To investigate the possible risk factors for treatment failure in patients who had undergone Preserflo Microshunt (PMS) implantation, using anterior-segment optical coherence tomography (AS-OCT) to analyze the internal structures of the bleb.The PMS blebs of 54 patients were evaluated with AS-OCT. A mathematical model was used to calculate the total filtering surface of the episcleral fluid cavity (EFC) and the hydraulic conductivity (HC) of the bleb wall. Complete and qualified success were defined as IOP between 6 and 17 mmHg with or without glaucoma medication. The relation between baseline characteristics and probability of bleb success was analyzed by bivariate and multivariate logistic regression. The main outcome measures were mean bleb wall thickness (BWT), reflectivity (BWR), HC, mean horizontal and vertical diameter and total filtering surface (TFS) of the EFC.2/mmHg, was negatively correlated with bleb surface  and wall´s thickness .Blebs from 74% patients were considered as complete success and 26% as failure. BWR and BWT increased linearly up to the first year in both groups. BWR was higher in the group failure (p = 0.02) and BWT in the group success (p<0.001). EFC was wider and shorter in the success group . Higher TFS showed a negative correlation with IOP . Higher baseline IOP was associated with success of PMS by multivariate analysis (p = 0.01). Mean HC, 0.034 ± 0.008 (μL/min)/mmAS-OCT revealed that successful PMS blebs could show either thick hyporreflective walls or wide filtering surfaces with thin capsules. A higher baseline IOP increased the probability of surgical success. The Preserflo MicroShunt  belongs to a group of relatively new microtube shunts without an end plate designed to restrict the outflow due to a reduction in the luminal diameter . The pre3 has been increased by 3 orders of magnitude in comparison to that with traditional tube shunts (P = 0.008 mmHg) . Both eyes could be included with a one-month interval between surgeries for uncomplicated cases. Although patients with previous failed minimally invasive glaucoma surgery (MIGS) can be recruited, none of them had other types of MIGS implantation before their inclusion in the study. Exclusion criteria were angle closure, congenital and neovascular glaucoma. Eyes with a history of previous filtering surgery (TB) were included when no sign of filtration was present at the slit lamp  and by AS-OCT . In these cases, the PMS was implanted avoiding the previous filtration site. PMSs located inferiorly were also excluded from the study. Three patients were excluded from the study due to loss of follow up before the first year.Preoperative baseline characteristics included sex, age, slit-lamp biomicroscopy, number of glaucoma medications, IOP measurement using Goldmann applanation tonometry, gonioscopy, central corneal thickness using ultrasound pachymetry , dilated fundus examination, visual field analysis , visual acuity , glaucoma type, previous glaucoma surgery (type and number) and lens status.Postoperative evaluation was performed at 24 hours, one week, one month, 3 and 6 months and one year. Data included in the study from bleb evaluation was collected at one month, 6 months and one year and will be explained in a separate section. IOP was measured at every visit and the number of glaucoma medications was collected at 6 and 12 months. The mean number of needling and/or surgical revisions were reported by the end of the follow-up period (one year).Definition of surgical success: IOP from 6 to 17 mmHg and ≥ 20% reduction from baseline, without medication (complete success) or with medication . Loss of light perception or any other serious adverse event  was considered complete failure and the patient was withdrawn from the study. Surgical revision or needling were not considered as a reason to be withdrawn from the study. All surgical revisions were performed with the use of a biodegradable collagen matrix  and mitomycin C 0.2 mg/ml.https://journals.lww.com/glaucomajournal/Fulltext/2021/10000/Changes_to_Corneal_Topography_and_Biometrics_After.8.aspx.The surgical technique has been previously reported by our group at : https:/AS-OCT was performed in all patients using the “Cross Line” imaging method included in the software of the Avanti Widefield OCT .Bleb wall´s reflectivity: Multilayer: “High”, “medium”, “low” and “very low”. Microcysts: “none or few” vs. “many”. Type of EFC: Grades 0, 1, 2, 3 and 4.2) at a unit pressure gradient (mmHg). The flow rate through PMS (Q) has been shown to be a linear function of pressure [Tubular flow (Q) and IOP [Calculation of the HC of the bleb wall: At 6 months and 1 year (once the maturation process of the bleb was completed), the flow though PMS (Q) was calculated using the IOP of each patient as explained above. The calculation of Q was necessary to calculate the HC, as well as the calculation of the total filtering surface with the “spherical cap” formula, detailed above (2) / IOP (mmHg).The HC is a physical characteristic of the bleb wall, defined by Parker  as the fpressure  and can pressure . Tubular and IOP : Flow thed above . HC = Q ® .A cross-sectional analysis was performed to analyze the relation between a total of 15 independent variables and two dichotomic variables named “complete success” and “qualified success”. The independent nominal variables were sex, laterality, pseudoexfoliation, combined phaco-PMS surgery, and bleb wall´s reflectivity (microcysts). The ordinal variables were bleb wall´s reflectivity (multilayer) and EFC. Numerical variables were number of preoperative and postoperative glaucoma medications, baseline IOP, IOP at one week, 1 month, 6 months and one year, bleb wall´s thickness, EFC diameter and height, total height , total filtering surface and HC of the bleb. Nominal variables were analyzed by the Chi Squared test and Fisher´s exact test, while ordinal and numerical variables were analyzed by paired sample t test and Wilcoxon signed-rank test when the variables did not follow a normal distribution. The SAS software, version 9.4  was used for the analysis. Boxplots, bar graphs and dot plots from the univariate analysis of the variables was performed with Stata 17All the variables included in the multivariate analysis that were statistically significant based on a p < 0.05 level were included in the Logistic Regression Model to assess the prognostic factors for bleb success. The model used the stepwise method. Inclusion criteria was set at α ≤ 0.15 and elimination criteria was β ≥ 0.05. The analysis was performed 6 and 12 months after surgery. The SAS software mentioned previously for the bivariate analysis was used to build the logistic regression model. The variables included in the model are available at The PMS was implanted in 54 eyes of 51 patients who were followed up for one year. Baseline characteristics of the study population, divided by the main groups of overall success versus failure, are shown in No statistically significant differences were found between groups except for the baseline IOP, that was significantly higher in the complete success group . The groups of combined vs. non-combined surgery showed comparable rates of complete success (p = 0.93). The main type of glaucoma in the study population was primary open angle glaucoma , 3 patients had pseudoexfoliative glaucoma and were analyzed together with POAG patients.Mean (± SD) IOP (mmHg) decreased significantly from 21.1 ± 6.5 at baseline to 12.03 ± 0.4 at the final follow up visit (p<0.001). Similarly, the number of IOP-lowering medications decreased significantly from 2.7 ± 0.7 at baseline to 0.18 ± 0.5 at 1 year (p<0.001). Compared to baseline values, the overall mean IOP decreased by 43.1% and 42.6% at postoperative month 6 and 12. The overall rate of complete and qualified success at 6 months and one year was 79.6% / 7.4% and 74% / 7.4% respectively. Bleb failure was observed in 12.9% of the patients at 6 months and 18.5% at one year. Bleb fibrosis was managed by surgical revision using a biodegradable collagen matrix  and MMC 0.2 mg/ml applied with sponges for 2 minutes , p = 0.04; 0.04 ± 0.06, 0.03 ± 0.06 (μL/min)/mm2/mmHg, P = 0.27 No significant correlations could be found between age, gender, pseudoexfoliation, combined surgery, central corneal thickness, baseline mean number of glaucoma medications, MD and VFI with surgical success and mean IOP at 6 months and 1 year. The percentage of patients that underwent surgical revision among those who were on 1 glaucoma medication prior to surgery was 0% vs. 20% among those who were on 2 or more glaucoma medications.One year after surgery, thicker bleb walls were less reflective, . The bivariate analysis between IOP and bleb wall´s thickness showed a negative and significant correlation , while the mean IOP was significantly higher in the group with higher reflectivity of the bleb wall . The total filtering surface and the IOP showed a negative and significant correlation at 6 months  and one year . At 6 months and one year, the mean IOP was significantly lower in patients with EFCs grade 2–4 compared to 0–1 . One year after surgery, blebs grade = 0 showed higher IOPs than the other bleb types (16 ± 0.5 mmHg vs. 11.6 ± 0.3 mmHg (p = 0.001). Blebs that grade 0–1 at month 1 showed significantly higher mean IOPs at one year (14 ± 1.2 mmHg) than blebs grade 2–3 (11.6 ± 0.6 mmHg), p = 0.04. Blebs with higher filtering surfaces showed lower hydraulic conductivities . A higher baseline IOP and a lower IOP at 1 year increased the probability of complete surgical success  The AS-OCT analysis of the bleb morphology in patients who had undergone PMS implantation with adjunctive MMC 0.2 mg/ml showed specific quantitative and qualitative features of the wall and EFC, most likely related to the design, composition, restriction to flow and IOP curve reported for this device , 6. One The thickness of the bleb wall increased linearly over the course of the study, showing a negative correlation with the IOP , comparable to previous reports about TB . Unlike A combination of different factors explains the variety of functioning blebs observed with the PMS . These i2- Baerveldt implant. Only lower preoperative IOP was significantly associated with treatment failure in univariable and multivariable analyses [Baseline demographics and clinical factors were analyzed as possible risk factors for surgical failure. Only a higher baseline IOP increased the probability of success in the multivariate analysis, probably due to a higher presence of aqueous that separates the tissues and increases the area of filtration. Gedde et al., in a recent publication about the treatment outcomes in the Primary Tube vs. Trabeculectomy study after 5 years of follow up reported similar results with the 350 mmanalyses . A risk analyses . CombineThe absence of a plate at the end of the tube might seem like a step backward in history. Epstein back in 1958 developed probably the first tube-shunt, a tube without an end-plate that was unfortunately doomed to fibrosis . Fortuna2 vs. 44.7 mm2 PMS). In that respect, the PMS bleb would resemble TB more than tube-shunts, showing both of them a higher hydraulic conductivity of the bleb wall to compensate for the reduction of the filtering surface. In the case of PMS, (there is no data about the HC of TB), the HC is 2 orders of magnitude greater through the PMS bleb wall than through the Baerveldt capsule (0.02 vs. 0.0003 (μL/min)/mm2/mmHg) [According to our results, the size of the PMS bleb is comparable to TB  , but is m2/mmHg)  and compm2/mmHg) . Wilcox One of the limitations of this study is the concentration of MMC used in this group of patients (0.2 mg/ml). Even though there is still not enough clinical evidence to recommend the use of a higher concentration of MMC, some studies have shown a trend toward a higher probability of surgical success with 0.4 mg/ml .In conclusion, we have demonstrated that PMS works through a hybrid mechanism of action between trabeculectomy and tube-shunts that opens up the possibility to reconsider its actual position in the glaucoma filtering surgery spectrum, too close to trabeculectomy. Further clinical investigations about the safety and efficacy of this device compared to traditional tube-shunts, will elucidate its real utility and cost-effectiveness, since recently published studies have shown opposite cost-effectiveness results of Preserflo vs. trabeculectomy in the US Medicare system and the UK National Health Service , 30.


