Blood pressure variability (BPV) has been reported to be a predictor of cardiovascular and some cognitive diseases. However, the association between napping and BPV remains unknown. This study aimed to explore the association between napping and BPV.A cross-sectional study including 105 university students was conducted. Participants’ 24 h ambulatory blood pressure monitoring (24 h ABPM) were measured, and napping behaviors were investigated. BPV were measured by the 24 h ABPM, included standard deviation (SD), coefficient of variation (CV), and average real variability (ARV).r = 0.250, P = 0.010), nighttime CV of systolic blood pressure (SBP) , 24 h WCV of DBP , 24 h ARV of SBP  and 24 h ARV of DBP . Compared with the no napping group, 24 h WCV of DBP, daytime CV of DBP, and daytime SD of DBP were significantly higher in participants with napping duration >60 min. With multiple regression analysis we found that nap duration was an independent predictor for 24 h ARV of SBP  and 24 h ARV of DBP .Among the participants, 61.9% reported daytime napping. We found that nap duration was significantly associated with daytime CV of diastolic blood pressure (DBP) (Napping durations are associated with BPV among university students. Especially those with napping durations >60 min had a significantly higher BPV than those non-nappers. Blood pressure variability (BPV) is a concept used to characterize continuous dynamic fluctuations in blood pressure. BPV can be described in short-term variability  and long-term variability  . There aAmong university students, late bedtime and daytime napping are extremely prevalent, due to a variety of factors including academic stress, socialization, coffee intake, and uncontrolled use of social media . A meta-r = 0.35), (ii) statistical power = 90%, (iii) Alpha = 5%, (iv) correlation coefficient of the null hypothesis (r = 0.0), (v) dropout rate = 20%. The sample size of 102 could provide 90% statistical power to test the significant correlations.Our study was conducted in a University in Hunan Province, China from 2020 to 2021. The study recruited university students through a convenience sampling method by flyers or posters. The sample size of the present correlation study was calculated using PASS 2021. Since no previous studies have reported the association between nap and BPV. We used the correlation coefficients between sleep and blood pressure in previous studies, previous studies reported correlations within the range of between 0.25 to 0.45 , 19. DetIn our study, we included university students who (i) provided written informed consent in the study, (ii) are university students during the 2020–2021 period; (iii) students with normal sleep cycle . The exclusion criteria included the following: (i) pregnancy, (ii) taking antihypertensive and hypnotics, (iii) hyperthyroidism, (iv) sleep disturbance or drinking caffeine on the day of the trial, (v) incomplete sleep records, (vi) 24 h ambulatory blood pressure monitoring was ineffective. General characteristics  were measured by questionnaire. Moreover, all participants underwent physical examinations .They completed the 24 h ambulatory blood pressure monitoring (24 h ABPM). Weight was measured using calibrated body composition apparatus (TANITA-MC780MA) and height was measured using a stadiometer. The present study was approved by the Research Ethical Review Committee Board of Hunan Normal University (2019–88). Finally, 105 students were included in the final analysis.All participants were scheduled to undergo 24 h ABPM measurement using a noninvasive, validated device . During the 24 h measurement period, the device was programmed to record readings of each parameter every 30 min during the nighttime (between 23:00 to 7:00) and every 15 min during the daytime (between 7:00–22:59). Recordings will be set to read missing values if they were outside systolic blood pressure (SBP) readings of 60–280 mmHg and diastolic blood pressure (DBP) readings of 30–190 mmHg. The recordings including at least 10 during the daytime and 5 during the nighttime were considered to be valid. . Blood pTotal number of measurements was summarized and the following parameters of short BPV were calculated. Basic indicators (standard deviations (SD) and coefficients of variation (CV = SD* 100/BP) for SBP and DBP) were calculated by ABPM directly. The average real variability (ARV) calculates the average of the differences  between consecutive BP readings: k+1−BPk| . Weightek+1−BPk| . The weiThroughout the 24 h ABPM period, participants were asked to fill out a 24 h behavior diary that included daytime naps and nighttime sleep. Participants were asked to fill diary sleep records at the end of the day. Based on the diary, we obtained the following indicators: nap duration, nap frequency, bedtime, time of awakening, and duration of nighttime sleep.–60 min, and >60 min. LSD-t test was conducted for pairwise comparison between groups to detect whether there were significant differences in BPV within the groups.All statistical analyses were performed using IBM SPSS 20.0 for Windows  and R Studio software. Participants’ 24 h ABPM indicators, basic characteristics and sleep were described using mean (±SD) and frequency (%). Pearson's correlation coefficient and multiple linear regression was used for analyzing the relationship between daytime nap duration and BPV. To test the potential nonlinear associations between napping and blood pressure variability , we used restricted cubic spline regression models with age and sex adjusted. In addition, we divided the nap duration into three groups: no napping (0 min), 02, mean bedtime was 00:19, mean nighttime sleep duration 7.52 ± 1.33 h/day, and total sleep time 8.16 ± 1.44 h/day. The proportion of students who slept no more than 6 h/day and ≤7 h/day was 8.57% and 48.57%. There were 61.9% of participants reported daytime napping and the average duration of napping was 1.05 ± 0.56 h/day.A total of 105 university students  were included for the present study. Their mean age was 18.84 ± 1.21 years, mean BMI was 21.01 ± 3.05 kg/mAmong the 105 university students, 68.60% had normotensive 24 h, daytime and also nighttime blood pressure. The mean 24 h SBP was 107.03 ± 6.81 mmHg, mean 24 h DBP 66.50 ± 5.32 mmHg, mean daytime SBP 108.66 ± 7.06 mmHg, mean daytime DBP 68.10 ± 5.70 mmHg, mean nighttime SBP 101.76 ± 7.21 mmHg, and mean nighttime DBP 61.83 ± 5.90 mmHg .r = 0.250, P = 0.010), nighttime CV of SBP , 24 h SD of DBP , daytime SD of DBP , nighttime SD of SBP , 24 h WCV of DBP , 24 h WSD of DBP , 24 h ARV of SBP  and 24 h ARV of DBP  (We found that nap duration was significantly correlated with daytime CV of DBP (= 0.003) .P < 0.05) (The nap duration was categorized into three groups: no napping (0 min), 0–60 min, and >60 min. A pairwise comparison revealed that there was significant difference between the nap duration >60 min group and the no napping (0 min) group, and 24 h WCV of DBP, daytime CV of DBP, and daytime SD of DBP were higher in the nap duration >60 min group than the no napping group ( < 0.05) .P for nonlinearity = 0.990, 0.441, 0.919, 0.886, 0.958, 0.878, 0.341, and 0.859, respectively)  .P < 0.05). Longer nap duration was associated with higher daytime CV of DBP , higher CV of SBP at night , higher 24 h WCV of DBP , higher 24 h ARV of SBP  and higher 24 h ARV of DBP   , 4.In the current study we found that in university students insufficient nighttime sleep and late bedtime were quite common. Longer nap duration was correlated with increased BPV, including daytime CV of DBP, nighttime CV of SBP, 24 h SD of DBP, daytime SD of DBP, nighttime SD of SBP, 24 h-WCV of DBP, 24 h-WSD of DBP, 24 h ARV of SBP and 24 h ARV of DBP. Especially for young adults with nap duration >60 min, 24 h WCV of DBP, daytime CV of DBP, and daytime SD of DBP were significantly higher than those without daytime napping. In addition, with Multiple regression analysis we found that nap duration was an independent predictor for nighttime CV of SBP, daytime CV of DBP, 24 h WCV of DBP, 24 ARV of SBP and 24 h ARV of DBP.–9 h. Yet, notably the percentage of participants with nighttime sleep duration ≤6 h was 8.57% and 48.57% for ≤7 h. Among university students, insufficient nighttime sleep has been shown to be detrimental to health . Thus far, the majority of studies on sleep and BPV have focused on patients with obstructive sleep apnea and little evidence is available with respect to the relationship between napping and BPV among the general population. Further investigations demonstrating relationships between nap duration and BPV are warranted, especially larger prospective studies.In our study, 61.9% of the university students reported participating in daytime napping. We did not find an association between abnormal BP and nap duration (Supplementary Table S1). It is probably the participants in our study are young and in a physical healthy condition. But we found a positive correlation between nap duration and BPV among university students. There are several explanations or potential mechanisms for the findings. Firstly, daytime napping may be associated with inefficient sleep (high level of sleep fragmentation) . It has ased BPV –47. Thirased BPV . The bloased BPV , 50. Ther = 0.238) and daytime diastolic BPV (r = 0.258)  . Further= 0.258) . Therefo= 0.258) . The dis= 0.258) . However= 0.258) . When as= 0.258) . Further= 0.258) . Not onl= 0.258) , 60. In = 0.258) . However= 0.258) . PreviouOur findings help to elucidate the relationship between nap duration and BPV indicators, which will facilitate further in-depth studies. The present study also has some limitations. Firstly, ambulatory blood pressure measurement data were difficult to obtain, so the present study was conducted using a relatively small sample. Secondly, in the present study the sleep data is self-reported, there could be some recall bias. Future studies are recommended to assess napping characteristics more accurately by wearing a wrist actigraphy for multiple consecutive days. Also, our study did not take certain important factors into account, such as dietary information and physical activity that are related to sleep and BP. Future related studies should take these factors into consideration. Finally, this study is an observational study and can only provide correlations between sleep characteristics and BPV and cannot prove the causality.Short sleep duration and late bedtime are quite common among university students. Nap duration is independently associated with BPV among university students. Especially, those with daytime napping >60 min had a significantly higher BPV than those without daytime napping.


