Anecdotal reports of a paradoxical exacerbation of hypotension in response to a bolus of a balanced isotonic crystalloid solution containing acetate buffers in dogs under general anesthesia was studied in a prospective clinical trial. The response to three different balanced isotonic crystalloid solutions administered as an intravenous bolus to dogs experiencing hypotension while anesthetized for elective orthopedic or dental procedures was investigated. None of the subjects experienced a paradoxical hypotensive reaction or an increase in blood pressure in response to a fluid bolus.The aim of this prospective, randomized, nonblinded, controlled clinical trial was to compare mean arterial blood pressure (MAP) and heart rate (HR) during an intravenous bolus of three different balanced isotonic crystalloid solutions in euvolemic, anesthetized dogs with hypotension. Thirty healthy dogs  weighing at least 15 kg that presented for elective orthopedic or dental surgical procedures at the Ryan Veterinary Hospital for Small Animals of the University of Pennsylvania were included in this study. Anesthetized hypotensive patients (defined as a MAP ≤ 65 mmHg), were administered an infusion of Lactated Ringer’s solution (LRS), Plasma-Lyte (PLYTE) or Canadian Plasma-Lyte (PLYTECA), selected at random. The infusion was administered over 15 min via a volumetric fluid pump. Differences in oscillometric MAP and HR between time points and across treatments were evaluated by mANOVA. Intravenous isotonic crystalloid infusions over 15 min did not significantly change MAP or HR in hypotensive dogs under general anesthesia. Neither LRS, PLYTE nor PLYTECA exacerbated hypotension or caused tachycardia. Various theories have been brought forward to justify this effect, of which the most common is the cardiovascular effects of rapid infusions of acetate  and magnon rates ,4,5. Hypon rates ,7,8,9. Aon rates . Hypovolr 15 min . Howeverr 15 min ,12. In a therapy . Differe2+ content . Both are otherwise identical in their pH, electrolyte compositions and osmolarity (294 mOsm L−1). The composition of the three crystalloids used in this study is outlined in Crystalloid solutions contain solutes of low molecular weight (<500 g/mol) . They ar2+ concentration to observed changes in MAP and HR. We hypothesized that the administration of PLYTE as an IV bolus is associated with a higher incidence or magnitude of hypotension and tachycardia than PLYTECA, and that LRS, which contains no supplemental Mg2+ nor acetate, but instead contains Ca2+, would lead to an increase in MAP and HR.The aim of this study was to compare the effects of three different isotonic crystalloids , PLYTE and PLYTECA) administered as an intravenous bolus on MAP and HR during anesthesia-induced hypotension in dogs and assess the contribution of ionic buffers (acetate vs. lactate) or MgStudy designProspective, randomized, nonblinded, controlled clinical trial.AnimalsThe study was approved by the University of Pennsylvania’s Institutional Animal Care and Use Committee. Thirty adult dogs were included in this study. All dogs were client owned and anesthetized for elective orthopedic or dental surgery at the Ryan Veterinary Hospital for Small Animals. The inclusion criteria were body weight > 15 kg, at least 6 months of age, no known systemic illness, normal physical examination with the exception of a surgical orthopedic condition or mild dental disease, and complete blood count, packed cell volume, total solids and serum biochemical profile within the reference range.Anesthesia−1 IV or 0.02 mg kg−1 IM acepromazine  and 0.03 mg kg−1 IV or 0.05 mg kg−1 IM oxymorphone  for premedication 15 to 30 min before aseptic placement of an IV catheter  in a cephalic vein. Anesthesia was induced with propofol  administered to effect and maintained with isoflurane at a concentration needed to maintain an adequate depth of anesthesia , as judged by an experienced anesthetist. All patients were maintained on spontaneous ventilation during the recording period. Regional anesthesia was included as part of balanced anesthetic protocols and varied  depending on the procedure. An IV infusion of LRS was administered at a rate of 2–5 mL kg−1 r−1 by means of a volumetric fluid pump , starting at induction and maintained throughout anesthesia. Antibiotics (cefazolin), if indicated, were administered slowly intravenously for antimicrobial prophylaxis after induction and repeated every 90 min thereafter until closure of the surgical site. After endotracheal intubation, heart rate (HR) was monitored with a lead II ECG, with gel-coated ECG pads (Ambu A/S) affixed to the right and left front paws and left hind paw, oxygen saturation was monitored by means of pulse oximetry and mean blood pressure was measured by oscillometry with a multi-parameter and anesthetic agent monitor . For oscillometric blood pressure measurement, an inflatable cuff , the width of which measured 40% of the circumference of the limb, was used. Cuffs were placed either on the thoracic limbs, just distal to the elbows or on pelvic limbs proximal to the tarsus. Although the site of blood pressure measurement was not standardized between patients, it remained constant during the entire recording period for each individual patient. All vital parameters were measured and recorded every 5 min, except body temperature which was measured rectally with a digital thermometer  at 15 min intervals. Temperature was maintained above 37.2 °C by means of circulating warm water beds placed between the operating tables and the patient, and a Bair Hugger  that provided forced warm-air flow to the patient.All dogs received 0.01 mg kg−1). Thus, patients weighing 25 kg and above received a maximum of 250 mL over a 15 min period. Fluid rates administered to patients less than 25 kg were limited to 10 mL kg−1 over 15 min. Baseline physiological values (Time point 0) were recorded just prior to the start of the infusion. The anesthetist was not blinded to the fluid type assigned to the patient. During the course of the treatment, the anesthetic depth  was kept unchanged unless the anesthetic plane was too light for the procedure in progress . Start of surgery did not occur in any case before completion of the fluid bolus to minimize the effect of surgical stimulation on the vital parameters studied. The study was terminated at the end of the infusion regardless of whether normotension was established by the end of the intervention. If hypotension persisted, standard anesthetic procedures in place at this institution were followed to achieve normal blood pressure.Following two consecutive MAP measurements less than or equal to 65 mmHg taken at 5 min intervals (time points −5 and 0) prior to onset of surgery, a third party then performed randomization using the “randbetween” function  with personal computer software . Ultimately, patients were administered the selected crystalloid as an IV bolus over 15 min with a volumetric infusion pump set at 999 mL/h for patients over 25 kg, or 10 mL per kg over 15 min for patients weighing less than 25 kg. The fluid rates used to deliver fluid boluses to each subject was limited by the maximum rate of the pumps , a statistical analysis suggested that the sample size was sufficient to detect changes in blood pressure and HR equivalent to 20% and 35% from baseline, respectively, when the alpha = 0.05 and at 80% power.All statistical analyses were performed using a commercial statistical software . Normality of data distribution was assessed for all variables using the Anderson–Darling test. Repeated-measures 2-way ANOVA with Bonferroni post hoc comparisons were performed with the general linear model tool for normally distributed data and medians of non-normally distributed variables were compared between groups by means of Mood’s median test. Despite the small number of patients included in this study (n = 13), PLYTE (n = 9) and PLYTECA (n = 8). Age was not normally distributed (p < 0.005). Recruitment ceased once the target n = 30 was reached. Although weights were normally distributed  amongst all subjects, the mean body weight in the LRS group was significantly smaller than in the PLYTECA group (p = 0.049) (−1. The mean fluid rate administered to subjects in the LRS group (8.5 mL kg−1) was significantly greater than in the PLYTECA group (6.8 mL kg−1) (p = 0.048). No adverse effect was observed in any group as a result of the infusions.Between August 2015 and March 2016, a total of 30 adult dogs , with ages of 8 months to 8 years (median 2.5 years old), were recruited in this study and were randomly assigned to three treatment groups: LRS (= 0.049) . The meaThe MAP and HR values for all subjects at each time point during each treatment were normally distributed. The mean time to onset of hypotension occurred at 25 min (LRS), 26 min (PLYTE) and 29 min (PLYTECA).p > 0.05) (p > 0.05). Mean body temperatures were within normal limits at the start of treatment and did not differ significantly between groups . No adverse effect was observed in any group as a result of the infusions.Following the onset of hypotension, the administration of either LRS, PLYTE or PLYTECA as a rapid intravenous infusion did not result in a statistically significant change in MAP at 5, 10, 15 or 20 min ( > 0.05) . Further−1 bolus, whereas three patients in the PLYTECA group underwent similar increases in blood pressure between t = 5 min and t = 10 min. In the LRS group, only two patients had increased MAP compared to baseline values, and both occurred only at t = 20 min.Despite the lack of significant effect of treatments on MAP and HR over the treatment period, in the present study, one patient in the PLYTE, three patients in the PLYTECA and two patients in the LRS group underwent a decrease in MAP from baseline after 5 min of administration of a fluid bolus, with small and variable increases in HR. One patient in the PLYTECA group underwent a decrease in MAP between t = 5 min and t = 10 min. Four patients in the PLYTE group had increases in MAP from below to above threshold for hypotension within 5 min of administration of a 10 mL kgIn agreement with previous studies investigating the effects of isotonic crystalloid fluids in anesthetized dogs ,12,16, t−1) crystalloid solution that contains lactate as a buffer instead of acetate. Of note, in contrast with PLYTE and PLYTECA, LRS does not contain supplemental Mg2+, but instead is supplemented with 3 mEq L−1 of calcium. LRS has not been associated with the occurrence of paradoxical cardiovascular responses in dogs. Hypotension following the rapid IV administration of balanced isotonic crystalloid solutions may be explained by the ionic or buffering molecules in the solution: increases in Mg2+ can cause vasodilation as it inhibits smooth muscle contraction. Although mechanisms of Mg2+-induced vasodilation are not fully understood, it has been postulated that Mg2+ directly competes with extracellular calcium (Ca2+) signaling on the surface of vascular smooth muscle. The involvement of endothelial nitrous oxide as a result of increased ionized magnesium concentration has also been suggested [2+ administration may lead to hypotension [Anecdotally, administration of PLYTE infusions has resulted in a paradoxical response characterized by transient hypotension and tachycardia, whereas PLYTECA and LRS are not associated with this response. LRS is another isotonic . Although the experimental protocol prescribed a 10 mL kg−1 fluid infusion over 15 min, patients weighing more than 25 kg received less than 10 mL kg−1 over the 15 min period. This may account for the smaller, albeit not statistically significant, median % change in MAP between the PLYTECA group compared to the LRS group.Importantly, we detected a statistically significant difference in the weight of dogs between the LRS and the PLYTECA group. Fluid rates were calculated based on patient weights, but were also limited by the maximum fluid rate of the pumps that were used (999 mL hAlthough it was specified in the experimental protocol that inhalant levels were to be maintained at a fixed level for the duration of data acquisition, the exact levels of anesthetics required to keep the patient at an adequate plane of anesthesia may have varied considerably between subjects. Additionally, the end tidal inhalant levels were not recorded nor controlled. It is possible that the depth of anesthesia may have been a more important contributor to the continued hypotension in the subjects of this study, rather than the initiation of a rapid IV fluid infusion.Blood pressure monitoring was performed indirectly via oscillometric BP monitor. These monitors provide systolic, mean and diastolic blood pressure values by analyzing the pulse pressure oscillations through a cuff as it is occluded. Apparatus-specific algorithms were used to calculate the systolic and diastolic pressures, whereas the mean blood pressure was measured as the pressure where pulse pressure oscillations are highest. Oscillometric blood pressure monitors provide a better estimation of mean blood pressure in adult medium- to large-breed dogs under anesthesia compared to the Doppler technique . AdditioRecent evidence also suggests that blood pressure measurements are poor predictors of hemodynamic response to fluid administration . In hypoIn conclusion, the crystalloids used in the present study did not differ in their effect on BP and HR following rapid IV infusions in hypotensive anesthetized dogs. Future studies aimed at comparing different fluid therapy for inhalant anesthetic-induced hypotension in dogs would benefit from documenting continuous hemodynamic measures instead of intermittent blood pressure values.


