those of other studies for various reasons. A similar study conducted in patients with first-episode schizophrenia who also attended an outpatient clinic reported a significant increase in waist circumference and triglyceride levels after a 1-year follow-up, but the researchers did not observe significant changes in the other MetS parameters38. However, their patients exhibited improved dietary habits and positive and negative psychopathological symptoms but significantly increased antipsychotic medication use during this period, so their results are not comparable to ours. A rapid increase in body weight gain and waist circumference during the first year with stabilization afterward has been reported in patients with FEP in a 2-year follow-up study6. Some studies have suggested that sex is related to MetS development. Male rather than female FEP patients are more predisposed to insulin resistance and dyslipidemia43; MetS prevalence has been reported to be slightly higher in men than women younger than 50 years, and the trend reverses after 50 years of age44. Moreover, male sex has been related to the observed body weight gain and waist circumference increase in patients with FEP6. Additionally, men of white ethnicity appeared to have a particular vulnerability to the emergence of central obesity, exhibiting increased waist size39. In contrast, no differences in the prevalence of MetS between men and women at the 1-year follow-up have been reported, although more women fulfilled the waist circumference MetS criterion38. Along these lines, it is worth noting that the underrepresentation of women in clinical trials and the underutilization of paced therapy, for example, in women with ischemic heart disease, can greatly vitiate the interpretation of many epidemiological and clinical studies on sex and gender issues45. Our results show that waist circumference was the most prevalent MetS parameter in both men and women, although the increase was greater in men. Therefore, our study adds evidence that waist circumference measurement could be a suitable noninvasive parameter in the follow-up of metabolic risk in patients with FEP who attended mental health centers and the necessity of more effective psychoeducational programs to improve lifestyle habits.Concerning lifestyle, patients consumed more calories and exercised less, and more patients consumed tobacco, cannabis and alcohol on a daily basis than HC subjects. These results are in line with previously published studies and indicate the high prevalence of unhealthy habits in the early stages of psychotic disorders and the necessity of developing specific and intensive programs to improve health habitsWe aimed to identify, by using regression analysis, the models that best explained the MetS parameters at baseline and after the 1-year follow-up. For this purpose, we used backward elimination regression to reduce the number of predictors while mitigating the multicollinearity problem. Notably, we identified different contributors to baseline MetS parameters. We found 5 of the 6 models to be statistically significant, with a mean of 1.8 risk factors contributing to each model. Thus, sex, age, BMI, dietary intake, physical activity, daily tobacco use, daily cannabis use, and eCPZ doses were risk factors that distinctly contributed to MetS parameters at baseline. After a 1-year follow-up, we created two different models for each MetS parameter, the first one using risk factor data obtained at baseline and the other with the data obtained at the 1-year follow-up. In the first situation, 4 out of 6 possible models were statistically significant, and the number of predictor risk factors averaged 3.8. In the second situation, all 6 models showed statistical significance, and the number of risk factors contributing to each model was 4.2. Notably, fasting glucose at 1 year was better predicted from baseline predictive factors.46.This study has some limitations that must be addressed. First, the sample was small, and the sex distribution was unbalanced. Therefore, stratified analyses could not be properly performed. Additionally, the number of individuals included in the follow-up study along with the many predictors considered may classify this study as an exploratory study, and the results should be confirmed in larger samples. This study was conducted in patients with ROP, 92% of whom were on antipsychotic medication at the beginning of the study. Thus, even though it reflects a real-world situation, it may not reflect the situation in naïve patients. Moreover, a 1-year follow-up is short, and the results of educational interventions in lifestyle and their contribution to MetS parameters could need longer periods to be evaluated. Finally, other etiologic factors, such as genetic variants or personality traits, that might be implicated in the development of MetS abnormalities in patients with ROP were not studied. In this sense, it is worth mentioning a recent study that revealed, by using genome-wide association study (GWAS) data, a significant genetic correlation between MetS-related traits, CRP and schizophreniaIn conclusion, we found worse values of the MetS