Alterations in kidney function and increased risk of kidney diseases in patients with inflammatory bowel disease (IBD) have been reported, but the causal relationship remains unclear. Herein, Mendelian randomization was employed to identify the causal effect of inflammatory bowel disease on kidney function and the risk of chronic kidney disease (CKD), urolithiasis, and IgA nephropathy.The International Inflammatory Bowel Disease Genetics Consortium provided the summary-level genome-wide association study (GWAS) data that correlates with Crohn's disease (CD) and ulcerative colitis (UC). GWAS data for estimated glomerular filtration rate from serum creatinine (eGFRcrea), urine albumin–creatinine ratio (uACR), and CKD were obtained from the CKDGen Consortium, and GWAS data for urolithiasis were obtained from the FinnGen consortium. The summary-level GWAS data for IgA nephropathy were obtained from the meta-analysis of UK-biobank, FinnGen, and Biobank Japan. Inverse-variance weighted was used as the primary estimate. Furthermore, the Steiger test was used to validate the direction of causality.The inverse-variance weighted data revealed that genetically predicted UC significantly increased uACR levels, while genetically predicted CD significantly increased the risk of urolithiasis.UC increases the levels of uACR, and CD increases the risk of urolithiasis.The online version contains supplementary material available at 10.1186/s40001-023-01128-0. Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), has become globally significant in the twenty-first century . IBD is HLA-DQ/DR, CARD9, HORMAD2), which may explain why these two conditions tend to have a higher incidence of co-occurrence than expected by chance [A retrospective cohort study of over 80,000 individuals showed that IBD is associated with an increased risk of chronic kidney disease (CKD) . A Swediy chance . Measurey chance . HoweverMendelian randomization (MR) is an approach that generates more reliable evidence for causal relationships using genetic variants that are robustly linked with exposures, which could avoid confounding bias inherent in observational studies. Previous MR studies have reported on numerous risk factors associated with IBD, as well as the causal relationship between IBD and other diseases –13. NeveThe present study was conducted in accordance with the “STROBE-MR” statement .https://www.ibdgenetics.org/) provided the summary-level GWAS data correlated with UC and CD. The GWAS data for UC included 13,768 patients and 33,977 controls, and the GWAS data for CD included 17,897 patients and 33,977 controls.The International Inflammatory Bowel Disease Genetics Consortium  provided the summary-level GWAS data associated with eGFRcrea, uACR, and CKD. Meta-analysis of the GWAS data for eGFRcrea included 567,460 persons of European ancestry. For individuals 18 years or younger, the Schwartz formula was used to calculate eGFRcrea, while adults had their eGFRcrea calculated according to the Chronic Kidney Disease–Epidemiology Collaboration (CKD–EPI) equation. Meta-analysis of GWAS data for uACR included 547,361 subjects of European ancestry. uACR was evaluated in mg/g, calculated as urinary albumin (mg/l) divided by urinary creatinine (mg/dl), and then multiplied by 100. Meta-analysis of GWAS data for CKD included 64,164 European ancestry cases and 561,055 controls of European ancestry. CKD was defined as an eGFRcrea below 60 ml/min/1.73 m2. The details of the CKDGen Consortium have been introduced by Teumer et al. and Wuttke et al. [https://r7.finngen.fi/pheno/N14_UROLITHIASIS). The definition of urolithiasis was based on ICD-10 (N20–N23). The summary-level GWAS data for IgA nephropathy were acquired from the meta-analysis of FinnGen, UK-biobank, and Biobank Japan (https://www.ebi.ac.uk/gwas/studies/GCST90018866). Meta-analysis of GWAS data for IgA nephropathy included 15,587 cases of European ancestry, 462,197 European ancestry controls, 71 cases of East Asian ancestry, and 175,288 East Asian ancestry controls.The CKDGen Consortium  and (2) SNPs for the UC or CD were not in linkage disequilibrium (LD) via clumping process . We identified 86 SNPs related to UC and 115 SNPs related to CD from European-ancestry participants of the IIBDGC. To test for weak instrumental variable bias, we calculated F statistics using the formula F = R2(n-k-1)/k(1-R2), where R2 is the proportion of the variance of the exposure explained by the instrumental variables, n sample size, and k number of genetic variants). If the F statistics for the instrument–exposure association is much greater than 10, the possibility of weak instrumental variable bias is low. To remove the kidney-related SNPs , we used a threshold of 5 × 10–8, and then applied MR–PRESSO to eliminate any outliers before conducting each MR analysis.The genetic instruments were chosen based on the following criteria: (1) single nucleotide polymorphisms (SNPs) associated with UC or CD with genome-wide significance (The random-effect inverse variance weighted (IVW) method was performed as the major approach, while MR–Egger and weighted median (WM) methods were used to improve the IVW estimates by providing more robust estimates over a broader range of scenarios . The IVW method is an efficient analysis when all genetic variants are valid instrumental variables . The MR–P < 0.05 were considered statistically significant.All analyses were conducted by the packages TwoSampleMR (version 0.5.6) and MRPRESSO (version 1.0) in R platform (version 4.2.2). F = 77.48) were chosen to genetically predict UC, and 115 index SNPs (F = 89.83) were chosen to genetically predict CD. After removing all the outliers by MR–PRESSO, the MR estimates from specific methods of evaluation the causal effect of UC or CD on kidney function are presented in Fig. β = 0.008, 95%CI 0.003 to 0.013, p = 0.002)  , and CD and urolithiasis . Although heterogeneity was found in some results, it did not invalidate the Mendelian randomization estimates, because the present study used random-effect IVW, which may have balanced the pooled heterogeneity. For both significant and non-significant estimates, the leave-one-out analyses are shown in Fig. To assess the robustness of the above outcomes, we conducted sensitivity analyses, which involved leave-one-out analysis, Cochran's Q test, and MR–Egger intercept test. MR–Egger intercept tests demonstrating that there was no horizontal pleiotropy in present study Table . Nonetheβ = 0.008, p = 0.003; OR = 1.048, p = 0.013) remained consistent with the previous result.Moreover, the Phenoscanner tool was used to whether test any of the chosen SNPs were correlated with potential risk factors. SNPs rs13407913, and rs17391694 were associated with body mass index and obesity, rs13430791 was associated with diabetes, rs1297256 was associated with hypertensive renal disease, and rs3129871 was related to disorders of mineral metabolism. After removing these SNPs, estimates for UC on uACR and CD on urolithiasis  and kidney function/disease  using large-scale GWAS data. Importantly, our results show that UC increases the levels of uACR, and CD increases the risk of urolithiasis. The current study, however, has several limitations. First, the enrolled individuals were almost European, thus the causal effect of IBD on the levels of uACR and the risk of urolithiasis in other ethnic populations remains unknown. Second, the GWAS of IgA nephropathy were from a trans-ethnic population (73% European and 27% East Asian). Hence, we need to cautiously interpret the conclusion that there is no causal relationship between IBD and IgA nephropathy. Third, our findings only report alterations in kidney function and increased risk of urolithiasis in patients with IBD, thus further investigations are required to address underlying mechanisms. Notably, microphysiological systems could be an ideal approach to investigating the role of the gut-kidney axis in IBD . BesidesIn conclusion, UC and CD affect the levels of uACR and increase the risk of urolithiasis, separately. The renal involvement in patients with IBD can be categorized into secondary diseases caused by IBD, co-occurring disease with IBD, and IBD drug-induced nephrotoxicity. As the rate of renal involvement in patients with IBD may be currently underestimated or even overlooked in clinics, monitoring of kidney function should be considered in clinical practice in patients with IBD.Additional file 1: Table S1. MR estimates from different methods of assessing the causal effect of IBD on kidney function. Figure S1. Non-significant Mendelian randomization association between UC and kidney function. (A) Scatter plot for genetically predicted UC on eGFRcrea; (B) Scatter plot for genetically predicted UC on CKD; (C) Scatter plot for genetically predicted UC on IgA nephropathy; (D) Scatter plot for genetically predicted UC on urolithiasis; UC, ulcerative colitis; eGFRcrea, estimated glomerular filtration rate from serum creatinine; CKD, chronic kidney disease; SNP, single nucleotide polymorphism. Figure S2. Non-significant Mendelian randomization association between CD and kidney function. (A) Scatter plot for genetically predicted CD on eGFRcrea; (B) Scatter plot for genetically predicted CD on uACR; (C) Scatter plot for genetically predicted CD on IgA nephropathy; (D) Scatter plot for genetically predicted CD on CKD; CD, Crohn’s disease; eGFRcrea, estimated glomerular filtration rate from serum creatinine; uACR, urine albumin to creatinine ratio; CKD, chronic kidney disease; SNP, single nucleotide polymorphism. Figure S3. Leave-one-out sensitivity analysis for UC on kidney function. (A) UC on eGFRcrea; (B) UC on CKD; (C) UC on IgA nephropathy; (D) UC on urolithiasis; UC, ulcerative colitis; eGFRcrea, estimated glomerular filtration rate from serum creatinine; CKD, chronic kidney disease. Figure S4. Leave-one-out sensitivity analysis for CD on kidney function. (A) CD on eGFRcrea; (B) CD on CKD; (C) CD on uACR; (D) CD on IgA nephropathy. CD, Crohn’s disease; eGFRcrea, estimated glomerular filtration rate from serum creatinine; uACR, urine albumin to creatinine ratio; CKD, chronic kidney disease.