The increasing trend of MAP in group I was not significant (p > 0.05); MAP in group II showed a gradual decrease and MAP in group III showed an increasing trend, and the difference between MAP after dialysis and before dialysis was significant (p < 0.05). Correlation analysis showed a significant positive correlation between ET-1 levels and MAP in Group III at Mid-D . This shows that serum ET-1 and NO levels are significantly higher than normal in MHD patients after arteriovenous endovascular fistula surgery, and both ET-1 and NO levels are changing during dialysis, and there may be a link between their changes and blood pressure changes. It is suggested that the blood pressure fluctuations that occur during dialysis in MHD patients may be related to endothelial cell dysfunction.Hemodialysis (HD) is the most common renal replacement therapy for patients with end-stage renal disease (ESRD) and can significantly reduce mortality and improve the quality of life of patients. The occurrence of intradialytic hypotension and intradialytic hypertension are important risk factors for death and disability during dialysis in patients with ESRD, yet their etiology remains unclear, and some studies suggest that nitric oxide (NO) and endothelin-1 (ET-1) may play an important role in these hemodynamic alterations. For this purpose we examined the changes in NO and ET-1 levels during hemodialysis in 30 patients on maintenance hemodialysis (MHD) after arteriovenous fistula surgery. Thirty dialysis patients were divided into group I , group II  and group III  according to the change of blood pressure (BP) during hemodialysis, with 10 cases in each group. BP of MHD patients were measured Pre-dialysis (Pre-D), at 1 h of dialysis (1h-D), at 2 h of dialysis , at 3 h of dialysis (3h-D), and at the end of dialysis (Post-D); and blood samples were taken from the arterial end at Pre-D, Mid-D, and Post-D to measure NO and ET-1 levels. The results of the analysis showed that as dialysis proceeded and ended, the NO levels in the three groups gradually decreased, with significant differences compared with those before dialysis ( Hemodialysis (HD) was clinically applied in the 1960s and is currently the most commonly used blood purification therapy for the treatment of end-stage renal disease (ESRD) . In receStudies , 9 have 30 patients who underwent regular hemodialysis after arteriovenous endovascular fistula in our hemodialysis center from January 2020 to December 2021 were selected. Medical history, physical examination, X-ray examination, electrocardiogram, echocardiogram, and relevant laboratory tests were taken at the time of enrollment. A mercury column sphygmomanometer was used to measure BP in the right upper arm of patients, and 30 patients with ESRD were divided into three groups according to the changes in BP during HD, with 10 patients in each group: patients with stable BP during HD were group I; patients with hypotension during HD were group II, mainly manifested by a sudden drop in systolic blood pressure (SBP) with symptoms, SBP <90 mmHg or SBP drop ≥20 mmHg, or at least 50% of the dialysis treatment process showed systolic blood pressure <90 mmHg or SBP decrease ≥20 mmHg; hypertension during HD was the Group III, which mainly showed normal blood pressure or hypertension before dialysis, but the mean arterial pressure (MAP) increased more than 15 mmHg during dialysis compared with that before dialysis.Patients with ESRD aged >18 years, dialysis age >3 months, 2–3 dialysis sessions per week, 3.5–4 h per session. Combined with sleep apnea syndrome, insulin resistance syndrome and other diseases that more significantly affect ET-1 and NO levels.Patients with tumors; patients with failed kidney transplants; patients with abnormal mental behavior; patients with 2 interruptions or transfers from dialysis treatment; patients with acute complications such as infections and bleeding.All MHD patients were dialyzed 2 to 3 times a week for 4 h each time with Baxter CTl90 dialyzer, Fresenius 4008B or 4008S dialysis machine with blood flow rate of 250 mL/min and dialysate flow rate of 500 mL/min, normal heparin anticoagulation and bicarbonate dialysis.Including age, sex, primary disease, BP, dialysis time, previous cardiovascular disease, and biochemical indexes . In ESRD patients, the age of dialysis (months), type of dialyzer used, ultrafiltration volume, BP Pre-dialysis (Pre-D), BP at l, 2, and 3 h of dialysis, and BP at the end of dialysis (Post-D) were recorded, and the brachial BP on the non-endovascular side was measured. Each measurement was taken 3 times and the mean value was taken.The blood specimens were collected at Pre-D, 2 h of dialysis  and at Post-D, respectively, by lowering the blood flow rate to 50 ml/min and taking blood specimens at the arterial end of the dialysis line after stopping ultrafiltration and ineffective dialysis for 1 to 2 min.Patients in both groups were measured by dedicated medical staff with an electronic sphygmomanometer in a lying position with the measuring arm at the same level as the heart and the sphygmomanometer. 3 groups of dialysis patients rested for 10 min before dialysis, and the blood pressure was measured Pre-D, at 1 h of dialysis (1 h-D), at 2 h-D, at 3 h of dialysis (3h-D) and at Post-D on the upper arm without fistula. MAP = (SBP - diastolic blood pressure)/3 + diastolic blood pressure.blood samples were drawn from the arterial end of HD patients at Pre-D, at Mid-D and at Post-D. The detection of NO was performed by chemiluminescence method, and the kit was purchased from Nanjing Jiancheng Institute of Biological Engineering; the detection of ET-l was performed by enzyme-linked immunoassay, and the kit was purchased from ADL, USA. The reference range of normal value of NO: (39.00 ± 11.00) μmol/L; the reference range of normal value of ET-1: (50.8 ± 7.58) pg/mL.α = 0.05 was the test level.SPSS 22.0 statistical software was used to analyze the data, Prism 7.0 was used to create the statistical graphs. Count data were expressed as rates (%) with a chi-square test. The measurement data were described as mean ± standard deviation  using t or F test. correlation between ET-1 and MAP was analyzed using pearson correlation analysis. p > 0.05) were found between group I, group II and group III in terms of general information such as gender, age, dialysis age, dry weight, water loss and primary disease   .p > 0.05). As dialysis progressed and ended, the NO levels in the three groups gradually decreased and were significantly different from those Pre-D (p < 0.05); the ET-1 levels in group III gradually increased and were significantly different from those Pre-D (p < 0.05), while the increasing trend of ET-1 levels in group I and group II was not significant (p > 0.05)  .p > 0.05). As dialysis proceeded, the increasing trend of MAP in group I was not significant (p > 0.05); MAP in group II showed a gradually decreasing trend, and the MAP Post-D was significantly lower than that Pre-D (p < 0.05); MAP in group III showed an increasing trend, and the MAP Post-D was significantly higher than that Pre-D (p < 0.05)  .r = 0.847, p = 0.002)  .With the improvement of socio-economic level and people's living conditions in China, more and more ESRD patients can choose continuous hemodialysis (MHD) as an alternative therapy. However, intradialytic hypotension and intradialytic hypertension due to fluctuations in BP during dialysis in patients with MHD are important risk factors for cardiovascular and cerebrovascular complications, morbidity and mortality, and all-cause mortality in dialysis patients , 15. RecIt is now believed that vascular endothelial injury is an important pathophysiological basis for cardiovascular disease, and in chronic kidney disease, endothelial dysfunction is often seen in the early stages of disease development, with patients commonly having abnormal endothelial function . Studiesp < 0.05), showing the same change trend as their MAP changes. The correlation analysis of MAP and ET-1 in dialysis showed a significant correlation (p < 0.05), which suggests that serum ET-1 levels may be associated with the development of hypertension in dialysis.In this study, serum NO and ET-1 levels were found to be significantly higher than normal in patients with MHD, which is consistent with many literature reports –27. MeanIn conclusion, serum ET-1 and NO levels were significantly higher than normal in MHD patients after arteriovenous fistula surgery, and both ET-1 and NO levels were changing during dialysis, and there may be a link between their changes and blood pressure changes. suggesting that the blood pressure fluctuations that occur during dialysis in MHD patients may be related to endothelial cell dysfunction. As this study was a retrospective analysis, the conclusions obtained need to be supported by prospective studies with larger samples.


