Robot-assisted laparoscopic prostatectomy (RALP) requires pneumoperitoneum and the Trendelenburg position to optimize surgical exposure, which can increase intracranial pressure (ICP). Anesthetic agents also influence ICP. We compared the effects of propofol and sevoflurane on sonographic optic nerve sheath diameter (ONSD) as a surrogate for ICP in prostate cancer patients who underwent RALP.n = 18) or sevoflurane  anesthesia. The ONSD was measured 10 min after induction of anesthesia in the supine position (T1); 5 min (T2), 30 min (T3), and 60 min (T4) after establishing pneumoperitoneum and the Trendelenburg position; and at the end of surgery after desufflation in the supine position (T5). Respiratory and hemodynamic variables were also evaluated.Thirty-six patients were randomly allocated to groups receiving propofol , but not at other time points. The ONSDs at T2, T3, T4, and T5 were significantly greater than at T1 in both groups . Arterial carbon dioxide partial pressure, arterial oxygen partial pressure, peak airway pressure, plateau airway pressure, systolic blood pressure, pulse pressure variation, body temperature and regional cerebral oxygen saturation, except heart rate, were not significantly different between the two groups.The ONSD was significantly different between the propofol group and the sevoflurane group at T4 (5.27 ± 0.35 mm vs. 5.57 ± 0.28 mm, The ONSD was significantly lower during propofol anesthesia than during sevoflurane anesthesia 60 min after pneumoperitoneum and the Trendelenburg position, suggesting that propofol anesthesia may help minimize ICP changes in robotic prostatectomy patients.Clinicaltrials.gov identifier: NCT03271502. Registered August 31, 2017. Since robot-assisted laparoscopic prostatectomy (RALP) was first reported by Binder and Kramer in 2001, it has become the dominant surgical approach for prostate cancer treatment . HoweverAnesthetic agents can influence ICP during surgery. In propofol anesthesia, a dose-related decrease in cerebral blood flow, cerebral metabolic rate, and ICP have been reported , 8. SevoThe purpose of this study was to compare the effects of propofol and sevoflurane on ICP in prostate cancer patients who underwent RALP. We evaluated the sonographic optic nerve sheath diameter (ONSD) as a surrogate for ICP .ClinicalTrials.gov (NCT03271502). Written informed consent was obtained from all patients.This randomized clinical trial included 36 patients who underwent RALP at Asan Medical Center during September 2017. Ethical approval for this study was provided by the Institutional Review Board at Asan Medical Center, Seoul, Republic of Korea  on August 24, 2017. This study was registered with Patients who were scheduled for an elective RALP using the da Vinci™ robot system  were enrolled in this study. Patients with a history of cerebrovascular disease, those who refused to participate, and those younger than 20 or older than 79 were excluded.Patients were randomly assigned to two groups using web-based randomization software  . We usedAfter routine hemodynamic monitoring including electrocardiogram, non-invasive blood pressure, pulse oximetry, bispectral index  and regional cerebral oxygen saturation using near-infrared spectroscopy  were performed, preoxygenation was performed by administering 8 L/min of oxygen via facial mask before induction of anesthesia. Patients were randomly allocated into one of two groups according to a random table: the propofol group or the sevoflurane group. In the propofol group, propofol and remifentanil were infused continuously using a target-controlled infusion system to induce and maintain anesthesia. Propofol was adjusted to effect site target concentration of 1.5–3 μg/mL according to Marsh et al. . RemifenIn the both groups, 0.6 mg/kg of rocuronium was administered for muscle relaxation during anesthetic induction. In addition, 0.1–0.2 mg/kg of rocuronium was intermittently administered during surgery. During the operation, propofol, sevoflurane, and remifentanil were adjusted to maintain a bispectral index score of 40–60, and arterial blood pressure and heart rate within 20% of the baseline. An arterial line was placed in the radial artery to continuously monitor the arterial blood pressure. Mechanical ventilation was set to volume control mode and a tidal volume of 8 mL/kg of ideal body weight. A respiratory rate of 10–20 breaths/min was adjusted to maintain an end-tidal carbon dioxide concentration of 30–35 mmHg. Positive end expiratory pressure was not applied. Oxygen at 50% was supplied using medical air. Plasma solution A  as a crystalloid fluid was administered at a rate of 2–4 mL/kg/hr.The ONSD was measured by investigators trained in ocular sonography. Measurements were performed in the transverse and sagittal planes of both eyes; the final ONSD value was the average of the 4 measured values. A 7.5-MHz linear probe was used for ONSD measurement, which was measured at 5 time points. The ONSD was measured at 10 min after anesthetic induction in the supine position (T1), 5 min after establishing carbon dioxide pneumoperitoneum and a steep Trendelenburg position (45-degree incline) (T2), 30 min after establishing carbon dioxide pneumoperitoneum and a steep Trendelenburg position (T3), 60 min after establishing carbon dioxide pneumoperitoneum and a steep Trendelenburg position (T4), and at the end of surgery after desufflation of pneumoperitoneum in the supine position (T5).2), arterial oxygen partial pressure (PaO2), peak airway pressure, plateau airway pressure, systolic blood pressure, heart rate, pulse pressure variation, body temperature and regional cerebral oxygen saturation.At each time point, we also measured the following variables: arterial carbon dioxide partial pressure . Comparisons between the groups were performed using a Student’s t-test, Mann-Whitney U test, chi-square test, or Fisher’s exact test, as appropriate. A two-way repeated measures analysis of variance with Bonferroni post-testing was used to compare the ONSD, respiratory variables, and hemodynamic variables within and between the two groups. P values < 0.05 were considered significant. All statistical analyses were performed using IBM SPSS Statistics for Windows, Version 22.0 .In the previous study, the mean ± standard deviation of ONSD was 4.9 ± 0.4 mm during pneumoperitoneum and the Trendelenburg position under sevoflurane anesthesia . AssuminDuring the study period, 45 patients were screened. Three patients were excluded due to a history of cerebrovascular disease and six patients refused to participate. A total of 36 patients were included and were randomly allocated to either the propofol group or the sevoflurane group Fig. . DemograP = 0.096). Sixty minutes after carbon dioxide pneumoperitoneum and a steep Trendelenburg position (T4), the ONSD was significantly different between the two groups  . During pneumoperitoneum and the Trendelenburg position at T2, T3, and T4, sonographic ONSDs tended to increase continuously . In addition, there were no significant differences in regional cerebral oxygen saturation between the propofol group and the sevoflurane group at all predetermined time points under general anesthesia .There were no significant differences in PaCOups Fig. . HoweverP = 0.635). In addition, postoperative neurologic complications did not occur in both groups.There was no significant difference in the duration of hospital stay between the propofol group and the sevoflurane group (7.7 days vs. 7.6 days, The sonographic ONSD of propofol anesthesia was significantly lower than that of sevoflurane anesthesia 60 min after establishing carbon dioxide pneumoperitoneum and a steep Trendelenburg position in prostate cancer patients who underwent RALP. In addition, the sonographic ONSDs increase continuously after establishing carbon dioxide pneumoperitoneum and a steep Trendelenburg position in both groups.Anesthetics suppress the activity of electroencephalogram and reduce the cerebral metabolic rate. However, changes in cerebral metabolic rate and cerebral blood flow are inconstant and depends on how the anesthetic affects the cerebral vascular smooth muscle . SevofluMany studies have determined that carbon dioxide pneumoperitoneum and a steep Trendelenburg position could increase ONSD as a surrogate for ICP , 25–27. ONSD measurement using ultrasonography is a simple, non-invasive technique for ICP assessment. Previous studies have reported that sonographic measurement of ONSD strongly correlates with measurement performed by inserting an invasive catheter into one of the lateral ventricles or the brain parenchyma in various clinical situations, including RALP , 35, 36.The present study has the following limitations. We could not measure ICP because the difficulty and invasiveness of the procedure made it impossible to be carried out in non-neurosurgical patients. However, sonographic measurement of ONSD is a non-invasive technique and has been shown to accurately reflect increases in ICP , 43. AlsWe found that ONSD was significantly lower during propofol anesthesia than during sevoflurane anesthesia 60 min after carbon dioxide pneumoperitoneum and a steep Trendelenburg position in robotic prostatectomy patients. Our results suggest that propofol anesthesia might be used effectively to minimize intraoperative ICP changes in prostate cancer patients who are undergoing RALP using pneumoperitoneum and the Trendelenburg position.