AKI risk (AKIRisk-Index) was calculated from urine samples at 5 timepoints: baseline, immediately postoperatively and at 12, 24, 48, and 72 h post-surgery. AKIs were classified according to the KDIGO criteria. Contributing factors were identified in univariable and multivariable logistic regression. Predictive ability was assessed with the area under the receiver operator curve (ROCAUC). Among 31 patients (68.8%) that developed AKIs, 21 (44.9%) developed stage-3 AKIs, which required dialysis. AKIs were correlated with increased in-hospital mortality (p = .006), respiratory complications (p < .001), sepsis (p < .001), and multi-organ dysfunction syndrome (p < .001). The AKIRisk-Index showed reliable diagnostic accuracy starting at 24 h post-surgery . In conclusion, starting at 24 h after open aortic repair, the NephroCheck system showed adequate diagnostic accuracy for detecting the patients at risk for stage 3 AKIs.Acute kidney injury (AKI) is a common complication after complex aortic procedures and it is associated with relevant mortality and morbidity. Biomarkers for early and specific AKI detection are lacking. The aim of this work is to investigate the reliability of the NephroCheck bedside system for diagnosing stage 3 AKI following open aortic surgery. In this prospective, multicenter, observational study,— In short- and mid-term follow ups, AKIs are directly related to a poor outcome and reduced survival3. In the context of major surgery, the timely detection of an adverse outcome, like an AKI, enables the immediate initiation of specific treatment bundles. In clinical practise, an AKI diagnosis is based on patient urine output and serum creatinine levels. This established biomarker is disputed, due to its delayed increase, its non-specificity, and its low sensitivity4. However, over the years, the combination of two markers, tissue inhibitor of metalloproteinases 2 (TIMP2) and insulin-like growth factor-binding protein 7 (IGFBP7), has gained clinical acceptance for the early detection of AKIs. Currently, these markers are available as a bedside-testing kit, called NephroCheck6. This study aimed to assess the NephroCheck system for its ability to detect AKIs in fields of open aortic surgery.Acute kidney injury is an underestimated issue that occurs in a relevant proportion of patients that undergo open elective and emergency thoracoabdominal aortic repairThis prospective, multicentric, observational trial was reviewed and authorized by the Ethics Committees of three participating centres: University Hospital Aachen (EK010/19), Charité—University Hospital Berlin, and University Hospital Münster (2019-559-b-S). The study was registered at clinicaltrials.gov with the number NCT04087161. Written informed consent was obtained from all included patients, and the study was conducted in accordance with the Declaration of Helsinki and the STROBE criteria.7 and given a prevalence of 29% for postoperative AKI in TAAA patients8. The cohort of this study included 45 patients that were scheduled for aortic procedures that required suprarenal cross-clamping, from January 2019 to December 2021. Exclusion criteria were: age under 18 years, pregnancy, and terminal chronic kidney disease that required dialysis. Data were retrieved on demographic characteristics, comorbidities, and laboratory parameters from digitally maintained medical records.The minimum sample size for a power of 80% was calculated to be n = 29, taking into account the values for sensitivity and specificity of the test reported in a cohort of patients undergoing cardiac surgery 9. The protective measures to reduce organ ischemia include distal aortic perfusion with extracorporeal circulation, selective perfusion of the visceral arteries and renal perfusion with maximum 1 L 4 °C Custodiol  for both kidneys along with mild systemic hypothermia (32–33 °C). The mean arterial pressure was kept at 90 mmHg during the procedure. The use of a cerebrospinal fluid drainage and the peri-operative monitoring of motor evoked potentials are implemented routinely to attenuate neurological complications and spinal cord ischemia. Postoperatively, all patients were administered unfractionated heparin for anticoagulation. Patients requiring therapeutic dosing maintained a partial thromboplastin time range of 50–60 s, while the remaining individuals in the cohort received a daily dosage of 15,000 IU of unfractionated heparin. Furthermore, volume management during the initial postoperative phase involved the use of invasive hemodynamic monitoring. The goal during this period was to maintain a positive fluid balance. However, in cases where fluid overload and/or oliguria occurred, deresuscitation was implemented. This involved administering a maximum daily dose of 80 mg of furosemide to address the excessive fluid burden.The standardized, surgical protocol for open reconstruction of the thoracoabdominal aorta has been previously described in the literature2. The physicians involved in patients’ care were not aware of the results.Urine samples were aspirated from each patient’s urine catheter at 6 time points: preoperatively, immediately postoperatively, and at 12, 24, 48, and 72 h postoperatively. The samples were immediately centrifuged , and the supernatants were shock-frozen at − 80 °C. The NephroCheck system was applied, according to the manufacturer’s recommendations, to measure the concentrations of TIMP2 and IGFBP7. Then, the product of the concentrations of both proteins was calculated as AKIRisk Index, as follows: [TIMP2 × IGFBP7]/1000 (mg/L)+ > 6.5 mmol/L), severe metabolic acidosis (pH ≤ 7.2) and refractory volume overload10. The patients fulfilling these criteria received continuous veno-venous hemodialysis and are further referred to as the Stage 3 AKI group.The primary endpoint of this study was the association of AKIRisk-Index with the onset of AKIs requiring dialysis (AKI stage 3 of the KDIGO classification) after open aortic surgery. Indicators for continuous renal replacement therapy were: anuria, severe hyperkaliaemia  was diagnosed in patients with failure of two or more vital organ systems14. Acute respiratory distress syndrome (ARDS) was diagnosed according to the Berlin definition. It was classified in three categories, depending on the level of arterial hypoxemia: mild (ARDS 1), moderate (ARDS 2), and severe (ARDS 3)15. The severity of an AKI was classified according to the Kidney Disease Improving Global Outcomes criteria16: mild AKI was diagnosed in case of an increase of serum creatinine over 0.3 mg/dL within 48 h or 150% of baseline levels or if urine output was less than 0.5 mL/kg/h for 6 h. Further increase of serum creatinine up to 3 times the baseline level was considered moderate AKI and severe AKI was diagnosed in cases with a creatinine increase over 3 times the baseline level or urine output of less than 0.3 mL/kg/h for over 24 h or anuria for at least 12 h.Bleeding was defined as a rapid decrease in hemoglobin levels by at least 3 g/dL within a 24-h period, substantiated by CT-angiographic verification of ongoing blood loss or the presence of a hematoma. Massive transfusion was defined as a transfusion of at least 10 blood bags within a 24-h periodp value < 0.05 and p < 0.01; p values are expressed with the 95% confidence interval (CI). For categorical variables, the odds-ratio (OR) was calculated to evaluate risk factors, including patient demographics, comorbidities, and procedural details. For continuous variables, significant correlations were assessed with a univariable logistic regression analysis corrected with Firth’s bias correction; these models used the onset of AKI as the dependent variable. Univariable logistic regression analyses, corrected with the Firth’s bias correction, were also performed to examine associations between the development of AKI and the AKIRisk-index, daily urine output, serum creatinine level, and other postoperative complications.Continuous variables are reported as the mean (± standard deviation) or, in cases of heavily skewed distributions, as the median (25th–75th percentile limits). Categorical variables are presented as the frequency (n) and percentage. Significance was defined as a The multivariable logistic regression model was adjusted with variables that were clinically known to correlate with AKI. These variables were related to patient’s comorbidities and the 24-h postoperative AKIRisk-Index. The dependent outcome was AKI development.Receiver operating characteristic (ROC) curves were used to assess the ability of the AKIRisk-Index to predict postoperative dialysis treatment. The area under the ROC curve (ROC AUC) was calculated to evaluate the diagnostic value of the AKIRisk-Index measured at different time points. The cut-off value was selected for each time point with a prerequisite sensitivity (Se) of > 80%. The specificity (Sp) and likelihood ratio (LR) were adjusted accordingly. Statistical analyses were performed with SPSS software . Graphs were designed with SPSS software and GraphPad Prism version 8.0.0 for Windows .2 . 