Berry consumption has beneficial effects on blood pressure. Intestinal microbiota transform berry phytochemicals into more bioactive forms. Thus, we performed a systematic review of randomized clinical trials to determine whether berry polyphenols in foods, extracts or supplements have effects on both the profile of gut microbiota and systolic and diastolic blood pressure in humans. PubMed, Cochrane Library, Scopus, and CAB Abstracts (EBSCOhost) were searched for randomized clinical trials in humans published from 1 January 2011 to 29 October 2021. Search results were imported into Covidence for screening and data extraction by two blinded reviewers, who also performed bias assessment independently. The literature search identified 216 publications; after duplicates were removed, 168 publications were screened with 12 full-text publications assessed for eligibility. Ultimately three randomized clinical trials in humans met the eligibility criteria. One randomized clinical trial showed a low risk of bias while the other two randomized clinical trials included low, high or unclear risk of bias. Together the randomized clinical trials showed that berry consumption  for 8–12 weeks had no significant effect on both blood pressure and the gut microbiota. More randomized clinical trials are needed to determine the effects of berry consumption on the profile of gut microbiota and blood pressure in humans. The consumption of berry products is associated with reduced blood pressure ,2,3. ObsLarge prospective cohort studies support the association of the intake of flavonoid-rich foods such as berries and improved blood pressure. An investigation of habitual flavonoid intake in cohorts of the Nurses’ Health Study and Health Professionals Follow-Up Study found that the highest intakes of anthocyanin, primarily from berries, was associated with an 8% reduction in incident hypertension . SimilarIntervention trials have tested the impact of berry consumption on improved blood pressure and many, but not all, provide evidence suggestive of a causal relationship. A 12-week berry intervention showed significant reductions in systolic blood pressure and blood pressure variability, a predictor of coronary events , in highMechanisms explaining the beneficial effects of berry consumption on blood pressure include modulation of the activity of vasoactive molecules. Berry extracts have been shown to cause dose-dependent, nitric oxide-related vasorelaxation and protection against damage from reactive oxygen species in isolated coronary arterial rings . ImportaAs findings have accumulated on the beneficial effects of berry consumption on blood pressure, evidence increasingly supports a mediating role of the intestinal microbiota . SpecifiGiven the potentially integral role of the intestinal microbiota in mediating the impact of dietary berries on blood pressure, we performed a systematic review of randomized controlled trials examining the interplay of dietary berries, the intestinal microbiota and blood pressure. While others have recently reported on the relationship between anthocyanins and the microbiota  and berrThis review was registered on PROSPERO (CRD42020186414) on 22 November 2021. The review was conducted according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines . The seaThe searches were conducted on 29 October 2021 in the following electronic databases: PubMed, Cochrane Library, Scopus, and CAB Abstracts (EBSCOhost).https://sr-accelerator.com/#/polyglottranslate, accessed on 1 October 2021) was used to translate the searches [https://doi.org/10.11571/upei-roblib-data/researchdata:766 (accessed on 7 February 2021). The search identified human studies published from 1 January 2011 to 29 October 2021.An initial list of search terms was developed by a health sciences librarian for the 4 concepts explored in this review: (1) berries/polyphenols; (2) gut microbiota; (3) blood pressure; and (4) randomized trials. The finalized list of terms was translated to PubMed by a second health sciences librarian, including the Cochrane Collaboration’s highly sensitive filter for identifying randomised trials. Bond University’s IEBH Systematic Review Accelerator tool . Conflicts were resolved by review and discussion with all review authors. Extracted information is detailed in The assessment of risk of bias was conducting using the default assessment criteria in Covidence. This tool uses the Cochrane risk of bias domains including: sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting and other sources of bias . The iniThe literature search identified 216 publications that were imported from screening of which 48 duplicates were removed, 168 publications were screened with 156 publications determined to be irrelevant. Ultimately, 12 full-text publications were assessed for eligibility with 9 out of the 12 publications excluded primarily due to lack of dietary berry polyphenol interventions and not including primary outcome measures of the gut microbiota or blood pressure. A total of three randomized clinical trials met the eligibility criteria ,35,36. TAronia melanocarpa (black chokeberry), Fragaria ananassa, (strawberry), Rubus idaeus (raspberries), Rubus chamaemorus (cloudberries) and Vaccinium myrtillus (bilberry) with varying amounts of polyphenols. Placebo controls were used in two studies with one study providing generalized dietary advice to limit berry consumption. The duration of the study interventions ranged from 8 weeks to 12 weeks  and chlorogenic acids . Although there were no effects on blood pressure, one of the outcomes evaluated in this systematic review, both Aronia treatments (whole fruits and powder) improved vascular endothelial function, where flow-mediated dilation improved by ~1–2% [Aronia consumption has the potential to maintain cardiovascular health in healthy individuals. Furthermore, this same study found a positive correlation between Aronia-induced changes in abundance of some gut microbes  and beneficial effects of Aronia extract on flow-mediated dilation [Polyphenols have potent antioxidant, vasorelaxant, and anti-inflammatory actions. In one of the studies reviewed here , healthyby ~1–2% . A 1% imby ~1–2% . Thus, Adilation . TogetheAronia berry extract [Vaccinium myrtillus) are rich in anthocyanins and closely related to the North American blueberries (Vaccinium angustifolium) that we have studied. Our animal work shows that feeding blueberries to rats lowers systolic blood pressure [Two other studies met inclusion criteria in this systematic review ,36. They extract . Previou extract . It was pressure ,42 and 2pressure ,37. A sypressure . Some repressure , while opressure . The disParabacteroides. It is important to emphasize that large inter- and intra-individual variations exist in the human fecal microflora composition [A recent human study that evaluated the relationship between berries and both blood pressure and colonic microflora was excluded from our systematic review since it was observational in nature . Howeverposition , which iposition . Istas eposition . There wThe intestinal microbiota is investigated using a variety of approaches . AmplicoWhile berry polyphenols are well tolerated and considered safe in healthy people, contraindications to their use are important to note . PolypheThere are strengths and limitations of our systematic review. All screening, text review, data extraction, and bias assessment was completed independently by two blinded reviewers, with conflicts resolved by all authors in a process determined prior to beginning. Our conclusions are only as valid as the studies that met inclusion criteria. Any issues with the design and execution of randomized clinical trials will raise questions about the validity of the findings. One study scored consistently low in terms of risk of bias on the Cochrane scale , whereasBerry fruits are rich in flavonoids, phytochemicals that are metabolized by intestinal microbiota into more bioavailable and bioactive compounds. Diets rich in berries have been shown to lower blood pressure, benefiting CVD. This systematic review asked whether dietary berry interventions would alter both blood pressure and colonic microflora. Our results indicate that only three published randomized clinical trials addressed this question. There was no evidence that dietary berry interventions such as strawberries and bilberries benefitted both blood pressure and composition of the intestinal microbiome, although there were trends to cardioprotection in these studies. A more recent observational study evaluating human berry consumption prospectively did show a positive correlation between intake of berries, as well as flavonoids, lower blood pressure and microbiome composition. In fact, ~12% of the cardioprotection was attributed to changes in the gut microflora. We conclude that more studies are needed to answer the question, given the huge diversity of both microbes and berry flavonoids.