components triglycerides and waist circumference in patients with ROP than in HCs at baseline. The prevalence of abnormalities in MetS parameters in patients increased significantly during the first year of treatment despite improving lifestyle habits and decreasing antipsychotic medication. At 1 year, fasting glucose, waist circumference and HDL-c worsened. All the risk factors studied contributed to aggravated MetS parameters at the 1-year follow-up, although they made a modest contribution at baseline. The evidence shows that MetS components worsen from the early stages of psychotic disorders. It is necessary to investigate the contribution of risk factors for MetS if we are to develop and apply preventive programs for at-risk individuals.A cross-sectional study was conducted between patients with ROP (less than 3 months after being included in the EIP) and HCs. In addition, a longitudinal study was performed only in the patient group with two time points: baseline and after 1 year of follow-up.47. Exclusion criteria for both patients and controls included intellectual disability, pregnancy, substance dependence, physical disability, and the presence of cardiovascular, endocrine or metabolic disease. The local ethics committee approved the study in accordance with the ethical standards of the current (2013) version of the Declaration of Helsinki. A complete description of the study was given to participants before their inclusion in the study, and they were included if they gave written informed consent. We evaluated the patients at baseline and after 1 year of follow-up, while HCs were evaluated only at baseline. Six patients did not complete the follow-up study.The study included 69 outpatients with ROP and 61 HCs. Patients aged 18 to 35 years were seen at the early psychosis program, outpatient clinic facility of the Hospital Universitari Institut Pere Mata, Reus, Catalonia, Spain, and were diagnosed using the DSM-IV criteria. Figure 48, STAI49 and CDSS50. Pharmacological data regarding antipsychotic, antidepressant, benzodiazepine, and mood stabilizer use were also collected. Daily antipsychotic doses were converted into eCPZ, and benzodiazepine doses were converted into diazepam equivalents.The diagnosis was confirmed in patients using the psychiatric interview OPCRIT checklist v.4.0., which generates DSM-IV diagnoses for psychotic disorders. HCs were also screened by a trained psychiatrist to rule out past or current history of psychiatric disorders. In patients, psychopathological data were gathered with PANSS51. We also obtained information on the frequency, intensity, and duration of physical activity of all participants over the past 7 days by the International Physical Activity Questionnaire short version (IPAQ-SF)52. Tobacco, cannabis, and alcohol use was categorized as follows: no use, sometimes, regularly or daily.Food intake was registered using a 24-h recall obtained via clinical interview. We calculated the daily calorie and nutrient intake with CESNID 1.0 software as previously described1.According to the International Diabetes Federation (IDF), the diagnosis of MetS requires the presence of central obesity  plus any two of the four following factors: (i) elevated triglycerides ; (ii) reduced HDL-c ; (iii) elevated blood pressure  elevated fasting plasma glucose (≥ 100 mg/dL or previously diagnosed type 2 diabetes)33. Weight, height, and waist circumference were obtained by physical examination by a trained nurse, and body mass index (BMI) was calculated as weight (kg)/height2 (m). Systolic and diastolic blood pressure were taken at the upper right arm in a seated position.Fasting glucose, triglycerides and HDL-c were measured by spectrophotometry as previously describedFasting specimens were obtained by antecubital needle venipuncture (8–10 a.m.); CRP and fibrinogen levels were measured on the day of blood sampling in the morning. High-sensitivity CRP levels were quantified by immunoturbidimetry , and fibrinogen levels were quantified using the Clauss method with the Gernon Hemofibrin L Kit .2-squared test. Continuous variables that were normally distributed were compared by Student’s t test or by the general linear model if sex needed to be considered. The Mann–Whitney U test was used to compare groups when the dependent variable was either ordinal or continuous, but not normally distributed. The paired-samples t test or the Wilcoxon signed-rank test was used to compare baseline and 1-year follow-up among patients based on the normality of variables. We used Spearman’s rank correlation test to measure the strength of the relationship between variable pairs or partial correlation when sex was considered a confounding factor. Finally, multiple linear regression models with backward elimination were applied to identify the risk factors (independent variables) contributing to MetS components both at baseline and after 1 year of follow-up. Data are presented as adjusted correlation coefficients between the independent variables (predictors) and dependent variables (MetS component) .Data were processed using IBM SPSS Statistics, v.28.0 . Normality of variables was checked by the one-sample Kolmogorov–Smirnov test. Categorical variables were compared between patients with ROP and HCs at baseline and, in the ROP group, between baseline and 1-year follow-up by the χ