2 patients in the cohort had preoperative creatinine levels over 2 mg/dL—2.5 and 2.3 mg/dL. The most common aortic procedure was an open reconstruction for a thoracoabdominal aortic aneurysm (TAAA), Crawford type III . The next most common procedures were Crawford type II  and type IV  TAAA reconstructions , with a mean age of 58.4 ± 12.7 years. Details of patient comorbidities and procedural parameters are shown in Tables 7.7%, witThe AKIRisk-Index values were significantly correlated with the prevalence of postoperative stage 3 AKIs, starting from the 12-h time point after ICU admission . We also found significant correlations between the onset of AKI requiring dialysis and respiratory complications, including pneumonia , duration of invasive ventilation , and severe ARDS . In the stage 3 AKI group, 9 patients developed sepsis (42.9%), 8 were diagnosed with MODS (38.1%), and 7 were diagnosed with acute liver failure (33.3%). Patients that did not require dialysis did not develop any of these complications. The stage 3 AKI group experienced significantly higher frequencies of mass blood product transfusions , pulmonary bleeding , and revision thoracotomies , compared to the rest of the patients.We constructed a univariable logistic regression model with the Firth’s bias correction to analyse correlations between postoperative dialysis treatment and other adverse outcomes Table . We foun2 or greater preoperatively, 11 (44%) developed severe AKI after surgery. Starting at the 12-h time point, the test demonstrated some diagnostic ability , but its value became excellent at the 24-h , 48-h , and 72-h  time points. We calculated the optimal cut-off value for a sensitivity of at least 80%. Starting at the 12-h time point, a cut-off of > 0.14 (mg/L)2 was adequately sensitive, but at the cost of specificity . At the 24-h time point and later, the test’s accuracy and specificity improved, but the cut-off value had to be adjusted accordingly to 0.81 (mg/L)2. For the 12-h time point, when we set the cut-off value to > 0.3 (mg/L)2, we observed higher specificity and similar sensitivity  recruited from one centre. We found that the AKIRisk-Index showed significant diagnostic efficiency as soon as 12 h after surgery . The dependent variable for this model was AKI requiring RRT .This prospective, multicentre study confirmed that the NephroCheck bedside system was a feasible tool for detecting an AKI within the first hours after a major surgery, such as the open thoracoabdominal aortic repair. The current study was registered with an a priori protocol. Our findings were consistent with findings from previous studies that focused on AKIs after major surgery, including a systematic review19. Consistent with previous trials that investigated larger cohorts20, we found a 24% mortality rate among patients undergoing open thoracoabdominal aortic repair. We also found that severe AKI was the most frequent complication after surgery, and it was significantly associated with other severe complications. For example, postoperatively, we observed clear correlations between AKIs and surgical revisions (mainly re-thoracotomy), bleeding complications, mass transfusions, sepsis, and multi-organ failure, again in accordance with the literature21. Furthermore, respiratory complications were the foremost complication: patients that required dialysis needed longer invasive ventilation times (560 h vs. 10.5 h), were more susceptible to pulmonary infections (76.2% vs. 20.8%), and were prone to hypoxaemia in the setting of severe ARDS (47.6% vs. 4.2%). Thus, timely identification of patients at-risk for AKI and the early initiation of preventive measures play an important role in patient’s recovery during the postoperative phase.Mortality and morbidity are highly clinically relevant after open and endovascular thoracoabdominal aortic repair22. Furthermore, confounding factors such as renal reserves, intravascular volume status and hemodynamic alterations may affect the changes in serum creatinine and urine output, limiting the accuracy of these parameters in diagnosing structural renal damage25. Specific renal biomarkers are able to detect tubular damage before changes in kidney function take place and thus enabling the diagnosis of AKI in its subclinical phase26. Their clinical applicability has been assessed in previous trials. For example, urinary neutrophil gelatinase associated lipocalin (NGAL) was correlated with postoperative AKIs that might require dialysis. However, the reliability of serum NGAL could not be confirmed20. A previous study validated the combination of TIMP2 and IGFBP7 for predicting AKIs in critically ill patients7. TIMP2 and IGFBP7 are biomarkers of cellular stress caused by inflammation and ischaemia in the early phase of tubular cell injuries. Indeed, these cytokines operate as paracrine signalling molecules when cellular damage occurs and promote the expression several tumor suppressor proteins like p53, p27 and p21, which in their turn inhibit cellular proliferation29. Keeping the cell cycle arrested at the G1 phase, is a temporary, energy-preserving, protective measure, which can end in fibrotic scaring of the organ tissue if prolonged30. In this notion, the NephroCheck bedside system calculates the AKIRisk-Index based on the concentrations of TIMP2 and IGFBP7 in patient urine and aims to detect this early warning signal of cellular stress, before manifest kidney dysfunction takes place.Serum creatinine and urine output are established markers of manifest kidney dysfunction, yet they may fail to accurately capture tubulointerstitial injury, before the impairment of the glomerular filtration rate becomes apparent31 and was also found to be significantly, inversely correlated with kidney tissue recovery during follow-up7. Despite the growing body of evidence for the potential benefit of NephroCheck in perioperative setting, the inclusion of AKIRisk-Index measurements in diagnostic bundles has been met with scepticism by some physicians, who emphasize the need of further clinical validation32. For patients at risk for AKI after cardiac and abdominal surgery, early intervention and implementation of the KDIGO guidelines, as identified by biomarkers, has been shown to successfully attenuate the development of severe AKI and need for RRT34. Validated biomarkers, which accurately identify the patients, who may benefit from preventive interventions, are recommended in combination with clinical assessment in order to optimize the timing and type of interventions to improve patient outcomes35.Clinical evaluation of AKIRisk-Index has been investigated in several settings since the approval of NephroCheck by the Food and Drug Administration in September 2014. For patients undergoing cardiac surgery, the AKIRisk-Index reliably predicted the onset of AKI in the first postoperative dayp = 0.01) after adjusting for age, gender, hypertension and chronic kidney disease.This was our motivation for assessing the NephroCheck in patients that underwent thoracoabdominal aortic repair. In this prospective, observational study, we found that the NephroCheck was a feasible tool for predicting postoperative AKI in 45 patients undergoing open aortic repair. It showed reliable predictive accuracy starting at 24 h after surgery. This finding was confirmed after adjusting for confounding factors. Indeed, the multivariable regression analysis confirmed that the postoperative NephroCheck measurement showed prognostic value in predicting AKIs . Thus, our findings confirmed our working hypothesis, which was that the NephroCheck could be useful as an adjunct for diagnosing AKIs after open aortic surgery. When we focused on the large subgroup of patients from one centre, we observed that the NephroCheck had high diagnostic capacity, even at 12 h after surgery . The increased accuracy in this subgroup, compared to the entire cohort, might be explained by differences in operative protocols and management strategies between the participating centres.In our detailed analysis, both creatinine serum levels and a positive NephroCheck result were significantly correlated with the onset of AKI. However, a ROC-curve analysis revealed that the NephroCheck bedside system provided more reliable diagnostic accuracy than serum creatinine 2 threshold, which is in line with findings in current literature indicating susceptibility of the biomarkers to changes in urine concentration37. Our analysis confirmed the cut-off value of 0.3/mg/dL)2, but only for the 12-h measurement . At subsequent time points, we found that adjusting the cut-off value provided better specificity without impairing the test’s sensitivity.Recent studies established a cut-off value of > 0.3 (mg/L)38. Yet, the scope of this work was to investigate the practicability of the NephroCheck bedside system in clinical routine according to the manufacturer’s instructions, which do not recommend correction for dilution and, therefore, assessment of urine concentration was not included in our study protocol. Finally, although our study results were convincing, the methodology was strong, and the test quality was good, the analysis was conducted in a hypothesis-generating manner; thus, the findings require further clinical validation.This study had some relevant limitations. First, there was a small number of patients. This was partly due to the low numbers of thoracoabdominal aortic procedures performed world-wide annually. Moreover, this study was conducted between 2019 and 2021, during the COVID-19 pandemic; this situation caused serious inclusion issues for at least 2 years. Second, although we applied an a priori study protocol, several pre-, intra-, and postoperative parameters could not be standardized. For example, intraoperative decisions were based on the performing surgeon’s experience, and the postoperative course and ICU treatments were performed according to hospital standards. Indeed, despite the fact that we observed higher predictive accuracy when the NephroCheck was performed in a centre with a large variety of procedures, it is likely that a higher level of intra- and postoperative standardization would be favourable to its clinical reliability. Furthermore, given the susceptibility of AKIRisk-Index to changes in urine concentration, adjusting for urine osmolarity would support a more precise interpretation of the presented resultsIn this prospective multicentre study, we confirmed the diagnostic accuracy of the NephroCheck bedside test for predicting postoperative AKIs that required dialysis in patients that underwent open thoracoabdominal aortic repair. We demonstrated that the test was accurate when performed within the first 24 h after surgery.Supplementary Information.


