Postoperative delirium (POD) is a common complication in elderly patients after hip fracture surgery. Our study was to investigate whether intraoperative mean arterial pressure variability (MAPV) was associated with POD in elderly patients after hip fracture surgery.In this retrospective cohort study, patients aged 65 years and older undergoing hip fracture surgery were included. The correlation between MAPV and POD was investigated using univariate and multivariate logistic regression. Covariate-related confounding effects were eliminated with propensity score matching (PSM) analysis. Then, a subgroup analysis was conducted to further examine the associations between MAPV and POD.P < 0.001). All covariates between the two groups were well balanced after PSM adjustment. A significant correlation between MAPV and POD was found in the PSM analysis .Nine hundred sixty-three patients with a median age of 80 years (IQR: 73–84) were enrolled. POD occurred in 115/963 (11.9%) patients within 7 days after surgery. According to multivariate regression analysis, MAPV > 2.17 was associated with an increased risk of POD (OR: 2.379, 95% CI: 1.496–3.771, An increased intraoperative MAPV may be a predictor for POD.The online version contains supplementary material available at 10.1186/s12877-023-04425-9. Postoperative delirium (POD) is a common complication of hip fracture surgery , 2. The Several factors may contribute to POD , 10. ResIn this study, we proposed an indicator, namely, intraoperative mean arterial pressure variability (MAPV), for quantifying blood pressure fluctuations. We hypothesized that high MAPV is associated with a higher risk of POD.In this retrospective cohort study, patients aged 65 and older who underwent hip fracture surgery at the First Medical Centre of the Chinese PLA General Hospital between January 1, 2014, and December 31, 2018, were included. The Chinese PLA General Hospital's Ethics Committee Board approved this study (protocol number: S2019-311–03) and waived informed consent requirements.The inclusion criteria were as follows: 1) patients aged 65 years and older; and 2) patients who underwent hip fracture surgery. A person who underwent a second surgery for hip fracture was considered a new patient. The exclusion criteria were as follows: 1) missing data on intraoperative blood pressure; and 2) missing information on primary medical records.Data were collected from the anesthesia information management system. A manual filter was applied to the raw data values in which either the systolic blood pressure or the diastolic blood pressure was 0 mmHg. The electronic hospital information system was used to collect demographic, preoperative and postoperative data and data on medication use. Laboratory tests were performed within three days before the surgery.The patient’s arterial blood pressure was measured from the time they entered the operating room to the time they left. Invasive blood pressure measurements were collected continuously, and non-invasive blood pressure measurements were collected every three or five minutes. All blood pressure values were recorded every 30 s.The MAP was calculated as follows: (systolic blood pressure−diastolic blood pressure)/3 + diastolic blood pressure. Continuous invasive measurements as well as non-invasive measurements were used to extract the MAP. If both the invasive and non-invasive blood pressure measurements were available at a given time point, the information from the invasive measurement was used in the analysis since it is a direct measurement of the MAP as opposed to an estimation derived from the oscillometric measurement.The variability in a patient's blood pressure record was calculated to quantify fluctuations in blood pressure during surgery. Consequently, a patient with more blood pressure fluctuations has greater blood pressure variability than a patient with a relatively constant blood pressure during surgery. We developed an indicator of intraoperative MAPV to measure blood pressure fluctuation. MAPV was calculated as follows:The primary outcome was the incidence of POD within seven days after surgery. Neurologists confirmed the diagnosis based on descriptive words in the medical records. The diagnostic criteria were proposed and demonstrated in a previous study . The detAccording to the available literature and clinical plausibility, we selected the following potential confounding variables: age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) physical status, diabetes mellitus, hypertension, cardiovascular disease, cerebrovascular disease, chronic obstructive pulmonary disease (COPD), dementia, alcohol consumption, fracture type, white blood cell (WBC) count, hemoglobin level, red blood cell (RBC) count, albumin level, anesthesia method, duration of surgery, use of benzodiazepines, dexmedetomidine, or glucocorticoids, and emergency surgery.Receiver operating characteristic (ROC) curves were used to determine the optimal MAPV cutoff value for predicting POD. Multivariate and univariate logistic analyses were then conducted to investigate the correlation between MAPV  and POD. Univariate logistic regression analysis was performed for the correlation between MAPV and POD in model 1. In the multivariate logistic regression analysis, model 2 was adjusted for age, sex, BMI, ASA, hypertension, diabetes mellitus, cardiovascular disease, cerebrovascular disease, COPD, dementia and alcohol consumption. Model 3 was adjusted for WBC count, RBC count, hemoglobin level, albumin level, anesthesia method, duration of surgery, and use of benzodiazepines, dexmedetomidine or glucocorticoids. In model 4, all variables in models 2 and 3 were accounted for.We used propensity score matching (PSM) to pair the treatment and control patients with similar propensity scores. A multivariate logistic regression model was used to compute propensity scores based on the probability that patients had a different MAPV level . MatchinTo investigate the correlation between MAPV and POD by sex, age, cerebrovascular disease status, ASA physical status, and anesthesia method, subgroup analyses were conducted after logistic regression analysis of model 4. Subgroup predictions of POD by the MAPV value were summarized in a forest plot.P value < 0.05.Each statistical model was run using R 4.0.5 . Missing data were imputed using the random forest method in the ‘mice’ package. The median and interquartile range (IQR) are presented for continuous data and were compared with the Mann‒Whitney test. Frequencies with percentages are expressed for categorical variables and were compared with the χ2 test or Fisher’s exact test. For all tests, statistical significance was determined by a two-sided Retrospective analyses were conducted on 973 patients over 65 years old who underwent hip fracture surgery at the Chinese PLA General Hospital's First Medical Center between January 2014 and December 2018. In the final analysis, 963 patients were included after excluding 8 patients due to a lack of records and 2 patients due to a lack of blood pressure values  and high MAPV . The baseline characteristics of the groups are presented in Table When conducting ROC analysis, the appropriate cutoff value was selected to maximize the sum of sensitivity and specificity in Supplementary Fig. P < 0.001 (model 1)). The ORs of MAPV in multivariate logistic regression were 1.277 (model 2), 1.375 (model 3), and 1.246 (model 4). Therefore, MAPV played an independent role in POD  of 1.385  . In total, 471 patients MAPV ≤ 2.17 group) were matched with 157 patients (MAPV > 2.17 group). As shown in Fig. .17 groupP < 0.05, Fig. Additionally, in each subgroup, the MAPV ORs were significant for sex and anesthesia method .