Transplant Renal Artery Stenosis (TRAS) is a recognized vascular complication after kidney transplantation. The overall risk predictors of TRAS are poorly understood.Retrospective analysis of patients with suspected TRAS (Doppler ultrasound PSV > 200 cm/s) who underwent angiographic study in a single center between 2007 and 2014. All patients with stenosis > 50% were considered with TRAS. Stenosis restricted in the body of the artery was also analyzed in a subgroup.274 patients were submitted to a renal angiography and 166 confirmed TRAS. TRAS group featured an older population , more frequent hypertensive nephropathy , higher incidence of Delayed Graft Function (DGF)  and longer Cold Ischemia Time (CIT) . In multivariable analyses, DGF  was independent risk factors for TRAS. DM and CIT showed a tendency towards TRAS. The compound discriminatory capacity of the multivariable model  is significantly higher than systolic blood pressure and creatinine alone . In body artery stenosis subgroup, DGF  and Diabetes Mellitus (DM)  were independent risk factors for TRAS.In our transplant population, DGF increased more than 3-fold the risk of TRAS. In the subgroup analysis, both DGF and DM increases the risk of body artery stenosis. The addition of other factors to hypertension and renal dysfunction may increase diagnostic accuracy.clinicaltrials.gov (n° NCT04225338). The clinical suspicion is further corroborated by Doppler Ultrasound indicating decreased blood flow in the transplant renal artery with a peak systolic velocity > 200 cm/s. The gold-standard treatment option to restore kidney perfusion is the percutaneous transluminal angioplasty with the placement of a stent.,The main risk factors associated with TRAS, reported in small cohorts, are elderly recipients, Delayed Graft Function (DGF), Cytomegalovirus (CMV) infection, Diabetes Mellitus (DM), acute rejection, and increased Cold Ischemia Time (CIT).Although some risk factors are well defined in other studies, there is still a considerable proportion of patients with clinical suspicion who are unnecessarily referred to angiography. The aim of this study is to assess the risk factors for TRAS in suspicious patients for this comorbidity, in a single-center large cohort. By selecting the patient more accurately, it is possible to reduce costs and avoid exposing the patients to unnecessary exams.This single-center retrospective study includes data from all adult kidney transplant recipients with suspected TRAS who were referred for angiography at Hospital do Rim between January 2007 and December 2014. The clinical research developed, used the medical records of the Hospital do Rim patients and tabulated data from the Collaborative Transplant Study (CTS).Patients with clinical suspicion of TRAS , were submitted to Doppler Ultrasound of the transplanted kidney artery. Patients with Peak Systolic Velocity (PSV) > 200 cm/s measured by Doppler ultrasound were referred for renal angiographic confirmation. Patients with angiographic stenosis > 50% were considered to have TRAS.Lesions were differentiated according to their location, in the iliac artery, in the graft anastomosis, renal artery body, renal artery branches, and polar arteries. In order to differentiate possible interferences of surgical techniques, an analysis of a subgroup only with post-anastomotic lesions in the artery body was also performed.mice package in R) to handle Missing Values (MV). The authors used a predictive mean matching model for numeric variables, logistic regression (logreg) for binary variables (with 2 levels), and Bayesian polytomous regression (polyreg) for factor variables (≥2 levels). The authors did not impute missing values for the outcomes. The imputation step resulted in 5 complete data sets, each of which contains different estimates of the missing values for all 274 patients in the TraSStudy cohort. After imputation, the authors pooled and merged all 5 datasets to perform stepwise logistic regressions. Sensitivity analyses were conducted in each of the generated datasets.The authors used multiple imputations  and 95% Confidence Intervals (95% CI) to estimate the relative risk. Regression models were built by using a stepwise approach, limiting to 11 variables per step or per model since the authors found 108 individuals with non-TRAS and 166 with TRAS. A sub-group analysis was performed in patients with lesions restituted to the artery body, excluding those with ostial, distal branches, and iliac artery lesions.,Normally distributed data were presented as mean ± SD and skewed data as median (Interquartile Range [IQR]). Normality of distribution and variances were checked using histograms, the Kolmogorov-Smirnoff test, normal probability plots and residual scatter plots. Chi-Square or Kruskal-Wallis or two-tailed During this period, 6,362 kidney transplants were performed at Hospital do Rim, 274 (4.3%) of them had clinical suspicion of TRAS. After the arteriography, 166 (60.6%) cases were confirmed with