Chronic kidney disease (CKD) is on the increase globally. Prevention of this condition is ideal, however early detection of the disease becomes desirable where the disease process has begun as there are known interventions which can slow the progress to end stage renal disease (ESRD). This study aimed at detecting the profile of some modifiable risk factors for CKD in a cohort of household heads in a rural community with limited resources for managing chronic kidney diseases.The study was conducted in a rural community in southeast Nigeria. One hundred and forty five household heads from randomly selected households were interviewed. Their blood pressures were taken and their urine tested. The data was analyzed using SPSS version 21. Simple frequencies and means were calculated.A total of 145 house hold heads were enrolled. Their mean age was 45.08 (19.65) years. Forty-seven percent had no prior knowledge of their blood pressure and 31.5% were found to be hypertensive. Only one study participant (1%) had ever had a urinalysis test and proteinuria and glycosuria were found in 50.4 and 27.9% respectively. Most (75%) patronized patent medicine vendors for their primary healthcare while 31.8% had taken herbal mixtures in the past.There are presently many modifiable risk factors for the development of chronic kidney disease in rural communities in south-east Nigeria. Urgent targeted intervention is required to forestall an epidemic of CKD in the near future. Globally, chronic kidney disease (CKD) prevalence has been noted to be on the increase both in children and adults . PresentPresently, there is a strong advocacy towards prevention of CKD achievable through some simple and easily available tools and strategies like routine monitoring of blood pressure, blood sugar and urine for infection. Unfortunately, most people with these CKD predisposing illnesses are not aware that they have these illnesses. Even people who have urinary tract infections (UTI) often take it to be malaria and treated as such , 6. NeveIn view of the huge challenges of management of CKD and potential benefits of surveillance on the early symptoms and signs of the risk factors at the community level, it will be expedient to evaluate the extent to which communities watch out for these indices. In most African communities, the extent of awareness on health as well as their health-seeking behavior of the entire household is determine by the household-head’s level of knowledge and awareness on health related issues . It is uThe study was conducted in Mbogodo, a rural community in Nkanu West Local Government Area (LGA) in Enugu South-East Nigeria.This was a cross-sectional descriptive study. A multistage sampling technique was used to select a community in Nkanu-West of Enugu state Nigeria. Study location was Mgbogodo, a rural community with a population of about 30, 000 for both adults and children, with estimated 590 households. There are average annual rainfall of 30 cm and maximum temperature of 35 °C. It has a tropical rain forest vegetation and malaria is holo-endemic in this region. The community is agrarian in nature with few female petty traders. There is a General hospital and a health center, both about 3 km away from the community.et al [Three hundred and sixty four households were enumerated out of which 305 households were selected randomly to participate in the study. The decision to select 305 households was based on absolute response rate of 87 and 49.3% for the first response and second response reported by Fekete et al  and, theR mercury sphygmomanometer and the average documented subsequently.The study involved two phases. The first phase was enumeration of the households in the community. The households that participated in the second phase were selected randomly from the list of the enumerated households. This was to ensure even selection and to prevent skewed of households that would participate in the study and give a better representation of the community. The selected households were revisited and researchers then created rapport with heads of the selected households explaining the purpose of the study as well as obtained consent to participate. They were then asked to visit the community health center for the second part of the survey- health facility-based clinical assessment and investigation. Since the survey was a component of a bigger study which involved laboratory investigations and anthropometric measurements, the selected households were requested to visit the health center for other aspects of the study. While in the health center, interviewer- administered semi-structured questionnaire which has both closed and open ended questions was used to obtain information on their age, educational status, knowledge of the symptoms of urinary tract infections, potential causes of kidney injury, prior knowledge of their blood pressure, previous history of having done a urine test, symptoms experienced in their previous illnesses and their health seeking behavior. The respondents were asked to select one major symptoms of UTI from a list of symptoms and the selected option was checked on the questionnaire, while they were asked to list conditions that can cause kidney injury and their responses written down on the questionnaire. They were allowed to mention as much as they could but only correct options were documented. For the urinalysis, The respondents were previously advised to take adequate water just before coming to the health centre. At the health centre, urine was collected from each of them in a universal container. Urinalysis was done immediately with Combi-9 rapid test kit and results were documented in case record forms. Standard practices were observed during blood pressure measurement. The measurement was taken 30 min later to allow adequate time for rest. Two different measurements of the blood pressures of the study participants were taken on the right arm in sitting position using HensonData management was done with SPSS software version 21 Chicago Illinois. Frequencies and means of continuous variables were found. Results of urinalysis done with the Combi 9 dipstick and the presence of protein was described in levels; negative, trace, 1+, 2+, and 3+. Proteinuria was taken as “1+ or more” reading on the combi urine test kit. Blood pressure was classified as normal: systolic blood pressure (SBP) 90–119 mmHg or diastolic blood pressure (DBP) 60–79 mmHg, Prehypertension SBP 120-139 mmHg or DBP 80 -89 mmHg and Hypertension (HTN) was defined as SBP greater than 140 mmHg and DBP greater than 90 mmHg according to American Heart Association. Hypertension is further classified into Stage 1 HTN: SBP 140–159 or DBP 90-99 mmHg, Stage 2 HTN: SBP ≥ 160 or DBP ≥ 100 mmHg.One hundred and ninety eight household heads from the 305 selected presented to the health center, giving cooperation rate of 64.9% 198/305). A total of 145 household heads responded to the study, giving a consent rate of 73.2% (145/198)  of the respondents identified change in urine stream as a symptom of urinary tract infection, all other symptoms collected were only recognized by a small percentage (41.4%) of the respondents. Table  Most menThe number of the respondents that had prior knowledge of their blood pressure was 61 (47%.) The prevalence of hypertension among the respondents was 31.5% while 52.8% were pre-hypertensive. (Table Headache was the commonest symptom experienced during the last illness. Table  MajorityProtein was the most frequent 50.4%) abnormality found in their urine, followed by glucose (27.9%).  of the ingestion of herbal concoction is a limitation on this study. With emerging evidence on the contribution of herbal mixtures to incidence of kidney injuryKnowledge of kidney related symptoms was poor among the residents of Mgbogodo Southeast Nigeria. Majority had never done a urine test in the past. There was a high prevalence of high blood pressure in the population of which most were ignorant of. The services of patent medicine vendors were highly solicited in times of ill health. These are high risk factors for development of chronic kidney disease however they are all modifiable. Community health awareness and education programs may help in improving the health seeking behavior of this rural community to reduce or totally prevent the a rising prevalence of a possible CKD in future.


Accurate and practical assessment of the brain circulation is needed to adequately estimate the viability of cerebral blood flow regulatory mechanisms in various physiological conditions. The objective of our study was to examine feasibility of the contactless green-light imaging photoplethysmography (PPG) for assessing cerebral autoregulation by revealing the dynamic relationships between cortical microcirculation assessed by PPG and changes in systemic blood pressure caused by visceral and somatic peripheral stimuli. In anesthetized male Wistar rats, the PPG video images of the open parietal cortex (either with unimpaired or dissected dura mater), electrocardiogram, and systemic arterial blood pressure (ABP) in the femoral artery were continuously recorded before, during and after visceral  or somatic (tail squeezing) stimulation. In the vast majority of experiments with intact and removed dura mater, both spontaneous and peripheral stimulation-evoked changes in ABP negatively correlated with the accompanying alterations in the amplitude of pulsatile PPG component (APC), i.e., an increase of ABP resulted in a decrease of APC and vice versa. The most pronounced ABP and APC alterations were induced by noxious stimuli. Visceral painful stimulation in all cases caused short-term hypotension with simultaneous increase in cortical APC, whereas somatic noxious stimuli in 8 of 21 trials produced hypertensive effect with decreased APC. Animals with pressure 50-70 mmHg possessed higher negative cerebrovascular response rate of ABP-APC gradients than rats with either lower or higher pressure. Severe hypotension reversed the negative ratio to positive one, which was especially evident under visceral pain stimulation. Amplitude of the pulsatile PPG component probably reflects the regulation of vascular tone of cerebral cortex in response to systemic blood pressure fluctuations. When combined with different kinds of peripheral stimuli, the technique is capable for evaluation of normal and elucidation of impaired cerebrovascular system reactivity to particular physiological events, for example pain. The reported contactless PPG monitoring of cortical circulatory dynamics during neurosurgical interventions in combination with recordings of changes in other physiological parameters, such as systemic blood pressure and ECG, has the appealing potential to monitor viability of the cortex vessels and determine the state of patient’s cerebrovascular autoregulation. Adequate assessment of cerebral hemodynamics is an important task needed to be solved to estimate viability of the cortex and regulatory mechanism. The maintenance of adequate CBF is critical for proper supply of the brain with the necessary oxygen and energy substrates. As known, CBF depends on the blood pressure in cerebral arteries (ABP), the pressure in the cerebral venous system, and resistance of blood flow in small cerebral vessels . Blood pAt the level of the brain vessels themselves, CBF is controlled by active changes in vascular tone occurring at the level of the cerebral arterioles, a process referred to as cerebral autoregulation. This is an ability of the brain to maintain relatively constant blood flow despite changes in blood pressure . CerebraConsidering importance of CBF regulation, availability of convenient and accurate methods for its assessment in various physiological and pathological conditions is crucial. Various pain conditions are known to cause changes in systemic blood pressure and heart rate implying their influence on cerebral circulation . It was A wide variety of optical methods is used to evaluate non-invasively CBF in real time. Among them, the methods based on video recordings of the exposed brain under different illumination are very popular due to their low cost, simplicity of implementation, and no use of any dies . These mHere, we report experimental data that demonstrate feasibility to assess cerebral hemodynamic after processing video frames of the open brain that were recorded by the custom-made imaging PPG system at incoherent green illumination. The aim of our research was to reveal a relationship between variations of the systemic blood pressure (caused particularly by different pain stimuli in rats) and changes in CBF assessed by contactless, non-invasive, and cost efficient optical method.n = 11), 327 ± 53 g were used in this study. The animals were housed 2–5 per cage under standard laboratory conditions (12:12 light-dark cycle) with free access to food and water. They were deprived of food, but not water, for 16 h before each