The prevalence of CKD stage ≥ 3 was slightly higher in ALS cases than in controls (14.1 vs. 11.0%). In the adjusted models, CKD stage 2  and stage 3  were associated with increased ALS risk. In this cohort of ALS cases, eGFR and CKD stage ≥ 3  were not associated with prognosis. In this case–control study, higher CKD stages were associated with increased ALS risk, while in the prospective cohort of ALS cases, no indication of an association of CysC-based CKD on mortality was seen. In addition, our work strengthens the importance to evaluate renal function using a marker independent of muscle mass in ALS patients.Kidney function as part of metabolic changes could be associated with amyotrophic lateral-sclerosis (ALS). We investigated the associations between estimated chronic kidney disease (CKD), based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C equation, and the risk at onset and prognostic value of CKD for ALS. Between October 2010 and June 2014, 362 ALS cases  and 681 controls  were included in a population-based case–control study based on the ALS registry Swabia in Southern Germany. All ALS cases were followed-up (median 89.7 months), 317 died. Serum samples were measured for cystatin C to estimate the glomerular filtration rate (eGFR) according to the CKD-EPI equation. Information on covariates were assessed by an interview-based standardized questionnaire. Conditional logistic regression models were applied to calculate odds ratios (OR) for risk of ALS associated with eGFR/CKD stages. Time-to-death associated with renal parameters at baseline was assessed in ALS cases only. ALS cases were characterized by lower body mass index, slightly lower smoking prevalence, more intense occupational work and lower education than controls. Median serum cystatin-C based eGFR concentrations were lower in ALS cases than in controls (54.0 vs. 59.5 mL/min pro 1.73 m Metabolic alterations were observed in patients with ALS and in animal models contributing to the evidence that dysregulation in energy metabolism is associated with ALS risk4.Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease affecting progressively different parts of the body and going along with progressive motor neuron degeneration. The mean survival in ALS-patients is about 3–4 years. The precise aetiology and biological mechanisms underlying ALS remain unclear. During recent years, multiple factors contributing to the development and progression of ALS have been suggested8, metabolic hormones11, or inverse association with diabetes mellitus12. From a broader perspective, ALS appears generally associated with physical fitness13 and decreased incidence of chronic diseases14.Metabolic alterations appear causally linked to ALS disease progression as shown by case-control studies focusing on weight loss14 found a decreased risk association between prior kidney disease and ALS in an observational study, while in another study, existing kidney disease was associated with shorter survival15. The lack of information on possible relationships between ALS and kidney function is likely due to the fact that serum creatinine is generally used as a biomarker of kidney function in the general population. However, serum creatinine is heavily confounded in ALS patients by decreased muscle mass and venous creatinine actually correlates with fat free mass in patients with ALS16.Among chronic diseases possibly associated with ALS, kidney disease appears particularly interesting and under-studied. Indeed, Mitchell et al.17, it is generally recommended to evaluate kidney function using cystatin C-based equations. Cystatin C (CysC) is a lysosomal protein acting as an endogenous inhibitor of cathepsins18. CysC is also extensively expressed in neurons, astrocytes, endothelial and microglial cells in the brain and is also found in body fluids. Importantly, CysC is unaffected by several factors such as age, sex, and muscle mass19 and CysC concentrations were found to be a reliable marker for kidney function overall20. CysC based equations outperformed creatinine equations in evaluating kidney function in primary neuromuscular diseases21 and in ALS patients22.In clinical situations with secondary muscle mass loss or neurological diseases20. In addition, we used the prospective data of the ALS cases to investigate the prognostic value of cystatin- C based kidney function according to CKD-Epi stages in ALS with respect to overall survival.To date, little is known about the association of (chronic kidney disease) CKD with ALS onset and progression. In order to clarify the relation between kidney function and risk of ALS without the confounding effect of decreased muscle mass, we measured CysC concentrations and applied the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, based on CysC in a registry-embedded case–control study25. In brief, it is a population-based clinical-epidemiological registry with the aim to collect data on all newly diagnosed ALS cases in Swabia, a defined geographic region with approximately 8.4 million inhabitants in the South-West of Germany.The ALS registry Swabia has been described previously in detail26. Notifications of patients with suspected ALS were re-evaluated during the clinical course by the registry.All reported ALS cases were defined by the diagnosis of possible, probable or definite ALS according to the revised El Escorial criteria by an experienced neurologist24. Response in cases was 65% (20% refused and 15% could not be contacted) and in the population-based controls 19% .Patients registered between October 01, 2010 and June 30, 2014 were offered to provide informed consent to participate in a population-based case–control study. For each case (N = 362), two sex and age frequency-matched control subjects (N = 681) were randomly selected from the general population as registered in the regional registry office (“Einwohnermeldeamt”). The identified subjects were contacted by postal mail and invited to participate in the