Chronic kidney disease (CKD) affects ~10% of the adult population . The newPreservation of kidney function can be achieved through both non-pharmacological strategies and CKD-targeted pharmacological interventions . For decLuckily, nephrology is a fast-moving science. The novel obesity and diabetes pandemic has created the conditions for rapid knowledge generation. An example of the new knowledge is offered by the new treatments of diabetic kidney disease (DKD). Until recently, prevention of DKD progression was based around strict blood pressure (BP) control, using renin–angiotensin system blockers that simultaneously reduce BP and proteinuria, adequate glycemic control and control of cardiovascular risk factors. New drugs which modify intrarenal haemodynamics (such as renin–angiotensin (RAS)–aldosterone pathway modulators and sodium–glucose cotransport inhibitors (SGLT2i)) can preserve the kidney from damage by decreasing intraglomerular pressure independently of blood pressure and glucose control, whereas other novel agents  offer kidney protection in proteinuric patients through their antifibrotic mechanisms. The new guidelines have now included as a first-line therapy the use of SGLT2i in addition to RAS inhibition, and as an additional risk-based therapy, glucagon-like peptide 1 receptor antagonists (GLP1-RA) and non-steroid MRA .In addition, a couple of years ago, the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial  demonstrWhile studying the implementation of the new guidelines, and trying to understand the new threshold for residual risk in DKD, a number of new treatments, derived from the basic research pipeline, are likely to be soon proposed. Recent progress in the understanding of mechanisms leading to CKD has shown that nephron loss is associated with inflammation, myofibroblast activation, tissue hypoxia, cell loss by apoptosis and senescence and extracellular matrix (ECM) deposition. Upregulated Nox expression and the decreased Nrf2 expression result in oxidative stress. The injured renal resident cells upregulate NLRP3 inflammasome, MAPK, PI3K/Akt and RAAS signaling and release proinflammatory chemokines to recruit immune cells such as macrophages from bone marrow which multiply the inflammatory effects. Targeting these pathways is expected to ameliorate outcomes and further extend basic and clinical investigation in CKD .N)-derived catabolic products and delay uremic symptoms and in patients with CKD. Restriction in fruits and vegetables to prevent hyperkalemia has been one of the cornerstones of CKD nutritional approach. More recently, it has become clear that targeting patients’ nutrition is a necessary approach to prevent malnutrition, CKD complications and, possibly, disease progression. Recent cohort observational studies suggest that plant-dominant low-protein (PLADO) diets offer a better approach to nutritional treatment of CKD. The benefits of PLADO include increased fibre intake with reduced production of uraemic toxins by the gut microbiota, anti-atherogenic effects, better correction of metabolic acidosis and of CKD progression, and better control of hyperphosphataemia. The current concept is that restriction of plant foods as a strategy to prevent hyperkalaemia or undernutrition needs to be individualized to offer the benefit of PLADO without incurring hyperkalemia. However, proteins contained in plants are less anabolic than animal proteins and their constituent amino acids may be in part oxidized; therefore, amino acids contained in plant proteins may not completely be used for protein synthesis. Although PLADO has a preventive effect on the associated risk factors and influences CKD progression this anabolic potential may be low if used under protein-restricted regimens [In addition to the recent breakthroughs in the treatment of disease progression, new science is being developed for the treatment of CKD complications. During its course, CKD is characterized by the progressive development of a series of complications, such as hypertension, left-ventricular hypertrophy (LVH) anemia, hyperkalemia, hypervolemia, hyperphosphatemia with mineral and bone disorders (CKD–MBD), metabolic acidosis, hyperuricemia and wasting; all of these complications have been shown to be associated with adverse outcomes, and can contribute either individually or in association to the morbidity and mortality observed in CKD. New treatments are available for many of these complications. One of the new concepts regards the importance of lifestyle modification strategies for primary and secondary CKD prevention. Maintaining a healthy body weight, physical activity, avoiding tobacco smoking, moderating alcohol consumption and healthy diets  can prevent kidney disease . Dietaryregimens ,12. TherAnother new issue is on the treatment of metabolic acidosis. Small-scale trials in patients with CKD 3–5 have shown that hypobicarbonatemic metabolic acidosis promotes progression of CKD. Accordingly, the 2012 KDIGO guideline suggests base administration to patients with CKD when serum bicarbonate concentration is <22 mEq/L. However, recent observations in eubicarbonatemic patients with CKD suggest that also in these subjects, base administration ameliorates disease progression. If proven true, such knowledge would trigger a paradigm shift in the indication for alkali therapy in CKD .Journal of Clinical Medicine Special Issue. We hope the readers will enjoy and benefit from new insight.Overall, these are only a few examples of the fast-moving issues in the treatment of CKD and of its complications. Several of the issues dealing with the prevention and treatment of CKD are addressed in this volume. We thank the MDPI staff for their leadership in producing this


To investigate the effect of valsartan combined with nifedipine controlled-release Tablets on diabetic nephropathy (DN) patients with hypertension.The clinical records of 80 DN patients with hypertension registered in our hospital from April 2020 to April 2021 were collected. The records showed that 38 patients were treated with oral nifedipine controlled-release tablets (control group) and 42 - with oral valsartan combined with nifedipine controlled-release tablets (observation group). The improvement of serological indexes after treatment was compared and analyzed between the two groups.After treatment, the levels of fasting blood glucose (FBG), systolic and diastolic blood pressure, bone oligomeric matrix protein (COMP), thrombin regulatory protein (TM) and Microalbumin (mALB) in the observation group were lower than those in the control group (P<0.05), while the level of angiopoietin-1 (Ang-1) was higher than those in the control group (P<0.05). After the treatment, the levels of homocysteine (Hcy), Cystatin C (CysC) and transforming growth factor β1(TGF-β1) in the observation group were lower than those in the control group (P<0.05). The levels of adiponectin (APN), aldosterone (ALD) and gastric growth promoting factor (ghrelin) in the observation group after the treatment were lower than those in the control group (P<0.05).A combination of valsartan and nifedipine controlled-release tablets in DN patients with hypertension can effectively control blood glucose and blood pressure, improve the serological indexes such as COMP, TM, mAlb, Ang-1, Hcy, CysC, TGF-β1, APN, ALD and ghrelin, and potentially reduce and delay renal function damage. Diabetic nephropathy (DN) is a common complication of diabetic microangiopathy, and is responsible for 44% cases of end-stage renal disease.3For the treatment of such patients, in addition to the symptomatic treatment, strict control of hypertension should be carried out, and the target blood pressure should be lower than that of non-diabetic patients .In this study, serum indicators of diabetic nephropathy such as COMP, TM, mALB, Ang-1, Hcy, CysC and TNF-β1 were used as efficacy evaluation indicators of the clinical effect of valsartan combined with nifedipine controlled release tablets in patients with DN and hypertension.Clinical records of DN patients with hypertension, treated in our hospital from April 2020 to April 2021, were collected for retrospective analysis was performed. A total of 80 patients were included in the study . Records indicated that 38 patients (control group) were treated with nifedipine controlled-release tablets , and 42 patients (observation group) were treated with a combination of valsartan  and Nifedipine controlled-release tablets .• The history of Type-II diabetes for more than 6~10 years.• Clear manifestations and indications of renal dysfunction such as proteinuria, edema and hypoproteinemia;• Diabetic retinopathy;• Stromal hyperplasia and basement membrane thickening in glomerular mesangium, and glassy lesions in the wall of vascular arterioles visible during pathological examination;• Pathological examination  showed stromal hyperplasia and basement membrane thickening in the mesangium of glomerulus, and glassy lesions in the wall of arterioles of blood vessels.The mean value of three blood pressure measurements on different days (without medication), systolic blood pressure ≥ 140mmHg, and / or diastolic blood pressure ≥ 90mmHg.• Meets the above diagnostic criteria of DN and hypertension at the same time;• Complete medical records;• Good compliance during treatment;• No mental and neurological abnormalities.• Severe dysfunction of other organs;• Diabetic ketoacidosis.• Urinary tract diseases;• Contraindications to this study;• Pregnant and lactating women;• Lost for follow-up.The medical ethics Committee of our hospital had approved this study .All the medical records included basic information of patients and the related indexes, collected on the date of admission, three months after treatment and six months after treatment. Levels of FBG, systolic blood pressure and diastolic blood pressure were measured. Levels of renal vascular-related indexes COMP, Ang-1 and TM were detected by enzyme-linked immunosorbent assay kits .The level of mALB was detected by immunoturbidimetry assay kits. Levels of Hcy, CysC and TGF-β1 were measured using automatic biochemical analyzer . Levels of APN, ALD and ghrelin were detected by respective enzyme-linked immunosorbent assay kits .SPSS 22.0 was used for data processing. T-test is performed, with [n (%)] representing non grade count data, and the test method is xx̅± s) representing the measurement data. When p<0.05, the difference was considered statistically significant.Records of a total of 80 patients met the inclusion criteria of this retrospective study. The control group (n=38) included 22 males and 16 females, with the mean age of (55.26±8.11) years, the course of DN in this group was (8.44±1.72) years. The observation group (n=42) included 24 males and 18 females, with the average age was (56.83±7.58) years, and the average course of DN of (8.59±1.46) years. There was no significant difference between the two groups in gender, age and DN course (P>0.05). The changes of blood glucose and blood pressure before and after the treatment are shown in The results of this study show that valsartan combined with nifedipine controlled-release tablets can effectively improve the relevant serological indexes of DN patients with hypertension. The pathogenesis of DN is complex and includes hemodynamic changes, metabolic disorders, inflammatory response, involvement of the kinin system and other factors. The pathological characteristics of DN are mainly renal microvascular injury, which can lead to high glomerular perfusion, increase the glomerular filtration rate, activate the renin angiotensin system, increase the blood pressure and aggravate the degree of renal injury.In agreement with these studies, our results indicated that while treatment with both regiments was associated with a significant decrease in the FBG, systolic and diastolic blood pressure, a combined treatment with valsartan and nifedipine controlled-release tablets resulted in significantly improved clinical indexes of hypertension as compared to treatment with nifedipine alone.P<0.05), and the level of Ang-1 was higher than those in the control group (P<0.05). Our results suggest, therefore, that the combination of valsartan and nifedipine controlled-release tablets in the treatment of DN with hypertension facilitates better improvement the relevant serological indexes of patients as compared to nifedipine alone. Valsartan is a kind of angiotensin receptor antagonist, which can reduce blood pressure by inhibiting vasoconstriction. Nifedipine controlled-release tablet is a calcium channel antagonist, which can reduce blood pressure by relaxing arterial smooth muscle and expanding peripheral blood vessels. The combination of the two can play a synergistic role by reducing the vasoconstriction effect of angiotensin II and ɑ1 adrenoceptor, further improving the antihypertensive effect, delaying the progress of DN, and improving serological indexes.19Numerous studies focused on identifying serological markers, such as COMP, ANG-1, Hcy, Tm, mALB, Cys C, TGF-β1, etc, that are associated with DN and hypertension. COMP is a member of the cysteine inhibition family. The study of Chen S et al.This is a retrospective study with only 80 cases included. Additionally, there is no longer-term follow-up observation in combination with clinical treatment. These factors may result in a certain subjectivity, which may make the conclusions one-sided.The treatment of DN patients with hypertension with valsartan combined with nifedipine controlled-release tablets can further improve the curative effect and promote the improvement of relevant serological indexes. This study may provide some future references for the evaluation of the therapeutic effect of different treatment regimens in DN patients with hypertension.LC: Conceived and designed the study.LC & HZ: Collected the data and performed the analysis.LC: Was involved in the writing of the manuscript and is responsible for the integrity of the study.All authors have read and approved the final manuscript.