experiment. The Institutional Animal Care and Use Committee of the Pavlov Institute of Physiology of the Russian Academy of Sciences approved all experimental procedures. The experiments were conducted in accordance with the guidelines set by the European Community Council Directives 86/609/EEC, with the Ethical Guidelines of the International Association for the Study of Pain, and EU Directive 2010/63/EU for animal experiments. After the end of each experiment, the rat was sacrificed by intravenous injection of a lethal dose of urethane (>3 g/kg). All possible efforts were made to minimize animal suffering and to use only the number of animals necessary to produce reliable data.Experiments were performed with the open cortex of a rat’s brain. Adult (8–14 weeks) male Wistar rats  and α-chloralose  as it was described in detail previously . BrieflyTwo kinds of stimulations  were used in our experiments. To induce visceral nociception, a colorectal distension was performed as described previously . It was After the surgery, the rat was kept in rest during 40 min to minimize the effect of postsurgical reaction. The total duration of the experiment was 30 min. It consisted of four successive series in which the following stimulations were applied: (1) innoxious visceral, (2) tactile somatic, (3) painful visceral, (4) painful somatic. The minimum time interval between series was 5 min. In each series, the data containing the cortex images, ECG, and ABP were recorded continuously while the rat was consistently in the following physiological states: baseline (90 s), stimulation for 1 min, and relaxation (90 s).Parameters of cortical blood flow were measured by using home-made imaging PPG system . PhotogrAll videos were recorded at 100 frames per second with resolution of 752 × 480 pixels and saved frame-by-frame in the hard disk of a personal computer. Such a frame rate is sufficient to solve the research task since it provides eight or more readings per cardiac cycle of a rat. ECG and ABP in the femoral artery were recorded simultaneously with video. Digital electrocardiograph  operating at the sample frequency of 1 kHz was used to record ECG synchronized with video frames with accuracy of 1 ms. ABP in the femoral artery was continuously monitored with a pressure transducer  at the sample frequency of 10 kHz and recorded in the personal computer using Spike2 software .® platform. To evaluate CBF dynamics we used an amplitude of the pulsatile component (APC) of the photoplethysmographic waveform that shows modulation of the light reemitted from the brain at the heartbeat frequency  sizing 3 × 3 pixels, which corresponds to the area of 40 × 40 μm•filtfilt function in Matlab® to perform zero-phase digital filtering of the waveforms. Filtered PPG waveform is shown in Third, we calculated PPG waveform as frame-by-frame evolution of average pixel value in every small ROI. An example of an unfiltered waveform averaged within one of the ROIs over raw, non-stabilized frames is shown in •Fourth, in every small ROI, we assessed a mean PPG pulse from which the parameter APC was estimated. Algorithm of the mean PPG pulse estimation is illustrated in •Fifth, to quantify the APC dynamics, we selected four big ROIs nearby different cerebral arteries (see an example of such selection in t-test for paired samples (parametric method) evaluated during 13 s before and 13 s just after the stimuli. Pearson’s parametric correlation was used to assess the relationship of ABP and APC. While calculating the Pearson coefficient of correlation, we compared the ABP trace with each of the APC traces, all of them recorded during 3 min: 60 s before, 60 s during, and 60 s after the physiological stimulation. To identify significant fluctuations in ABP, we used the rule of three STD calculated for the baseline before physiological stimuli.In total, 21 experiments were carried out with 11 rats: reaction on four different physiological stimuli was monitored in all of them while keeping the dura mater intact, whereas 10 rats were measured after the dura mater was removed. In every experiment, we assessed the dynamics of APC in four big ROIs. Therefore, 84 APC traces were analyzed. In each experiment, four courses of APC in big ROIs were compared with a single course of ABP. To assess the dynamics of ABP during physiological stimuli, we performed a comparative analysis using the dependent An example of spatial distribution of the parameter APC over the open rat’s cortex is shown in To assess the reaction of the ABP on a physiological stimulus, we selected 13-s trace recorded prior the stimulus application, and compared the ABP averaged over this trace with that averaged over the next 13 s just after stimulus application. The choice of the averaging windows with duration of 13 s was due to ideas about the autoregulation of hemodynamics, which can smooth out the effect of the stimulus at later stages. The hemodynamic responses on four different stimuli for one of the rat are shown in P = 0.20 and 63.7 ± 17.9 vs. 63.6 ± 16.1 mmHg; P = 0.97, respectively. However, significant diminishing of the mean ABP was observed in the case of innocuous visceral stimulus: 67.5 ± 17.1 mmHg before stimulus vs. 61.5 ± 16.8 mmHg after, P < 0.001. Such a drop of the mean ABP was even more pronounced in the case of painful visceral stimulation: 64.2 ± 17.9 vs. 55.2 ± 16.7 mmHg, P < 0.001. At the same time, there were no differences in ABP responses on stimuli depending on the presence of a dura mater.A comparative analysis revealed that the hemodynamic response in rats was significantly different in visceral and somatic stimuli. Moreover, the reaction did not depend on the intensity of stimulation. It is worth noting that in the group average, no difference in responses to tactile and painful stimuli was revealed in the case of somatic stimulation: 67.0 ± 16.8 vs. 65.0 ± 17.2 mmHg; Nevertheless, the observed absence of the ABP reaction on the painful somatic stimulation in the group average might be explained by qualitative difference in rat’s reaction on this stimulus. As seen in r < −0.87, P < 0.001. However, APC positively correlates with mean arterial pressure in few exceptions; one of them is shown in As one can see in n = 336. The histogram of the correlation coefficients between these variables is shown in Correlation analysis of the relationship between ABP and APC was carried out for PPG waveforms calculated in each big ROI in every stimulation sessions for all rats. The total number of traces for the correlation analysis was P < 0.05) in the session of painful somatic stimulation for rat #8 with dura mater. Much greater variations in the correlation coefficient were observed in the same session for the same rat but without dura mater: between 0.23 and 0.81. However, resection of dura mater in other rats led to the opposite effect: 0.23 < r < 0.85 with dura mater vs. 0.92 < r < 0.98 without dura mater in rat #7. We believe that this behavior shows that, with the general tendency for the responses of cerebral arteries on painful stimuli to be similar, some of them have their own characteristics. Nevertheless, no correlation was observed (P > 0.05) between some pairs of the ROIs in 6 of 21 experiments possibly due to the impaired mechanism of autoregulation.It should be noted that four big ROIs were selected in vicinity of different cerebral arteries for each rat. The correlation analysis has revealed in the most of cases (15 of 21 experiments) substantial positive pairwise correlation between APC dynamics assessed nearby different arteries. For example, the Pearson coefficient varied from 0.65 to 0.95  occurred as unrelated with the external impact. The parameter CRR was estimated for these jumps, as well. For each series of four stimulations we calculated the mean response rate and plotted it as a function of the averaged systemic pressure in One can see that the response rate is negative for the most of the experimental series . ExceptiCerebral autoregulation is usually assessed by direct measurements of CBF and mean ABP with subsequent analysis of their temporal courses to reveal their relationship . VariousOur experiments have shown that in the vast majority of cases, both the spontaneous jumps of the systemic blood pressure and its changes in response to either visceral or somatic stimulation in anesthetized rats lead to counter-phase variations of the APC of the PPG waveform measured in the rat’s cortex. These observations can be explained by a reflex change in the tone of cerebral vessels in response to changes in perfusion pressure. Such a behavior of the vascular tone in general corresponds to the behavior of the cerebrovascular reflex, the main physiological meaning of which is aimed at maintaining the constancy of cerebral perfusion under conditions of fluctuating systemic blood pressure. In other words, APC follows the local vascular resistance that is varying under the influence of systemic arterial pressure. Therefore, the APC of PPG waveform can be considered as a measure of the cerebral vascular tone.At the same time, disappearance of the negative feedback between perfusion and ABP in rat #3 is most likely due to the disruption of autoregulation under conditions of pronounced reduction in blood pressure. Such a behavior corresponds to a clinical situation caused by stable systemic hypotension when the cerebral vessels are maximally dilated against the background of a pronounced decrease in blood pressure so that further fluctuation of blood pressure does not lead to a significant additional decrease in vascular tone. In turn, the negative feedback was lower also in animals with systemic ABP higher than 70 mmHg, suggesting the hypertension-induced impairment of cerebrovascular reflex. The most efficient negative feedback observed in the range of 50-70 mmHg of systemic ABP seems to be quite logical in view of previously published results . These rOur study has disclosed for the first time that visceral and somatic types of pain lead to preferentially opposite changes in the parietal cortex regional CBF. Previously the unidirectional circulatory responses of this area to pain signals from internal and external parts of the body were proposed . In contThe observed opposite effect of visceral and somatic noxious inputs on cortical vasculature can be mediated by several potential mechanisms. For instance, previous studies, including our, have revealed that visceral and somatic pain stimuli produce different patterns of neuronal activity in the caudal ventrolateral medulla , nucleusIn consensus with conclusions of recent studies devoted to CBF imaging by fiber array of optical infra-red sensors , we assuIn summary, we have developed a novel method for contactless, dynamic assessment of spatial temporal variations of blood pulsations in cerebral vessel related to changes in blood supply to the cortex caused by physiological stimuli. It was done by video recording of an open brain illuminated by incoherent green light simultaneously with ECG and ABP. We hypothesize that the parameter APC is a measure of cerebral vascular tone that varies in response to fluctuations in systemic blood pressure. In the case when the autoregulation is disrupted by systemic hypotension, the correlation between ABP and APC reverts the sign. The reported contactless PPG monitoring of cortical circulatory dynamics during neurosurgical interventions in combination with synchronized recordings of systemic blood pressure and ECG, has the appealing potential to determine the state of patient’s cerebrovascular autoregulation. Moreover, responses of cerebral hemodynamics to different pain-producing manipulations can be revealed, helping thus to prognosticate individual outcomes and optimize treatment to a given patient’s need. The proposed method may also play a diagnostic role in extra-cranial cardiovascular disorders and chronic pain conditions, elucidating the pathology-induced alterations in cerebral regulatory mechanisms.All datasets generated for this study are included in the article/The animal study was reviewed and approved by the Institutional Animal Care and Use Committee of the Pavlov Institute of Physiology, Russian Academy of Sciences.OL conceived and designed the study, provided preparation of animals, collected the experimental data, and wrote, reviewed, and edited the manuscript. OM drafted the manuscript, revised the data analysis, and wrote and reviewed the manuscript. MV designed and manufactured the optical – electronic part of the experimental setup, and collected the experimental data. VZ designed the software for images acquisition and collected the experimental data. AK conceived and designed the study, administered the project, performed the data analysis, and wrote, reviewed, and edited the manuscript. All authors provided critical feedback and helped to shape the research, analysis, and manuscript.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.