study. After written informed consent was obtained, study nurses visited the participants for a standardized interview and blood sampling. The standardized instruments and tests were performed identically in ALS cases and controls. Information on body mass index (BMI), smoking status, educational attainment, family history of ALS, occupation work intensity and medical history of hypertension, diabetes mellitus, chronic heart disease, and myocardial infarction was collectedIn addition, ALS cases were actively followed-up annually and interviewed. To update vital status record linkage with the central registration offices in Baden-Württemberg and Bavaria were performed . In case of death, the date of death was obtained from the local registration office.All methods were carried out according to international, national, and state rules in implementing the ALS registry in Swabia. We obtained approval of the ethical committees of Ulm University and the regional physician chambers ("Landesaerztekammer Baden-Wuerttemberg" and "Landesaerztekammer Bayern").g and 4 °C . Blood specimens were transferred into 0.5–1.0 mL aliquots with screw tops on the same day and stored at − 80° Celsius until further analysis. CysC (mg/L) was measured in serum using an immunonephelometric assay . All laboratory analyses were performed in blinded fashion at the Biomarker Laboratory of the Department of Internal Medicine II-Cardiology, Ulm University Medical Center.According to a common standard protocol for cases and controls, blood samples were transported in cooled containers to the study center. Serum was obtained by centrifugation for 10 min at 2000 RPM×27 CKD stages were categorized according to cut-points suggested by Inker et al.28 Adjustment variables were identified by Directed Acyclic Graphs (DAG)29. Models were conditioned on age and sex, and adjusted for BMI, diabetes mellitus, and smoking (ever)  and 95% confidence intervals (CI) for the association of renal function (i.e. stages of CKD and ALS. Glomerular filtration rate (eGFR) was calculated based on the CKD-EPI CysC equationThe Cox proportional hazards model was adjusted for age and sex. Additional adjustment for diagnostic delay, site of onset, ALS-functional risk score (FRS), body mass index, self-reported diabetes and smoking (ever) status were applied to calculate hazard ratios (HRs) for overall survival in ALS cases only . Survival times were calculated until date of death, date of tracheostomy with invasive ventilation (TIV) or date of the last systematic mortality update , whatever came first. The proportional hazards assumption was assessed graphically. Sensitivity analyses excluding the El Escorial categories "clinically suspected" and "clinically possible" were performed in the adjusted model. All provided p-values are two-sided. The statistical software package SAS release 9.4  was used.2), slightly lower smoking prevalence (ever: 48.7% vs. 49.2%), more intense occupational work  and lower education (≥ 10th grade: 44.8% vs. 56.1%) than controls. ALS onset was lumbar (n = 120 [33.2%]), bulbar (n = 116 [32.0%]), or cervical (n = 106 [29.3%]). Based on the revised El Escorial criteria, more than 70% of ALS cases had a probable or definite clinical diagnosis.In the case–control study data from 362 cases (mean age 65.7 SD 10.6) years, 59.4% male) and 681 controls (mean age 66.3 (SD 9.9) years, 59.5% male) were included (Table 0.6 years2), while the prevalence of CKD stage 3 and more was higher in ALS cases than controls (in sum 14.1 vs. 11.0%). Compared to controls, ALS cases had higher prevalence of hypertension (48.4 vs. 46.5%) and CVD (51.4 vs 49.6%), while self-reported CKD (1.3 vs. 2.9%) was less prevalent, and diabetes mellitus (10.5 vs. 10.5%) was identically reported.The median serum CysC concentration was numerically higher in ALS cases than in controls (0.91 vs. 0.88 mg/L). Concerning renal function, the eGFR was lower in ALS cases than in controls   Table . CKD sta2), longer median diagnostic delay (7.0 vs. 5.0 months) and higher median ALS-FRS (43 vs. 38 points) (Table 2). Survivors were characterized by lower CKD stages.317 (88%) of 362 ALS cases, died during a median follow-up of 89.7 months. Compared to the deceased, survivors were characterized by younger mean age (62.6 vs. 66.2 years), were more frequently male (77.8% vs. 56.8%), had a higher a mean BMI  and the model 4c further adjusted for body mass index, self-reported diabetes and smoking (ever)  Table .Table 4HThe study was conducted within the population-based ALS registry Swabia, which started to prospectively recruit newly diagnosed ALS cases in the South-West of Germany in October 2010. In the case–control study a slightly higher prevalence of CKD stages ≥ 3 was evident in ALS-cases compared to controls. In the models however, after adjustment for covariates an inverse association between eGFR with ALS risk was found. Concerning kidney function, CKD stage 3 more than doubled the ALS risk when compared to stage 1 as reference group. In the cohort of ALS cases, no clear associations of eGFR and CKD stages with all-cause mortality were observed, indicating that CKD has no prognostic value in ALS.14 reported a lower prevalence of kidney disease as a comorbid condition among patients with ALS than in the control population. The differences could be related to differences in the study population , the disease definition  and the mean age of the study samples, which was about five years higher in our population. Our findings concerning increased ALS risk among patients with decreasing eGFR and increasing CKD stages are consistent with previous observations concerning age of onset and duration of ALS15. In their case–control study, previous kidney disease was associated with the duration of ALS disease15. Yet, how CKD might influence ALS prognosis still remains to be investigated.In the present study, we found a higher prevalence of CKD according to biomarker measurements of renal function among ALS cases than