In chronic kidney disease (CKD), like in IgA nephropathy (IgAN), cardiovascular (CV) mortality and morbidity are many times higher than in the general population, and left ventricular hypertrophy (LVH) is an independent risk factor for CV disease. This follow-up study investigated the association between left ventricular mass index (LVMI) and renal or cardiovascular outcomes.We examined 118 IgAN patients prospectively. LVMI and LV geometry was investigated using echocardiography. The primary combined endpoints were total mortality, major CV events, and end-stage renal disease. Secondary endpoints, i.e.—cardiovascular or renal endpoints,—were also examined separately.p < 0.01). We divided the patients into two groups based on the LVMI cut-off suggested by the literature. The presence of LVH caused a worse prognosis in primary (p < 0.001), renal endpoints (p = 0.01), and also in CV endpoints (p = 0.001). The higher LVMI in men significantly worsened the prognosis in all endpoints. Concentric hypertrophy meant a worse prognosis. Independent predictors of LVMI were gender and eGFR in uni- and multivariate regression and hemoglobin levels only in logistic regression. Independent predictors of the primary endpoint were LVMI, eGFR, gender, obesity, HT, DM, and metabolic syndrome in Cox regression analysis.Sixty seven percent were males, mean age 53.5 ± 13.5. Mean follow-up time: 184 months. LVMI inversely correlated with eGFR (corr. coefficient: -0.365; Increased LVMI may predict the progression to end-stage renal disease and CV events in IgAN. Determining LVMI may be a useful parameter not only in CV risk but also in the stratification of renal risk in CKD. Chronic kidney disease (CKD) is a leading risk factor for cardiovascular (CV) disease, which reduces patients' life expectancy and causes a significant financial burden . The preThe high mortality of CKD patients is primarily due to the high incidence of CV events, of which the development of LVH is a well-known risk factor . LVH is Data from a Japanese cross-sectional study (CKD-JAC) published in 2019 revealed that LVH and other risk factors  may also affect renal progression in patients with renal impairment independently from the cause of CKD , 16. RedOur study aimed to assess the prognostic significance of LVMI in IgAN. We wished to find out whether elevated LVMI was a predictor of major CV events including myocardial infarction, stroke, revascularization, cardiac death, and ESKD development, independent of other classical risk factors. Subsequently, we also wish to determine the relationship between LVMI and renal function, and the importance of LV geometry change.We prescreened 122 patients with renal biopsy confirmed IgAN, 3 patients were excluded due to corticosteroid treatment and 1 patient withdrew her informed consent because she moved to another country. We included 118 patients in the study and we analyzed their data prospectively . Patients with severe comorbidities  and treated with corticosteroids were excluded. End-stage renal disease (CKD-5) and renal replacement therapy or a history of kidney transplantation were also exclusion criteria. A 24-h blood pressure monitor was used to determine the patient’s 24-h average systolic and diastolic blood pressure, pulse pressure, and diurnal index by Meditech ABPM devices. At the start of the study, echocardiography was performed (see below). Additional CV examinations  were also performed based on individual patients’ complaints.At the start of the patient enrollment, echocardiography measurements were performed and classic CV risk factors including—hypertension, carbohydrate metabolism disorder, obesity, lipid abnormalities, smoking—and patient medication such as antihypertensive drugs , and statins were also recorded. The obesity inclusion criterion was BMI over 30 kg/m2. Metabolic syndrome was defined according to the ATP III (Adult Treatment Panel III) criteria. The CKD-EPI formula was used to estimate renal function , stroke, and renal outcomes like the development of ESKD. Subsequently, CV and renal endpoints were analyzed separately as secondary endpoints.Echocardiography was performed with Aloka SSD 1400, two operators were involved in the study. Left ventricular mass (LVM) was calculated from 2D images of the left ventricular short-axis muscle area and apical left ventricular length (LVM = (5/6 area * length)). The assessment of left ventricular mass index (LVMI g/m2) was obtained according to the formula of Devereux; the cardiac mass was indicized also with lean mass. LVMI was determined based on the Cornell criterion and indexed for height (in meters). The left ventricular ejection fraction (LVEF) was calculated by calculating the diastolic and systolic left ventricular volumes using the unidirectional Simpson method: EF = ((Dvol-Svol) / Dvol) * 100. Based on the measured LVMI and relative wall thickness (RWT) values, four different categories of the left ventricle geometry were identified: (1) normal  (N), (2) concentric remodeling  (CR), (3) eccentric hypertrophy  (EH) and (4) concentric hypertrophy (elevated LVMI and elevated RWT) (CH). Diastolic function was determined by mitral inflow and pulmonary venous flow based on conventional spectral Doppler measurements. We also measured the ratio of the E wave to the A wave (E / A ratio), the isovolumetric relaxation time (IVRT), and the deceleration time of the E wave. LVH was defined as abnormal RWT and/or LVMI.2 test for categorical variables. The relationship between two continuous variables was assessed by a bivariate correlation method (Pearson’s correlation). The LVMI influencing factors were examined by uni- and multivariate linear regression analysis. We also used logistic regression uni- and multivariate analysis to assess the associations between LVMI and other covariates. Survival was assessed with the Mantel-Cox log-rank test. The effect of factors influencing survival was analyzed with Cox regression analysis. Data analysis was performed using SPSS version 22.0 , and p < 0.05 was considered statistically significant.For statistical analysis, we divided our patients into two groups according to the LVH determined by LVMI (limits were 115 g / m2 for men and 95 g / m2 for women) which is recommended by the literature. All values are mean ± SD unless otherwise indicated. Differences between the two groups were compared by Student’s t-test and Mann–Whitney U test for continuous variables and χnd Department of Internal Medicine Nephrology and Diabetes Center of the Clinical Center at the University of Pécs, who were followed for an average of 184 ± 82 months between 2003 and 2020. The mean age of patients was 53.5 ± 13.5 years, of whom 79 were male. The majority of patients (76%) were hypertensive and 25% were diabetic. The main clinical data and the incidence of risk factors are detailed in Table We included 118 patients with IgAN at the 2p < 0.01)  considered abnormal in the literature. Clinical data of patients divided into two groups based on the presence or absence of LVH are listed in Table When we analyzed 15 parameters by logistic regression analysis: age, obesity, eGFR, hemoglobin, carbohydrate metabolism disorder, and metabolic syndrome were significant influencing factors for LVMI using logistic regression univariate analysis Table .Table 2LOnly hemoglobin level was an independent predictive factor for LVMI using logistic regression multivariate analysis Table .Table 3Lp < 0.001), renal endpoints (p = 0.01), and also in CV endpoints (p = 0.001)  Fig. . The pre01) Fig. .Fig. 3Kan = 39) compared to non-hypertrophic patients  , patients with eccentric hypertrophy (n = 13)  and concentric remodeling (n = 39)  in cases of primary combined endpoints  were baseline renal function, hypertension, carbohydrate metabolism disorder, obesity, metabolic syndrome, gender, and LVMI, but, dyslipidemia and age were not significant. Significant influencing factors for the secondary renal endpoint were LVMI and eGFR and in the case of secondary CV endpoint LVMI and diabetes—see Table In our study, we found a correlation between LVMI and renal function in a homogenous immunocomplex-mediated CKD population of IgAN patients. The baseline renal function was an independent predictor of LVMI. In the case of higher LVMI, CV and renal composite endpoints were higher.It is well known that hypertension is a major factor in the development of LVH in chronic hemodialyzed patients . HoweverEchocardiography and ECG have been used to measure LVH in patients with CKD for many years. In patients with advanced renal disease (CKD 3–4), echocardiography may overestimate LVMI due to its dependence on the intravascular volume  while ECPrevious studies have shown that LVH is more common in patients with CKD than in the general population, affecting 40–78% of patients . In addiKnown CV risk factors such as baseline eGFR, proteinuria, and hypertension are also risk factors for CKD progression, contributing to the acceleration of renal function loss and progression to ESKD. However, the progression of CKD, which is a complex process, cannot be explained in all cases by these traditional risk factors.In our study, we analyzed the associated factors of LVMI and the predictive effect of LVMI for CV and renal endpoints. Based on the correlation between LVMI and GFR in IgAN, elevated LVMI may predict the progression of renal disease and CV events, especially in men, before reaching ESKD. In our IgAN patients, we found that the increased LVMI had a significant effect on both combined and renal and CV outcomes in males. This can be partly explained by the increased incidence of male CV events in general. Male IgAN patients had worse progression for CKD, in part due to more severe CV complications as known from an earlier study published by Deng et al. .Paoletti et al. observed similar results in non-homogeneous chronic kidney patients with higher LVMI than non-diabetic CKD patients in stages 3–4. In patients with stage 1 CKD, it was proved that LVMI is a good prognostic indicator of mortality . A similBy contrast, Tripepi et al. measured the risk of death and heart failure in CKD (CRIC study) and found that LVMI alone did not provide a clear prognostic value. The discrepancy between the studies may be explained by the fact that the patients of the CRIC study were not a homogeneous CKD population and included CKD patients with different etiologies, follow-up time was shorter and the endpoints were different (only death and de novo heart failure). In our study, we examined a homogeneous patient population with IgA nephropathy , and witEckardt et al. examined the type of LVH in CKD. They found that the prognosis was the worst in those with eccentric LVH and intermediate in those with concentric LVH . PaleottWe suggest that an increased LVMI and a decreased eGFR may synergistically have an impact on the poor prognosis. Worsening renal function, higher incidence of LVH, and CV complications resulting in a worse prognosis and impaired left ventricular geometry (higher LVMI). As a result of this, LVH and impaired renal function seem to be enhancing processes for each other. But the connection between the deterioration of kidney function and LVH is not elucidated.Animal and human studies showed that elevated FGF23 levels in CKD can induce the development of LVH. It has also been confirmed that activation of local RAAS via the FGF23-mediated process promotes myocardial hypertrophy and fibrosis . So, theSome studies examined different biomarkers in the pathomechanism of LVH in CKD. Kim et al.  in CKD pIncreased RAAS activity and hypertension in CKD also increase the incidence of vascular events thus RAAS blockade is the standard treatment  in these patients in general and also for the patients who have IgAN –47. BaseIn our study, there was no significant difference in the use of a RAAS inhibitor between LVH and non-LVH patients. Based on this observation, RAAS may not be so important in the evaluation of