Fibroblast growth factor-23 (FGF23) has been associated to left ventricular (LV) hypertrophy and heart failure (HF) severity. We aimed to investigate the clinical correlates and prognostic value of intact FGF23 (iFGF23) in HF patients.Patients with stable HF and left ventricular ejection fraction (LVEF) < 50% were prospectively enrolled, managed according to current recommendations and followed over time. iFGF23 was measured at baseline with a fully automated immuno-chemiluminescent assay.We enrolled 150 patients . First, second, and third iFGF23 tertiles were < 35.2 pg/mL, 35.2–50.9 pg/mL, and > 50.9 pg/mL. LVEF decreased from the first iFGF23 tertile to the third tertile (p = 0.014). N-terminal pro-B-type natriuretic peptide (NT-proBNP) increased from the first to the third tertile (p = 0.001), while peak oxygen consumption decreased (p < 0.001). Thirty-five patients (23%) experienced the primary endpoint , and 26 (17%) the secondary endpoint . On multivariable analysis, iFGF23 independently predicted the primary endpoint on top of age, gender and LVEF , age, gender and eGFR , as well as age, gender and NT-proBNP . iFGF23 even reclassified patient risk on top of all the 3 models, with NRI values of 0.65 (95% CI 0.30–1.01), 0.55 (95% CI 0.25–0.88), and 0.60 (95% CI 0.24–0.96), respectively (both p < 0.001).Circulating iFGF23 is associated with disease severity and outcome in HF patients with reduced and mildly reduced ejection fraction.The online version contains supplementary material available at 10.1186/s12872-023-03441-2. Fibroblast growth factor 23 (FGF23) is a peptide hormone mainly synthetized in the bone, regulating phosphate balance by blocking renal tubular phosphate reabsorption and inhibiting the synthesis of 1,25-dihydroxyvitamin D  in diffepost-hoc analysis of the Trial of Intensified vs. Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) has questioned the predictive power of FGF23 [Over the past years, FGF23 has emerged as a possible HF biomarker . For exaof FGF23 .Most of the studies published so far have reported the clinical value of FGF23 tested with enzyme-linked immunosorbent assays directed to either C-terminal FGF23 (cFGF23). A novel, fully automated FGF23 assay measuring selectively the biologically active hormone, the intact FGF23 (iFGF23), has become available , but theIn this study, we aimed to assess correlates and prognostic value of iFGF23, tested with an automated assay, in a fully characterized cohort of patients with systolic HF.We enrolled 150 consecutive patients with systolic HF (left ventricular ejection fraction - LVEF < 50%), in a tertiary referral centre for HF , between June 2015 and December 2016. HF was diagnosed according to contemporary guidelines . All patBlood samples were drawn after an overnight fasting period and a 20-minute supine rest , and theEstimated glomerular filtration rate (eGFR) was calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.Patients underwent follow-up visits every 6 months or as clinically indicated. In December 2022, two independent interviewers retrieved data from the electronic health records and administrative data and through phone calls to the patients, relatives, or general practitioners. The primary endpoint was all-cause death or HF hospitalization at 5 years, and the secondary endpoint was all-cause death at 5 years.2 or Fisher test were adopted for qualitative variables. Predictors of iFGF23 levels were searched among all baseline characteristics  and R . Normal distribution was assessed through the Shapiro-Wilk test. Normally distributed variables were reported as mean ± standard deviation while non-normally distributed variables as median and interquartile range (IQR). Categorical data were reported as absolute numbers and percentages. According to variable distribution, ANOVA or Kruskal-Wallis test were used for multiple comparisons among groups. χPatient survival across iFGF23 tertiles was evaluated using the Kaplan-Meier method and Log-Rank statistics (Mantel-Cox). All baseline variables were considered as possible predictors of outcome on Cox regression analysis. The independent prognostic value of iFGF23 was assessed on top of 3 models: age, gender and LVEF (Model 1), age, gender and eGFR (Model 2), age, gender and NT-proBNP (Model 3). This analysis was conducted only for the primary endpoint, given the low number of secondary endpoint events. The number of variables in the models was selected based on the rule of one variable per ten events (and approximating 35 to 40). The added value of iFGF23 was assessed also in terms of continuous net reclassification improvement (NRI).Two-tailed p values ≤ 0.05 were deemed significant.2), and median NT-proBNP was 953 ng/L (354–2024 ng/L) . Median age was 65 years (54–74 years), 82% were males, and 72% were in New York Heart Association (NYHA) class I-II. Renal function was globally preserved (eGFR 73 ± 24 mL/min/1.73 m2/kg) and LVEF decreased from the first to the third tertile, while NT-proBNP increased. Even PTH levels increased form the first to the third tertile of iFGF23.Median iFGF23 was 41.8 pg/mL (30.6–55.6 pg/mL) and the first, second, and third tertile were < 35.2 pg/mL, 35.2–50.9 pg/mL, and > 50.9 pg/mL, respectively. As reported in Table Among all baseline variables, only eGFR  and LVMI  displayed an independent association with iFGF23 levels (Table The median follow-up period was 4 years (2–5 years). Patients in the third tertile of iFGF23 had a shorter survival free from either the primary or the secondary endpoint Fig. . Thirty-We report that higher iFGF23 levels are associated with greater disease severity and worse outcome in patients with stable HF with reduced or mildly reduced EF (Fig. FGF23 plays a key role in regulating phosphate homeostasis. Elevated FGF23 levels increase fractional phosphate excretion at kidney level and inhibit PTH synthesis and secretion by parathyroid cells . On the Renal function, assessed by eGFR, emerged as another independent predictor of iFGF23 in our study. The inverse correlation between eGFR and iFGF23 is likely due to both direct and indirect mechanisms, consisting in the reduced renal excretion of iFGF23 and increased phosphate levels, respectively, following decreasing renal function. Nevertheless, iFGF23 values in our cohort was still in the normal to high-normal range, in line with other studies investigating cardiovascular setting and without severe renal impairment [There is experimental evidence that FGF23 may enhance RAAS activity , althougStimulation of RAAS activity has been postulated as one of the mechanisms underlying the association between FGF23 and LV hypertrophy . AvailabOur findings that iFGF23 is an independent predictor of outcome in patients with HF is in line with previous evidence reporting FGF23 as a correlate of HF-related outcome, in patient with or without kidney disease . NotablyFGF23 is increasingly recognized as a marker and a mediator of disease progression in HF. Our findings support the role of iFGF23 as a player in cardiac remodelling following renal dysfunction and a tool for risk stratification in HF patients. Characterization of the clinical significance of iFGF23 is of great relevance given the availability of different pharmacological approaches for FGF23 blockade. These include inhibitors of gastrointestinal sodium/hydrogen exchanger isoform 3 such as tenapanor , and cinSeveral limitations must be acknowledged. Serial measurements of iFGF23 were not performed, therefore changes in iFGF23 during the follow-up and their influence on patient outcome cannot be assessed. Moreover, we report data from a single tertiary centre and a quite small cohort, which may limit the generalizability of our findings.In conclusion, circulating iFGF23 is associated with disease severity and outcome in HF patients with reduced and mildly reduced ejection fraction.Below is the link to the electronic supplementary material.Additional File Table 1: Univariate predictors of outcome


This study aimed to assess the relationship between chosen antioxidants, namely selenoprotein P (SELENOP), peroxiredoxin-5 (Prdx-5), renalase and selected cardiovascular consequences tested in ambulatory blood pressure monitoring (ABPM) and echocardiography (ECHO). In our work, cardiovascular consequences refer to higher mean blood pressure (MBP) and pulse pressure (PP) on ABPM, as well as to left atrial enlargement (LAE), left ventricular hypertrophy (LVH) and lower left ventricular ejection fraction (LVEF%) on ECHO. The study group consisted of 101 consecutive patients admitted to the Department of Internal Medicine, Occupational Diseases and Hypertension to verify the diagnosis of Obstructive Sleep Apnoea (OSA). Each patient underwent full polysomnography, blood tests, ABPM and ECHO. Both selenoprotein-P and renalase levels correlated with different ABPM and ECHO parameters. We found no correlation between the peroxiredoxin-5 level and none of the tested parameters. We point to the possible application of SELENOP plasma-level testing in the initial selection of high cardiovascular-risk patients, especially if access to more advanced examinations is limited. We further suggest SELENOP measurement as a possible indicator of patients at increased left ventricular hypertrophy risk who should be of particular interest and may benefit from ECHO testing. Increased oxidative stress is a major contributing factor in cardiovascular disease (CVD) pathogenesis. Disbalance between reactive oxygen species (ROS) and antioxidants leads to a decrease in the bioavailability of nitric oxide (NO), endothelial dysfunction, and damage to numerous cellular structures. Therefore, antioxidants are often proposed as promising agents in both the diagnosis and therapy of CVDs. Despite growing evidence supporting the role of antioxidants in CVD pathogenesis, the measurement of antioxidants is not officially recommended for initial CVD diagnosis or cardiovascular risk assessment.Selenoprotein P (SELENOP) belongs to a group of selenocysteine-containing selenoproteins, along with glutathione peroxidases (GPx), thioredoxin reductases (TrxR) and iodothyronine deiodinases (DIO) . It is mRenalase is a flavin adenine dinucleotide-dependent amine oxidase that serves as a scavenger enzyme. It oxidizes isomeric forms of β-NAD(P)H and recycles them by forming β-NAD(P)+. This action protects cells from the accumulation of β-NAD(P)H isomers that may inhibit other enzymatic reactions . The imp2O2, and peroxinitrite  + 0.6 . The left ventricular mass index (LVMI) was calculated, by dividing the LVM value by the body surface area (BSA), expressed in square meters. The body surface area was calculated using the formula of Du Bois: BSA [m2] = 0.007184 × (body weight [kg]) 0.425 × (body height [cm]) 0.725. The relative wall thickness (RWT) was calculated using the following formula: RWT = (IVSDd + PWDd)/LVEDd. The results of ABPM and ECHO in the study group are presented in Transthoracic echocardiography was performed using the ALOKA ProSound SSD-5500 SV, equipped with a 3.5/2.7 MHz transducer . The results were evaluated using the criteria of the American Society of Echocardiography . Using an M-mode echocardiogram, following Penn convention, left ventricular end-diastolic diameter (LVEDd) and left ventricular end-systolic diameter (LVESd), interventricular septum diastolic diameter (IVSDd) and posterior wall diastolic diameter (PWDd) were measured. The mean of three measurements was recorded with an accuracy of 1 mm. The ejection fraction (EF) was determined from the apical four-chamber and two-chamber views, with the biplane Simpson’s method. The left ventricular mass (LVM), expressed in grams, was calculated using the formula suggested by the American Society of Echocardiography (ASE), modified by Devereux et al. (1986): LVM = 0.8 × [1.04 × (LVEDd+ PWDd+ IVSDd)t-test. For non-normally distributed quantitative variables, the Mann–Whitney U test was used. For qualitative variables, the chi-square test of maximum likelihood was used. To determine the relationship between the examined variables, correlation and regression analyses were conducted. In the case of normal distribution, the Pearson correlation r factors were determined whereas, in the case of non-normal distribution, the Spearman r factors were applied. Multivariable stepwise backward regression was used to identify possible predictor variables for pulse pressure, left atrium diameter and left ventricular hypertrophy. Three separate analyses were performed with PP, LA and LVH as dependent variables. At each step, independent variables were removed from the model based on p-values. Results with p < 0.05 were considered statistically significant.Statistical analyses were conducted using the Dell Statistica 13 software . The quantitative variables were expressed as means and standard deviations. The qualitative variables were expressed as percentages. The distribution of variables was tested with the W-Shapiro–Wilk test. In the case of the quantitative variables of normal distribution, a further statistical analysis was performed using the Ethical approval for this study was obtained from the Bioethics Committee of Wroclaw Medical University. Informed consent was obtained from all subjects before the study.ClinicalTrials.gov Identifier: NCT05040516.In our study, patients with diagnosed hypertension (subgroup A) had statistically significantly lower selenoprotein P levels than patients without HT (subgroup B). Levels of peroxiredoxin-5 and renalase did not differ significantly between these groups. In terms of ABPM/ECHO parameters, patients with elevated blood pressure had significantly higher MBP, PP, and LA diameter and were more likely to have left ventricular hypertrophy. These results are shown in When dividing patients by the diagnosis of OSA (subgroup C and D), we did not find any significant differences in selenoprotein P, peroxiredoxin-5 and renalase levels, as well as in MBP values, LA diameter and the occurrence of LVH. However, patients with OSA (subgroup C) had significantly higher PP and the possibility of LVH. These results are shown in Comparison of results based on the criteria of median selenoprotein P, peroxiredoxin-5 and renalase levels showed that patients with selenoprotein P level ≥ median (subgroup E) had lower MBP, PP and LA diameter values and were less likely to develop LVH than patients with selenoprotein P level < median (subgroup F). None of the considered parameters differed significantly between patients with peroxiredoxin level ≥ median (subgroup G) and < median (subgroup H). Division by the median of renalase disclosed significantly lower PP and LA diameter values in patients with renalase level ≥ median (subgroup I) than in the subgroup with lower renalase levels (subgroup J); there were no differences in MBP, LVEF and LVH incidence between these subgroups. The analysis of selected ABPM/ECHO parameters based on the division by laboratory parameters is presented in No differences in laboratory parameters  levels were found when dividing patients by the median of MBP (subgroup K and L). However, both selenoprotein P and renalase levels were notably lower in patients with PP value ≥ the median (subgroup M) than in patients with lower PP values (subgroup N). Division by the median of MBP showed no differences between these subgroups in terms of LVH incidence. On the contrary, patients with higher PP (subgroup M) had a notably higher incidence of LVH than patients with PP lower than the median (subgroup N). These results are shown in Analysis based on selected ECHO parameters showed that selenoprotein P and renalase levels were significantly lower in patients with LA diameter ≥ median (subgroup O) than in patients with LA diameter < Me, as well as in patients with diagnosed LVH (subgroup T) than in subjects without LVH (subgroup U). Patients with lower LVEF% (subgroup R) had markedly lower PP values than patients with LVEF% ≥ median (subgroup S). On the other hand, PP was significantly higher in patients with higher LA diameter (subgroup O) and in patients with LVH (subgroup T). None of the tested laboratory parameters differed significantly between people with lower or higher LVEF% (groups R vs. S). Analysis based on selected ECHO parameters is presented in p < 0.05), MDBP , MBP (r = −0.28), p < 0.05), PP , IVSEDD , PWEDD , LA  and LVMI . Renalase level correlated in a negative linear manner with PP , IVSEDD  and LA . The results of correlation analysis are presented in In this study, negative linear correlation was found between selenoprotein P and certain ABPM and ECHO parameters, namely: MSBP  are a superfamily of selenium-free and haeme-free peroxidases able to catalyse the reduction of hydrogen peroxide, alkyl hydroperoxides and peroxinitrite . In humap < 0.05). In the light of our previous results, the association between SELENOP and mean blood pressure may possibly be explained by SELENOP’s involvement in maintaining the right plasma TAS and keeping the redox balance.In our recent work, we have reported that a higher SELENOP level was independently associated with higher plasma TAS, and TAS was further associated with lower mean blood pressure values. The obtained results suggested an indirect connection between the SELENOP level and blood pressure. In this study, we report that hypertensive patients had significantly lower SELENOP levels than normotensive patients (p < 0.05), mean diastolic blood pressure , mean blood pressure (r = −0.28), p < 0.05) and pulse pressure . Furthermore, regression analysis revealed that low SELENOP levels was an independent risk factor for higher PP with a p-value under 0.01. In sum, a lower SELENOP level was associated with unfavourable cardiovascular consequences measured on ABPM–higher MBP, MDBP, MSBP and PP. This result points to the possible applicability of SELENOP measurement in the initial selection of high cardiovascular-risk patients, especially if access to more advanced examinations is limited. Proper cardiovascular risk stratification remains a fundamental step in the effort to reduce morbidity and mortality from cardiovascular diseases (CVDs) [In terms of the ABPM parameters, patients with SELENOP levels higher than the median had a notably lower mean blood pressure and pulse pressure when compared to the patients with lower SELENOP levels. We also found a negative linear correlation between SELENOP and mean systolic blood pressure  . It was p < 0.05). Based on the information provided, we suggest SELENOP measurement as a possible indicator of patients at increased LVH risk who should be of particular interest and may benefit from ECHO testing. The application of SELENOP measurement in the risk stratification seems more achievable than aiming to increase its level with therapy. Selenium supplementation may be a promising strategy in preventing hypertension and its cardiovascular consequences; nevertheless, this issue is more complex. Data on selenium supplementation are inconclusive as both beneficial and harmful effects have been reported [In terms of ECHO parameters, we have found a negative linear correlation between SELENOP levels and both LVMI (r = −0.33) and RWT (r = 0.20). Moreover, patients with SELENOP levels higher than the median had notably lower left atrium diameter and were less likely to develop left ventricular hypertrophy  and a low renalase level was an independent risk factor for higher pulse pressure in the regression analysis with a p-value under 0.05. We thus hypothesise that renalase may be more involved in keeping the balance between systolic and diastolic blood pressure rather than in regulating crude blood pressure values. However, taking into consideration the complexity of renalase activity and its enzymatic and non-enzymatic properties, many more studies are needed to elucidate this issue.The notion that renalase serves to degrade catecholamines has been dismissed; however, many studies still point to its involvement in blood pressure regulation. The reports on this subject are inconclusive. Many studies indicate higher renalase concentration in hypertensive patients ,42, and In our study, independent risk factors for LVH included a higher pulse pressure on ABPM, higher body mass index (BMI), lack of antihypertensive treatment and the diagnosis of obstructive sleep apnoea (OSA). Interestingly, mean blood pressure values were less effective in predicting LVH than pulse pressure; thus, we propose PP as the preferable parameter to be used in CV risk stratification and selecting patients who require further care and treatment. Independent risk factors for left atrium enlargement included higher PP and higher BMI, but also more advanced age and male gender. These results stay consistent with other studies on LA diameter, BMI and gender .Obstructive sleep apnoea was an independent risk factor for LVH. It should be underlined that when dividing patients by the diagnosis of OSA (groups C and D), we did not find any differences in MBP values; however, patients with OSA had significantly higher PP. We indicate OSA patients as the group of special interest and recommend their PP to be checked even if blood pressure remains within the normal range. Interestingly SELENOP levels did not differ significantly between patients with and without OSA, suggesting that SELENOP may rather be involved in the pathomechanism of primary than secondary hypertension. Authors should discuss the results and how they can be interpreted from the perspective of previous studies and of the working hypotheses. The findings and their implications should be discussed in the broadest context possible. Future research directions may also be highlighted.This study has some limitations. In terms of the study group, the limitations are the small size of the group and the relatively small percentage of patients without OSA and without abnormal body weight. In terms of the research methodology, the limitations of the ABPM analysis include the absence of separate measurements from the hours of daily activity and the measurements from the hours of night rest, the lack of assessment of the diastolic function of the left ventricle in the ECHO examination and the subjective selection of antioxidants.In our study, both selenoprotein-P (SELENOP) and renalase levels correlated significantly with different ambulatory blood pressure monitoring (ABPM) and echocardiography (ECHO) parameters. We found no correlation between the peroxiredoxin-5 level and the tested parameters. A lower SELENOP level was associated with unfavourable cardiovascular consequences measured on ABPM–higher mean blood pressure, mean diastolic blood pressure, mean systolic blood pressure and pulse pressure, as well as on ECHO–increased left ventricle mass index and relative wall thickness. We point to the possible application of SELENOP plasma-level testing in the initial selection of high cardiovascular-risk patients, especially if access to more advanced examinations is limited. We further suggest SELENOP measurement as a possible indicator of patients at increased left ventricular hypertrophy risk who should be of particular interest and may benefit from ECHO testing. In this study group, renalase levels did not differ significantly between subjects with or without diagnosed hypertension. However, our analysis revealed that renalase level correlated in a linear negative manner with pulse pressure, and low renalase level was an independent risk factor for higher pulse pressure in the regression analysis. Given that reports on renalase are inconsistent, its clinical use appears to be delayed until its exact function is recognised.