Acute brain injury is the sudden and reversible loss of brain self regulation capacity as a disruption of the blood-brain barrier that conditions metabolic and inflammatory disorders that can exacerbate acute kidney injury in a critical setting; specifically it has been described that the alterations of the internal environment that come from the severity of the acute kidney injury increases the risk of endocranial hypertension and cerebral edema; in this context, injuries should be identified and treated in a timely manner with a comprehensive approach. Continuous renal replacement therapy is an extracorporeal purification technique that has been gaining ground in the management of acute kidney injury in critically ill patients. Within its modalities, continuous venous venous hemofiltration is described as the therapy of choice in patients with acute brain injury due to its advantages in maintaining hemodynamic stability and reducing the risk of cerebral edema. Optimal control of variables such as timing to start renal replacement therapy, the prescribed dose, the composition of the replacement fluid and the anticoagulation of the extracorporeal circuit will have a significant impact on the evolution of the neurocritical patient with acute kidney injury. There are limited studies evaluating the role of hemofiltration in this context. Acute brain injury (ABI) is the sudden and reversible loss of brain autoregulation capacity as a consequence of a disruption of the blood-brain barrier (BBB) that conditions metabolic and inflammatory alterations that lead to cerebral edema and increased intracerebral pressure (ICP) . ABI is Studies in patients with traumatic brain injury and aneurysmal subarachnoid hemorrhage have shown that about 89% develop dysfunction of at least one non-neurological organ and this correlates with the severity of brain damage , 3. AmonThe effect of ABI on kidney function is attributed to changes in the management of natremia, with hyponatremia being the most frequent hydro electrolytic alteration in neurocritical patients, a consequence of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) or of the cerebral salt-wasting syndrome as a result of the increase in natriuretic peptides that may occur post acute subarachnoid haemorrhage and pituitary surgery. Likewise, the activation of the visceral sympathetic system in patients with ABI produces systolic hypertension that can reduce renal blood flow due to myogenic effect with increased tubular sodium reabsorption , 5.On the other hand, the systemic inflammation that occurs after traumatic ABI generates functional alterations and apoptosis in renal tubular epithelial cells that can lead to subclinical acute kidney injury (AKI) .The majority of patients with traumatic ABI are young with previous normal kidney function; however, even in them an incidence of acute kidney injury is reported that ranges between 8% and 23% with significantly increases the risk of morbidity and mortality, with a higher incidence of tentorial herniation being described , 6–8.On the other hand, ischemic and hemorrhagic stroke occurs in older patients with multiple comorbidities, and the incidence of AKI in these patients is 14% and 21% respectively, showing higher mortality in patients with ischemic stroke . The etiThe severity of AKI has deleterious effects on the integrity and permeability of the BBB that exacerbate intracerebral hypertension through the following mechanisms Figure 1Ischemic AKI is associated with increased production and decreased clearance of proinflammatory cytokines, tumor necrosis factor alpha (TNF α) stimulates the sympathetic nervous system and leads to reduced cerebral blood flow and might contribute to cytotoxic brain edema by mediating expression of type 4 aquaporins (AQP4) on astrocytes. Moreover, has been reported upregulation of toll like receptor type 4 (TLR-4) in the hippocampus causing local inflammation, leads to symptoms of cognitive impairment in patients with AKI –14.Metabolic acidosis secondary to AKI activates acid-sensing ion channels, resulting in cellular influx of sodium and calcium. This leads to cell membrane depolarization, cellular injury, and potentially cell death. Brain intracellular acidification leads to oxidative deamination of glutamate through glutamate dehydrogenase and thus altering neurotransmitter balance , 14.AKI is associated with downregulation of organic acid transporters (OAT) at the renal tubular level  and at the brain level (OAT3), this lead to reduction in uraemic toxin renal excretion and reduces the efflux of drugs and organic solutes from the brain, respectively, leading to increasing the risk of drug accumulation and toxicity , 14.An interference with the transporter of L arginina (CAT1/SLC7A1) during AKI may both potentially cause the accumulation, as well as the depletion of amino acids and neurotransmitters within the brain , 15.Therefore, early diagnosis and management of AKI is considered pertinent in order to reduce the risk of in-hospital mortality.The management of patients with AKI and ABI is based on a comprehensive approach with standard conservative measures such as ventilatory support, neuroprotection and adequate treatment of the hemodynamic state with fluids and vasopressors that allow maintaining the mean arterial pressure and with it the cerebral and renal perfusion pressure.An important pillar in the management of AKI once established is renal replacement therapy (RRT) in a timely manner. Among the modalities of regular use in critical care unit, we can highlight conventional intermittent hemodialysis (HD), sustained low efficacy daily dialysis (SLEDD) and continuous renal replacement therapy (CRRT), which do not differ significantly in terms of to the mortality rate in these patients; however, the evidence suggests a greater benefit of hybrid and continuous therapies given their better hemodynamic tolerance with a decrease in the risk of brain edema, which is especially relevant in patients with ABI , 17.After ABI, patients are at risk for cerebral edema, elevated ICP, and cerebral ischemia due to breakdown of the blood-brain barrier (vasogenic edema) and disrupted cerebral blood flow autoregulation that may be exacerbated in HD by several mechanisms: the idiogenic osmole hypothesis, reverse urea effect, and the rapid exchange of bicarbonate frequently seen shortly after initiation of HD and preceded by hypotension, which lowers cerebral perfusion pressure (CPP) which in turn may increase ICP by compensatory cerebrovascular vasodilatation with the formation of additional idiogenic osmoles even in non-trauma patients. Several trials have demonstrated increases in intracranial pressure in chronic HD patients , 19. BecCRRT can be applied under four modalities that meet the substrate of all the biophysical principles of hemodialysis: Continuous slow ultrafiltration (SCUF), continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD) and continuous venovenous hemodiafiltration (CVVHDF), the which should be prescribed in a dynamic and individualized way according to the clinical characteristics of the patient and therapeutic objectives, and can be established sequentially , 23.CVVHD is based on diffusion whereby blood flows through a semipermeable membrane against a sterile dialysate solution with flow in the opposite direction. Solute exchanges depending on the molecular size of the solutes, concentration gradients, membrane cut-off and exchange duration. Diffusion is more efficient in the clearance of small-molecular-weight substances  .CVVH is based on convection whereby a pressure gradient is generated across a semipermeable membrane and plasma water and solutes are removed through the pores of the membrane. To compensate for unwanted losses of fluid and electrolytes, replacement fluid is administered. Convection is more efficient at the clearance of large molecular- weight substances  and is usually prescribed in inflammatory conditions based in the clearance (e.g. sepsis and post cardiovascular surgery) . HoweverIn AKI, urea and other solutes as circulating cytokines are increased. In ABI, those solutes pass into the brain because the blood-brain barrier is disrupted. This influx is initially compensated by astrocytes taking up additional ions and water. However, this compensation mechanism is limited and thereby cerebral edema (cytotoxic edema) can become worse. As CRRT, mainly convective modalities removes gently fluid, solutes, and inflammatory cytokines, CVVH has been postulated as beneficial in patients with intracranial hypertension .One of the most widely used modalities in the context of critical care patients is CVVH, this technique allows a gradual reduction in the concentration of uremic toxins and fluids, avoiding sudden changes in serum osmolality and favoring hemodynamic stability, advantages that give it superiority over intermittent hemodialysis in the context of the patient with ABI. There is no enough evidence to recommend any CRRT modality over other, but physiologically, convective therapies may result more efficient , 23, 24.The loss of physiological cerebrovascular autoregulation experienced by the patient with ABI results in a loss of the linear relationship between brain volume and ICP becoming exponential, meaning that a small increase in volume will induce a major increase in intracranial pressure (Langfitt curve). Moreover, the variables such as cerebral blood flow and CPP will depend directly on the mean arterial pressure and of cardiac output, hence the relevance of maintaining hemodynamic stability during CRRT , 26.CVVH complies with the hemodynamic profile due to the removal of pro-inflammatory cytokines and myocardial depressing factors, as well as an increase in the concentration of vasoactive peptides such as endothelin 1 that exerts its vasoconstrictor effect during therapy .By using CRRT, the aim is to prescribe an delivered dose of therapy to patients, especially in terms of acid-base balance, electrolyte balance and hemodynamic stability, which are cornerstones of the survival of patients in critical care, being decisive in ABI.The effluent flow is an estimation of CRRT dose with several limits, appropriately mentioned by the authors below. The Kidney Disease Improving Global Outcomes (KDIGO) group recommends a EFV of 20 - 25 ml/Kg/h ; however, since there is a difference between the effective dose and the prescribed dose (related to circuit pauses), a dose of 30 - 35 ml/Kg/h is proposed to achieve the proposed objective that has been related to better outcomes –29.The delivered dose in CVVH depends on several factors such as blood flow through the vascular access, the effective time of treatment, the preservation of the extracorporeal circuit through adequate anticoagulation and the location of the replacement fluid . Tools have been defined to measure the adequacy of the 0CRRT, however, there are still challenges to establish the control of the prescribed dose in this scenario, the four measurements of the quality of the dose in CRRT are: the clearance administered, the ratio of effective to prescribed dose, therapy time, and solute control .In terms of time of initiation of CRRT, there is lack of evidence in AKI, even more when associated to ABI. Several studies have suggested that strategies for starting RRT early (2 - 7.6 hours after randomization) vs late (31 - 57 hours after randomization) do not differ significantly in mortality or RRT - free days in critical units; however, neurocritical patients were not included in these studies –33. SomeOne of the factors that significantly impacts in the effectiveness