a diagnosis of TRAS . Both grMost of the recipients were submitted to hemodialysis before transplantation and time on dialysis was similar between the groups . Living donor transplant was more prevalent in the non-TRAS group  and consequently, CIT was higher in the TRAS group  .The median time between the transplant and arteriography was 5 months in the TRAS group and 6 months in the control group . Prior tAlthough the TRAS group had a higher prevalence of patients infected with CMV, there was no statistically significant difference between the groups . The choIn the TRAS group, the prevalence of patients that developed DGF after transplant surgery was higher . Despite the higher prevalence of patients undergoing retransplant in the TRAS group , this variable was not statistically significant in the univariate analysis.Most patients used an immunosuppression regimen that included Tacrolimus, Prednisone, and Azathioprine or Mycophenolate. The TRAS group had a higher percentage of triple treatment that included Mycophenolate, but there was no statistical significance.In order to identify the independent factors for TRAS in suspicious patients, a stepwise method was performed. As a data-driven method, data on height, diabetes, serum creatinine, HDL-cholesterol, time since transplantation, peritoneal dialysis, DGF, CIT, SBP, and hypertensive nephropathy prior to transplantation were incorporated into the multivariate analysis model . As expeAs seen in The present study's population sample has similar characteristics compared to previously published cohorts. In our center, 2.6% of kidney transplanted recipients had a diagnosis of TRAS, which is in line with that found in the literature of 1%‒23%.In both groups, it is possible to observe an average of PSV much higher than the cut adopted. In a systematic review, there are authors who adopt the PSV cut between 200‒300 cm/s.Diabetes is a known risk factor for atherosclerosis, due to the greater endothelial permeability to lipid macromolecules in the coronary arteries, which can compromise other vascular beds, including renal arteries. Willicombe et al.,As expected, pre-arteriography serum creatinine, systolic blood pressure, and diastolic blood pressure were significantly different between both groups.,,Audard et al.Despite some studies pointing to CMV infection as an independent risk factor for TRAS, the present study did not confirm the same result. Audard et al.In multivariate analysis, peritoneal dialysis was also demonstrated as an independent factor for TRAS, however, the authors believe that due to the low representativeness of this condition in relation to hemodialysis, it may have generated a sampling bias. Therefore, the authors have no scientific basis to justify this variable as statistically representative. The same occurs with height, which was shown to be a protective factor. In view of the current literature and the available knowledge, the authors have not found justification to explain this finding. The stepwise model mathematically selects data variables and disregards previous knowledge, thereat those variables were included in the model based on their initial statistical weight.The accuracy of the variables found in This study has limitations, despite presenting data from a large volume center. The main limitation is that it is a retrospective and single-center study. However, it is unlikely that prospective randomized studies in the scenario of TRAS involving intervention are feasible, given the complications resulting from graft stenosis and consequent renal loss. Some donor information was not available for being collected in the present study's registry.Thus, the authors can conclude that the well-established criteria for TRAS as risk factors such as creatinine and arterial hypertension were present in this study. DGF and diabetes also showed a strong correlation for the appearance of TRAS, as already described in smaller studies. Although the authors have one of the largest series on the subject, it is clear that there is a need for even greater multi-centers studies to clarify some controversial points such as CMV infection, acute rejection, and CIT. These variables tended to be a risk factor but were not statistically significant in the present study.Helio Tedesco Silva Junior has received research grants and travel and consulting honoraria from Novartis, Sanofi and Pfizer. The remaining authors have no conflicts of interest to disclose.Gabriel Kanhouche: Study design, data acquisition, statistical analysis and writing of the manuscript.Gustavo Rocha Feitosa Santos, Henry Campos Orellana, Attilio Galhardo, Ana Carolina Buso Faccinetto, Manoela Linhares Machado Barteczko, Julia Bernardi Taddeo: Data acquisition.Luiz Sérgio F. de Carvalho: Statistical analysis and writing of the manuscript.Renato Demarchi Foresto: Writing and revision of the manuscript.Valdir Ambrósio Moises, Helio Tedesco-Silva, José Medina Pestana: Study design, writing and revision of the manuscript.Adriano Henrique Pereira Barbosa: Study design, data acquisition, statistical analysis, writing and revision of the manuscript.The authors declare no conflicts of interest.


Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been observed in several large cardiovascular outcome trials to significantly reduce the incidence of major cardiovascular event (MACE) with type 2 diabetic patients. The clinical trials of GLP-1 RAs, including lixisenatide, exenatide, liraglutide, semaglutide, albiglutide, and dulaglutide, are associated with a significantly 14% lower risk of MACE in patients with T2DM and a history of CV disease, and with a nonsignificantly 6% lower risk in patients without history of CV disease. Some of the interpretation with GLP-1 RA trials suggested the possible role of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in primary prevention of cardiovascular diseases in nondiabetic individual, echoed by a recent editorial redefining the role of GLP-1 RAs being beyond glycaemic control. The narrative review provides an in-depth insight into GLP-1 RA use guideline in different countries and regions of the world and examines the safety and concern of GLP-1 RA use. The narrative review draws the comparison of GLP-1 RA use between diabetic and nondiabetic individual in terms of cardiovascular and metabolic benefits and points out the direction of future clinical trials of GLP-1 RAs in nondiabetic individuals. The focus of the review is on GLP-1 RAs' preventive roles in nondiabetic individuals with cardiovascular disease, chronic kidney diseases, obesity, dyslipidaemia, hypertension, nonalcoholic fatty liver diseases, polycystic ovarian syndrome (PCOS), and perioperative complications of bariatric surgery, albeit in small studies and subset analysis of clinical trials of diabetic patients. Glucagon-like peptide (GLP) was first discovered through research demonstrating a sustained insulin release in response to oral glucose load when compared with the intravenous glucose load . GLPs' eThe authors performed an extensive literature review in Ovid MEDLINE, Ovid Embase, CINAHL, Web of Science, and PsycINFO (Ovid) by using the following Medical Subject Heading (MeSH) terms including GLP-1 RA, guideline, safety, cardiovascular disease, chronic kidney diseases, obesity, dyslipidaemia, hypertension, nonalcoholic fatty liver diseases, polycystic ovarian syndrome, and perioperative complications of bariatric surgery. The review has identified 4594 publications related to GLP-1 RAs' safety, guidelines in different countries, and potential preventive roles. After scanning the titles and the abstracts to remove duplication, case reports, and editorial comments, we have included 75 publications for full text screening to identify the relevant discussion points regarding GLP-1 RA's potential roles in nondiabetic population in this review. The authors have applied the Oxford Equator PRISMA checklist  to satisGLP-1 RAs have high efficacy on controlling blood glucose with low risk of hypoglycaemia like metformin. They have beneficial effects on CVD prevention, albuminuria, and weight loss similar to Sodium Glucose Cotransporter 2 (SGLT2) inhibitors . GLP-1 RGLP-1 RAs have been suggested in several major cardiovascular outcome trials (CVOTs) as potential treatment not only for T2DM and atherosclerotic cardiovascular disease but also in T2DM patients with manifest HF. In the LEADER trial in T2DM patients, liraglutide against placebo decreased the risks of cardiovascular death, myocardial infarction, and stroke with no significant effects on HF hospitalizations ; similarFurther exploration of GLP-1 RAs in nondiabetic patients, a mild improvement of left ventricular function has recently been demonstrated in patients with ST-segment elevation myocardial infarction (STEMI) treated acutely with the GLP-1 analogue liraglutide for 7 days . SimilarIn placebo control trial with diabetic patients, GLP-1 RAs reduced the risk of the broad composite kidney outcome significantly by 17%, in particular with a 26% reduction in macroalbuminuria . To dateThe analysis of renal endpoints in large placebo-controlled CVOTs of GLP-1 RAs in patients with T2DM either with cardiovascular comorbidities or at high risk of cardiovascular disease suggests that GLP-1 RAs may be renoprotective even when corrected for glycaemic control . GLP-1 RObesity is on the rise and has now been defined as a chronic disease with serious health consequences and associated with increasing prevalence of type 2 diabetes , 37. A sWhile changes in diet, behavioural modifications, and physical activity have typically been the foundation of weight management, weight loss achieved by these interventions alone is often limited and unsatisfactory . BariatrPharmacotherapy may be considered in obese patients with a BMI of 30 and above or in patients with lower BMIs with weight-related complications . The devAnother RCT comparing semaglutide with liraglutide and placebo in nondiabetic patients demonstrated a 7.8% weight loss in the liraglutide 3.0 mg group . InteresIn summary, GLP-1 RAs have been well placed as the forerunner of pharmacological intervention for obesity in both diabetic and nondiabetic population .There are no direct clinical trial examining GLP-1 RA effects on cardiometabolic variables including blood pressure and dyslipidaemia. In the recent liraglutide trial with obese nondiabetic patients, both changes between baseline and week 56 of systolic and diastolic blood pressure were significantly different between the liraglutide group and the placebo group with a risk difference of -2.8 mmHg (95%Cl -3.56 to -2.09) and -0.9 (95%Cl -1.41 to -0.37), respectively . ,SimilaNonalcoholic fatty liver disease (NAFLD) is highly prevalent in diabetic patients associated with ASCVD, diastolic dysfunction, and HFpEF. More than one-third of patients with NAFLD have diastolic dysfunction, coronary microvascular dysfunction, and myocardial fibrosis , 48. In In summary, there is no direct trial evidence of GLP-1 RAs' effects of improving and preventing NAFLD in nondiabetic population.GLP-1 RAs have been studied in the treatment of PCOS because of their effectiveness in reducing weight and the associated improvement in hyperandrogenism and metabolic parameters . GLP-1 R2 [Open-label clinical trials exploring the effect of exenatide on body mass in overweight or obese women with PCOS showed a significant reduction in body weight, ranging from -3.1 to -6 kg and a corresponding decrease in BMI between -1 and -3.1 kg/m2 . In addi2 .The systematic review examined the effects of GLP-1 RAs on PCOS-related subfertility and irregular periods. Exenatide compared with metformin demonstrated a significantly greater number of spontaneous pregnancies in the exenatide group, after 24 weeks of treatment . AnotherIn summary, there is some trial evidence of GLP-1 RAs' effects on prevention of PCOS through weight reduction in nondiabetic population .2 [“GLP-1 Receptor Agonist interVentIon for poor responders afTer bariAtric Surgery (GRAVITAS)” investigated the safety and efficacy of subcutaneous injections of the liraglutide on glycaemic control in patients with persistent or recurrent T2DM after bariatric Roux-en-Y gastric bypass or vertical sleeve gastrectomy. The conclusion drawn from the study stated that irrespective of the type of surgery, liraglutide can treat the persistent or recurrent postbariatric surgery complication of T2DM by optimising glycaemic control along with a needful weight loss. The GRAVITAS trial raised the questions of GLP-1 RA's role especially preoperatively to aid on reducing perioperative complication beyond diabetes and other associated cardiovascular complications in nondiabetic patients as there is currently no direct trial evidence of GLP-1 RAs' effects on prevention of perioperative and postoperative complications of bariatric surgical individual, especially in nondiabetic population (Bariatric surgery is the most commonly performed procedures and the most effective intervention for obesity with BMI over 30 kg/m2 . GLP-1 r2 . GLP-1 i2 . A recen2  “GLP-1 Rpulation . FurtherThere are numerous reports and reviews of potential safety issues associated with the use of GLP-1 RAs including gastrointestinal symptoms, hypoglycaemia, pancreatitis, injection site reaction, and allergy/angioedema.The most frequently reported adverse effects of GLP-1 RA therapy were gastrointestinal symptoms . Of thesSecond commonly reported adverse effect of GLP-1 RA was gastroparesis. GLP-1 RA have been shown to delay gastric emptying that may increase the risk of nausea, and longer duration of action may have a lesser effect on gastric motility, thus leading to less nausea . Long-acGenerally, the risk of hypoglycaemia in patients taking GLP-1 RAs alone was low, and similar across all GLP-1 RAs , 69. TheThere has been conflicting evidence on GLP-1 RAs use and risks of pancreatitis including some studies suggesting a slightly increased risks , while oOverall, there has not been a clear cause and effect relationship described between GLP-1 RAs and pancreatitis , 77. TheSymptoms that may occur include pruritis, rash, or erythema, with pruritis being the most frequently reported injection site symptom . GeneralGLP-1 RAs are synthetic peptides, which may lead to antibody formation, like other subcutaneously administered peptides . AntibodAs summarised in