The instantaneous wave-free ratio (iFR) is an invasive coronary physiological index that is not inferior to fractional flow reserve- (FFR-) guided revascularization. The indexes of iFR and FFR are similar and closely correlated, but there are a few key differences. Previous studies suggested that patient characteristics and lesion severity could induce discordance between iFR and FFR. This study aimed to clarify the hemodynamics and lesion characteristics that influence discordance between iFR and FFR. In this retrospective study, we enrolled 225 patients (304 lesions) who underwent clinically indicated invasive coronary angiography and both iFR and FFR examinations between 2012 and 2017. We included only patients who underwent right heart catheterization and had blood pressure and heart rates recorded immediately prior to iFR and FFR. Discordance (iFR ≤0.89 and FFR >0.8 or iFR >0.89 and FFR ≤0.8) was observed in 80 lesions (26.3%). The heart rate, rate-pressure product, and cardiac index tended to be higher in the iFR ≤0.89 group than in the iFR >0.89 group. These trends were not seen between the FFR ≤0.8 group and FFR >0.8 group. A multivariate analysis showed that independent predictors of iFR ≤0.89 and FFR >0.8 discordance were female sex and higher rate-pressure product. iFR >0.89 and FFR ≤0.8 discordance was rare in hemodialysis patients. Even if iFR is functionally significant in intermediate stenosis, additional FFR evaluations should be considered for women, especially those with a high rate-pressure product, to avoid unnecessary percutaneous coronary intervention. If iFR is not functionally significant with intermediate stenosis in hemodialysis patients, then further FFR evaluations are unnecessary. Percutaneous coronary intervention (PCI) performed under the guidance of fractional flow reserve (FFR) has been associated with significantly fewer adverse events than PCI performed under angiographic guidance –3. The iIn this retrospective study, we enrolled patients who underwent clinically indicated invasive coronary angiography as well as both iFR and FFR examinations between 2012 and 2017. Because we defined the hemodynamic status using the rate-pressure product and right heart catheterization parameters, we limited the analysis to patients who underwent right heart catheterizations and had blood pressure and heart rates measured just before the iFR and FFR. All patients had at least one intermediate lesion with stenosis with a diameter >25% on quantitative coronary angiography. We excluded lesions in the left main trunk and those in bypass grafts. Patients with ST-segment elevation myocardial infarction, non–ST-segment elevation myocardial infarction, or New York Heart Association class IV heart failure were excluded. In the present study, the discordance of iFR and FFR was defined either as iFR ≤0.89 and FFR >0.8 or as iFR >0.89 and FFR ≤0.8.Right heart catheterization was performed using a flow-guided Swan–Ganz thermodilution catheter via the brachial, internal jugular, or femoral veins. Hemodynamic parameters including central venous pressure, pulmonary artery wedge pressure, and cardiac index were measured just before coronary angiography. Thermodilution cardiac output was determined by injecting 10 mL of ice-cold saline in the right atrium. The average of several consecutive measurements with less than 10% variation was calculated. The rate-pressure product was defined as the systolic blood pressure multiplied by the heart rate (both were measured just before iFR measurements). Standard 12-lead electrocardiograms were also performed using the interpretive ECG-1550 . RV5 plus SV1, which has been associated with left ventricular hypertrophy, was calculated [Coronary angiography was performed according to standard clinical methods via the radial or femoral arterial approach. Quantitative coronary angiography was performed by an independent physician using a computer-assisted automated edge detection algorithm ; the physician was blinded to the results of the iFR and FFR. The external diameter of the contrast-filled catheter (5 Fr or 6 Fr) was used as the calibration standard. The percentage of the stenosis diameter during end-diastole was measured using the worst-view trace. Lesion lengths were measured as the distance between the proximal and distal shoulders in the projection demonstrating stenosis with the least amount of foreshortening.μg/kg/min. At the end of each measurement, the pressure sensor was retracted to the tip of the guide catheter to avoid pressure drift.Both iFR and FFR examinations were performed using either diagnostic or interventional guiding catheters. After administration of an intracoronary bolus of nitroglycerin, a pressure wire  was advanced to the tip of the catheter; the pressure was equalized against that measured through the guiding catheter. After pressure equalization at the tip of the guide catheter had been completed, the guidewire was advanced to a point distal to the stenosis. First, iFR was directly and automatically measured online using the Volcano Core system (Philips Volcano). Second, the FFR was measured during maximal hyperemia. Hyperemia in the target coronary artery was achieved either with an intracoronary bolus injection of 8-12 mg papaverine or with continuous intravenous administration of adenosine at 150 Normally distributed data are reported as means ± standard deviations (SD). Categorical data are reported as absolute values and percentages. Depending on the data characteristics, the four groups were compared using an analysis of variance, the Kruskal-Wallis test, or the chi-square test. Correlations between parameters were tested using Pearson's or Spearman's correlation coefficients. A multiple logistic regression model that included factors identified as potentially significant (p<0.1) in the univariate analysis was used. P value of <0.05 was considered to indicate statistical significance. Statistical analyses were performed using statistical software .The study protocol was performed based on the regulations of the hospital's ethics committee. All participating patients provided written informed consent. The study was conducted according to the principles of the Declaration of Helsinki.We enrolled 304 lesions from 225 consecutive patients in this study. The study patient characteristics are shown in Female sex (P=0.01), current smoking status (P=0.05), high rate-pressure product (P=0.02), and short lesion length (P=0.06) were potentially associated with discordance of iFR ≤0.89 and FFR >0.8 in the univariate analysis. The prevalence of diabetes mellitus (P=0.06), not being on hemodialysis (P=0.005), low rate-pressure product (P=0.02), and low cardiac index values (P=0.01) were potentially associated with discordance of iFR >0.89 and FFR ≤0.8 in the univariate analysis. The multivariate analysis showed that the independent predictors for discordance of iFR ≤0.89 and FFR >0.8 were female sex  and high rate-pressure product  . FurtherThe scatterplots showing the relationship between iFR and FFR for women and hemodialysis patients are shown in The present study resulted in three primary findings. First, 26.3% of the discordance between iFR and FFR occurred in cases of intermediate coronary artery stenosis. Second, the high rate-pressure product and female sex were independent predictors of discordance of iFR ≤0.89 and FFR >0.8. Third, the discordance of iFR >0.89 and FFR ≤0.8 rarely occurred in hemodialysis patients.The pressure wire-derived indexes of iFR and FFR are similar because both are calculated by comparing the coronary artery pressure to the aortic pressure. However, these two indexes differ in several important ways. The FFR is calculated under hyperemic conditions during the entire cardiac cycle. In contrast, the iFR is calculated under resting conditions during a specific period in the diastole.In our study, heart rate, rate-pressure product, and cardiac index tended to be higher in the iFR ≤0.89 group than in the iFR >0.89 group. These trends were not seen between the FFR ≤0.8 group and FFR >0.8 group. Although there was no significant correlation between the rate-pressure product and FFR, the rate-pressure product and iFR showed a weak, but significant, negative correlation  (The multivariate analysis revealed that female sex was an independent predictor of discordance of iFR ≤0.89 and FFR >0.8. Similarly, Lee et al. reported that female sex was significantly associated with low iFR and high FFR . The disIn our study, the multivariate analysis revealed that not being on hemodialysis was an independent predictor of iFR >0.89 and FFR ≤0.8 discordance. This means that discordance of iFR >0.89 and FFR ≤0.8 occurred rarely in hemodialysis patients. Morioka et al. reported that the iFR values tended to be lower in hemodialysis patients than in nonhemodialysis patients [When the aforementioned multivariate analysis of the factors influencing discordance between iFR and FFR was limited to lesions with 40-80% stenosis, which are commonly accepted as intermediate stenosis, female sex was an independent predictor of discordance of iFR ≤0.89 and FFR >0.8. Furthermore, not being on hemodialysis was an independent predictor of iFR >0.89 and FFR ≤0.8 discordance. Interestingly, the rate-pressure product was not a predictor of iFR ≤0.89 and FFR >0.8 discordance, but rather a predictor of iFR >0.89 and FFR ≤0.8 discordance (The iFR is advantageous because of its shorter procedure time, lower cost, and fewer postprocedure complications compared to FFR. The merits of FFR include its reproducibility and stability because it is measured under hyperemic conditions. In our study, when setting FFR as the gold standard, the sensitivity of iFR among women was lower and the specificity of iFR among hemodialysis patients was higher than those of our overall study population. When evaluating coronary artery stenosis with iFR, there is a tendency for women to have more false-positive results, and false-negative results are extremely rare for hemodialysis patients. Even if the iFR is functionally significant for intermediate stenosis, an additional FFR evaluation should be considered for female patients, especially those with high rate-pressure product, to avoid unnecessary PCI. If the iFR is not functionally significant for intermediate stenosis in hemodialysis patients, then further FFR evaluations are not necessary. Additional studies with a prospective study design and larger numbers of patients are necessary to validate the current findings.This study had some limitations. First, this was a retrospective observational cohort study conducted at a single center, and the number of study patients was relatively small. Second, discordance was observed in 26.3% of cases in this study, which was relatively higher than that observed in previous studies. Third, the prevalence rates of diabetes mellitus, hypertension, and hemodialysis were higher than those of previous studies. These comorbidities induce structural changes in the myocardium and reduce coronary capacity, which might influence the relationship between iFR and FFR. Furthermore, hemodialysis patients characteristically exhibit left ventricular hypertrophy, reduced arterial compliance, and impaired microcirculation, and the time from last dialysis to catheterization affected the results; therefore, we could not exclude the possibility of bias.Even if the iFR is functionally significant for intermediate stenosis, additional FFR evaluations should be considered for women, especially those with high rate-pressure product, to avoid unnecessary PCI. If the iFR is not functionally significant in cases of intermediate stenosis in hemodialysis patients, then further FFR evaluations are not necessary.