Biomedicines.Chronic kidney disease (CKD), as a worldwide threat to public health, is a key determinant of poor health outcomes, but the severity of the problem is probably not fully appreciated . CKD hasUMOD, encoding uromodulin, was the first identified mutation and the most common cause of ADTKD. The prevalence of ADTKD-UMOD remains unclear, and recent studies have shown that it represents up to 0.3~2% of all CKD patients [UMOD missense variants, of which two had not been previously reported. The abnormal functional expression of the mutated UMOD protein was also demonstrated in HEK 293 cell culture. They concluded that ADTKD-UMOD might represent a small but significant (1.31%) cause of CKD. Multi-center screening would provide a better understanding of the mutation landscape in Taiwan and contribute to the ADTKD research field.Polycystic kidney disease and congenital anomaly of the kidney and urinary tract are the most commonly seen genetic/congenital disorders leading to CKD. However, past studies have shown that ADTKD  may not be an uncommon type of CKD caused by heterozygous mutations . UMOD, eImmunoglobulin A nephropathy (IgAN) is the most common pathology noted in all primary glomerulonephritis (estimated to be at least 30%), and a multi-hit theory has been proposed by researchers . The assCKD is very commonly complicated by various comorbid illnesses, especially those with metabolic derangement. Good control of these comorbidities can often help to lessen CKD severity and its progression. Numerous studies have suggested goals of control for individual diseases, most notably for diabetes mellitus (DM) and hypertension. However, the applicability of these goals in CKD patients is somewhat questionable because their outcomes would be affected by not just one but many other factors. A good example is the application of HbA1c < 7% as a commonly accepted marker of good glycemic control. The level of HbA1c is affected by the half-life of red blood cells, the level of hemoglobin and other factors. CKD patients have shortened red blood cell half-lives and lower hemoglobin levels, unfavorably contributing to the formation of HbA1c and therefore its applicability as a stable marker of glycemic control . Longitu®) was shown to reduce the absorption of the gut-derived uremic toxins  and improve kidney histology in animal studies [Lactobacillus mixture in reducing kidney injuries by down-regulating gut-derived uremic toxin production. It is promising that nephrology practitioners might have the chance to prescribe “kidney probiotics” to CKD patients in the future.There is no panacea to cure CKD, even though researchers had devoted efforts toward it and clinical studies have shown promising results. Owing to its complexity, CKD management is still an unaccomplished aim. The development and clinical application of sodium-glucose cotransporter 2 inhibitor (SGLT2i) has led to a paradigm shift in the management of diabetic patients to benefit their cardiovascular and renal outcomes . The ext studies . It was  studies  has demoNevertheless, physicians should always pay attention to avoiding the unwanted adverse effects derived from treatment, if there are any. Nephrologists have treated renal anemia with erythropoietin over the past few decades, and have greatly reduced the need for blood transfusions and therefore transfusion-associated diseases. Besides the correction of anemia, erythropoietin might improve cardiac function by binding to a receptor on cardiomyocytes . HoweverKidney transplantation has been recognized to be the best and the ultimate resolution for patients with advanced CKD. However, we have to admit that transplantation would push back the advanced CKD stage to stage 3a (one transplanted kidney), which is still a CKD stage. There is no doubt that kidney transplantation greatly improves patient outcomes and life quality. However, transplantation itself is a risk factor for diabetes development due to chronic exposure to certain immunosuppressive agents, even in non-diabetic CKD patients. Lim et al. indicated that patients after kidney transplantation were actually in a CKD stage with an unavoidable risk of diabetes incidence, and they discussed the pathogenesis and prevention strategies in this Special Issue.As aforementioned, CKD is a serious threat to public health and is a never-ending story, even after kidney transplantation. Everyone in the nephrology field will have to participate and contribute continuous efforts to tackle this great challenge related to the pathogenesis and treatment of CKD.


In chronic kidney disease, IgA nephropathy, and left ventricular diastolic dysfunction have prognostic significance as well. However, the relationship between diastolic dysfunction, arterial stiffness, and renal function has not been fully elucidated.79 IgA nephropathy patients (aged 46 ± 11 years) and 50 controls were investigated. Tissue Doppler imaging was used to measure early (Ea) and late (Aa) diastolic velocities. Arterial stiffness was measured by a photoplethysmographic (stiffness index (SI)) and an oscillometric method (aortic pulse wave velocity (PWVao)).We compared the IgAN patients to a similar cardiovascular risk group with a preserved eGFR. A strong correlation was found between Ea/Aa and SI (p < 0.001), also with PWVao (p < 0.001), just in IgAN, and with eGFR (p < 0.001) in both groups. IgAN patients were divided into groups CKD1-2 vs. CKD3-5. In the CKD 3–5 group, the incidence of diastolic dysfunction increased significantly: 39% vs. 72% (p = 0.003). Left ventricle rigidity (LVR) was calculated, which showed a close correlation with SI (p = 0.009) and eGFR (p = 0.038). By linear regression analysis, the independent predictors of SI were age, E/A, and E/Ea; SI was the predictor of LVR; and E/A and hypertension were the predictors of eGFR.In chronic kidney disease, increased cardiac rigidity and vascular stiffness coexist with decreased renal function, which is directly connected to diastolic dysfunction and vascular stiffness. On the basis of comparing the CKD group to the control group, vascular alterations in very early CKD can be identified. In our study, we examined patients with IgA nephropathy, a chronic kidney disease, to identify those at high cardiovascular risk.Arterial stiffness and tissue Doppler echocardiographic parameters showed a significant association with kidney function; therefore, a common pathological vascular and myocardial remodeling can be assumed. Former large-scale studies revealed that CV mortality and morbidity in chronic kidney disease (CKD) are many times higher than in the general population, posing a global public health problem , 2. IgA Echocardiography is a widely used, valuable, noninvasive method for the determination of the left ventricular systolic and diastolic function (LVDD), which has prognostic significance in ischemic heart disease, heart failure, and end-stage renal failure –18. TissThis study was performed to investigate the association between LV diastolic function and arterial stiffness in relation to renal function in a homogenous group of CKD patients with IgAN and compare it with a similar healthy group. Our hypothesis was that the association between arterial stiffness and LV diastolic function could be more pronounced in patients with deteriorated renal function.Seventy-nine patients with IgAN and fifty control patients with a relatively similar, moderate CV risk were involved in this study from the 2nd Department of Internal Medicine, Nephrology, and Diabetes Center of the Clinical Center at the University of Pécs. The diagnosis of IgAN was confirmed by renal biopsy in all patients. The patients in the control group had preserved renal function and were also outpatients of our clinic with relatively similar cardiovascular risk. The local ethics committee approved the clinical study protocol (no. 3170/2008), and written informed consent was obtained from all participants.In this cross-sectional study, echocardiography was performed, and classic CV risk factors  and patient medication were also recorded. The metabolic syndrome was defined according to the ATP III (Adult Treatment Panel III) criteria. The obesity criteria were a BMI over 30 kg/m2. The CKD-EPI formula was used to estimate renal function . Patients with acute or chronic severe comorbidities  were excluded. Renal replacement therapy or a history of kidney transplantation were also exclusion criteria. A Meditech ABPM  device was used to determine the patient’s 24-hour average systolic and diastolic blood pressure, pulse pressure, and diurnal index. Additional CV examinations  were also performed based on the patient’s complaints. The atherosclerotic cardiovascular disease (ASCVD) risk score was calculated by the American College of Cardiology ASCVD Risk Estimator Plus calculator.DVP. The DVP includes two distinct waves during the cardiac cycle: the early systolic one that originates from the pressure wave at the time of the left ventricle ejection, which could be measured in the finger artery, followed by the second peak due to a reflected wave from the more peripheral segments, usually the aortic bifurcation. The SI is derived from the body height relative to the time difference between the forward and reflective pulse waves: SIDVP (m/s) = height/t. The recorded pulse curve profile is principally determined by the PWV of the large arteries [DVP values indicate increased vascular stiffness [In this study, we used the finger photoplethysmography method by the Pulse Trace System  to assess pulse-wave velocity (PWV) , 22. Thiarteries –25. Basearteries . Higher tiffness –28. The tiffness .DVP measurements, five-period samples were taken, and the upper and lower merits of DVP were deleted. The remaining three merits were averaged and used for further analyses, including the variability test. All measurements were made by the same experienced operator, blinded to all clinical data. The intraobserver coefficient of variation for SI was approximately 5.0% in our laboratory.Measurements were performed between 9:00 and 11:00 in the morning. Subjects were studied in the supine position after approximately 10 min of rest in a temperature-controlled and quiet environment. Patients were allowed to take their regular medications, but smoking, alcohol drinking, and caffeine consumption were prohibited on the day of examination. A single waveform was obtained by averaging the DVP profile for 30 s. To enhance the accuracy of the SIAn Aloka SSD 1400 echocardiography machine was used. Using 2D images of the length of the apical left ventricular segment and the area of the left ventricular short-axis muscle, the left ventricular mass (LVM) was calculated (LVM = (5/6 area * length)). The Cornell criterion was used to determine LVMI, and the result was indexed for height (in meters). The unidirectional Simpson method was used to determine the diastolic and systolic left ventricular volumes, providing the left ventricular ejection fraction (LVEF): EF = ((Dvol-Svol)/Dvol)*100. Based on standard spectral Doppler measurements, mitral inflow and pulmonary venous flow were used to evaluate diastolic function. We also calculated the isovolumetric relaxation