Drainage is indicated in many patients with a perinephric abscess (PA). Surgical drainage is associated with trauma and slow recovery, while percutaneous drainage can be ineffective in some patients. We report on 11 patients with PA treated by percutaneous nephroscopy combined with ultrasound-guided negative-pressure suction under local anesthesia.This case series included 11 PA patients operated on from January 2013 to June 2020. All patients received percutaneous nephroscopy combined with ultrasound-guided negative-pressure suction. Data, including operation time, volume of intraoperative blood loss, volume of intraoperative pus suction, time of postoperative drainage tube indwelling, time to restore normal body temperature, length of postoperative hospital stay, and intraoperative and postoperative complications, were collected.The age of the patients was 59 (53–69) years. Eight, six, two, and two patients had hypertension, type 2 diabetes, rheumatoid arthritis, and renal calculi, respectively. The operations were successful forall11 patients. Eight, two, and one patients required one, two, and three channels, respectively, to clear their abscess. The average operation time was 44 (30–65) min, and intraoperative blood loss was 16 (10–20) ml. The volume of intraoperative pus suction was 280 (200–400) ml, time of postoperative drainage tube indwelling was 8.2 (6–12) days, and time to restoring normal body temperature was 0.8 (0.5–2) days. The average postoperative hospital stay was 9.8 (7–14) days. No severe intraoperative or postoperative complications occurred. The postoperative follow-up time was typically 4.8 (3–8) months, and there were no recurrences.Percutaneous nephroscopy combined with ultrasound-guided negative-pressure suction might be a feasible method for treating PA. Escherichia coli is the most common cause of PA, followed by other Enterobacteriaceae , as well as Pseudomonas sp. and Enterococcussp. [A complicated urinary tract infection is an infection of either the upper or lower urinary tract in a patient at an increased risk of treatment failure or complications , 2. Compoccussp. , 3, 7–9.Due to the non-specificity and complexity of PA, delayed diagnosis, and the limitations of the available treatments, the mortality rate of patients with PA used to be as high as 40–50% .With the continuous advancement of medical techniques, the diagnosis of PA is no longer difficult, and there are more choices regarding treatment. Conventional therapy includes antibiotics and control of the infection source, but it cannot control the space-occupying effect of the abscess, and surgery maybe indicated , 2, 7. TThis study aimed to report on the details and outcomes of 11 patients with PA treated by percutaneous nephroscopy combined with ultrasound-guided negative-pressure suction under local anesthesia. The results suggest this novel method could be used for the effective management of PA.This retrospective study included all patients with PA treated by percutaneous nephroscopy combined with ultrasound-guided negative-pressure suction under local anesthesia from January 2013 to June 2020 in Zhejiang Provincial People’s Hospital. This study was approved by the Ethics Committee of Zhejiang Provincial People’s Hospital (No. 2021QT030). The requirement for informed consent was waived by the committee due to the retrospective nature of the study.The patients were placed in the prone position with a pad under their waist. A puncture point was selected at the site where the abscess was closest to the body surface while avoiding the major blood vessels and vital organs  according to intraoperative ultrasound  positioning. Local infiltration anesthesia using 15 ml of 2% lidocaine was performed. An 18 G puncture needle  was inserted to the clearest sonolucent area of the