of CRRT is the anticoagulation of the extracorporeal circuit, since the critical patient presents a systemic inflammatory state that gives rise to a misbalance between the level of procoagulant and anticoagulant proteins associated with endothelial dysfunction causes a prothrombotic state. Anticoagulation of the extracorporeal circuit can be performed with unfractionated heparin or low molecular weight heparin, complying with strict dosing protocols that prevent bleeding complications. In the context of the patient with ABI, alternative anticoagulation regimens should be chosen, given the high risk of intraparenchymal, subdural, or subarachnoid hemorrhage potentially associated with heparin-induced thrombocytopenia , 36.The KDIGO guidelines propose regional citrate anticoagulation (RCA) as an alternative method. In fact, it is recommended in the management of CRRT patients over other strategies, especially in patients with a high risk of bleeding, such as those with ABI .Citrate is a 191 Dalton negatively charged small molecule that exhibits a chelating action on divalent ions (Ca and Mg), inhibiting the calcium-dependent coagulation cascade. In addition to its anticoagulant effect, it is attributed a reduction in leukocyte activation, reducing the inflammatory reaction .The most commonly used presentation is that of trisodium citrate and it is described that the objective of the citrate concentration in the circuit must range between 4 - 6 mmol/L to achieve an ionic calcium concentration <0.4 mmol/L, a threshold that provides the anticoagulant effect, prolonging the half life of the extracorporeal circuit and reducing the risk of major bleeding , 36.Given its mechanism of action, the therapeutic use of citrate involves the risk of disturbances of acid-base and electrolyte balance  and since its metabolism  produces bicarbonate in a 1:3 ratio. Furthermore, it has been described that exogenous citrate reacts with carbonic acid and gives rise to sodium bicarbonate, which contributes to the development of metabolic alkalosis –38.via the inhibition of thrombin expression and activity in the brain, particularly in neurons, which suggests that NM could be a potential drug for the treatment of ischemic stroke patients (Other anticoagulants have been described such as Nafamostat mesylate (NM), a synthetic serine protease inhibitor, has been used in hemodialysis patients at a high risk of bleeding because of its short half-life. NM is a safe and effective anticoagulant for CRRT and allows sufficient filter survival without increasing the risk of bleeding in critically ill patients with AKI and bleeding tendencies . Nafamospatients , 41.The patient with ABI requires strict control of some variables of the CVVH such as the composition of the replacement fluid to reduce risk of complications . The useThe sodium balance is very important to avoid complications in neurocritical patients and to select the correct concentration of sodium in the replacement solution, the ultrafiltrable sodium value must be taken into account. The use of supraphysiologic sodium concentrations is suggested to maintain hemodynamic stability and prevent the increase in intracerebral pressure; however, commercially available replacement solutions used for CRRT contain a sodium concentration of 140 mEq/L, which is lower than the desired 150 - 155 mEq/L serum concentration needed to induce a hyperosmolar state sufficient to counteract the “reverse urea effect”. The effective final sodium concentration delivered to our patients on CRRT is also affected by the rate of delivery of at least 3 solutions: Anticoagulant Citrate Dextrose Solution-A (ACD-A) for RCA with a sodium concentration of 224 mEq/L infused as pre-pump fluid, other base intravenous fluids with 0.9% saline (154 mEq/L) used for medications delivered peripherally and hypertonic saline solution with 3% saline (513 mEq/L of sodium) which can be infused by continuous infusion peripherally preferably –46.In patients with chronic severe symptomatic hyponatremia and concomitant AKI who require CRRT and have risk conditions for osmotic demyelination such as traumatic brain injury, the increase in serum sodium should be gradual, with a daily rate of increase of 4 - 6 mEq/L . When usWithin the alterations of divalent ions, hypocalcemia can cause neurological disorders manifested as tonic-clonic seizures and since 60% of calcium total plasma is ultrafiltrable, a calcium concentration of 3 mEq/L in the replacement solution is recommended, this is especially relevant in the use of RCA .In a critically ill patient such as the patient with ABI, the rest of the CRRT modalities can also be used according to the clinical condition of the patient  according to the days of evolution and progress remembering that it is a dynamic therapy in which the progression of modalities can be carried out as necessary, either ultrafiltration (SCUF) or hemodialysis (CVVHD) and if necessary, use all modalities together as it would be CVVHDF when diffusion and convection are required to offer benefit to these patients.Critically ill patients with AKI present metabolic, electrolyte, inflammatory and hemodynamic alterations that exacerbate ABI and vice versa, so timely management could modify the course of its evolution. In this sense, the CVVH fulfills the appropriate profile to limit the pathophysiological interaction; however, prospective studies with a cohort are necessary to assess its impact on mortality.LC has the original idea, collect and order the bibliography and information. LC and LR made the design of the review article and wrote the text. AM and LR made the final revision and paper the paper for publication. 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.


At the bedside, we need to decide regarding the best PEEP for a specific patient at a specific point in time. In this short comment, we share our approach on titrating PEEP at the bedside in patients with acute respiratory distress syndrome (ARDS).In the recent ESICM guidelines on Acute Respiratory Distress Syndrome , the groN = 5). For a long time, the primary reason to apply PEEP was to improve arterial oxygenation. However, when it became clear that inhomogeneous lung tissue may play an important role in the pathophysiology of VILI, the major aim for PEEP titration was to get a more homogeneous lung tissue or, in other terms, to find an optimal balance between lung recruitment and overdistension. Also, clinicians should be aware of the detrimental effects of (high) PEEP on hemodynamics, especially right ventricular function. Therefore, at the bedside we need to find the right balance between lung recruitment and hyperinflation, while closely monitoring the hemodynamic response.In the original ARDS description by Ashbaugh , it was Today, three large RCTs have from slightly different perspective compared the effect of lower versus higher PEEP on clinical outcome. These studies are summarized in Table 2 table and TV was set at 6ml/Kg predicted bodyweight (PBW). In the personalized group, patients with focal ARDS received TV of 8ml/Kg PBW and PEEP between 5 and 9cmH2O. In the non-focal ARDS group, TV was set at 6ml/Kg PBW and PEEP titrated to reach an inspiratory plateau pressure of 30cmH2O. Of note, recruitability with PEEP was not evaluated. No significant difference was found in 90-day mortality between control group or personalized ventilation group. However, it appeared that 21% of patients in the personalized group were misclassified  and that misclassified patients had higher mortality as comparted to control group and to correctly classified patients. This study could be interpreted that a personalized approach to ventilator settings may have a beneficial effect on clinical outcome. Though, this remains to be established.A higher PEEP may only be beneficial in patients with potential for lung recruitment, but none of the three RCT’s evaluated the potential for lung recruitment prior to PEEP selection. Although not specifically evaluating higher versus lower PEEP, Constantin and colleagues  comparedlow PEEP/FiO2 table [2O (with Fio2 between 0.5 and 0.7). Of course, in patients with low chest wall compliance , higher PEEP levels may be selected. Although selecting the high PEEP/Fio2 table may seem justified by a meta-analysis demonstrating that higher PEEP/FiO2 may present benefit on clinical outcome in these patients [2 table [In patients with moderate and severe acute hypoxemic failure, we set PEEP immediately after endotracheal intubation according to the O2 table , which mpatients , none of2O in a single step. Response is evaluated after 10 min. If compliance and oxygenation do not decrease  and if PaCO2 does not increase (arbitrarily 10%), this patient has probably potential for lung recruitment and hence may benefit from higher PEEP level. We thus increase PEEP level (with maintaining TV ± 6ml/Kg PBW and driving pressure < 15cmH2O) until respiratory system static plateau pressure reaches 28-30cmH2O, according to the ExPress trial approach [2O. Potential for lung recruitment is evaluated daily and after transition to prone position (vice versa).Shortly after endotracheal intubation, we identify whether the patient we are managing has potential for lung recruitment. To this aim, we perform a PEEP-responsiveness test, which consists in increasing PEEP from 5 to 15cmH2O. In the control group, PEEP was titrated using the high PEEP/FiO2 table. The primary outcome, a composition score incorporating death and ventilator free days through day 28, was not different between the two groups. In a reanalysis of this study [2O) was associated with greater survival as compared to more positive or negative values. It should, however, be noted that application of esophageal pressure measurement as an estimation of pleural pressure may be complex and requires expertise. Practicalities for esophageal pressure manometry have been extensively discussed previously [However, in some patients, identifying the optimal PEEP may be more challenging, for instance, in patients with obesity because they could have low chest wall compliance, increased intraabdominal pressure, or very severe hypoxemic failure. In such patients, we use advanced respiratory monitoring to evaluate the impact of PEEP at the bedside. Measurement of esophageal pressure provides an estimation of global pleural pressure that allows calculating global transpulmonary pressure. Physiologically, it may be attractive to titrate PEEP to obtain end-expiratory transpulmonary pressure around zero, limiting alveolar collapse. This approach has been evaluated in the Epvent-2 trial, although PEEP was adjusted to achieve an end-expiratory transpulmonary pressure between 0 and 6 cmHis study , it was eviously .2O), severe hypoxemia or hypercapnia (≥ 48 cmH2O), routine echocardiography should be performed to search for acute cor pulmonale [2, which contributes to pulmonary hypertension.PEEP may increase pulmonary vascular resistance and such right ventricle afterload further deteriorating right ventricle function . In patiulmonale . If cor Other techniques have been used to quantify lung recruitment by PEEP, including CT scan, stress index, ultrasound, electrical impedance tomography (EIT) and recruitment-to-inflation ratio (assessment of de-recruitment with decreasing PEEP). However, these techniques are not feasible bedside (CT scan) or require further validation in clinical practice (other techniques).The decision to titrate PEEP at the bedside may be complex and without clear guidelines. In this manuscript, we outline an approach based on physiology and clinical experience.