time (IVRT), the E wave deceleration time, and the E wave to A wave ratio (E/A ratio). LVH was defined as abnormal RWT and/or LVMI. TDI was used to measure the early and late displacements of the lateral basal wall fragment closest to the left ventricle (Ea and Aa) and determine the E/Ea and Ea/Aa ratios. To exclude interindividual differences, two investigators examined all patients.2 test for categorical variables. The relationship between two continuous variables was assessed by a bivariate correlation method (Pearson’s correlation), and nonparametric variables were assessed by Spearman’s correlation. The factors that influence Ea and Ea/Aa were investigated using univariate and multivariate linear regression analysis. We also used linear regression analysis to assess the associations between Ea and other covariates. SPSS version 22.0  was used to analyze the data, and a statistically significant value of 0.05 was used.For statistical analysis, we divided our patients into two groups according to eGFR (CKD 1–2 vs. CKD 3–5). All values, unless otherwise stated, are mean ± SD. Differences between the two groups were compared by the Student’s t-test and Mann-Whitney U test for continuous variables and χBaseline clinical data are shown in Table Based on eGFR, IgAN patients were separated into two categories (CKD 1–2 vs. CKD 3–5). The baseline characteristics showed significant differences in age, blood pressure, metabolic parameters , eGFR, and arterial stiffness parameters , as well as conventional echocardiography-measured parameters , tissue Doppler parameters , and left ventricle rigidity (LVR). There was no significant difference in ASCVD score, LV ejection fraction, LV end-diastolic diameter, hemoglobin, lipid levels, RAAS blocker usage, or central aortic systolic blood pressure (SBPao) between the two groups. But there were significantly higher diastolic dysfunction, proteinuria, and uric acid levels in the CKD 3–5 group . There was a strong negative correlation between Ea/Aa and SI , also with PWVao , and a positive correlation between Ea/Aa and eGFR  in IgAN patients  and diastolic function parameters: mitral inflow E and A wave ratio (E/A) , and E wave deceleration time (EDT) (r = 0.369). There was also a significant correlation between eGFR and diastolic function parameters: E/A , EDT , and tissue Doppler image parameters: Ea , E/Ea , and Ea/Aa  (Table In different stages of CKD (CKD 1 vs. CKD 2 vs. CKD 3 vs. CKD 4–5), there were significantly higher SI, PWVao, SBPao, and diastolic dysfunctions associated with the deteriorating renal function, but there was no significant difference between the advanced stages. There was significantly higher E/Ea  and lower Ea/Aa  in the early stages of CKD  to the control group, we found significantly higher SI  and PWVao  in the IgAN groups. There was no significant difference in SBPao between the groups. Diastolic dysfunction occurred significantly higher in the IgAN CKD 3–5 group compared to the control (p = 0.004) and the IgAN CKD 1–2 group (p = 0.003). The E/Ea ratio and the LVR increased significantly between the control vs. IgAN CKD 1–2 ; control vs. IgAN CKD 3–5 ; and between IgAN CKD 1–2 vs. IgAN CKD 3–5  groups. The Ea and the Ea/Aa ratio decreased significantly in the IgAN CKD 3–5 group compared to the control  and IgAN CKD 1–2 groups  ; HT + DM- (n = 18); HT + DM+ (n = 17)). We found a significant increase in SI , PWVao , E/Ea  and LVR , but a reduction in Ea  and Ea/Ea  compared both IgAN groups (CKD 1–2 and CKD 3–5) to a non-hypertensive, non-diabetic group with preserved renal function Fig. .By linear regression analysis, the independent predictors of SI were age, E/A, and E/Ea, and the independent predictors of PWVao were age and Aa. By linear regression analysis, the LVR independent predictor was only SI, and the eGFR predictors were E/A and hypertension. SBPao’s independent predictor was only E/A, but E/A independent predictors were age and eGFR; furthermore, Ea/Aa independent predictors were age and SI Table .Our study examined the relationship of conventional Doppler and tissue Doppler echocardiography parameters with renal function and arterial stiffness parameters in a homogenous, immunocomplex-mediated CKD population of IgAN patients. We found a correlation between Ea/Aa, and eGFR, SI, and PWVao in the IgAN group and the same in the control group in the cases of SI, PWVao, and eGFR, but not with SBPao.Based on our results in IgAN patients, the increase in diastolic dysfunction is observed by decreasing renal function, which is best described by E/A, EDT, and Ea as defined by TDI, similarly in CKD, which could have a close relation to arterial stiffness.Cardiovascular alterations (based on echocardiographic parameters) develop in the early stages of CKD (which was most pronounced in the IgAN CKD 3–5 compared to non-CKD controls). There may be a difference in the dynamics of these, which may stem from the etiology of the disease , but theSeveral previous studies have found an association between LV diastolic function and arterial stiffness in normal subjects. Cauwenberghs et al. studied 1233 subjects from the general population and showed that diastolic parameters are significantly correlated with cfPWV and central pulse pressure as measured by arterial tonometry . We founPrevious studies have shown that E/Ea, an estimate of LV filling pressure by Doppler echocardiography, is a predictor of all-cause mortality in patients with LV systolic dysfunction and after acute myocardial infarction , 33. AnoIn CKD, several conditions contribute to the pathogenesis of HFpEF, of which the central aortic blood pressure may be the most important such as peripheral arterial hypertension . Left veIn Escoli et al.’s review, they suggest patients with CKD and ESRD should be monitored regularly (perhaps every 1–2 years) for the development and assessment of the severity of LVH and cardiac fibrosis, most likely with serial echocardiography . NonetheHypertension is well known to be a major risk factor for the development of LVDD in patients on chronic hemodialysis . HoweverIn Shu’s KNOW-CKD study, LVDD was independently associated with adverse CV outcomes and all-cause mortality in patients with predialysis CKD . Liang eThe acceleration of renal function loss and progression to ESRD are both worsened by known CV risk factors, such as baseline eGFR, proteinuria, and hypertension, which are also risk factors for CKD progression. However, the progression of CKD, a complex process, cannot be explained in all cases by these traditional risk factors. This may also underline the importance of arterial stiffness measurement.Similar findings were made by Redfield et al. , who exaLVDD is closely linked to arterial stiffness because the uremic milieu predisposes patients with CKD to systemic arterial stiffness and myocardial interstitial fibrosis, ultimately leading to LVH and impaired LV relaxation and compliance , 55. ZanOur data revealed that hypertension is a highly common consequence in IgAN , 58, affSimilar results were also found in a population of rheumatoid arthritis patients in which inflammation is the main component . In the In the case of subgroup analysis, these accompanying factors such as hypertension and diabetes further worsen the patients’ CV risk, so special attention should be paid to them.Our results may highlight the potential contribution of increased pulsatile load and LV-arterial coupling to LV diastolic dysfunction in CKD. Given that LVDD is a main determinant of HFpEF, it can also be postulated that increased arterial stiffness is an important risk factor for developing HFpEF. In addition, arterial stiffness could be a good monitoring tool to assess LV diastolic dysfunction. Measuring arterial stiffness in routine clinical practice is a cheaper and simpler test than echocardiography, but should be used with due caution. The prevention of heart failure or, more importantly, a delay in the evolution of LV diastolic dysfunction may be good therapeutic goals for decreasing arterial stiffness.Our results showed that the values of tissue Doppler parameters and arterial stiffness can be useful for clinical evaluation. However, difficulties may arise during echocardiographic and arterial stiffness measurements. In some cases, specifically with the elderly, a lack of cooperation can be a problem.The arterial stiffness measurement is determined by two non-gold standard methods first is finger photoplethysmography, second an oscillometric method. Occasionally, there are difficulties in registering the digital pulse volume and pulse wave velocity. It may be problematic in some cases, mostly in elderly patients, to confidently separate systolic and reflective waves and thus assess the stiffness index. Atrial fibrillation and frequent atrial and ventricular ectopic activity could also limit correct pulse curve detection. We estimated and did not measure renal function. However, the use of eGFR is widely accepted throughout the literature. Data analyses may be weakened by the low number of our cases and the relatively low number of patients with CKD 4–5. The current study failed to look at the degree or progression of proteinuria. The evaluation of the results may also be weakened by the low number of female patients. We did not examine left atrial volume, myocardial strain, or strain rate. In our study, we examined only one etiology of CKD, IgAN.Despite these limitations, the results of this study highlight that the onset of target organ damage in CKD is predicted by TDI and arterial stiffness.Our results suggest that the simultaneous use of arterial stiffness and tissue Doppler echocardiography parameters (Ea and E/Ea) appears to be a suitable process to identify high-risk, asymptomatic CKD patients. Arterial stiffness elevation compared with a control group can indicate an increase in CV risk at an earlier stage of CKD.Lower Ea and higher E/Ea, PWV, or SI should call attention to those CKD patients who have higher renal and CV risk and need to be monitored more closely, referred for further CV tests, and given maximal nephroprotection. It is not the duration of the kidney disease but its progression and the loss of kidney function that is dangerous.Our findings support the role of tissue Doppler echocardiography and arterial stiffness measurement in the high-CV-risk population of CKD patients, which also helps to understand the relationship between heart abnormalities and renal impairment.In conclusion, impaired renal function gradually correlates with Ea, E/Ea, SI, and PWV parameters in patients with CKD. Decreased renal function is associated with decreased Ea and increased E/Ea, which could be responsible for a later poorer prognosis due to worse CV and renal outcomes. In the background, the role of common vascular and myocardial pathological remodeling could be hypothesized, which is worsened by metabolic changes and immunological alterations in this group of patients.Further large-scale, multicenter prospective studies are warranted to evaluate the role of CV risk factors in mediating the changes in the TDI and vascular stiffness parameters, as well as the complex relationships between CV disease and CKD.