fluid in the abscess’s center under ultrasound guidance. A small amount of pus was collected for routine bacterial culture and drug sensitivity tests. A fascial dilator  was used to dilate gradually from 8 to 20 Fr under the guidance of a guidewire  and then a 20 Fr outer sheath  was placed. An 18 Fr nephroscope  was inserted through the sheath. Then, negative-pressure suction  was used to aspirate the pus and tissues completely, and foreign body forceps  were used to remove necrotic tissue in the abscess .Only descriptive statistics were used. Continuous data are summarized using average (range). Categorical data are presented as Eleven patients with PA, including three males and eight females, were included in this study. Table Table Drainage is indicated in many patients with PA. Surgical drainage is associated with trauma and slow recovery, while percutaneous drainage can be ineffective in some patients , 10, 11.The risk factors for PA are diabetes, immunosuppression, pregnancy, neurogenic bladder, nephrolithiasis, indwelling urinary devices, and urinary obstruction , 2. Amon2 pressure, a long operation time, and waist myofascial injuries can spread the infection [It is generally considered that, for PA with diameter of < 3 cm with non-matured and liquified content, sufficient antibiotics should be applied in time as conservative systemic therapy , 2, 7. Fnfection .Rai et al.  and Ng eThe anesthesia methods for percutaneous nephroscopy are currently general anesthesia and combined spinal-epidural anesthesia . In patiThe establishment of a standard channel for percutaneous nephroscopy under local anesthesia could provide a good visual field while maintaining low perfusion and allowing the rapid and highly efficient clearing of pus by negative-pressure suction. For thick pus that cannot be easily aspirated, suction can be performed after repeated rinsing with normal saline. The locally necrotic tissues, organized blood clots, and pus moss can be aspirated after ultrasound disintegration or using foreign body forceps with nephroscopy. For septal abscess cavities, nephroscopy combined with ultrasound negative-pressure suction can be used to break the relatively thin septa under direct vision before aspirating the pus. For septal abscess cavities that cannot be reached through the first channel, multiple channels can be established under ultrasound guidance according to the sizes and ranges of the abscesses, but wide drainage tubes with multiple lateral holes have to be placed for each channel. For abscesses with liquefaction of necrotic tissues, a small amount of pus can still be drained from the drainage tubes after the operation. Thus, the drainage tube should be maintained in the patient, and sterilized normal saline could be used to rinse if necessary.We summarize the key points of this operation as follows. First, the center of the abscess should be selected as accurately possible to avoid the pain induced by large angle swings of nephroscopy. Second, low-flow perfusion should be performed to reduce pain and water pressure during rinsing. The puncture must be precise to avoid excessive bleeding, which could lead to an unclear visual field. Third, continuous negative-pressure suction during the operation could reduce the pressure in the abscess cavity, decrease the risk of bacteria and toxin backflow into the blood, and induce fluid exudation, reducing the incidence of postoperative urinary sepsis. Finally, the sites and numbers of channels used for nephroscopy should be appropriately planned under the guidance of ultrasound, and wide drainage tubes with multiple lateral holes should be placed in each channel after the operation to help obtain the best pus-clearing and drainage effects with minimal trauma.This study had some limitations. The patients were from a single center, and the sample size was small. In addition, only a short follow-up period was included. Prospective studies with a large sample size and long-term follow up are needed to verify our findings.In conclusion, this study suggests that percutaneous nephroscopy combined with ultrasound-guided negative-pressure suction might be feasible for treating PA. This method has the advantages of minimal invasion, complete drainage, rapid recovery, and fewer complications. Skillful operators could choose to apply this method.