In patients with morbid obesity there were significant correlations between chemerin and AS parameters such as aortic pulse wave velocity (p = 0.006) and subendocardial viability index (p = 0.009). In the same group adipocyte size was significantly correlated with another AS parameter, namely, aortic systolic blood pressure (p = 0.030). In normal-weight patients, blood vessel wall thickness positively correlated with AS parameters such as brachial (p = 0.023) and aortic augmentation index (p = 0.023). An important finding was the negative adipoR1 and adipoR2 immunoexpression in PVAT adipocytes of patients with morbid obesity. Additionally, we found significant correlations between blood vessel wall thickness and blood fasting glucose (p < 0.05) in both groups. Conclusions: Chemerin and adipocyte size could be predictive biomarkers for AS in patients with morbid obesity. Given the small number of patients included, our results need further validation. Background and objective: The development of arterial stiffness (AS) in obesity is a multifactorial and complex process. The pleomorphic actions of adipokines and their local activity in perivascular adipose tissue (PVAT) are potential modulators of AS appearance and progression. We aimed to assess the correlations between two adipokines , PVAT morphological changes  and AS parameters in the special subgroup of patients with morbid obesity. Material and methods: We enrolled 25 patients with morbid obesity and 25 non-obese patients, who were age- and gender-matched, untreated for cardiovascular risk factors, and admitted to hospital for laparoscopic surgical procedures (bariatric surgery for morbid obesity and non-inflammatory benign pathology surgery for non-obese patients). Before the surgical procedures, we evaluated demographic and anthropometric data and biochemical parameters including the studied adipokines. Arterial stiffness was evaluated using a Medexpert ArteriographTM TL2 device. In both groups, adipocyte size and vascular wall thickness as well as local adiponectin activity were analyzed in PVAT from intraoperative biopsies. Results: In our study, adiponectin ( Cardiovascular disease (CVD) is one of the leading causes of mortality, accounting for about a third of deaths worldwide ,2,3,4. TObesity leads to increased expression of pro-inflammatory adipokines and thus, maintains a constant inflammatory status , which cBased on the known role of cytokines and some adipokines secreted by PVAT, various current clinical studies are designed to determine its potential as a therapeutic target to lower arterial stiffness and cardiovascular risk . The infThe aim of this study was to evaluate the potential role of adipokines such as chemerin and adiponectin and PVAT morphological characteristics as biomarkers associated with arterial stiffness in patients with morbid obesity, given its role of independent cardiovascular risk factor.2) and 25 age- and gender-matched non-obese patients who were part of the control group (BMI < 30 kg/m2). The study period was January–May 2017. All patients were referred to the Third General Surgery Department of “St. Spiridon’’ Hospital for laparoscopic surgical procedures . Cardiological evaluation was part of preoperative assessments. Patients with any treated cardiovascular risk factors, medical or surgical comorbidities generating inflammation, or treated with drugs interfering inflammation were excluded. Also, patients who presented with any three of the five criteria for defining metabolic syndrome [We conducted a case-control study which included 25 consecutive adult patients with morbid obesity (body mass index [BMI] > 40 kg/msyndrome  or had c2), waist circumference, waist to hip circumference ratio (WHR) and index of central obesity (waist circumference to height ratio). We evaluated demographic parameters ; cardiovascular (CV) risk factors; anthropometric parameters; vital signs , diastolic blood pressure ); biological parameters ; as well as arterial stiffness (AS) parameters. Anthropometric measurements included BMI  were processed after venous blood collection in vacutainer tubes without anticoagulant and centrifugation. Chemerin, known as retinoic acid receptor responder protein 2—RARRES2, is a 14 kDa protein, 131–137 amino acids long, resulting from proteolytic cleavage of the inactive molecule [Arterial stiffness was assessed by oscillometric method using the Medexpert ArteriographTM TL2 device. After data entry into the software  and brachial blood pressure (BP) measurement, the AS parameters were generated: aortic pulse wave velocity (PWV), aortic and brachial augmentation index (Aix), systolic area under the pulse wave curve (SAI) and diastolic area below the pulse wave curve (DAI), diastolic reflection area (DRA), central BP and central pulse pressure (PP). The recommendations of the 2012 Expert consensus document  were folThe measurement protocol using the Arteriograph device involved the following steps: (1) recording general patient data ; (2) locating the area of maximum pulsatility of the brachial artery and positioning the device cuff at this level; (3) the initiation of measurements, with the patient lying on his back and tracking the recording of pulse waves on the monitor to observe the morphology of the route; and (4) the interpretation of the results. In addition, before and during the recording the examination was performed in a quiet environment; avoidance of speech and mobilization during the measurement were encouraged. When white coat hypertension was suspected, an attempt was made to reassure the patient and the measurement was repeated. Smoking and coffee consumption were suppressed at least 3 h before the examination, copious meals were avoided during this period, as was the administration of nitrates. Alcohol consumption was prohibited for a period of 10 h before AS measurements .3 were collected from the great/small epiploon region, including a visible small artery, for local adiponectin activity assessment. During laparoscopic bariatric surgery, intraoperative biopsy of abdominal perivascular fat (PVAT) was performed. Specimens of 1 cmSamples from both groups were collected, fixed in 4% formaldehyde solution, embedded in paraffin, cut in 2 μm sections, stained (hematoxylin-eosin staining—H&E) and examined with a Nikon Eclipse 50i microscope. The sections were also subjected to immunohistochemical assay and treated with anti-Adiponectin Receptor 1/ADIPOR1 antibody EPR6626 (ab126611) and anti-Adiponectin Receptor 2/ADIPOR2 antibody (ab77612), according to standard protocols. Images were captured and analyzed using Zeiss Observer Z1 Tissue FAXS 4.2 Cell analysis SystemAdipocyte; size and number per field were quantified on microphotographs. Examination of the sampled sections included separate analyses of five different fields on slides obtained from the two batches. Initially, the long and short axis of the adipocytes were determined in order to make an assessment of the order of cell size in the two groups. The adipocytes detected in the center and the four extremities of each image were morphologically characterized. Subsequently, histological changes of the vascular wall layers were analyzed and the thickness of vascular wall was measured. The fields selected for analysis were chosen from the four extremities of each histopathological image so as to include vessels with the most different caliber and wall profile. We added a scale bar for all the images, to permit comparisons between control and obese groups.Statistical analyses were performed using SPSS statistics software . Initially, the descriptive analysis of the variables was performed for the continuous type variables, calculating the mean, median, minimum and maximum values, quartiles and standard deviation. Skewness  and kurtosis (flattening coefficient) were determined to assess the normal distribution of continuous variables.t test) and ANOVA  were used. Pearson and Spearman (r) correlation coefficients were used to assess the presence of correlations between the studied variables. A natural logarithmic transformation was performed for the variables without a normal distribution. This transformation allowed us to use the Pearson coefficient to determine if there was a linear correlation between the studied variables. Kendall’s tau coefficient was used to evaluate correlations in the whole sample. For the subsequent analysis of the relationship between variables that met the threshold for statistically significant correlations, a simple linear regression was performed. After selecting several independent variables that influenced a dependent variable, a simple linear regression was extended to a multiple regression. A p-value ≤0.05 was considered statistically significant.To compare the mean values between two groups of continuous values in order to identify statistically significant differences, the t test .Our study included 50 patients divided into two equal groups according to the presence of morbid obesity. Statistical analyses included several demographic, anthropometric and paraclinical parameters, which are presented in Data on risk factors were included among the data on clinical characteristics of the patients that were collected for the study. In our data, smoking was a more frequent cardiovascular risk factor in normal-weight patients, while dyslipidemia was more frequently encountered in patients with morbid obesity.p = 0.002) and diastolic blood pressure values , and pulse pressure values . Various metabolic disorders, such as changes in lipid and carbohydrate profile parameters were also observed. Although there were no statistically significant differences between the two groups, the mean serum values of total cholesterol (p = 0.718), LDL-cholesterol (p = 0.76), VLDL-cholesterol (p = 0.919) and triglycerides (p = 0.86) were higher in patients with morbid obesity. Patients with morbid obesity had statistically significant higher mean serum values of fasting glucose (p = 0.002) and uric acid (p = 0.006) as well as parameters associated with insulin metabolism  (p < 0.05). Mean serum values of adiponectin (p = 0.0003), chemerin (p = 0.0001) and their ratio (p = 0.005), as markers of adiposity, were also significantly different between the two groups. All patients enrolled in the study were evaluated for arterial stiffness, but there were no statistically significant differences between the two studied groups. Patients with morbid obesity were associated with higher mean systolic  or SEVR  were observed in patients with morbid obesity , fasting glucose (p = 0.049), age (p = 0.020) and with AS parameters such as brachial AIx (p = 0.023), aortic AIx (p = 0.023) and DRA (p = 0.044). In patients with morbid obesity, adipocyte size was correlated with serum VLDL-cholesterol (p = 0.001) and triglyceride levels (p = 0.001) as biological parameters, and with aortic SBP (p = 0.030) as arterial stiffness parameter. As in normal-weight patients, blood vessel wall thickness was significantly correlated with blood glucose (p = 0.035) in patients with morbid obesity.In normal-weight patients, blood vessel wall thickness was significantly correlated with serum TNF-α levels  was performed. We observed a positive AdipoR1 immunoexpression for adipocytes from the control group and a reduced, even negative AdipoR1 immunoexpression for the adipocytes from the group with morbid obesity . At the Current data in the literature suggest that adipokines have a pleomorphic action responsible for arterial stiffness development. So, we studied the potential roles of circulating chemerin and local adiponectin activity in PVAT, as well as morphological features of abdominal PVAT in relation to arterial stiffness and with demographic, anthropometric and metabolic parameters in a special subgroup of patients with morbid obesity.p = 0.002 for fasting glucose). Insulinemia (p = 0.0004), insulin sensitivity (p = 0.0001) and insulin resistance (p = 0.001), as well as the mean serum levels of adiponectin (p = 0.0003), chemerin (p = 0.0001) and their ratio (p = 0.005) were parameters with statistically significant higher mean values in this group. In our study, patients with morbid obesity had higher serum values of lipid and carbohydrate profile parameters  and SEVR (p = 0.009) were reported in our study among patients with morbid obesity. SEVR, also known as the Buckberg index, is an arterial stiffness parameter correlated with coronary flow reserve, useful in assessing coronary microvascular circulation. SEVR is a measure of cardiac oxygen supply-to-demand ratio that can be estimated by noninvasive