among controls . In contrast, Mitchell et al.22 characterized renal function in 76 ALS patients and 30 controls based on both creatinine and CysC-based eGFR. There findings of no association between CysC-based eGFR-measurements and ALS are in contrast with our results for low CKD stages and previous studies suggesting a utility of CysC levels in ALS diagnosis32 or prognosis33. Other studies also did not find altered levels of CysC in ALS patients neither in blood nor in cerebrospinal fluid (CSF)34. A meta-analysis of these studies suggested decreased levels of CysC in CSF, but unchanged levels in the blood35, consistent with our results. Indeed, our results do not exclude that CysC, as an inhibitor of lysosomal cathepsins could have a translational potential through a CNS local effect, as was suggested in a mouse model of ALS36.Tetsuka et al.37. Critically, creatinine levels are confounded by loss of muscle mass in ALS. Indeed, Holdom and collaborators investigated the association of creatinine with disease progression16 and showed that blood creatinine concentration decreased with fat-free mass during progression16. Taken together, the previously observed relations between creatinine and disease progression are likely to be unrelated to kidney function. In all, the evidence available16 strengthens the importance to evaluate renal function using a marker independent of muscle mass in ALS patients, such as CysC-based eGFR20.While measuring renal function using CysC did not unambiguously relate ALS and CKD, levels of creatinine, another widely clinically used marker of renal function, however correlate with disease progression38, maintaining muscle mass may be associated with better prognosis.In addition, since serum creatinine levels appear negatively associated with ALS progression as a surrogate of decreased muscle mass rather than kidney function, and since moderate physical activity appears prognostically favorable24 with a median follow-up of 89.7 months. Strengths of our study are the population-based approach and the embedded case–control study with virtually complete follow-up of ALS cases. The phenotype distribution of ALS cases recruited in the case–control study was similar to the distribution in the epidemiological ALS registry Swabia Rosenbohm et al. (2017), suggesting little selection bias25.Some limitations need to be considered when interpreting the results of our study. Residual confounding cannot be ruled out. Therefore, for the case–control study part, no causal conclusion can be drawn. When generalizing the results of the case–control study, the low participation rate among controls should be considered. Due to the matched study design agegroup, sex and regional distribution were controlled. However, in the control group were more persons with higher school education (≥ 10th grade: 56.1% vs. 44.8%) and less intensive occupational work . Though we carefully used multivariable analysis in order to further adjust for potential confounder, the self selection of the control subjects may have resulted in differential estimates. CKD as a prognostic factor was analyzed in a cohort of ALS patients, who are representative for the ALS registry SwabiaTaken together, we found evidence for an association between CKD stages with ALS risk. However, in the cohort of ALS cases, no prognostic impact of CysC -based CKD on mortality was seen.Supplementary Information 1.Supplementary Information 2.


This study aimed to evaluate the efficacy of single‐pill combination (SPC) antihypertensive drugs in patients with uncontrolled essential hypertension. Through Searching Pubmed, EMBASE, the Cochrane Library, and Web of Science collected only randomized controlled trials on the efficacy of single‐pill combination antihypertensive drugs in people with uncontrolled essential hypertension. The search period is from the establishment of the database to July 2022. The methodological quality of the included studies was assessed using the Cochrane Risk of Bias Assessment, and statistical analyses were performed using Review Manage 5.3 and Stata 15.1 software. This review ultimately included 32 references involving 16 273 patients with uncontrolled essential hypertension. The results of the network meta‐analysis showed that a total of 11 single‐pill combination antihypertensive drugs were included, namely: Amlodipine/valsartan, Telmisartan/amlodipine, Losartan/HCTZ, Candesartan/HCTZ, Amlodipine/benazepril, Telmisartan/HCTZ, Valsartan/HCTZ, Irbesartan/amlodipine, Amlodipine/losartan, Irbesartan/HCTZ, and Perindopril/amlodipine. According to SUCRA, Irbesartan/amlodipine may rank first in reducing systolic blood pressure (SUCRA: 92.2%); Amlodipine/losartan may rank first in reducing diastolic blood pressure (SUCRA: 95.1%); Telmisartan/amlodipine may rank first in blood pressure control rates (SUCRA: 83.5%); Amlodipine/losartan probably ranks first in diastolic response rate (SUCRA: 84.5%). Based on Ranking Plot of the Network, we can conclude that single‐pill combination antihypertensive drugs are superior to monotherapy, and ARB/CCB combination has better advantages than other SPC in terms of systolic blood pressure, diastolic blood pressure, blood pressure control rate, and diastolic response rate. However, due to the small number of some drug studies, the lack of relevant studies has led to not being included in this study, which may impact the results, and readers should interpret the results with caution. High blood pressure significantly increases the incidence of stroke, myocardial infarction, heart failure, and chronic kidney disease and is the leading cause of cardiovascular disease and premature death worldwide. Single‐pill combination preparations are a hot topic in the field of treatment of essential hypertension. In this study, the efficacy of different single‐pill combinations (SPCs) in the treatment of patients with uncontrolled essential hypertension was evaluated by network meta‐analysis, and the optimal treatment