LVH. However, it should be noted that the blood pressure of the study population was well treated. Patients with IgAN exhibiting higher LVMI had a deteriorated renal function, and increased incidence of ESKD and CV complications in both sexes, compared to those with lower myocardial mass. However, this may be particularly important, since further progression of CKD may be accelerated in older age and with impaired renal function. More complications may develop with worse CV status in these patients, which may also worsen the prognosis by creating a “vicious circle”.Nohara et al. described that in early CKD (stages 1–3) patients, LVMI, urinary protein, and Hb levels were independently associated with factors for progression to dialysis . SimilarIn the latest meta-analysis by Maki et al., it was shown that LVM change may be useful as a surrogate marker the for benefits of interventions intended to reduce mortality risk in CKD ..It is conceivable that autoimmune pathways are activated in IgAN, and low-level inflammation can also contribute to the development of LVH and the increase of LVMI, so in IgAN, not only the deterioration of kidney function can lead to the development of LVH. In addition to all this, the endothelial damaging effect of autoimmune processes can also play a role in this. The type of disease can be a predictor or an aggravating factor of LVH in certain cases. Therefore, there may be differences in the development of LVH, for example, between IgAN and polycystic kidney disease. The common point of connection may be differences in the frequency of occurrence of hypertension and subtypes of LVH (eccentric or concentric hypertrophy). Further studies are needed to find out which type of LVH means a worse prognosis for which diseaseOur results indicated that LVMI the value obtained from echocardiography has prognostic significance, however, difficulties may occur during echocardiographic measurement. In some subpopulations, specifically the elderly, a lack of cooperation can be a problem. Renal function was determined by estimating GFR, which is widely accepted in the literature. The extent and change of proteinuria were not examined in the present study. The evaluation of the results may also be weakened by the low number of cases and especially the low number of female patients. To exclude interindividual differences, in the echocardiography exam two investigators examined all patients. We did not examine the histological abnormalities underlying progression, such as microvascular damage (TMA/MA = thrombotic microangiopathy/microangiopathy) in the kidney biopsy specimens. We did not focus on the changes in the LVMI in our cohort, although it would also have been an important parameter for prognosis.Despite these limitations, the results of this study highlight that the onset of target organ damage in CKD is predicted by increased LVH.Our results suggest that LVMI assessed by echocardiography appears suitable for setting an estimated prognosis in IgAN patients, the higher LVMI could be an independent prognostic factor for ESKD and CV events. Higher LVMI should call attention to those CKD patients who have higher renal and CV risk earlier stage of CKD (II-IV) and need to be monitored more closely, referred for further CV tests, and given maximal renal and heart protection.Our findings support the role of echocardiography in the high-CV risk population of CKD patients which also helps to understand the relationship between structural heart abnormalities and renal impairment. Based on all these seems concentric LV hypertrophy should be given special attention.In conclusion, impaired renal function gradually correlates with LVH in patients with IgAN, and there is also a strong relationship between myocardial mass and eGFR. Decreased renal function is associated with increased LVMI which is responsible for a poorer prognosis due to worse CV and renal outcomes. In the background, the role of common renal and myocardial pathological remodeling could be hypothesized.To confirm our results, further large-scale, multicenter, prospective studies are warranted to evaluate the role of CV risk factors in mediating the changes of the left ventricular geometry, as well as the complex relationships between CV disease and CKD.


Despite continuous advances in surgical and immunosuppressive protocols, the long-term survival of transplanted kidneys is still far from being satisfactory. Antibody-mediated rejection, recurrent autoimmune diseases, and death with functioning graft are the most frequent causes of late-kidney allograft failure. However, in addition to these complications, a number of other non-immunologic events may impair the function of transplanted kidneys and directly or indirectly lead to their failure. In this narrative review, we will list and discuss the most important nonimmune causes of late death-censored kidney graft failure, including quality of the donated kidney, adherence to prescriptions, drug toxicities, arterial hypertension, dyslipidemia, new onset diabetes mellitus, hyperuricemia, and lifestyle of the renal transplant recipient. For each of these risk factors, we will report the etiopathogenesis and the potential consequences on graft function, keeping in mind that in many cases, two or more risk factors may negatively interact together. Today, kidney transplantation is the preferred treatment for patients with end-stage kidney disease. Declining rates of acute rejection have led to improvements in short-term kidney transplant survival, but long-term results are still far from being satisfactory. Apart from death with functioning graft, chronic antibody-mediated rejection and recurrence of autoimmune diseases are the major limits for long-term graft survival ,2,3,4,5.In this paper, we will review the most important nonimmunologic causes of death-censored kidney allograft failure.2, but in older and extended criteria donors (ECDs) the eGFR may be considerably lower. Although any functioning kidney transplant is cost-effective, compared to remaining on dialysis on a waitlist . Ne. Ne41]. An important, still unsolved issue in CNI monitoring is the relationship between current therapeutic drug monitoring based on blood levels and the intracellular concentration of CNI. CNI exert their action inside T lymphocytes. Studies show that blood levels do not reflect the intracellular concentration of CNI and may be misleading . In addiEnd-stage renal disease (ESRD) is a wasting illness and is often associated with a higher risk of cardiovascular diseases and many other comorbidities. A retrospective analysis of the United States Renal Data System Registry reported that compared to preemptive transplantation, waiting times of 0 to 6 months, 6 to 12 months, 12 to 24 months and over 24 months conferred a 17%, 37%, 55%, and 68% increase in risk, respectively, for death-censored graft loss after transplantation [antation . Poor grantation .Arterial hypertension is frequently observed in RTRs and pathogenesis is multifactorial in most cases . Many paArterial hypertension not only increases the risk for cardiovascular events but can also deteriorate kidney allograft function. Several studies have shown that the higher the levels of blood pressure are, the higher is the risk of graft failure ,58,59,60Dyslipidemia is a common complication after kidney transplantation ,64 and iNew onset diabetes after transplantation (NODAT) is a frequent complication in RTRs, due by traditional and non-traditional pro-diabetic risk factors. The traditional risk factors are the same leading to development of diabetes type 2 in the general population. Non-traditional risk factors include perioperative stress, hepatitis C infection, cytomegalovirus infection, vitamin D deficiency, hypomagnesemia, and immunosuppressive medications, such as glucocorticoids, CNI, and mTOR inhibitors. Glucocorticoids may induce insulin resistance by different mechanisms, including impaired osteoblast function with consequent increase in visceral adiposity and lipolysis, leading to elevated free fatty acids , hepaticHyperuricemia is related to cardiovascular diseases ,117 and Although mounting evidence indicate that hyperuricemia may concur with other factors in inducing kidney damages, no robust data are available to support the routine use of pharmacotherapy for RTRs with asymptomatic hyperuricemia.In transplant recipients with poor kidney allograft function, anemia is frequent. Erythropoiesis stimulating agents (ESAs) may be used in the early posttransplant period to prevent renal hypoxia or in the late period to prevent cardiovascular complications. There is no evidence that treatment with ESAs may affect kidney function in RTRs. Rather, targeting higher hemoglobin levels may reduce the progression of allograft nephropathy .Epidemiological studies documented a marked risk of irreversible proteinuria in smokers ,138. Smo0 and >900 before and after intravenous administration of 20 mg furosemide. Unexpectedly, graft perfusion values were significantly higher in flexed, compared to neutral hip position. BOLD-derived cortico-medullary R2 ratio was significantly modified during hip flexion, suggesting an intrarenal redistribution of the oxygenation in favor of the medulla and to the detriment of the cortex. Although more data are needed, the authors suggest avoiding prolonged sitting for RTRs and favor exercises without major sustained hip flexion, such as rowing, for example [A retrospective study evaluated the impact on kidney function of active physical activity  versus nonactive patients in 2060 stable RTRs aged ≥18 years, with at least a 10-year follow-up. A slower decline of eGFR over time was observed in active RTRs compared to non-active patients . It is u example .Nutrition is an important medical aspect in kidney transplantation. During the acute post-transplant phase, some patients with a long history of CKD and dialysis are generally malnourished ,152. In In the long-term, a low-salt and high-fiber diet is recommended to prevent and treat obesity, diabetes, dyslipidemia, and hypertension. The Mediterranean diet exerts beneficial effects on CVD, diabetes, obesity, metabolic syndrome, and cancer ,159,160.Any severe infection can damage the kidney graft either because of rejection due to reduced immunosuppression or because of treatment with nephrotoxic anti-infective drugs such as aminoglycosides, vancomycin, amphoterin, quinolones, anti-fungal, and anti-viral agents. Urinary tract infections (UTI) are frequent but usually respond well to antimicrobials or do not need treatment if asymptomatic. However, frequent recurrence of UTI may be associated to an increased risk of chronic rejection . UTI mayCandidosis, aspergillosis, and mucormycosis may cause severe renal disease usually in the early post-transplant period. BK polyoma virus is the most frequent cause of infective late graft failure. Infection occurs during childhood and remains latent in the tubules. In kidney transplant recipients, the reactivation of BK virus may occur. The diagnosis of BKV is made between 6 and 12 months post-transplantation, more often after treatment of rejection and in patients receiving strong immunosuppression ,165. BK In conclusion, today many kidney transplant are lost because of death with functioning graft (47%), chronic allograft nephropathy (29%), acute rejection (2.8%), hyperacute rejection (0.1%), nonlethal cardiovascular events (2%), technical complications (0.8%), recurrent glomerulonephritis (3.2%), noncompliance (2%), and other causes (11.8%) .A personalized approach to care for clinical signs leading to nonimmune kidney graft failure, including adherence to prescriptions, avoiding drug toxicities, controlling arterial hypertension, treating dyslipidaemia, caring for new onset diabetes mellitus, treating hyperuricemia, and suggesting a healthy lifestyle may contribute to prolonged renal transplant function, and give better and longer lives to transplant recipients.