validated methods [p = 0.005) [Yoo et al.  demonstr methods , and is  methods . The cur methods . In a re methods ,44, demo= 0.005) ,46. So, p = 0.035), and are a marker of subclinical atherosclerosis in diabetic patients [Chemerin is also a determinant of endothelial dysfunction, with high titers negatively correlated with flow-mediated dilatation (odds ratio of 1.58) and arterial stiffness (odds ratio of 3.75) in hypertensive patients . Our respatients . In our p = 0.030), a parameter of AS, in patients with morbid obesity. Similar to our results, Arner et al. [In peripheral tissues, chemerin induces tissue enlargement, while stimulating inflammation and angiogenesis in adipose tissue ,49. Obesr et al.  demonstrr et al. . Regardir et al. . Knowledge regarding the relationship between PVAT and arterial stiffness among those with obesity is limited, and many confounders affect the ability to infer causality .White visceral fat has an essential role in the production of adipokines, while PVAT through direct contact with blood vessels has a paracrine role, modulating cardiovascular effects, independent of obesity . On the Studying different adipokines that could regulate the atherosclerotic process might provide new opportunities for developing potential biomarkers predictive for AS, which is especially important in apparently healthy obese individuals. Clarifying the relationship between adipokines and established markers of atherosclerosis is an effective approach to refine the characterization of cardiovascular risk in patients with obesity and prevent CVD . GrowingCompromised bioavailability of adiponectin also has been established as an independent risk factor for type 2 diabetes and cardiovascular diseases . Some stp = 0.0003), a finding which is distinct from other published data and could suggest the presence of adiponectin resistance. Histopathological studies demonstrated that serum adiponectin levels were negatively correlated with adipose tissue mass. Low adiponectin titers correlate with the development of insulin resistance, type 2 diabetes or metabolic syndrome [Mean serum adiponectin levels were significantly higher among morbidly obese patients (syndrome ,71,72. Ssyndrome ,74. Thissyndrome . A high Our study has some limitations. Firstly, the most important one is the small number of patients included; our results could be seen as preliminary results which need further studies for validation. Secondly, it would have been preferable that patients with morbid obesity to be their own witnesses over a period of 6–12 months. Such a design involves some ethical limitations because it would be required a repeated biopsy and a longer observational period for study. Thirdly, we proposed the study of local adiponectin activity from abdominal PVAT, under the assumption that it shares similar properties with other regions of perivascular fat. The studied adipokine chemerin and adipocyte size in abdominal PVAT could represent predictive biomarkers for arterial stiffness in patients with morbid obesity. Although our study did not demonstrate the relationship between adiponectin and parameters of AS, the negative/weak immunoexpression of its receptors in abdominal PVAT could influence this process. In addition, our results could be influenced by the metabolic status of the patients studied. Given the small size of our sample, the current results need further validation.


Higher ferritin and white blood cell concentrations were also found in patients with CKD diagnosed with MAFLD than peers without MAFLD (both p = 0.01). Compared to children without MAFLD, a higher delta of BMI-SDS, eGFR levels, and microalbuminuria levels was found in patients with MAFLD. Conclusions: Due to the negative influence of the COVID-19 lockdown on cardiometabolic health in childhood, a careful management of children with CKD is warranted.Background: Both direct and indirect effects of COVID-19 have been found in all age groups. In particular, adult data demonstrated significant changes in patients with chronic and metabolic disease , and metabolic associated fatty liver dysfunction (MAFLD)), while similar pediatric evidence is still limited. We aimed at investigating the impact of the COVID-19 pandemic lockdown on the relationship between MAFLD and renal function in children with CKD due to congenital abnormalities of the kidney and urinary tract (CAKUT). Methods: A total of 21 children with CAKUT and CKD ≥ stage 1 underwent a comprehensive evaluation within 3 months before and 6 months after the first Italian lockdown. Results: At follow-up, CKD patients with MAFLD presented higher BMI-SDS, serum uric acid, triglycerides, and microalbuminuria levels and lower eGFR levels than those without MAFLD (all  The ongoing coronavirus disease 19 [COVID-19] pandemic has disrupted lives across all countries , with a More interestingly, a close relationship between COVID-19 and chronic diseases , and chronic liver, lung, and kidney disease) has been recently described both in adults ,12,13 anBoth conditions are chronic, progressive diseases with an increased global prevalence ,31 shariIn light of the impact of COVID-19 and lockdown measures on adult chronic diseases  ,34 and tn = 5); (ii) occurrence of urinary tract infection (UTI) (n = 3) and of COVID-19 infection (n = 5) between the two observation points. Therefore, we enrolled 21 patients. No patient dropouts occurred.A total of 34 children and adolescents aged 5–17 years with congenital abnormalities of the kidney and urinary tract (CAKUT)-related CKD stages 1–4 consecutively attending our Nephrology Clinic for a regular follow-up were retrospectively selected. Patients observed within 3 months (from December 2019 to February 2020) before and within 6 months (from May 2020 to November 2020) after the end of the first Italian lockdown were retrospectively identified. Exclusion criteria were considered as: (i) denied consent to be included in the study or to undergo any procedure (The Ethics Committee of our university approved the study (0010396/i). Written informed consent from all the children and their parents was obtained prior to commencing the study for diagnostic procedures and for anonymous processing of the data for retrospective studies.Moreover, a historical cohort of 21 patients matched for age and sex, examined between 2004 and 2007 and who underwent two follow-up visits with an interval time between the two visits of 11–14 months, was also selected.Anthropometric, laboratory, and instrumental data were retrospectively collected from the clinical charts between December 2021 and May 2022.At every follow-up visit (before and after lockdown), all the enrolled subjects routinely underwent a comprehensive clinical, biochemical, urinary, and instrumental assessment. In our clinical practice, these evaluations are commonly included in the regular follow-up to ensure an accurate monitoring of renal function in such at-risk patients.Physical examinations were conducted by trained physicians. Anthropometric measurements were obtained in a standing position while lightly clothed and without shoes, as described elsewhere . Blood pressure was obtained by three oscillometric measurements taken with an appropriate-sized arm cuff every five minutes, and high blood pressure levels were confirmed by using the auscultatory method . Blood samples were collected after an overnight fast .Daily proteinuria was measured as described elsewhere . AlbuminSerum creatinine levels were estimated through the Jaffe method, as traditionally used in our laboratories. Due to the absence of the modified assay for creatinine, the eGFR was calculated by using the original Schwartz equation and then normalized to the ideal body weight-derived body surface area .MAFLD diagnosis was based on the radiological evidence of hepatic steatosis and the presence of at least one of the following criteria, namely, overweight/obesity, T2D, or evidence of metabolic dysregulation (defined as the presence of two or more of these conditions: (1) Waist circumference > 95th percentile for age and sex; (2) Blood pressure > 95th for age, sex, and height; (3) Triglycerides > 150 mg/dL; (4) HDL < 40 mg/dl; (5) prediabetes; (6) homeostasis model assessment-insulin resistance (HOMA-IR) score > 2.5; and (7) C-reactive protein (CRP) levels > 2 mg/L) ,23. Data were expressed as mean ± SD or proportions (%). We classified the study population according to MAFLD presence/absence, and we compared the main features between these groups at baseline and at follow-up observations. The delta between both observations (pre- and post- lockdown) was also calculated for the main characteristics, and differences in these values in patients with and without MAFLD were examined.p < 0.05.Differences for continuous variables were analyzed with the independent sample t-test for normally distributed variables and with the Mann–Whitney test in case of non-normality. Qualitative variables were compared by using the Chi-square or Fisher’ exact test, as appropriate. Significance was considered at the level of The IBM SPSS Statistics software, Version 24 , was used for all statistical analyses.p = 0.04). At follow-up, CKD patients with MAFLD showed higher BMI-SDS and DBP-SDS values than those without MAFLD (both p = 0.03). Moreover, increased serum uric acid, triglycerides, and microalbuminuria levels and lower eGFR levels were found in children with MAFLD compared to those without MAFLD  (p = 0.01). The mean age of the study population was 10.63 ± 4.8 years. The main characteristics at baseline (pre-lockdown) and at follow-up (post-lockdown) of patients stratified according to pediatric MAFLD definition are shown in ctively) . As inflp = 0.01), of eGFR levels , and of microalbuminuria levels .Compared to patients without MAFLD, children with MAFLD showed—between the two observation points—a significantly higher delta of BMI-SDS . Compared to the present cohort, in the historical group, 6/21 patients (28.5%) were diagnosed with MAFLD (p = 0.69), and a significantly lower increase of MAFLD parameters was observed  compared to those observed in the present cohort .In the historical cohort, the mean age (10.8 ± 5.1 SDS) was similar to that of the examined cohort for this research  represent crucial steps in this sensitive period of life .Nevertheless, our observations contributed to add and expand current knowledge of the impact of the COVID-19 lockdown on the renal health of children with preexisting chronic diseases, such as MAFLD and CKD. Based on our preliminary but intriguing data, we speculate that the adverse effect of the COVID-19 lockdown on kidney function in children with MAFLD and CKD might be due to a vicious circle realized by the shared pathophysiological factors  and by certain environmental determinants, including increased physical inactivity and sedentary behaviors, related to the lockdown . In factBesides the well-known direct impact of COVID-19 on people’s health ,48, seveHowever, this research has some limitations that need to be mentioned. The design of our preliminary study was retrospective, and the number of enrolled subjects—although well-phenotyped at both observation points—was limited. Both aspects prevent the generalizability of our results, but we were able to draw findings of clinical relevance. Moreover, data regarding WC, CRP, and HOMA-IR values were available only in a non-significant group of patients. Hepatic steatosis was diagnosed by liver ultrasound—as commonly used in clinical practice—instead of by biopsy . Indeed,In view of the dangerous liaison of MAFLD with CKD ,39 and o