regimen was selected according to SUCRA values, and the results showed that the angiotensin II receptor blocker (ARB)/calcium‐channel blockers (CCB) combination had a significant advantage in lowering blood pressure. The search strategy is built around the PICOS tool: (P) population: patients with uncontrolled essential hypertension; (I) Intervention: use of single‐tablet combination drugs; (C) Comparison group: monotherapy, free combination of blood pressure reduction; (O) Results: Antihypertensive effect of patients with essential hypertension included systolic blood pressure, diastolic blood pressure, blood pressure control rate, and diastolic response rate after treatment. (S) Study type: Randomized controlled trial. (S) Study type: Randomized controlled trial. The detailed search strategy is shown in Table 2.22.2.1All included studies were clinical randomized controlled trials (RCTs).2.2.2Patients with essential hypertension with systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg after at least 4 weeks of monotherapy or free combination therapy and adults older than 18 years.2.2.3The experimental group was given SPC antihypertensive drugs to treat essential hypertension, and the control group was given other antihypertensive drugs to treat essential hypertension.2.2.41)Change of SBP in the office after treatment;2)The change value of DBP in the office after treatment;3)BP control rate (SBP < 140 mmHg and DBP < 90 mmHg);4)DBP response rate (patients with a mean sitting DBP < 90 mmHg at the end of treatment and/or a decrease in mean sitting DBP of 10 mmHg).2.31)Patients with secondary hypertension;2)Nonclinical randomized controlled trials;3)Literature with incomplete data or inability to obtain full text;4)Guidelines, reviews, conferences, meta‐analyses, animal and cell experiments;Repeat publications.2.4Use the document management software EndNote X 9.0 to filter and exclude documents. Two review authors first screened the titles of replicates, nonrandomized controlled trials, review papers, conference papers, and meta‐analyses. Two review authors then read abstracts to identify included and excluded studies. Finally, the remaining literature was read in its entirety by two review authors and further determined for inclusion. In this process, the two researchers independently screened the literature and finally compared the remaining literature; If they are the same, they are eventually included, and if they are different, they are discussed and resolved by a third investigator.2.5Standardized and preselected data extraction tables were used to record data to be included in studies under the following headings: (1) author, (2) year of publication, (3) country, (4) study participants, (5) total sample size, (6) mean age, (7) intervention, and (8) study period.2.6Two researchers independently assessed the risk of bias (ROB) in accordance with the Cochrane Handbook version 5.1.0 tool for assessing ROB in RCTs. The following seven domains were considered: (1) randomized sequence generation, (2) treatment allocation concealment, blinding of (3) participants and (4) personnel, (5) incomplete outcome data, (6) selective reporting, and (7) other sources of bias. Trials were categorized into three levels of ROB by the number of components for which high ROB potentially existed: high risk (five or more), moderate risk (three or four), and low risk (two or fewer).2.7Statistical analysis using Stata 15.1 and Review Manager 5.3. According to the characteristics of the data type, the effect size that can reasonably reflect the overall data was selected. If the analysis data were continuous data, the effect size was the mean difference (MD). The odds ratio (OR) was used if the data were binary. Effect sizes were presented with 95% confidence intervals (CI).p‐value > .05, the consistency is verified.We used Stata 15.1 and based on the PRISMA NMA instruction manual, to simulate chains using Markov chain Monte Carlo simulation chains in a Bayesian‐based framework for NMA aggregation and analysis.Stata software was used to present and describe the network diagrams of different single‐pill combination drugs in the treatment of essential hypertension. The intervention network map is an intuitive representation of the evidence base, where each node in the generated network map represents a different intervention and different control conditions, and the lines connecting the nodes represent direct head‐to‐head comparisons between interventions. The size of each node and the width of the connecting line are proportional to the number of studies.33.1The initial research resulted in 7024 references. After removing duplicates, reading the titles and abstracts of the remaining 3410 references, again excluding 3326 references after screening for potential studies, and searching the remaining 288 references in full text, of which 256 did not meet the eligibility criteria . The last 32 studies were included in this study. After removing duplicates, the titles and abstracts of the remaining 3410 references were read. After screening for potential studies, 3326 references were again excluded, and the remaining 288 references were searched in full text. Of these, 256 did not meet the inclusion criteria . The final 32 studies were included in the meta‐analysis ,A total of 32 randomized controlled trials involving 16 273 people with uncontrolled essential hypertension were included. Eleven SPC were compared, namely Amlodipine/valsartan (8 studies),3.43.4.1P‐values for indirect and direct comparisons between all studies were tested for consistency and inconsistency, and p‐values were greater than .05, indicating that the effect of consistency between studies was acceptable. Details will be shown in Table All In terms of systolic blood pressure, 32 studies covering 14 interventions were included, and the network map is shown in Figure 3.4.2P‐values for indirect and direct comparisons between all studies were tested for consistency and