This article describes data set of the profile of patients diagnosed with Diabetic Nephropathy (DN) undergoing hemodialysis and followed-up by Hemodialysis Service in medical centers in Goiânia, Go, Brazil. These data describe specifically the demographic, clinical, and lifestyle variables of 101 patients. In addition, these data provide detailed clinical associations about the profile of patients diagnosed with DN and which are made publicly available to enable critical or extended analyzes. For further interpretation of the data presented in this article, see the research article: Do GST polymorphisms influence in the pathogenesis of diabetic nephropathy? . Specifications tableValue of the data•The data show the hyperglycemia may negatively influence the diabetes mellitus (DM) patient׳s clinical status for diabetic nephropathy (DN) development.•The pre-hemodialysis patients’ presented high-level blood urea, due to the presence of an inadequate diet and /or inadequate treatment, respectively. However, the increased in the level of urea was not consistently associated with the reduction of GFR.•The dataset demonstrated that the smoking habits contributed to DN development in association with others risk factors.•These data may be relevant, due to the prevalence of 76.24% of the patients with blood pressure levels inconsistent, indicating systemic arterial hypertension associated with DM act as comorbidity factors for DN development.•These data allow other researchers to extend the statistical analyses.1p = 0.04), GFR  and DAP  were higher in subjects who did not follow the diet correctly  in 101 diabetic nephropathy (DN) patients hemodialysis treatment from the medical centers of the metropolitan region from Goiânia, GO, Brazil. The information on demographic features, lifestyle, time with type 2 Diabetes mellitus and the main exams associated with DN control were collected through questionnaires and clinical records’ analysis.The clinical variables, the fasting plasma glucose, HbA1c (glycohemoglobin), creatinine, pre- and post-hemodialysis blood urea levels, glomerular filtration rate (GFR), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and body mass index (BMI) were obtained, too. Lastly, for the lifestyle variables, the physical activity, eating habits, alcohol consumption and smoking from all the 101 patients were characterized. The GFR was estimated by the Cockfrot-Gault formula, which considers the levels of creatinine, weight, and age. The criteria established by the American Diabetes Association These data were conducted following the ethics statement from the Helsinki Declaration and was approved by the Institutional Ethics Committee . All the participants signed a Free and Informed Consent Form.Data about life, occupational history, smoking history, alcohol consumption, general health conditions, previous diseases, and other anamnesis were obtained during interviews with the patients. Only patients who had smoked for at least one year before the DM diagnostic were considered as smokers. For alcohol consumption, some individuals reported drinking only occasionally or socially.p < 0.05 was considered as statistically significant. All statistical analyses were conducted using RStúdio software (v.1.0.153).The values for


To investigate potential associations between intraocular pressure (IOP) and cerebrospinal fluid pressure (CSFP) in patients with primary open-angle glaucoma (POAG) and healthy subjects.  Forty-three subjects were recruited. Weight and height were measured to calculate body mass index (BMI), along with blood pressure, heart rate, visual acuity, and IOP. Biometrics exam, corneal pachymetry, peripapillary retinal nerve fiber layer (RNFL) thickness, and macular thickness were assessed. The visual field exam was performed on all patients, and both pattern standard deviation (PSD) and mean deviation (MD) were considered. CSFP was estimated indirectly by using the mathematical formula CSFP = 0.44 × BMI + 0.16 × diastolic pressure − 0.18 × age − 1.91, based on the previous scientific studies. The TLCPD was calculated as follows: IOP−CSFP. p < 0.05) difference was found between the two groups for several parameters. Specifically, the CSFP was lower in patients with POAG than in healthy subjects . Anamnestic TLCPD was found to be significantly (p < 0.001) higher in patients with POAG compared to healthy subjects. A significant (p < 0.05) correlation was found between anamnestic TLCPD and MD (r = −0.31), inferior RNFL thickness (r = −0.29), superior RNFL thickness (r = −0.27), IOP (r = 0.22), and CSFP (r = −0.46).  A significant ( The CSFP was lower in glaucomatous patients compared to healthy subjects, whereas the TLCPD was higher in glaucomatous patients compared to healthy subjects, even though this difference was not statistically significant. A higher TLCPD may damage the RNFL, resulting in functional visual field impairment. The term glaucoma comprises a heterogeneous group of diseases with some characteristic features, including structural optic nerve head (ONH) damage and visual field loss. It has been proven that high intraocular pressure (IOP) is a risk factor for glaucoma, and that lowering IOP can decelerate disease progression . HoweverOther risk factors for glaucoma indicated in previous studies include age, decreased central corneal thickness, race, familial history of glaucoma, reduced ocular blood flow, low blood pressure, myopia, and lower ocular perfusion pressure –5. Each Many recent studies have reported that cerebrospinal fluid pressure (CSFP) and translamina cribrosa pressure difference (TLCPD) have a potential role in the pathogenesis of glaucomatous optic neuropathy –13. The Although many studies have shown that CSFP and the TLCPD seem to play a role in primary open-angle glaucoma (POAG), little is known about other parameters involved in the pathogenesis of glaucoma and those that may affect CSFP and TLCPD are age, blood pressure, body mass index (BMI), IOP, central corneal thickness (CCT), and structural and perimetric parameters .The purpose of this study was therefore to evaluate the relationship between IOP and CSFP, as well as systemic and ocular parameters in healthy and glaucomatous subjects.This research is a prospective study that has been approved by the Institutional Review Board of University Policlinic San Martino, Genoa, Italy, and was conducted in accordance with the principles of the Declaration of Helsinki. Patients joined the study after having signed a written informed consent. All subjects recruited for this study were selected at the Eye Clinic of University Policlinic San Martino, Genoa, Italy. All the clinical measurements were performed during the morning clinical session between 9.00 am and 12.00 am.2.The study included forty-three subjects . All patients were questioned about their demographics, clinical history, ophthalmic history and ophthalmic medications, and systemic diseases and systemic medications. All participants underwent measurements of height (m), weight (kg), heart rate (HR) (bpm), and blood pressure (mmHg) in a standardized manner. Arterial hypertension was defined as a systolic blood pressure (SBP) > 140 mmHg, and/or a diastolic blood pressure (DBP) > 90 mmHg, and/or self-reported current treatment for arterial hypertension with antihypertensive medications. BMI was calculated using the formula body mass divided by the square of the body height and expressed in units of kg/mp=0.29) from the calculated CSFP ; [The ophthalmic examination included measurements of visual acuity (VA), measurements of IOP using a calibrated Goldmann applanation tonometer, and slit-lamp examination of the anterior segment including gonioscopy and fundus. Biometric examination with IOLMaster  evaluated axial length (AL) (mm), anterior chamber depth (ACD) (mm), and corneal curvature (degrees). All patients underwent a spectral domain optical coherence tomography (SD-OCT) examination with RTVue SD-OCT , in order to evaluate the thickness of the peripapillary retinal nerve fiber layer (RNFL), the foveal thickness (microns), and CCT (microns). The Humphrey 24-2 Swedish interactive threshold algorithm standard perimeter  was used to evaluate the visual field. To estimate the CSFP, a formula cited in Xie et al.'s study was used: CSFP = BMI × 0.44 + 0.16 × diastolic BP − 0.18 × AGE − 1.91 –17. Whentively); –17 howevFurthermore, the TLCPD was calculated as IOP−CSFP. Both current and anamnestic TLCPD were calculated by using the data on the patients' files. For the anamnestic data, we used the information collected at the first visit, and when missed, we used younger data found in the file, but not the data of the last visit.n = 26) and healthy subjects (n = 17).The recruited participants were classified into two subsets: POAG patients , any history or slit-lamp evidence of angle-closure glaucoma, history of ocular surgery or laser treatments, history of ocular trauma, use of systemic steroids, any other systemic medication known to affect the retina, any neurological condition known to affect the visual field, and previous history of brain surgery that would affect the pressure and structural changes of the optic nerve.t-test was used. When the distribution of the data was nonnormal, a Mann–Whitney test was used. Pearson correlation coefficient was used to analyze the correlations among all the parameters. A p value <0.05 was considered statistically significant. A multivariate analysis was performed to verify the effect of age, gender, and BMI on the correlation studied.The data were evaluated by descriptive analysis. When the distribution of the data was normal, a two-tailed paired The descriptive parameters measured in the POAG and healthy group are summarized in In the POAG group, 18 patients were suffering from high blood pressure treated pharmacologically and one of these patients was also suffering from noninsulin dependent diabetes mellitus (NIDDM) treated with glibenclamide.In the healthy group, one subject had a positive family history of glaucoma and 8 subjects were suffering from high blood pressure treated pharmacologically. Of these, 4 were suffering from cataracts (2 right eyes and 2 left eyes) and one was suffering from NIDDM. Of the healthy patients without hypertension or positive family history of glaucoma, 6 were affected by cataracts solely in the left eye, and one patient had previously had an acute attack of glaucoma in the right eye, so we considered only the left one. Lastly, another nonhypertensive healthy patient without positive family history of glaucoma was suffering from NIDDM treated with glibenclamide.p < 0.001); VA, refractive error, and superior RNFL thickness (p=0.001); weight ; and height and inferior RNFL thickness .As shown in r correlation coefficients performed to assess possible correlations between all considered parameters. When a multivariate analysis was performed, age, gender, and BMI did not have significant effect on the considered parameters such as MD, PSD, RNFL, foveal thickness, and TLCPD.Tables Discussions about CSFP's importance to the ONH and, in particular, its potential role in the pathogenesis of glaucomatous optic neuropathy have been ongoing for 40 years, beginning with Volkov in 1976 , followep < 0.001, p=0.235), anamnestic TLCPD was statistically significant , which confirmed the idea that decreased ICP produces increased TLCPD and leads to glaucomatous damage [Although the studies from Berdahl et al. were limited by small samples of patients, their findings suggested that glaucomatous optic neuropathy was associated with low CSFP, while ocular hypertension was associated with high CSFP , 22. Oths damage . These sp values <0.05, p values <0.05, Tables r = −0.299), superior (r = −0.273) and inferior (r = −0.294) RNFL thickness, and MD (r = −0.319) (Tables r = 0.269), BMI (r = −0.356), IOP (r = 0.223), and CSFP (r = −0.456). Importantly, the negative correlation between anamnestic TLCPD and RNFL thickness agrees with the results previously reported by Siaudvytyte et al. [As shown in r = −0.27 and infee et al.  who founThese results are particularly significant when considering the data from the literature concerning the well-known risk factors for glaucoma onset and progression. The literature consistently shows that increasing IOP and age are the major risk factors for the development and progression of glaucoma . SimilarOur results have two main limitations: Firstly, the sample size of our study was small  and consists solely of Caucasian patients. The results may not be transferable across all populations, and further studies should be conducted with larger sample sizes. Moreover, we also used a calculation to indirectly calculate the CSFP, which may not equal the true orbital CSFP . HoweverIn conclusion, this study showed that the estimated CSFP was significantly lower in POAG patients compared to the control group, whereas the TLCDP in POAG patients was higher, even if the difference was not statistically significant, than in the control group, but clinically, the data of anamnestic TLCDP were more useful and showed both significant difference between the two groups and good correlation with other clinical parameters. These results agree with previous studies. The CSFP may lead to stress on the peripapillary RNFL, as demonstrated by the RNFL values. As a result, patients will have corresponding functional damage, detectable by the values of MD and PSD in perimetry. Therefore, our findings suggested that orbital CSFP was a counter-pressure to IOP and was an important determinant of TLCPD, the pathophysiology and physiology of the optic nerve head, and pressure-related diseases, such as glaucomatous optic neuropathy.