Urolithiasis, a prevalent chronic kidney disease affecting all age groups, can be influenced by nutritional factors. The incidence of urolithiasis in Asian countries ranges from 1% to 19.1%, attributed to geographical and lifestyle differences. In Iran, several risk factors, including ethnicity, dietary habits, gender, and age, are associated with urolithiasis. This study aimed to assess the impact of nutritional factors on kidney and urinary tract stone formation. This case-control study enrolled 127 newly diagnosed urolithiasis patients, and 127 matched healthy participants between February to May 2017. Exclusion criteria included diabetes and acute or chronic renal failure. Data were collected using the Food Frequency Questionnaire (FFQ) and analyzed using chi-square and logistic regression tests. Water , natural juices , mineral water , legumes , butter, cream, or peppermint , and ice cream  had a significant protective effect against kidney and urinary tract stone formation. Conversely, tea consumption , beverages , coffee , bread , meat , liver , fish , and various canned foods  were significantly associated with kidney and urinary tract stone risk. These findings showed that the risk of urinary stones formation had a significant relationship with dietary habits. Therefore, the correct dietary pattern and sufficient fluid consumption may play an important role in preventing urinary stones. Renal stone disease, also known as urolithiasis, is a prevalent chronic condition affecting individuals of all ages . The incThe association of urinary stones with diet is somewhat known, but there are controversial cases in this area. For example, while the shortage of protein intake is one of the major causes of endemic rocks in developing countries such as Iran, India, and Turkey, high protein consumption is one of the most important factors in the formation of stones in industrialized countries. It is believed that there is no reason to justify an increase in protein intake and a higher incidence of urinary stones . In the Based on our observations in society, we recognized the need to study the underlying factors contributing to urolithiasis. This study focuses on urolithiasis in Ilam, a province in Iran with a higher prevalence than other provinces. Additionally, meat consumption is relatively higher in Ilam, raising questions about its potential association with urolithiasis. Our study aims to promote awareness among healthcare professionals and the general public about the frequency of fluid and food consumption to prevent kidney and urinary tract stone formation. We also aim to inform educational programs to increase patients' awareness of urolithiasis and its causes to prevent and reduce recurrence.Given these considerations, health education focusing on dietary and lifestyle modifications for individuals with kidney and urinary tract stones holds promise. In this study, we primarily investigate the association between nutritional factors and the formation of kidney and urinary tract stones, guided by input from health experts. Importantly, there is a dearth of research on the epidemiology of urinary stones, and the fluid intake and diet patterns in urolithiasis patients remain unclear. Furthermore, there is limited information on the preventive effects of fluid consumption on urinary stone formation. Therefore, this study aimed to determine the effect of nutritional factors on the formation of kidney and urinary tract stones in Northeast Iran in 2017.This case-control study was conducted in Ilam health centers from February to May 2017. A total of 127 patients with urolithiasis and 127 control subjects without kidney stones were included in the study. The control group was selected to match the urinary tract characteristics of the case group. Individuals with diabetes, acute or chronic renal failure, and those on dialysis or under special care were excluded.The sample size was calculated using the Cochran formula with a 0.05 error and a 95% confidence interval (1.96) . PatientDemographic and disease characteristics were collected for both groups. Physical activity levels were assessed using the Baecke Physical Activity Questionnaire (BQ) . Data weStatistical analysis was conducted to assess the relationship between the independent variables and the dependent variable. Binary logistic regression was employed to predict the effect of the independent variables on urolithiasis. Additionally, data were analyzed using the chi-square test and logistic regression model. The analysis was performed using SPSS 20 software, following the necessary data exploration and modeling steps. The dependent variable of interest was the presence of urolithiasis, while the independent variable comprised various nutritional factors. These included types of market bread, local bread, meat, rice, liver, chicken and poultry, all types of canned food, fish, eggs, legumes , sausages, salami, and burgers, salad, greens, nuts and dried fruits, all kinds of fruits, milk, whey, yogurt, cheese, butter, cream, snacks, chocolate, all types of cakes and pastries, sugar, tomato, ice cream, shrimp, carbonated beverages, beverages, dough, coffee, natural juices, industrial juices, minerals, water, and tea.In this study, 254 subjects participated, with 127 subjects included in the case group and 127 in the control group. 180 subjects (70.9%) were male, and 74 (29.1%) were female. The two groups matched regarding age and sex. The demographic characteristics of patients with kidney stones and healthy subjects are shown in The effect of fluid intake and dietary factors on urolithiasis was examined using logistic regression models. The analysis included both crude and adjusted models, controlling for baseline variables such as age, body mass index, physical activity level, geographic region, specific health profession, use of thiazide diuretics, alcohol intake, drinking sugar cola, coffee intake, and dietary intake of calcium, animal protein, sucrose, magnesium, sodium, phosphorus, potassium, vitamin D, and total fluid . The typThe consumption of soft drinks or syrup of less than 2 glasses per day did not show a significant effect on the reference level (never). However, weekly and daily consumption of soft drinks significantly increased the odds ratio of developing kidney and urinary tract stones . Weekly and rare consumption of natural juices showed a significant protective effect against kidney and urinary tract stones . Similarly, weekly and rare consumption of industrial juices was associated with a lower risk of kidney and urinary tract stones compared to never consuming them .Daily consumption of mineral water compared to the reference level (never) as a significant protective factor reduced the odds ratio of kidney and urinary stones up to 82% . On the other hand, weekly and daily consumption of coffee increased the odds ratio of developing kidney and urinary tract stones . The variables were categorized into four groups: never (<1 glass per day), rarely (2-3 glasses per day), weekly (4-5 glasses per day), and daily (at least 6 glasses per day).A logistic regression model was employed to investigate the association between diet type and the risk of urolithiasis, as shown in The odds ratios for kidney and urinary tract stones were higher in individuals who consumed fish daily , weekly , and rarely  compared to those who never consumed fish. Weekly consumption of canned food also had a significant effect, with individuals who consumed canned foods weekly being more likely to develop kidney and urinary tract stones than those who never consumed them .Daily and weekly consumption of legumes had a significant effect on the reference level (never) so that the odds ratios of individuals consuming legumes weekly  or daily  were less likely to have kidney and urinary tract stones than people who never eat legumes.The consumption of butter and cream exhibited a significant protective effect, reducing the risk of kidney and urinary tract stones. Individuals who consumed cream and butter daily had a 70% lower risk of developing these stones than those who never consumed them . Similarly, when examining ice cream consumption, the odds ratios for daily and weekly intake were 0.203 , indicating a decreased likelihood of kidney stones and urinary tract issues. Even rare consumption of ice cream showed a reduced risk, with an odds ratio of 0.233 , compared to individuals who never consumed it.et al. [According to the findings of this study, fluid consumption had a significant relationship with the formation of kidney and urinary tract stones. Increasing fluid intake reduces the concentration of compounds that can lead to deposition in the urine. On the other hand, it reduces the free crystalline particles in the urine . There iet al. . In his et al. .Diet can change urine chemistry and affect stone formation. Studies have reported varying calcium and oxalate levels in patients, with some showing high levels and others showing low levels -27. In cPrevious research has demonstrated that consuming cola and carbonated beverages can lead to increased oxalate secretion, which contributes to the formation of calcium oxalate stones . Demograet al. also found that the consumption of lemon juice could be a potential treatment for patients with urinary calcium stones [et al., coffee consumption reduced the risk of renal and urinary tract stones [et al., increasing fluid intake to 2 liters of urine resulted in a significant reduction in calcium and oxalate concentrations and reduced the rate of recurrence of stones [Moreover, other studies indicated that mineral water containing calcium and magnesium could serve as a preventive and therapeutic agent for kidney and urinary tract stones , 35. Aram stones , supportt stones . This waf stones .It is widely acknowledged that increasing fluid intake is beneficial for patients with urinary stones. However, limited information is available regarding the specific effects of different beverages on the formation of urinary stones . This stThe findings regarding tea consumption are also inconsistent. In Curhan's study, consuming various types of tea, coffee, and alcoholic beverages (with or without caffeine) was associated with a reduced risk of urinary stones, while no relationship was found between the consumption of bicarbonate beverages and the risk of urinary stones . The hetet al. found no significant correlation between bread consumption and kidney and urinary tract stones, which is inconsistent with the present study [et al. [According to our findings, dietary intake was significantly correlated with the formation of urolithiasis. Daily consumption of various types of market bread increased the odds ratios of urinary stones, which aligns with the results reported by Trinchieri . Howevernt study . Further [et al. , who obset al. reported that the consumption of animal protein can increase the risk [et al. observed a significant relationship between fish consumption and the risk of renal stone formation [et al. [Liver consumption had a significant relationship with the risk of developing renal and urinary tract stones, although this relationship has not been directly mentioned in previous studies. However, Neun the risk . Chard eormation , consist [et al. .et al. [et al. [Our study demonstrated that regular consumption of legumes reduced the risk of developing kidney and urinary tract stones. Our findings contradict the study by Dai et al. , which o [et al. . The diset al. [Furthermore, our study revealed that the consumption of ice cream reduced the chance of developing kidney urolithiasis. This finding contrasts with the findings of Khani et al. , who didThe heterogeneity in findings across these studies may be attributed to differences in food consumption frequencies and lifestyle habits among the study populations. It is important to note that diet plays a significant role in determining urine chemistry and can influence the risk of stone formation. Numerous studies have explored different diets and their lithogenic and prophylactic effects, particularly in calcium oxalate urolithiasis. Among the diets studied, those with high and low amounts of calcium and oxalate, either separately or combined, have been the most extensively examined -27. SeveEvidence from these studies suggests that calcium restriction can improve oxalate absorption and excretion while increasing calcium intake can bind more oxalate in the intestine and reduce its presence in the urine. This mechanism is supported by two large prospective studies showing a reduced risk of stone formation with increased dietary calcium intake , 31. On et al. in 2014, the effect of unhealthy eating habits on the formation of urinary stones was high. Urinary factors, such as high protein diets and significant urinary citrate levels in patients, were identified as important risk factors for kidney stone formation [In our study, the statistical population was divided into healthy individuals and patients, excluding other groups of patients with conditions such as acute or chronic renal failure, diabetes, dialysis patients, or those under special care. In a study by Nouvenne ormation .Our study had some limitations, such as the length of the Food Frequency Questionnaire (FFQ), which was time-consuming and sometimes led to incomplete responses from patients , 39. AddThe findings of this study emphasize the significant impact of dietary factors on the occurrence of kidney and urinary tract stones. It is evident that careful adherence to specific dietary patterns can substantially reduce the prevalence of these conditions.