inconsistency, and all p‐values were greater than .05, indicating that the effect of consistency between studies was acceptable. Details will be shown in Table All For diastolic blood pressure, 31 studies involving 13 interventions were included, and the network map is shown in Figure 3.4.3p‐values for indirect and direct comparisons between all studies were tested for consistency and inconsistency, and all p‐values were greater than .05, indicating that the effect of consistency between studies was acceptable. Details will be shown in Table All Regarding BP control rate, 24 studies involving 14 interventions were included, and the network map is shown in Figure 3.4.4p‐values for indirect and direct comparisons between all studies were tested for consistency and inconsistency, and all p‐values were greater than .05, indicating that the effect of consistency between studies was acceptable. Details will be shown in Table All Regarding the DBP response rate, 22 studies involving 11 interventions were included, and the network map is shown in Figure 3.5We constructed separate funnel plots for all outcome measures to test for possible publication bias. From the funnel plot, we can see that the points on both sides of the line are basically symmetrical, and we did not find any significant publication bias. Funnel plots of posttreatment SBP, posttreatment DBP, BP control rate, and DBP response rate are shown in Figure 4In this review, we compared the antihypertensive efficacy of different SPC drugs in people with essential hypertension whose blood pressure remains uncontrolled despite monotherapy. A total of 32 randomized controlled trials, including 11 different SPC, were included, including 16 273 patients with uncontrolled essential hypertension, which is a considerable sample size. Our study shows that SPC drugs are better than monotherapy in reducing systolic and diastolic blood pressure and improving blood pressure control. Among them, in terms of systolic blood pressure, Irbesartan/amlodipine drug treatment has the best effect. In terms of diastolic blood pressure and diastolic blood pressure response rate, Amlodipine/losartan drug treatment has the best effect, and Telmisartan/amlodipine drug treatment has the best effect on blood pressure control rate. Overall, we believe that ARB/CCB combination formulations have the best antihypertensive effect.Essential hypertension is characterized by slow onset and lack of characteristic symptoms, mainly by higher‐than‐normal blood pressure. The drug treatment of essential hypertension has many schemes. Most hypertensive patients need to use two or more drugs to achieve the target value of blood pressure.Among the many SPC drugs, the combination of calcium channel blockers and renin‐angiotensin system inhibitors (RASI), either angiotensin‐converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), has been shown to be effective and safe in the treatment of patients with hypertension.Overall, our study has some clinical significance. First of all, SPC antihypertensive drugs have a significant effect on the treatment of essential hypertension. Secondly, when monotherapy is less effective in the treatment of essential hypertension, SPC preparation can be chosen, and combined with our findings, the ARB/CCB combination is the best combination.5Our study is the first network meta‐analysis comparing the efficacy of SPC in people with uncontrolled essential hypertension. The quality of randomized controlled trials included in this review was generally high, including 32 studies with 16 273 patients with uncontrolled essential hypertension, which is a very large sample size, and we tried to include as many studies as possible to compare the efficacy of different types of SPC, which provides newer and more comprehensive evidence‐based recommendations.But our study shares some limitations with the studies on which it is based. First, There are many types of SPC, some drugs were not involved, and the lack of relevant randomized controlled trials had some impact on the results. Second, differences in patient population, baseline clinical value, drug dose, and duration of treatment across all RCTs may have influenced the results. In addition, some of our studies are small in number, and evidence for direct comparisons of some interventions is limited. Readers should interpret the results with caution, and future studies will need to be supplemented with more large and high‐quality randomized controlled trials. In conclusion, due to the inherent complexity of SPC, including the dose of SPC, the combination of SPC, and the lack of relevant literature and sample sizes, more relevant studies are needed to demonstrate this result. It also highlights the need for further expansion of relevant studies.6In our study, we recommend the use of SPC antihypertensive drugs for blood pressure control, and the ARB/CCB combination is preferred. However, the data from this study and the results of previous clinical trials demonstrate the efficacy of SPC in the treatment of uncontrolled essential hypertension and support the recommendation that for patients who do not achieve target blood pressure with low‐dose antihypertensives, SPC selection may reach the target blood pressure more quickly than increasing the dose of monotherapy. Due to the large variety of SPC drugs, high‐quality randomized controlled trials with large sample sizes are still needed to evaluate the efficacy of single‐tablet combination preparations in the treatment of hypertension. Readers should interpret the results with caution.Mengxin Xie interpreted the data, wrote the initial manuscript, and was involved in the data analysis. Tianjiao Tang was responsible for the collection of all relevant papers. Hongsheng Liang was responsible for the supervision of the study. Both authors have read and agreed to the published version of the manuscript.The authors declare no conflict of interest.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.