R2 and P value in search of important variables for outcome prediction. The chngpt package in R indicated the threshold point of the age factor directing the better future functionality of the stroke patients. Datasets revealed the threshold of the age set at 79 the most appropriate. Admission Barthel Index, Age, ipsilateral internal carotid artery resistance index (ICA RI), ipsilateral vertebral artery (VA) PI, contralateral middle cerebral artery (MCA) stenosis, contralateral external carotid artery (ECA) RI, and in-hospital pneumonia are the significant predicting variables. The higher the age, in-hospital pneumonia, contralateral MCA stenosis, ipsilateral ICA RI and ipsilateral VA PI, the less likely patient to recover from functional deficits as the result of acute ischemic stroke; the higher the value of contralateral ECA RI and admission Barthel Index, the better chance to full functional recovery at 1-year follow up. Parameters of pre-intervention datasets could provide important information to aid first-line clinicians in decision making. Especially, in patients whose age is above 79 receives diminish return in the benefit to undergo such intervention and should be considered seriously by both the patients and the physicians.The treatment of acute ischemic stroke is heavily time-dependent, and even though, with the most efficient treatment, the long-term functional outcome is still highly variable. In this current study, the authors selected acute ischemic stroke patients who were qualified for intravenous thrombolysis with recombinant tissue plasminogen activator and followed by intra-arterial thrombectomy. With primary outcome defined by the functional level in a 1-year follow-up, we hypothesize that patients with older age are at a disadvantage in post-stroke recovery. However, an age-threshold should be determined to help clinicians in selection of patients to undergo such therapy. This is a retrospective chart review study that include 92 stroke patients in Changhua Christian hospital with a total of 68 evaluation indexes recorded. The current study utilized the forward stepwise regression model whose Adj- The treatment of acute ischemic stroke is heavily time-dependent, and even though, with the most efficient treatment, the long-term functional outcome is still highly variable. In general, there are 3 clusters of parameters that influence the treatment outcome; these are the pre-intervention baseline characteristics, such as age, sex, body weight, co-morbidities, nature of the stroke, etc; secondly, interventional methods; and lastly, post-interventional care, including method of secondary prevention, rehabilitation program and much more. Though the advent of current stroke therapy guideline abide the bridging therapy as gold standard treatment, there is still a lack of knowledge as to the suitability and long term functional assessment in terms of threshold of age.,2 Additionally, all of the patients who underwent intra-arterial thrombectomy in Changhua Christian Hospital also received carotid doppler examination as part of the protocol. This offers additional data for evaluation in this study.In this current study, the authors selected acute ischemic stroke patients who were qualified for intravenous thrombolysis with recombinant tissue plasminogen activator and followed by intra-arterial thrombectomy, following the 2018 American Heart and Stroke Association’s guidelines.The primary goal of this study was to investigate whether pre-thrombectomy treatment parameters and baseline characteristics can offer valuable information in predicting patients’ long-term functional outcomes in acute ischemic stroke patients who underwent intravenous thrombolysis followed by intra-arterial thrombectomy. Secondly, we attempt to finalize the age threshold as to stroke bridging therapy, which allowing clinicians to better select the appropriate candidate embracing favorable outcomes.In this current study, all patients were selected from Changhua Christian Hospital with a retrospective chart review conducted by the Department of Neurology. Participants were selected based on the confirmed diagnosis of first acute ischemic stroke and underwent intravenous thrombolysis therapy with recombinant tissue plasminogen activator (rtPA), followed by intra-arterial thrombectomy. Patients were selected based on the current indication for intravenous thrombolysis of presenting within 4.5 hours of the onset of symptoms and did not have any contraindications to receive rtPA. CT angiography perfusion scan was followed in these patients to screen for candidates to receive intra-arterial thrombectomy.Additional inclusion criteria are neuroimaging confirmed anterior circulation obstruction, above 18 of age, non-recurrent stroke was documented of and were followed for at least 1 year. Patients with intracerebral hemorrhage, aneurysm rupture, cerebral arteriovenous malformation, and recurrent stroke were excluded. Initially, there are 200 patients fitted in to the inclusion and exclusion criteria. With 50 patients lost follow-ups, 49 patients mortality due to the internal medicine diseases, and, 9 patients’ dropped out of the study due to recurrent stroke episode, that lead to the total 92 patients was selected fulfilling the study protocol the year of between 2015 and 2017 . Informed consent was obtained in the usual way as the procedures were the usual standard of care. As the study is retrospective in nature, the informed consent was waived and approved by the committee. The stored patients’ information was well stored at the Basement 2 of Department of neuroimaging. Locker room, which was in charge by Dr Chi-Kuang Liu.All patients were evaluated for adequacy of thrombolytic therapy (rtPA) at the ED by the in-charge physician (The window of time for the rtPA was set at ≦ 4.5 hours from symptom onset) A thorough evaluation of every single patient was carried out before the administration of r-tPA, including neuroimaging, and the patient’s stroke severity was recorded using the NIHSS score. Shortly after the r-tPA, the patient’s baseline specific aspects were documented, together with the demographic information, NIHSS score, Barthel index, mRS, and blood biochemistry.The indications for IAT were findings of major artery stenosis  with a suitable access location in order for the procedure to be carried out, that is, terminal intracranial ICA, and the first or second branch of the MCA. The IAT procedure was performed with informed consent from the patient or family. One 8F right femoral sheath was inserted and 1 6F Neuro Max long sheath was advanced up to the stenotic site, then 1 3Max Penumbra aspiration reperfusion catheter was inserted coaxially via the guiding catheter and navigated to the proximal part of the occluded MCA to remove the thrombus.A post-procedural immediate outcome was evaluated by a neuroradiologist (Dr Chi Kuang Liu) using the modified thrombolysis in cerebral infarction (mTICI) score. The TICI score was defined as the following: 0 = no perfusion; 1 = penetration, but no distal branch filling; 2a = perfusion with incomplete (<50%) distal branch filling; 2b = perfusion with incomplete (>50%) distal branch filling; and 3 = full reperfusion with filling of all distal branches. A satisfactory result was defined as a TICI score of 2b or 3. Whenever there was a disagreement between the physicians, a third physician would make the final assessment. The intima-media thickness of the mid-portion of the common carotid artery was measured on the ipsilateral side of the index stroke event. The parameters of peak systolic velocity (PSV), end diastolic velocity (EDV), resistance index (RI)  and pulsatility index (PI)  of the common carotid artery, ICA, ECA, VA, and OA were measured bilaterally. The reversal of blood flow in the OA was also measured. Forward flow was defined as blood flow detected out of the stenotic ipsilateral carotid artery, whereas reverse flow was defined as blood flow into the carotid artery.,6 The machine Philips iE33 7 automatically calculated the plaque index on both the ipsilateral and contralateral sides of the cerebral lesion. The approximate time of assessing the extracranial artery blood flows by carotid duplex was 30 minutes.All procedures were conducted by a stoke neurologist team in a specialized angiography clinic at the Changhua Christian Hospital, Taiwan. Cervical carotid artery ultrasound examination (Philips iE33 7-Mhz linear transducer) was performed upon the patient once upon arriving at the emergency room. Cross-sectional B-mode scanning was performed to check for intraluminal plaque material and the longitudinal screening method was adopted to confirm the presence of plaque. Two physicians assessed and classified plaques into subtypes 1, 2, 3, or 4 according to the International Classification System.CTA examinations were performed using a second-generation dual-source CT scanner . Perfusion data sets were post-processed on a Siemens Multimodality Workplace Workstation , yielding mean transit time (MTT), cerebral blood volume (CBV), cerebral blood flow (CBF), and time to peak (TTP) maps. In addition, the CT stroke protocol was performed on a dual source CT scanner (Siemens Definition Flash). Pre- and post-contrast CT scans of the head were performed with the following parameters: 120 kilovolts (peak) (kVp), 220 mA (auto), 64_0.6 mm collimation, 0.28 s/rotation, and table speed of 1 mm/rotation. CT angiography was performed from the aortic arch to the vertex with the following parameters: total 60 cc of iodinated contrast agent was injected at 5 mL/s , 5- to 10-seconddelay, 100/140kVp, auto mA, 0.28 s/rotation, 0.6-mm-thicksections, and table speed of 4 cm/rotation. CTA data were automatically processed by the technicians, including multiplanar 5 mm maximum intensity projection reconstructions and 5-mm axial reformates or CTA source images. The CTP technique included 45-second scanning reconstructed at 0.5-second intervals to produce a series of 90 sequential images for each of the 8 sections, covering a total of 40mm from the basal ganglia to the lateral ventricles. CTP scanning parameters were the following: 80 kVp, 150 mA, total 50 cc iodinated contrast agent injected at the rate of 5 mL/s.Primary outcome in this study was to identify any significant change in the functionality of patients who underwent treatment, which is done by assessment of NIHSS score, mRS score, and Barthel index both upon admission to the hospital and at 1-year (12 months) follow- ups. The regular followed at the outpatient settings were also documented 3, 6, 12 months post treatment. Additionally, using statistical methods, described in the following section, to determine whether any of the pre-intervention variables have a significant impact on the functional outcome.http://links.lww.com/MD/H383) were recorded. Authors use principal component analysis (PCA) to integrate the prognostic variables into an aggregative index, prognosis, which is an index that takes into account all 4 outcome variables and their contribution to the overall outcome. Then using the forward stepwise regression model to determine which, if any, of the 68 independent variables had a significant effect on the prognosis. Authors end up with only eleven variables and only 7 of which had statistically significance.Data was collected from 92 stroke patients with a total of 68 independent pre-interventional indexes and 4 outcome variables .To facilitate the analysis, the data is first divided into pre-interventional and outcome variable, which are classified into categories, orders, and continuations. The outcome variables include the following: Follow up CT cerebral bleeding, outpatient recorded NIHSS, outpatient recorded mRS, outpatient recorded Barthel Index, and the remaining 68 variables are classified as pre-interventional independent variables  to integrate the outcome variables into an aggregative index, prognosis. According to equation , each principal component recombines the original variables into a