An increase in cerebral blood flow is frequent after traumatic brain injury (TBI) and can lead to brain swelling and refractory intracranial hypertension. We hypothesized that Transcranial EcoDoppler (TCD) monitoring could be useful to detect the cause of intracranial hypertension in these patients. Our main objective was to investigate if the increase of velocity in the middle cerebral artery (MCA) on TCD could be associated with intracranial hypertension.We retrospectively studied TBI patients consecutively monitored with TCD. Hyperemia was defined as MCA mean velocity higher than 80 cm/s. Intracranial hypertension was considered when hyperosmolar therapy, hyperventilation, or deep sedation was used.p < 0.001). Intracranial hypertension was significantly associated with hyperemia, occurring in 92.5% of hyperemic and 51.3% of non-hyperemic patients (p < 0.001). Moreover, we found that hyperemia preceded severe intracranial hypertension (p < 0.0001). In a logistic regression model, hyperemia was the only variable significantly correlated with intracranial hypertension .We found hyperemia in 40 patients out of 118 (33.9%). On average, it started at day 2.1 ± 0.9 from admission and significantly increased (MCA velocity at day 1: 74 ± 25 cm/s vs. 109 ± 36 cm/s at day 4; Hyperemia was frequent in our population of TBI patients and preceded intracranial hypertension. TCD monitoring, if performed on a daily regular basis, can be a useful method to detect this phenomenon and to guide the therapy. It could be a tool for a cause-oriented therapy of intracranial hypertension. Management of severe head trauma is based on the prevention of secondary damage. In the first phase after trauma, it mainly consists of the early detection of hypoxia and hypotension; afterwards, one of the most important treatment is the control of intracranial pressure and the maintenance of adequate cerebral perfusion pressure. No accurate bedside measurement of cerebral blood flow is possible to date, and surrogate evaluation of flow through pressure is recommended. In this setting, we have no definitive tools to understand if cerebral perfusion pressure is adequate. Recently, several authors hypothesized that a normal response of arteriolar caliber to the variation of cerebral perfusion pressure, the so-called autoregulation, could be a marker of adequacy of flow. On the other side, when this response is altered, an increase in cerebral perfusion pressure can induce an increase in cerebral blood flow. This phenomenon is frequently observed after traumatic brain injury (TBI) and can lead to brain swelling and refractory intracranial hypertension .Transcranial eco-Doppler (TCD) offers a non-invasive and easily reproducible method for evaluating cerebral hemodynamics , 7 and wIn this monocentric retrospective study, we included traumatic brain injured patients consecutively admitted from May 2017 to January 2023 in the Neurointensive Care Unit of “A. Gemelli” University Hospital in Rome. The inclusion criteria were as follows: age > 18 years, GCS on admission in Emergency Department ≤8, at least one TCD recording every 24 h during the first 96 h after admission in the Neurointensive Care, Intracranial pressure (ICP) monitoring. Excluding criteria were as follows: Lindegaard index >3 or CT angiography suggestive of vasospasm, patients who died in the first 48 h. By using a threshold of 80 cm/s as TCD mean velocity in MCA, patients were divided into two groups: hyperemic and not hyperemic. A condition of intracranial hypertension was considered present if hyperosmolar therapy (first tier), hypocapnia (second tier), or deep sedation (third tier) was administered, according to ICP results. Consent for participation was waived due to the retrospective design of the study, and since no patient information was extracted except for research purposes. Anonymity was guaranteed.All eligible patients’ electronic medical records were reviewed by two researchers . Age, type of intracranial injury, bilateral MCA values on TCD, natremia, ICP, Glasgow Coma Scale (GCS) score at the admission in neuro-ICU and daily thereafter, therapies for ICP control and neurosurgical treatment were recorded for subsequent analysis. Confounders such as hyperthermia, hypovolemia, hematocrit and systemic abnormalities, hypercapnia, hypocapnia not driven by ICP control, glycemia disorders were excluded before including the data collected. Based on intracranial injury, different types of lesions were observed .We assumed as hyperemic all those patients who presented an MCA velocity above 80 cm/s in the period of observation, after excluding extracranial causes . Only thAll TCDs were performed in NeuroIntensive Care after admission by an experienced sonographer . Toshiba Xario 200 with a 2 MHz probe and a dedicated preset was used. The temporal and submandibular sonographic window was used to record velocities in MCA and extracranial internal carotid arteries (ICA) respectively. ICP monitoring was part of neurological multimodal monitoring and included intraparenchymal, subdural, or ventricular systems.t-test and chi-square test were carried out for comparisons between groups for categorical variables, as appropriate. Results were expressed as means ± standard deviations (SD). To analyze the utility of several variables for predicting the development of intracranial hypertension, an order logistic regression model was performed. For all tests, statistical significance was considered as p < 0.05.Data were analyzed using Stata software V.14.1 by two authors . Anova for multiple comparisons was carried out for quantitative variables, 2 = 2.113; p = 0.715).We found 376 severe head injured patients in our database. Of these, 118 were considered for the analysis. Missing TCD values was the most frequent cause for exclusion. This occurred in 144 cases, due to the unavailability of the TCD system. Other conditions included death before 48 h (11 patients), presence of vasospasm (2 patients), absence of intracranial pressure monitoring (45 patients), and other confounders . In the study group, 40 out of 118 (33.9%) were classified as hyperemic, while 78 patients as not hyperemic. The most common lesions were focal contusions (20%) and acute subdural hematoma (47%), with no difference between groups   and in the most severe lesions  . Only 3 hyperemic patients did not need therapies for high ICP.On average, hyperemia started at day 2.1 ± 0.9 from admission, and increased during the stay in ICU for the next days  . This wa < 0.05) . Hyperemt = 4.818, p < 0.0001)  .p < 0.001)  .The main result of this study was that hyperemia was frequently observed by TCD in patients with a severe head injury. In these cases, MCA velocities increased in the days following the diagnosis and were associated with intracranial hypertension. Hyperemia on TCD significantly preceded intracranial hypertension and was associated with the severity of trauma and younger age.Measurement of cerebral blood flow after trauma has been the object of several studies in recent years and conflicting results have been reported . Since mPrevious papers on TCD should be regarded according to these important results , 13, 15.By using PET at days 1–3 after trauma, Launey et al. found high values of CBF in the presence of a reduced metabolic rate of oxygen, confirming the presence of true hyperemia . This isOn the other hand, these methods are not available everywhere, and we need practical bedside tools to understand these phenomena. In this study, we used TCD daily after trauma and considered hyperemia when the increase of cerebral blood flow velocity was associated with Lindegaard index <3 or with the absence of large arterial vasospasm on angio CT . Our resTaken together with PET studies, our data suggest that an abnormal flow-metabolism coupling could be present, and an autoregulation test should be performed to guide the treatment. This could have important clinical implications, since therapies aimed at controlling hyperemia, such as the strict control of CPP in the lower range of autoregulation, cautious use of mild hypocapnia, and an analgosedation targeted on monitor tools that avoids sudden increase of metabolism, could decrease the extent of intracranial hypertension.Several limitations should be considered in this study. First of all, this was a retrospective analysis, and many missing data, mainly due to the unavailability of the TCD, reduce the power of these results. Furthermore, the diagnosis of hyperemia was based on TCD observations and the calculation of the Lindegaard index, confirmed by angio-CT in not all the cases. The threshold value was considered, based on previous observations . The autHyperemia was frequent in our population of patients with severe traumatic brain injury and significantly preceded intracranial hypertension. TCD monitoring, if performed on a daily regular basis, can be a useful method to detect this phenomenon and to guide the therapy. It could be a tool for a cause-oriented therapy of intracranial hypertension.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required from the participants or the participants’ legal guardians/next of kin because consent for participation was waived for the retrospective design of the study, and since no patient information was extracted except for research purpose. Anonymity was guaranteed.CG: Data curation, Formal analysis, Methodology, Software, Writing – original draft. EI: Data curation, Writing – review & editing. AS: Data curation, Methodology, Writing – review & editing. LP: Data curation, Writing – original draft. FS: Supervision, Writing – review & editing. NM: Supervision, Writing – review & editing. MP: Supervision, Writing – review & editing. AC: Conceptualization, Data curation, Methodology, Supervision, Writing – original draft, Writing – review & editing.