Reduced occlusal function is a main characteristic of orthognathic patients. The present study aimed to investigate the extent of therapy-induced functional improvements in occlusal function using a digital diagnostic method.This prospective clinical study included 41 orthognathic patients  and 10 control patients  with neutral skeletal and dental configurations. The patients were divided into classes I, II and III based on their cephalometry. Digital occlusal registrations in habitual occlusion in an upright sitting position were taken before (T1) and after (T2) therapy using the T‑Scan Novus  application.p < 0.001), time of occlusion (p = 0.004), occlusal asymmetry (p = 0.001), anterior antagonism (p < 0.001) and posterior antagonism (p < 0.001). After therapy, the occlusal pattern increased in both therapy groups, where class III patients became indistinguishable from the controls, and class II patients differed only in posterior antagonism (p = 0.035).Class II and III patients showed a significantly less efficient occlusal pattern than the untreated controls regarding total antagonism (The digital occlusal registration method proved to be a useful diagnostic tool and provided new insights into therapeutic effects in orthognathic patients. By precisely adjusting the occlusal function, masticatory performance improved significantly.Severe malocclusion leads to a significantly lower masticatory performance for patients, which can be improved by orthognathic therapy and captured by digital occlusal registration. The correction of malocclusion in orthognathic patients plays a key role in the rehabilitation of masticatory function , 2. WithReduced tooth antagonism and/or a prolonged occlusion time resulting in reduced masticatory performance has been reported in different clinical trials , 10. To to implement a digital registration technique in a clinical setting of interdisciplinary orthognathic treatment,to examine orthognathic patients differentiated by skeletal class and the extent of malocclusion longitudinally before and after treatment, andto quantify the therapeutically induced effects on occlusal function.Therefore, this study aimedThis observational cohort study with a prospective approach was approved by the local Institutional Ethics Committee of the University Medical Center Goettingen (ethics number 7/1/16). The study was carried out according to the principles of the Declaration of Helsinki and is listed in the German Clinical Trials Register. All patients participated in the trial on a voluntary basis after receiving comprehensive information about the aim and design of the study and signing an informed consent form. This report complies with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for observational studies . A sampln = 5; Table Forty-six orthognathic patients  who received interdisciplinary treatment  participated in the trial. The patients were recruited from the Department of Orthodontics and underwent operation at the Department of Oral and Maxillofacial Surgery at the University Medical Center Göttingen. All data were collected from March 2019 to February 2021 and were analysed by a single investigator (BW). Of the 46 patients initially screened, 41 patients  were finally included in the study  with an angle class II occlusion; overjet median 8.1 ± 2.3 mm and overbite median 1.5 ± 2.9 mm; Wits appraisal median 5.6 ± 4.3 mm and ML-NL  median 30.5 ± 15.6°.Class III: 20 subjects  with an angle class III occlusion; overjet median −1.35 ± 3.4 mm and overbite median 0 ± 2.3 mm; Wits appraisal median −7.3 ± 4.9 mm and ML-NL median 27.75 ± 12.2°.The patients were classified into two groups according to their skeletal deformity, and we included a control group with a neutral skeletal morphology.Control group: 10 subjects  with an angle class I occlusion; overjet median 2.05 ± 1.1 mm and overbite median 1.75 ± 1.7 mm; Wits appraisal median −0.6 ± 1.3 mm and ML-NL median 22.75 ± 5.1°. All controls had a complete dentition of natural teeth (no implants or prosthetic restorations—premolar agenesis was neither an exclusion nor an inclusion criterion). The exclusion criteria for the controls were the presence of temporomandibular disorders (TMDs), open bite, traumatic deep bite, crossbites, nonocclusions, and asymmetries.In each group, digital occlusal registration was performed using T‑Scan Novus and the associated software T‑Scan 9.1 . The system allows for occlusal registration with an electronic occlusion foil of 100 µm thickness (compressible to 64 µm). The software enables the analysis and archiving of each patient’s registration by creating an individual patient-specific virtual dental arch, as seen in Fig. Statistical analyses were performed using SPSS Statistics version 26 . The Shapiro–Wilk test was used to test the variables for normal distribution. Accordingly, none of the measurement parameters, except for the parameter “time of occlusion”, were normally distributed. For this reason, the data were subsequently analysed using the Kruskal–Wallis test for independent samples and adjusted for multiple testing using Bonferroni correction. Post hoc tests were then performed for the analysis of dependent variables between groups. Analysis of related samples was performed using Wilcoxon tests.p < 0.05. Study-specific measurement parameters were examined using descriptive statistics and reported as medians and interquartile ranges. To account for individual configurations, such as premolar agenesis or therapeutic premolar extractions, and to compare them with the fully edentulous study patients, a recording of antagonism in percent was chosen.The significance level was set at The parameters total antagonism, occlusal asymmetry, and anterior and posterior antagonism were thus output as percentages, and the associated medians and interquartile ranges were determined. In addition, the time of occlusion  was recorded, rounded to the nearest hundredth of a second, and the associated medians and interquartile ranges were also determined for each associated measurement period Tables  and 4.TaTo determine the error of the occlusal registration method, the controls were recorded again, the occlusal parameters were remeasured by the same examiner after a minimum one-week interval, and the Dahlberg method  was applp = 0.071). The sex distribution in all three groups was well balanced. The results of the descriptive analysis of the occlusal parameters for all patients and controls at T1 and T2 are listed in Tables The demographic data for all patients, detailed clinical characteristics of the patients and controls and the type of intervention are shown in Table At timepoint T1, the independent sample analysis for the variables revealed strong significant differences over all study groups for all analysed parameters. The intergroup analysis performed by post hoc tests also revealed significant differences in almost all parameters between both therapy groups compared to the controls.p < 0.001). In addition, the parameter “time of occlusion” was twice as long than that of the controls (class II/class III p < 0.001), and occlusal asymmetry was more than four times higher in class II patients (p = 0.006) and more than five times higher in class III patients (p < 0.001). With respect to anterior antagonism, the patients with skeletal class II had no contact between antagonistic teeth, resulting in insufficient anterior antagonism (p < 0.001). Class III patients had approximately one-third of the possible occlusion contacts (p = 0.020). With respect to posterior antagonism, both groups showed less than two-thirds of the possible occlusion contacts (class II/class III p < 0.001). In comparing the therapy groups, no significant differences could be detected for any parameter.Overall, the parameter values reflected noticeably reduced occlusal function in skeletal class II and class III patients. It was evident that both therapy groups had occlusion on only half of their teeth, which was significantly different than in the controls  and posterior antagonism (p = 0.035). When comparing the therapy groups, no significant differences could be seen for any of the parameters.At timepoint T2 (9 months after surgery), all variables of the patients with skeletal class II and skeletal class III showed a clear convergence with the level of the controls. The independent samples analysis for the variables revealed significant differences concerning total and posterior antagonism. All other variables showed no significant differences when comparing the therapy groups to the controls. Post hoc analysis clarified that skeletal class III patients were indistinguishable from the control sample, whereas patients with skeletal class II still showed slightly significant differences concerning total antagonism . Many publications have described the clear superiority of quantitative and qualitative T‑scan procedures compared to conventional qualitative methods, primarily because they avoid the subjective interpretation of the practitioner . The relThe statistical analysis of the present study results indicated an inefficient masticatory function of patients with a severe skeletal malocclusion compared to controls. This was particularly evident when considering the parameters “total antagonism” and “time of occlusion”. Both treatment groups preoperatively required significantly more time from the initial to the final tooth contact in maximum intercuspation and they presented with significantly less tooth antagonism, which suggests an inefficient functional status , 10. MorThe parameter “occlusal asymmetry” showed a significantly different bilateral occlusal pattern between controls vs. both skeletal class II and class III patients. To date, there do not exist data for orthognathic patients about possible asymmetry with a side-specific distribution of occlusal contacts. Only for adults with neutral occlusion has a side-specific asymmetry with a Δ of 5.2 in maximum static occlusion been described . This isAfter orthognathic therapy, the results in this study showed that for almost all occlusal parameters, a clinically significant improvement could be detected for the orthognathic patients, and they showed parameter values similar to those of the control group. Patients with a skeletal class III showed consistent values for each parameter. Only patients with a skeletal class II showed a persistent significant difference for the parameter “total antagonism” at timepoint T2, which, according to the post hoc test, was primarily attributable to deviations in posterior antagonism. This could result from the fact that one-third of the class II subjects were treated with isolated mandibular advancement, whereas in the class III patients, almost all of them were treated with bimaxillary surgery.Regarding the impact of orthognathic therapy on asymmetries, the existing literature refers primarily to skeletal or soft tissue effects . TherefoIn reviewing the study results and considering that the occlusal registrations were performed by only one clinically experienced examiner, the results can be accepted as valid and conclusive to describe the effects of orthognathic therapy. Above all, the changes in the parameter “occlusal time”, which had not been determined previously, highlight the diagnostic value on the one hand and the therapeutic value of the orthodontic/surgical therapy on the other. Based on the reduced occlusion time and the increase in total antagonism in both therapy groups, the enhancement in occlusal function resulting in an increase in masticatory efficiency was shown.Digital occlusal registration could be clinically implemented with an easy and fast approach in orthognathic therapy. Digital occlusal registration proved to be a useful diagnostic tool and provided new insights into therapeutic effects. Patients with severe malocclusion are characterized by inefficient occlusal function compared to controls and develop increased masticatory efficiency after orthognathic therapy.