new set of several independent variables. The coefficient of XIn the current study, prognosis is an outcome variable that is influenced by the need of follow up cerebral CT in case of suspected intracranial bleed, the NIHSS score, mRS score, and Barthel index. The relationship is shown in the below equation (2):The exploratory data analysis section was performed with the ggplot2 package in R. Authors describe the statistics of variables in order to understand the simple information of the data.Multiple regression model The equation (3) was shown below.Multiple regression is to explore the correlation between the independent variable and the dependent variable and to build a regression model.R2 being only 0.3106, the model has a relatively low explanatory power. In order to improve the model, forward stepwise regression model is then used.In our research, authors regarded all variables in pre-intervention as independent variables, and prognosis as a dependent variable, and built a multiple regression model. Authors find that only a few variables are significant, however, with Adj-2. Forward stepwise regression model,8 AIC is a standard for assessing the complexity of statistical models and measuring the superiority of statistical model fit the data. The model with the lowest AIC value should be given priority when selecting the model. This is done by adding the independent variables one by one until the additional contribution of any one of the variables does not provide any statistical significance. Finally, the authors identified eleven variables with only 7 of them are significant .nt Table . This me3. Segmented linear regression That is, there are different relationships between the variables in these regions. The following equation (4) is a threshold equation model:Segmented linear regression is a method when the independent variables clustered into different groups.In this equation “e” is the threshold parameter, and “x” is the predictor with threshold effect, “z” denotes additional predictors.Authors estimate a segmented linear regression model to determine if there is a threshold for independent variable age that would mark as a boundary for poor prognosis with statistical significance. The package authors utilized is chngpt package in R and uses the formula built in forward stepwise regression.Table The patients’ Barthel Index on admission is averaged to a value of 13.42 . This suggested that patients who presented with acute ischemic stroke were already disabled upon admission. The patients’ average age is 65, the youngest patient is 25, and the oldest patient is 88. It showed the majority of patients who suffered from stroke are elderly patients. The average value of ipsilateral internal carotid artery resistance index (ICA RI) is 0.7259, with a minimum value of 0.5100, and a maximum value of 1.7700. The average value of ipsilateral vertebral artery (VA) RI is 0.7815, with a minimum value of 0.5300, and a maximum value of 1.0000. The average value of contralateral external carotid artery (ECA) RI is 0.9466, with a minimum value of 0.7400, and a maximum value of 2.3100. This indicates that stroke was more likely to occur in a person with high arterial stagnation. The average value of contralateral middle cerebral artery (MCA) stenosis CTA is 0.3216, with a minimum value of 0.0000, and a maximum value of 1.0000. The average value of in-hospital pneumonia is 8.413, with a minimum value of 5.0000, and a maximum value of 10.0000.Furthermore, admission Barthel Index, age, ipsilateral ICA RI, ipsilateral VA PI, contralateral ECA RI, contralateral MCA stenosis on computed tomography angiography (CTA), and in-hospital pneumonia are the most significant variables based on the dataset analysis Table .R2 of original model is 0.3106 and the P value of original model is .07819. The Adj-R2 of forward stepwise model is 0.4588 and the P value of forward stepwise model is 3.137e−09. The result showed that the forward stepwise model is superior to the original model.Table P value = .00212), age , ipsilateral ICA RI , ipsilateral VA PI , contralateral MCA stenosis CTA , contralateral ECA RI  and in-hospital pneumonia  are the significant variables.In Table Using the aforementioned equations (2) and (3), shown once again below. If the age is increased by 1 year, the prognosis value will increase by 0.017807, from equation (3). Then setting equation (2) is equal to equation (3), authors inferred that patients with older age were more likely to receive a followed- up CT of the head due to potential intracranial bleeding, a higher NIHSS and mRS scores, and lower Barthel Index score upon discharge. Using the same logic hypothesis, the authors arrive at the same conclusion with other variables such as ipsilateral ICA RI, Ipsi VA PI, contralateral MCA stenosis CTA, and in-hospital pneumonia.Prognosis = 0.218(Followed-up CT) + 0.566(NIHSS) + 0.528(mRS) - 0.595(B.I)Prognosis = −0.026867(admission Barthel Index) + 0.017807(Age) + 2.493430(Ipsi ICA RI) + 0.214155(Ipsi VA PI) + 0.546799 - 1.148134(Contra ECA RI) - 0.437726(Stroke right left) + 0.561732 - 0.449998  + 0.006712(CTP mismatch) + 0.140513(Admission CT The Alberta stroke programme early CT score)On the contrary, if the value of contralateral ECA RI rises by value of one, the prognosis will decrease by 1.148134. That hints as below, the higher the value of contralateral ECA RI, the less chance having follow- up CT cerebral bleeding, and the better opportunity to full functional recovery. Other variables, admission Barthel index and magnetic resonance arteriography ipsilateral collateral flows values, show similar trends as above.Figure P value = .008757).According to the result of the segmented linear regression, the authors made the age beyond 79 as 1, and below 79 as 0, and conduct a simple linear regression to determine if there is a statistical difference between the 2 samples. The result is shown in Table The current study demonstrated the higher the age, the less likely a stroke patient might recover from receiving treatment with intravenous thrombolysis followed by intra-arterial thrombectomy. This finding is especially resourceful for first-line clinicians in selecting candidate patients whom to receive such treatment and as a predictive tool to weigh out the benefit and risk. We believe this is the first paper that pinpointed the age threshold as an important indicator of functional outcome in acute ischemic stroke patients underwent such treatment.,10 As most of the collected patients more or less had the tandem stenosis both/or intra-cranially, the presence of the patent of the posterior vasculature stands as an important compensatory collateral flows that can minimize the stroke severity or post bridging therapy induced cerebral hemorrhagic or ischemic eventsAs far as pre-intervention carotid doppler parameters, the higher the ipsilateral vertebral artery resistance index, which indicates compromised blood flow starting at the inlet of posterior circulation, therefore in the event of acute ischemic stroke of the anterior circulation, there are less available blood flow to rescue the ischemic brain cells and leading to higher risk of functional disability in such selected patients.Interestingly, the current study showed that the higher the value of contralateral external carotid artery resistance index leads to a better functional outcome in ischemic stroke patients. We hypothesize that impaired contralateral blood flow re-directs blood flow toward the opposite side, which is the ischemic hemisphere, that is sufficient to prevent the progression of the disease and is meaningful in predicting the long-term functional outcome in patients.R2 of the forward stepwise regression is only 0.4588, and the Adj-R2 of the simple linear regression is only 0.06361, which both can be attributed to the relatively small sample size (N = 92), therefore, the model had low explanatory power. It would increase our confidence in our observation if future studies with larger sample size and still showed similar trends.The authors used different statistical analysis methods to identify specific variables and whether each had a significant impact on the overall prognosis. However, the Adj-The statistical analysis method we used was all supposed that there were linear relation between outcome variables and pre-interventional variables, therefore, authors use multiple linear regression and segmented regression as study models. However, it might be nonlinear relationship between 2 variables, and this should be considered in future studies to tailor consistency between the model and the real-world situation.Based on the current literature, the golden stroke treatment strategy remains the intravenous thrombolytic bridging with intra-arterial thrombectomy. However, no all of the medical facility, in particular the rural areas around the world, could be under great medical insufficiency due to either lack of medical man power or surgery technical training. The cut off point for this group of stroke patient are still treated with empirical experiences and their long-term outcome is yet to be thoroughly investigated. Though 65-year-old, in general has been recognized a cutoff point age that could differentiate between younger or elder age group, the treatment long term outcome could not be applied successfully on the stroke patients receiving bridging therapy. There exists a gap between real world reality and textbook statics information.A major strength of this study is low heterogeneity among participants, given that most patients came from the surrounding local communities and shared the same ethnic group. Other strengths were technical consistency, as the same technician performed all of the carotid duplex scans, and the ability to compare each patient’s functional scores 1 year after the treatment allowed adequate time to also observe functional improvement. However, this could also potentially introduce confounding factors, such as different types of rehabilitation programs that participants may have attended within the year. The major shortcoming of the current study is of relatively small sample size (N = 92) as well as the fact there was no placebo group for comparison. Besides, the homogeneity in the ethnic group might not be able to represent other ethnic groups and therefore the general application can be limited in such regard.Our current study shows several highlights listed as bellows, the higher the age, in-hospital pneumonia, contralateral middle cerebral artery stenosis on computed tomographic arteriography, ipsilateral internal carotid artery resistance index and ipsilateral vertebral artery pulsatility index, are correlated with higher risk of functional disability, whereas higher the value of contralateral external; carotid artery resistance index and Barthel Index on admission showed relative better likelihood in improving functional outcome in the long-term in acute ischemic stroke patients who underwent intravenous thrombolysis followed by intra-arterial thrombectomy (bridging therapy).Pre-intervention parameters can potentially serve as important indicators to aid first-line clinicians in decision making. Especially, in patients whose age is above 79 receive diminished return in the benefit to undergo such intervention and should be considered seriously by both the patients and the physicians.This work was supported in part by the National Science and Technology Council, Taiwan, R.O.C., under Grant no. MOST 110-2118-M-A49-002-MY3 and MOST-110-2634-F-A49-005, in part by the Higher Education Sprout Project of the National Yang Ming Chiao Tung University and Ministry of Education, Taiwan, R.O.C., and in part by Ministry of Education Yushan Scholar Program, Taiwan, R.O.C. We are grateful to the National Center for High-performance Computing for computer time and facilities. Our team would like to thank Ms Giulia Mengato for her proofreading.The authors have no conflicts of interest to disclose.Writing – review & editing: Yang-Hao Ou and Chih Ming Lin