Elevated blood pressure presents a global health threat, with rates of hypertension increasing in low and middle-income countries. Lifestyle changes may be an important driver of these increases in blood pressure. Hypertension is particularly prevalent in African countries, though the majority of studies have focused on mainland Africa. We collected demographic and health data from 513 adults living in a community in rural Madagascar. We used generalized linear mixed models to assess body mass index (BMI), age, sex, and attributes related to household composition and lifestyle as predictors of blood pressure and hypertension. The prevalence of hypertension in this cohort was 49.1% . Blood pressure, as well as hypertensive state, was positively associated with age and BMI. Lifestyle and household factors had no significant relationships with blood pressure. The prevalence of hypertension was similar to that found in urban centers of other African countries, yet almost double what has been previously found in Madagascar. Future research should investigate the drivers of hypertension in rural communities worldwide, as well as the lifestyle, cultural, and genetic factors that underlie variation in hypertension across space and time. Elevated blood pressure affects millions of people around the world , with thThe prevalence of hypertension in low and middle-income countries (LMICs) is increasing , 7. In fIn LMICs, the prevalence of hypertension tends to be greater in urban areas than rural ones , 9. Thisevolutionary mismatch—the concept that differences between the current environment and the one in which humans evolved have direct consequences for health [The relationship between changing lifestyles and health can be understood through the lens of evolutionary medicine, and more specifically, r health . In the r health . Becauser health . An evolr health , which ir health .We investigated body mass index (BMI), age, sex, and blood pressure in an economically developing rural population in Madagascar. This region is increasingly shifting to a reliance on cash crops, such as vanilla, producing a cascade of factors that increase both stress and access to factors of the post-industrial lifestyle, including alcohol and processed foods. More generally, Madagascar is interesting because of its unique ecological and genetic factors, including an admixture of individuals with African and Austronesian ancestry . Thus, tBuilding on previous research described above, we investigated predictors of blood pressure and hypertension in rural Madagascar. Focusing on key correlates in previous studies, we predicted that elevated blood pressure covaries positively with BMI and age , 25, andThis study took place in Mandena, Madagascar (approximately -18°42'00” S 47°50'00” E), an agricultural village of approximately 3,000 people in the SAVA region . Rice production is central to subsistence agriculture in this population, and vanilla is generally sold as a cash crop.Data were collected over three field seasons in Mandena: (1) Seven weeks from July to August 2015; (2) four weeks from July to August 2016; and (3) four weeks from May to June 2017. Importantly, data collection began at the start of vanilla season, a period when farmers are spending considerable amounts of time monitoring, harvesting, and preparing the crop for sale, including protecting their crops from theft in the field and processing harvested vanilla beans in the village. The SAVA region in particular is tightly connected to global vanilla distribution; as such, communities in the area experience marked seasonal and yearly fluctuations in crop yields and market prices, financial security , and stress.This study is nested within a larger project that utilized an evolutionary perspective to understanding the relationship between changing lifestyles and health outcomes in this Malagasy village. As new projects were initiated, modifications were made to improve data collection and to collect new health metrics. As such, variation in cohort size and certain data collection procedures exists across the three field seasons, as documented below. All study procedures were approved by Duke University’s Institutional Review Board (Protocol C0848) and by Malagasy health authorities.The study included a total of 1,142 measurements of blood pressure and other health metrics from 513 adults enrolled over the three field seasons . During each field season, individuals first learned about the project through a town-hall style meeting led by the village president at a central building in Mandena. Interested individuals were encouraged to return to the building in the following days to enroll in the study. To maintain anonymity in the records, each participant was given a unique identification number that was used in all subsequent surveys.2; normal ≥18.5 to <25 kg/m2; overweight 25–30 kg/m2; obese ≥30 kg/m2 [Through a Malagasy translator, each participant provided informed written consent and completed a general health survey, coupled with measurements of height, weight, temperature, blood pressure, and heart rate. All blood pressure and heart rate measurements were taken with the Omron 10 Series Upper Arm Blood Pressure Monitor . Individuals were required to sit for at least five minutes before the first blood pressure reading, and at least five minutes separated a total of up to three different readings. We used a standard bathroom scale that was purchased in Madagascar to measure weight, and a tape measurer adhered to a vertical wooden beam in the central building to measure height. Height and weight measurements were used to calculate BMI as weight in kilograms divided by the square of height in meters. Following standard guidelines, individuals were categorized as: underweight <18.5 kg/m30 kg/m2 . Any parComparison of data collection across the three study years are shown in We used household size (number of people) as a proxy for stress, as assessed using the general health survey in 2015. We also collected data on tobacco and alcohol usage in the previous week (yes/no).We used generalized linear mixed models (GLMM) to analyze blood pressure, with one reading per participant from 2015 and all readings from participants in 2016 and 2017 . To incorporate the decrease in blood pressure over repeated readings, we included individual ID and measurement  as random effects, and BMI, age, and sex as fixed effects. We then used model selection and averaging to predict both systolic (SBP) and diastolic (DBP) blood pressure as continuous variables. All analyses were run in R .We were also interested in investigating the relationship between hypertension and factors related to transitions toward industrialization. Using the ACC/AHA guidelines outlined in Whelton et al. , we defiFinally, we investigated lifestyle and household predictors based on data from 2015 (N = 47). We used model selection and averaging of generalized linear models to predict SBP and DBP based on BMI, age, sex, alcohol consumption and tobacco usage in the previous week (y/n), and household size (number of people).Of the 513 participants, we identified 49.1% as hypertensive (Stages 1 and 2 combined). Of those that were not hypertensive, we found that 8.4% had elevated blood pressures, with only 42.5% having clinically normal measurements . OverallIn statistical analyses of SBP and DBP, we found that both were positively predicted by age and BMI, but not by sex . SimilarFurther analyses revealed no significant effect of lifestyle and stress-related factors that we investigated , although sample sizes were smaller than the overall cohort. Full results and demographic data are provided in the Supporting Information.The overall prevalence of hypertension in this rural Malagasy community was nearly 50%. This is higher than what is reported in many rural communities on mainland Africa , 26, 30,We found that BMI covaried positively with measures of SBP and DBP. These patterns mirror previous studies of blood pressure in rural communities , 35, 36.While there is a positive association between BMI and hypertension, it is interesting that only 1.2% of individuals are classified as obese. It is possible that additional metrics related to body mass and metabolism, such as waist circumference, would better elucidate patterns in this population . BecauseOlder age significantly predicted hypertensive state, a finding that is in line with many other studies , 30, 36.Contrary to our predictions, sex did not have a significant effect on hypertension, even within specific age groups (data not shown). While previous studies have found higher blood pressure in men than women , studiesTo our knowledge, this is only the second study to examine blood pressure in rural Madagascar. A previous study also found a positive relationship between age and hypertension, and raised concerns over the risk of a hypertension epidemic in Madagascar’s progressively aging society . StrengtIn conclusion, we discovered a remarkably high prevalence of hypertension in an agricultural community in rural Madagascar. Our research raises a number of questions to address in future studies, including research aimed at understanding the drivers of hypertension throughout the life course. Future studies in this region could incorporate data on dietary sodium intake and family history of hypertension, along with metrics of stress, including stress associated with vanilla production. More generally, our study contributes to the growing body of literature that calls for making the study of hypertension in rural communities a priority in global health research , 35, 45.S1 FigThe third measurement is lower than the first.(EPS)Click here for additional data file.S2 FigThe dashed line indicates the minimum blood pressure value for hypertension.(PDF)Click here for additional data file.S1 Table(PDF)Click here for additional data file.S2 Table(PDF)Click here for additional data file.S3 Table(PDF)Click here for additional data file.S1 Dataset(XLSX)Click here for additional data file.