Glomerulonephritis (GN) represents a common cause of chronic kidney disease, and treatment to slow or prevent progression of GN is associated with significant morbidity. Large patient registries have improved the understanding of risk stratification, treatment selection, and definitions of treatment response in GN, but can be resource-intensive, with incomplete patient capture.To describe the creation of a comprehensive clinicopathologic registry for all patients undergoing kidney biopsy in Manitoba, using natural language processing software for data extraction from pathology reports, as well as to describe cohort characteristics and outcomes.Retrospective population-based cohort study.Tertiary care center in the province of Manitoba.All patients undergoing a kidney biopsy in the province of Manitoba from 2002 to 2019.Descriptive statistics are presented for the most common glomerular diseases, along with outcomes of kidney failure and mortality for the individual diseases.Data from native kidney biopsy reports from January 2002 to December 2019 were extracted into a structured database using a natural language processing algorithm employing regular expressions. The pathology database was then linked with population-level clinical, laboratory, and medication data, creating a comprehensive clinicopathologic registry. Kaplan-Meier curves and Cox models were constructed to assess the relationship between type of GN and outcomes of kidney failure and mortality.Of 2421 available biopsies, 2103 individuals were linked to administrative data, of which 1292 had a common glomerular disease. The incidence of yearly biopsies increased almost 3-fold over the study period. Among common glomerular diseases, immunoglobulin A (IgA) nephropathy was the most common (28.6%), whereas infection-related GN had the highest proportions of kidney failure (70.3%) and all-cause mortality (42.3%). Predictors of kidney failure included urine albumin-to-creatinine ratio at the time of biopsy , whereas predictors of mortality included age at the time of biopsy  and infection-related GN .Retrospective, single-center study with a relatively small number of biopsies.Creation of a comprehensive glomerular diseases registry is feasible and can be facilitated through the use of novel data extraction methods. This registry will facilitate further epidemiological research in GN. Unfortunately, the rare nature of these diseases has impaired advancements in the epidemiological understanding and pharmacological treatment of GN, which in turn has limited our ability to slow disease progression with more tolerable treatments. It is important to note that although these diseases are individually uncommon, they collectively affect millions of individuals worldwide and are the most common cause of kidney failure requiring kidney replacement therapy and/or transplantation in individuals below the age of 50.911 Therefore, in addition to being an important cause of morbidity and mortality, GN has a significant adverse economic and personal impact in society.Glomerulonephritis (GN) are a heterogeneous group of rare immune-mediated kidney diseases that are associated with significant morbidity and mortality. Furthermore, registries provide an opportunity for collaboration between clinicians and researchers as well as different centers.1315 Fortunately, a kidney biopsy is typically required for the accurate diagnosis of GN, and therefore it is possible to identify most individuals in a particular location who have biopsy-proven GN. In Manitoba, all kidney pathology data since 2002 are readily available in the form of individual kidney biopsy reports, with findings on light microscopy, immunofluorescence microscopy, and electron microscopy reported for each biopsy and summarized in a single report. In addition, these data can be linked to administrative, laboratory, medication, and hospital data via the Manitoba Centre for Health Policy (MCHP), to form a comprehensive clinicopathologic registry. In this article, we discuss the creation and aims of the Manitoba Glomerular Diseases Registry, and the baseline demographic and outcome  data for biopsy-diagnosed kidney disease in the province of Manitoba.The establishment of large patient registries, designed to capture all patients with GN in a given geographic region, have been successful in improving our understanding of the natural history of GN and with identifying potential participants for clinical trials. A national survey of Canadian nephrologists indicated that most nephrologists support the establishment of GN registries and that they would be willing to enroll their patients in such a registry.Since 2002, all kidney biopsies performed in Manitoba have been interpreted and reported at a single site—the Health Sciences Centre in Winnipeg, Manitoba, Canada. The biopsy reports are stored at the Department of Pathology as individual Microsoft Word and PDF documents, and each report contains demographic data  as well as comprehensive pathological data. We extracted data from all biopsy reports from all patients who underwent a native kidney biopsy in the province for any clinical indication between January 1, 2002, and December 31, 2019, excluding patients who underwent transplant or donor implantation kidney biopsies.Supplementary Table S1. Data were extracted and outputted in a structured tabular format that could easily be reviewed by members of the research team and that could be parsed computationally for linkages with other databases, and for further downstream analyses. For this reason, the CSV  format was selected for the output, as it is a very simple tabular format that can be recognized by Microsoft Excel. Below is a description of the approach used to extract data.A list of data extracted is presented in Whereas PDF documents only contained textual information, the Microsoft Word documents often contained pictures, in which patient information  was presented within. The information stored in the biopsy reports was semi-structured, in the sense that most reports contained the same main sections, namely, patient information, gross description, microscopic description, immunofluorescence, electron microscopy, and diagnosis. However, these sections were not always presented in the same order, some were absent, and the data within the sections were presented in highly variable language. This is a Python port of the Apache Tika library that is built to extract text from different types of files . The Tesseract optical character recognition engine was installed and used in conjunction with Tika to extract the text from the figures in the Word documents.To automate the extraction of the data from the biopsy reports, the Python language was selected to build the application. The tika-python library was used.regular expressions. Regular expressions, also called regexes for short, are rooted in theoretical mathematics and computer science.20 Regular expressions nowadays are available in many popular programming languages . A regular expression is made up of metacharacters (these act as the rules and instructions of the regular expression to ensure the desired data are retrieved) and literal characters . It helps to see regexes as a language: In this context, literal characters can be seen as words and metacharacters as grammar. A regular expression can be designed to search, in a generalized way, for all data that match a specific pattern in the text.The main tool used to extract all the relevant information from the biopsy reports is called The data that needed to be extracted could take many forms and have a range of possible values. A specific regular expression was designed to recognize and extract each of these