The severe forms of asthma represent a major burden, because of severity of symptoms, costs and impact on everyday life. Recently, Mepolizumab (MEP) was approved and marketed for the treatment of hypereosinophilic severe asthma. This anti-IL-5 monoclonal antibody reduced exacerbation rates and oral corticosteroid (OCS) use in well selected patients. The aim of this study was to evaluate the characteristics of patients receiving MEP in a real-life setting. Thus, we describe a retrospective analysis of patients treated with MEP in six centres in North Western Italy, including those who participated in the main regulatory trials.The baseline data, before prescription, from six North Western Italy severe asthma clinics, between June 1st 2017 and December 31st 2017, were evaluated. The collected real-life data were then compared with those of SIRUS, MENSA, DREAM and MUSCA trials.p <  0.0001). The incidence of polyposis was also significantly higher in our sample . The daily average dose of OCS was lower in our real-life patients (9 mg), if compared with SIRIUS (13.7 mg), MENSA (13.2) and MUSCA (13), and similar to the data published in DREAM (10.8).Sixty-five patients were included . Main observed differences with regulatory trials could be observed in eosinophils blood count at baseline, where the mean of our real-life patients (653 cells/μL) was overall higher than the one of all trials  differed. These data, for the first time, could represent a basis for a more accurate prescription of the drug. Asthma is a common chronic respiratory disease, which prevalence ranges between 1 and 18%, with slight variations among Countries, and according to selection criteria and methodology , a “seveThis is a retrospective analysis of patients from six severe asthma clinics of North West Italy , which were the first clinics to have the product available. All patients meet the ATS/ERS criteria for uncontrolled severe asthma  and the All procedures described herein were performed as per standard of care. The study was observational, with approved and commercialized drugs. No approval from the Ethics Committees was required according to the Italian laws. The privacy rules were applied and all patients provided an informed consent to be treated.t-test one sample and a Z-test one proportion when indicated. A p value of ≤0.05 was considered to be significant.All patients receiving MEP in the aforementioned period were included in the analysis. Arithmetic mean and standard deviation were used for the descriptive statistics. To compare data of our patients with those of the four mentioned clinical randomised, double-blind, placebo-controlled studies –11, a weStarting from June 1st, 2017 to December 31st, 2017, 65 severe hypereosinophilic asthmatic patients were treated. All patients were classified as step 4/5 GINA [1) of 73 ± 18%. Fifty-three out of 65 patients (82.5%) were receiving daily OCS therapy at the time of inclusion, with a mean dose of 9.2 mg (±9.2) of prednisolone . The mean eosinophils level at baseline, before treatment, was 653 cells/mmc (range 150–1987), with a mean historical value in the previous year of 1046 cells/mmc (range 320–6000). Nasal polyps were documented (by fiberoptic rhinoscopy and/or computerized tomography) in 47 (72%) subjects. 7/65 (11%) patients come from the previous regulatory trials conducted at our centres.The control of the disease was evaluated with validated asthma control test (ACT) at baseline with a mean value of 16.6 ± 4.7 (range 6–25). Also lung function test prior to MEP evidenced a mean forced expiratory volume at the first second (FEVp <  0.0005), DREAM , MENSA and SIRIUS . Concerning gender, MEP was given to 29/56 women (45%) in the real-life sample. A statistically significant difference towards the four examined trials was seen with the DREAM study (387/621 p = 0.0033) and the MUSCA study . Concerning smoking habit, in our sample 17/65 (26%) were current or former smokers at baseline. If in DREAM, MENSA and MUSCA study the percentage of smoking people was similar to which observed in our sample, the same cannot be said about the SIRIUS study, where the percentage of smokers was higher .The mean age in our real-life sample was 56 years, with a statistically significant difference compared to MUSCA  in SIRIUS, 61 (±17.9) in MENSA, 60 (±16.0) in DREAM and 55 (±14.5) in MUSCA, all value with a statistically difference <  0.0001. The range of eosinophils, in the previous and current years, was broadly distributed with a mean value of 1046 (range 320–6000) cells/μl and 653 (range 150–1987) cells/μl, respectively. Matching these results with those of previous clinical trials, a mean value of 653 (±381) cells/μl was recorded in our cohort, whereas in the four randomized trials the concentration of eosinophils at baseline  was lower, all with a statistically significant difference (p <  0.0001). Comparing our data with that of the MUSCA study, where eosinophils were categorized in two ranges, we observed a statistically significant difference in both groups . The mean exacerbation rate of our population was 3.0 (±1.8), not different from of SIRIUS , MUSCA , and lower than in MENSA  and DREAM . The percentage of subjects hospitalized or requiring emergency room visit, was higher in our sample (31%) as compared to SIRIUS  and MENSA , similar in MUSCA  and lower in the DREAM trial .The duration of asthma was also considered, calculated as the difference between the date of first MEP administration and the reported first occurrence of asthma symptoms. The range spans widely from 2 to 68 years, but only 7 patients complained of symptoms before the age of 20 years. The average age of onset of asthma was 38 years, with a mean duration of 18.2 (±14.2) years. In this context our data parallel those collected in the main clinical trials. Pulmonary function was evaluated according to Global Lung Function Initiative (GLI) predictions , and thep = 0.1715), in SIRIUS , MENSA  and MUSCA  trials. The daily dose was on average higher than in our sample. Finally, ACT was somewhere used to evaluate the QoL, but this aspect was difficult to compare, since different instruments were used in the different studies. When the presence of nasal polyps was assessed by endoscopy [p = 0.0003), 19% in MUSCA (p <  0.0001) and 10% in DREAM (p <  0.0001). No data were available from the SIRIUS study. This may be explained by the strict inclusion criteria of the regulatory trials that were not applied to our real-life patients. Also, it has to be considered that the association of polyposis, asthma and hypereosinophia is quite frequent, and usually underdiagnosed [The use of OCS is a main determinant in severe asthma. Among our real-life patients, 53 had a daily prescription of OCS . Only in the DREAM study the daily dose was similar to our patients,  , as compd asthma , no limid asthma .With the commercialization of MEP severe uncontrolled hypereosinophilic asthma certainly achieved more expanded therapeutic improvement. The clinical data about efficacy  together with the safety profile are promising. It is true that, in comparison with the regulatory trials, in real life, the high level of blood eosinophils count is essential to decide for the IL-5 antagonism strategy. The possibility of decreasing the OCS burden would be regarded as a relevant socio-economical advantage .Nevertheless, this observational trial evidenced some discrepancies between real life patients and clinical trials. The age at first administration and gender are probably not relevant, whereas the presence of eosinophils blood count at baseline or the presence of nasal polyposis are of importance. Also, it seems from the real-life observation that a more precise judgement would require at least 1 year of treatment.One of the main endpoints of all biological drugs remains, in severe asthma, the reduction of the use of OCS or inhaled corticosteroids  and in tWe report herein the characteristics of a real-life patient population compared to the “formal” trials, showing some apparent discrepancies among the populations. In general, the demographic and clinical aspects were similar among the patient groups, but the groups themselves displayed some differences that could be taken into account for a more refined definition of the appropriate prescription.


Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease in the developed world. Until 2016, the only treatment that was clearly demonstrated to delay the DKD was the renin-angiotensin system blockade, either by angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. However, this strategy only partially covered the DKD progression. Thus, new strategies for reno-cardiovascular protection in type 2 diabetic patients are urgently needed. In the last few years, hypoglycaemic drugs, such as sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists, demonstrated a cardioprotective effect, mainly in terms of decreasing hospitalization for heart failure and cardiovascular death in type 2 diabetic patients. In addition, these drugs also demonstrated a clear renoprotective effect by delaying DKD progression and decreasing albuminuria. Another hypoglycaemic drug class, dipeptidyl peptidase 4 inhibitors, has been approved for its use in patients with advanced chronic kidney disease, avoiding, in part, the need for insulinization in this group of DKD patients. Studies in diabetic and non-diabetic experimental models suggest that these drugs may exert their reno-cardiovascular protective effect by glucose and non-glucose dependent mechanisms. This review focuses on newly demonstrated strategies that have shown reno-cardiovascular benefits in type 2 diabetes and that may change diabetes management algorithms. Diabetic kidney disease (DKD) is the first cause of chronic kidney disease, leading to premature death and end-stage renal disease (ESRD) in the developed and developing world. In response, multiple potential therapeutic agents have been tested, focusing on the treatment of hyperglycaemia and hypertension, mainly directed at the renin-angiotensin system blockade ,2,3,4. HThe SGLT2 is expressed in the proximal tubule of the kidneys and is responsible for 90% of renal glucose reabsorption. SGLT2 inhibitors promote the urinary excretion of glucose and, consequently, lower blood glucose levels. Interestingly, these drugs scarcely provoke hypoglycaemia, as their effect is not related to beta cell function or modifications in insulin sensitivity . SGLT2 iIn this review, we describe the new strategies for reno-cardiovascular protection in patients with type 2 diabetes and their potential mechanisms. We cover the most important studies focused on the renoprotection exerted by SGLT2 inhibitors, GLP-1RAs, and DPP-4 inhibitors in DKD patients.Patients with diabetes have a higher prevalence of cardiovascular morbidity and mortality compared to the general population . It is w2) is unknown, given the fact that those patients have been systematically excluded from clinical trials [In the late 80’s to early 90’s, an ACEi, enalapril, demonstrated its effectiveness in reducing mortality in patients with heart failure ,17. Latel trials .p = 0.07) was observed in the aliskiren arm during the follow-up of approximately 2.7 years [After the previously mentioned results, and based on preliminary studies demonstrating an added effect on decreasing albuminuria with a dual RAAS blockade , later r.7 years . Consequ2, randomly assigned to receive empagliflozin at −10 or 25 mg or a placebo on top of standard care. Death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke was decreased in the empagliflozin group (10.5%) compared to the placebo group (12.1%) . Interestingly, this benefit was higher in older patients (>65 years) and with HbA1c ≤ 8.5%. Empagliflozin more significantly decreased cardiovascular death (3.7% vs. 5.9%) and death from any cause (5.7% vs. 8.3%) compared to placebo , as well as hospitalization for heart failure . HbA1c levels were similar in both groups. In contrast, in previous studies, empagliflozin was associated with a decrease in HbA1c levels in patients with type 2 diabetes [2 and/or macroalbuminuria) [2. Treatment with empagliflozin showed benefits in terms of incident or worsening nephropathy (12.7% vs. 18.8% in placebo group)  and progression to macroalbuminuria (11.2% vs. 16.2%) . Patients receiving empagliflozin demonstrated a decrease in the doubling of serum creatinine compared to the placebo group , as well as a lower rate of renal replacement therapy initiation (0.3% vs. 0.6%)   see . eGFR de2. The mean eGFR was 76.5 ± 20.5 mL/min/1.73 m2; 22.6% presented microalbuminuria and 7.6% presented macroalbuminuria. Canagliflozin administration significantly decreased HbA1c levels, as well as blood pressure and body weight. In the canagliflozin group, deaths from cardiovascular cause, non-fatal myocardial infarction, and non-fatal stroke were significantly decreased by 14%  [The Canvas Program studied the cardiovascular and renal effects of canagliflozin (100 mg or 300 mg) versus placebo in 10,142 type 2 diabetic patients with a previous history of cardiovascular disease or two or more cardiovascular risk factors and eGFR > 30 mL/min/1.73 mt-years) . Regardi2. The study included 17,160 patients, 40.6% with cardiovascular disease and 59.4% with multiple cardiovascular risk factors. The mean eGFR was 85.2 mL/min/1.73 m2 and only 7% of patients had an eGFR <60 mL/min/1.73 m2. Dapagliflozin significantly decreased HbA1c levels, body weight, and blood pressure [The dapagliflozin effect on cardiovascular events (DECLARE-TIMI 58) evaluated the effects of dapagliflozin (SGLT2 inhibitor) versus placebo on cardiovascular and renal outcomes in patients who had, or were at risk for, cardiovascular disease. Eligible patients were older than 40 years old, had type 2 diabetes, a history of cardiovascular disease or more than two classical cardiovascular risk factors, and an eGFR ≥ 60 mL/min/1.73 mpressure . There wpressure .2 , a 20% reduction of cardiovascular death, myocardial infarction or stroke , and a 29% reduction of hospitalization for heart failure . Canagliflozin group showed a decreased eGFR slope compared with the placebo group (−3.19 ± 0.15 vs. −4.71 ± 0.15 mL/min/1.73 m2 per year), which means a difference of 1.52 mL/min/1.73 m2 per year. Rates of adverse events were similar in both groups. In conclusion, the use of canagliflozin in type 2 diabetic patients with established kidney disease on top of renin-angiotensin system blockade was safe and decreased the risk of kidney failure and cardiovascular events [The renoprotective effect of SGLT2 inhibition has become evident in the last 3 years. However, until now its use has been limited to patients with eGFR > 45 mL/min/1.73 m2 . A recen placebo . Patientr events .GLP-1RAs are glucagon-like peptide-1 (GLP-1) molecule analogues. GLP-1 is an incretin secreted by intestinal enteroendocrine L-cells in response to food intake, which increases insulin secretion in a glucose-dependent manner . GLP-1 Rp < 0.001) [2, as well as in patients with cardiovascular disease at baseline. In concordance, semaglutide also reduced the MACE composite outcome when compared to placebo during a follow-up period of 2.1 years in the trial to evaluate cardiovascular and other long-term outcomes with semaglutide in subjects with type 2 diabetes (SUSTAIN-6)  [p < 0.0001) [In the liraglutide effect and action in diabetes: evaluation of CV outcome results (LEADER) trial, Liraglutide was shown to decrease three-point MACEs and death from cardiovascular causes in a 3.8 year follow-up when compared to the placebo added to standard care  . There w 0.0001) . This deConversely, other GLP-1RAs did not demonstrate clear cardiovascular benefits. In the evaluation of lixisenatide in acute coronary syndrome (ELIXA) trial, lixisenatide exhibited non-inferiority when compared to a placebo added to standard care during a 25 month follow-up in patients with established cardiovascular disease, but did not reduce the incidence of the composite cardiovascular outcome . Nonethep = 0.003) [p = 0.005) [When it comes to evaluating the renoprotective effects of GLP-1RAs, trials usually examine a composite outcome of new-onset persistent macroalbuminuria, persistent doubling of serum creatinine, end-stage renal disease, or death due to renal causes. A secondary renal outcome analysis of LEADER showed a reduced incidence of this composite outcome in patients receiving liraglutide  . Recentl= 0.005) . This fi= 0.005) . Whetherp < 0.0001). However, no changes in body weight were found with the IDegLira treatment. Hypoglycaemic episodes, although were rarely described, were more frequent when compared to the rates displayed in DURATION-8 and AWARD-10, which may be related to the addition of insulin.Despite their promising cardiovascular and renal protective effects, there are still very few trials that verify the positive outcomes of SGLT2 inhibitors and GLP-1RAs used in combination. In the randomized controlled trial 104-week results—once-weekly exenatide plus once-daily dapagliflozin vs. once-weekly exetanide or dapagliflozin alone (DURATION-8), patients with type 2 diabetes inadequately controlled by metformin were randomly assigned to receive exenatide plus dapagliflozin, exenatide alone, and dapagliflozin alone . During Considering the evidence, the combination of the SGLT2 inhibitor and GLP-1RAs has proven to be safe and well tolerated. The rates of adverse effects are similar to those described in monotherapy and of a mild to moderate intensity. Hypoglycaemic episodes were barely described, although no trials have evaluated their safety in populations with established chronic kidney disease, where there is a higher risk of antidiabetic treatment related hypoglycaemia. Greater reductions of HbA1c, body weight, and blood pressure were observed in combined treatments. Despite these results, cardiovascular outcomes and/or DKD progression with add-on therapy have not been analyzed in the previous trials. Therefore, more studies are needed to evaluate these events.+), among other metabolites and electrolytes, are reabsorbed by the tubular cells, mainly in the proximal portion . Glucose is absorbed together with Na+ by sodium-glucose co-transporters 1 and 2 (SGLT1 and SGLT2) located at the apical membrane of the tubular cells. Although both transporters are expressed in the tubular cells, the major part of the glucose (90%) is reabsorbed by SGLT2 [+ is further reabsorbed by other transporters, of which the Na+/H+ exchanger isoform 3 is the most important (NHE3) [+ via the Na+/K+ ATPase [+ contributes importantly to glucose homeostasis and to the maintenance of the intraglomerular tone. In diabetic patients, due to glomerular hyperfiltration, glucose and Na+ levels are increased in the lumen of the tubules. In response, the tubular reabsorbing mechanisms are upregulated both by an increase in the activity or expression of the transporters mentioned above [+ blood levels rise, contributing to hyperglycaemia and hypertension. In addition, the enhanced reabsorption in the proximal tubule, decreases Na+ flow to the distal tubule and activates the macula densa. Both SGLT2 inhibitors and GLP-1RAs increase natriuresis, leading to the restoration of the tubuloglomerular feedback, which results in afferent arteriole vasoconstriction and, finally, in a reduction of the intraglomerular pressure. SGLT2 inhibitors have a more important natriuretic effect than GLP-1RAs, most probably related to the direct blockade of the tubular Na+ uptake mediated by SGLT2 and/or the impairment of the Na+/H+ exchanger isoform 3 (NHE3) activity, which is glucose-dependent and seems to be indirectly blocked by SGLT2 inhibition [+-K+-2Cl− cotransporters and epithelial Na+ channels, when compared to untreated littermates, suggesting that SGLT2 modulates the Na+ reabsorption of several tubular transporters [Blood glucose level and the reduced blood pressure produced by SGLT2 inhibitors and GLP-1RAs have undeniable beneficial effects in terms of cardio-renal protection. However, other independent pathways have also been described and may potentially be relevant to explain their renoprotective effects. Both drugs have natriuretic properties that produce hemodynamic effects on the kidneys. In healthy subjects, glucose and sodium  . Glucoset (NHE3) ,41 and N+ ATPase , both loed above  and by aed above ,45. Therhibition   or placebo (n = 55). They found that linagliptin significantly reduced albuminuria from baseline by 28%, compared to placebo, after 24 weeks of treatment. Of note is that an effect on albuminuria was already seen after 12 weeks of treatment [2, and 15.2% had an eGFR below 30 mL/min/1.73 m2). Linagliptin reduced the progression of the albuminuria category  by 14% , although the composite renal endpoints of sustained ESRD, death due to renal failure, or a sustained decrease of 50% or more were not different [The indications for Dipeptidyl Peptidase 4 Inhibitors in patients with type 2 diabetes and CKD have been analyzed over the last 10 years. In early 2010, diverse studies involving a small number of patients demonstrated the safety and efficacy of an adjusted dose of vildagliptin in patients with advanced CKD in hemodialysis and peritoneal dialysis ,61. In areatment . In the reatment . The lasDiabetic kidney disease is the leading cause of premature death and end-stage renal disease in the developed world. Until 2016, the only treatment that demonstrated to be able to attenuate DKD was a renin-angiotensin system blockade, either by ACEi or ARB. However, the partial effectiveness of these agents means that new therapeutic strategies are still needed to delay or prevent progression to ESRD. In recent years, the reno-cardiovascular safety profile of SGLT2 inhibitors and GLP-1RAs has been demonstrated ,68,69,70


Venous sinus stenosis (VSS) is a type of cerebral venous vascular disease. Cerebral autoregulation is an indicator of cerebral arterial function. The cerebral circulatory system is composed of the venous system and arterial system. Impaired venous function may affect arterial function. Thus, cerebral venous stenosis may influence cerebral autoregulation.In this case, a 50-year-old woman with transient blindness and headache was admitted to the hospital. The patient was diagnosed with VSS. A stent was placed at the stenosis. The stent released the intravenous pressure and remitted the patient’s symptoms. Measurements of dynamic cerebral autoregulation (dCA) were performed at 3 time points: before stenting, after stenting, and 3 months later. The dCA gradually improved after stenting.VSS may have an influence on cerebral autoregulation, and effective treatment improves cerebral autoregulation in patients with VSS. Cerebral autoregulation (CA) is a physiological mechanism that maintains a stable cerebral blood flow within a wide range of blood pressure fluctuations. CA is an indicator of cerebral arterial function. Research has indicated that impaired CA is associated with cerebral small vessel disease, cerebral hemorrhage, and unilateral middle cerebral artery stenosis –3. TheseIn this case, transcranial Doppler ultrasound and noninvasive continuous blood pressure measurements were used to obtain high temporal resolution blood flow velocity and blood pressure records. Dynamic cerebral autoregulation (dCA) was then calculated by transfer function analyses based on the response of blood flow to the transient changes in blood pressure .2O. Magnetic resonance venography suggested stenosis at the border of the transverse sinus and sigmoid sinus on the right side . The raw waveforms were sampled at 100 Hz for both arterial blood pressure and cerebral blood flow velocity. A cross-correlation function was used to achieve beat-to-beat alignment of data. To down sample the data to 1 Hz, a third-order Butterworth low-pass filter (cut-off at 0.5 Hz) was applied as an anti-alias filter. Dynamic cerebral autoregulation was evaluated using transfer function analysis [2: 37.1 mmHg. One day after the venous sinus stenting, the dCA of the patient was as follows: gain (right side), 0.74 cm/s/mmHg; gain (left side), 0.84 cm/s/mmHg; phase difference (right side), 43.77 degrees; phase difference (left side), 51.62 degrees. End-tidal CO2: 37.8 mmHg. The patient’s symptoms were significantly relieved. Three months after intracranial stenting, the dCA of the patient was as follows: gain (right side), 0.91 cm/s/mmHg; gain (left side), 0.76 cm/s/mmHg; phase difference (right side), 82.73 degrees; phase difference (left side), 71.20 degrees. End-tidal CO2 was 37.6 mmHg. Figure In this case, transcranial Doppler ultrasound was used to measure high temporal resolution blood flow velocity. The relative low cost, ease of use, non-invasiveness, and excellent temporal resolution of transcranial Doppler ultrasound make it an ideal tool for examination of cerebrovascular function in both research and clinical settings. However, it cannot be used in patients with insufficient bilateral temporal bone windows for insonation of the middle cerebral artery. Measurements of dCA were performed at 3 time points: before stenting, after stenting, and 3 months later. The patient need to avoid alcohol and exercise 12 h before the measurement. And the measurements were made in a quiet, specialized laboratory with a constant temperature between 22 and 24 °C. Transcranial Doppler  was used to evaluate cerebral blood flow velocity. The 2 MHz probe was fixed to a special head frame and detect blood flow velocity in the middle cerebral artery non-invasively at a depth of 45 to 60 mm. A servo-controlled plethysmograph  was used to record the natural arterial blood pressure of the right middle finger placed at the heart level. And a capnograph attached to a mask on a nasal tube was used to monitor end-tidal COanalysis . We usedVSS is a type of cerebral venous vascular disease. Several studies reported venous sinus stenting is a feasible treatment for refractory idiopathic intracranial hypertension and VSS –12. HeadThe underlying pathophysiology of cerebral vein occlusion remains controversial in clinical and experimental studies, in particular for the related hemodynamic and metabolic alterations , 17. CurThough several studies reported venous sinus stenting is a feasible treatment for refractory idiopathic intracranial hypertension and VSS , 15, the