data points, considering both the type of data  and the text that is usually in its vicinity. The latter was not necessarily trivial, as the same information could be presented in many ways . The challenge was to strike a balance between designing regular expressions that were specific enough to collect only the information of interest (without confusion) and general enough to recognize all textual variations that appeared in the different biopsy reports.An iterative development strategy was used to train the algorithm. This began with 10 annotated biopsies indicating the desired output for each variable from which the algorithm was developed. The algorithm was refined using another sample of 20 biopsies, followed by a third test of 50 biopsies, with biopsies specifically selected to represent a range of pathological diagnoses and microscopic features as well as varying times within the study period. Errors in the algorithm output were identified in each iteration and subsequently corrected. Following the third iteration, the algorithm was 100% accurate in identifying all variables apart from primary and secondary diagnosis. Therefore, the algorithm was applied to all available biopsy reports, creating the pathology registry. A random audit was conducted on a total of 100 biopsies by one of the authors , with each biopsy analyzed in its entirety for the fidelity of the algorithm output. At least 5 biopsies from each year in the study period were included in the audit. The output of light microscopic, immunofluorescence, and electron microscopic features was without error. In one biopsy with a diagnosis of lupus nephritis (LN), the algorithm omitted the activity and chronicity indices; these were, therefore, independently verified for each biopsy demonstrating LN. Similarly, in one biopsy with a diagnosis of IgA nephropathy, the algorithm incorrectly reported the Oxford score; Oxford scores were, therefore, independently verified in the individual biopsy reports where applicable. In addition to the random audit, each primary and secondary diagnosis was independently verified on all 2421 biopsies. using each individual’s personal provincial health identification number to create a comprehensive clinicopathologic registry. Manitoba Health provides health care services to Manitobans through a single-payer public health care system, resulting in near-complete claims data available for the majority of the population. Databases linked were the Manitoba Health Insurance Registry (patient registry and coverage dates), Medical Services (physician claims data), Canadian Institute for Health Information (CIHI) Discharge Abstract Database (DAD) , the Shared Health Diagnostic Services database (laboratory diagnostics), the Drug Program Information Network (DPIN) database (drug prescriptions), Vital Statistics (date and causes(s) of death), and Canada Census data (to ascertain socioeconomic status and dwelling location). Descriptions of databases and years accessed are presented in Supplementary Table S2. The creation of the registry and the linkage was approved by the University of Manitoba Health Research Ethics Board (HS24601(H2021:031)), and by each of the data providers.Once the biopsy data were extracted into a single CSV file, a data linkage was created with the Population Health Research Data Repository at the MCHPIn this article, we present the incidence and prevalence of glomerular disease, along with other nonglomerular kidney diseases based on kidney biopsy diagnosis in Manitoba, using a retrospective, population-based cohort design. Demographic, clinical data, including baseline laboratory results, comorbidities, and prescriptions of disease-modifying medications, are presented.24 The groups include proliferative glomerulonephritis, nonproliferative glomerulonephritis, diabetic nephropathy, tubulointerstitial disease, vascular disease, deposition diseases, and hereditary kidney diseases. Patients with a normal or nondiagnostic biopsy due to inadequate sampling of kidney tissue were not classified. A full list of proliferative and nonproliferative glomerulonephritis included can be found in Supplementary Table S5. Diabetic nephropathy was considered on its own, separate from other nonproliferative glomerulonephritis. Tubulointerstitial diseases included acute tubular injury, acute and chronic interstitial nephritis, light chain cast nephropathy, and light chain proximal tubulopathy. Vascular diseases included thrombotic microangiopathy and ischemic glomerulopathy/hypertensive kidney disease. Deposition diseases include AL amyloidosis and monoclonal immunoglobulin deposition disease. Hereditary diseases included Alport syndrome/hereditary nephritis, Fabry disease, and thin basement membrane nephropathy. In Diseases were initially classified into 7 broad groups, in an approach described previously.For individuals with multiple biopsies, if the initial biopsy was nondiagnostic, the index date was the first diagnostic biopsy. Conversely, if the initial biopsy was diagnostic, but a subsequent biopsy was nondiagnostic or showing sclerosis from the prior diagnosis, those individuals were classified by their initial diagnostic biopsy. For individuals with the same diagnosis on multiple biopsies, only the index biopsy was considered in the analysis. In some cases, the initial biopsy diagnosis  was followed up by a subsequent biopsy showing a very different diagnosis . In this instance, such individuals were counted in multiple categories and censored at the time of follow-up biopsy. For individuals with a biopsy identifying multiple disease processes , the acute process was considered the primary diagnosis, and the background pathology the secondary diagnosis.Supplementary Table S4).Comorbid conditions were assessed using the weighted Charlson Comorbidity Index and were drawn from data collected through medical claims and hospital admission data during the 3 years prior to date of biopsy. Socioeconomic status  and dwelling location  were derived from dissemination area–level information generated from the Canadian Census. Laboratory values were assessed ±3 months from the date of biopsy, and medications were assessed within 6 months post-biopsy. Medications were classified according to the Anatomical Therapeutic Chemical system .The main outcomes of interest include all-cause mortality and kidney failure and were compared between glomerular diseases. Kidney failure was defined as dialysis or kidney transplant; administrative data definitions are presented in Descriptive statistics, presented for the most frequently diagnosed glomerular diseases in the cohort, hereafter referred to as “common GN,” are expressed as mean ± standard deviation for normal continuous variables, median and interquartile ranges for non-normal continuous variables, and percentages for categorical variables. We constructed Kaplan-Meier curves for all-cause mortality and kidney failure. Cox proportional hazard models were developed to analyze the association between disease type and the outcomes of all-cause mortality and kidney failure. Individuals who had multiple biopsies that resulted in different diagnoses were excluded from the Cox models and Kaplan-Meier curves. Only complete cases were included in the analyses.For all 7 broad categories of kidney diseases, including nonglomerular diseases, we present descriptive statistics, expressed as mean ± standard deviation for normal continuous variables, median and interquartile ranges for non-normal continuous variables, and percentages for categorical variables.A total of 2421 native kidney biopsy reports between January 1, 2002, and December 31, 2019, were available, from 2278 individual patients. Of these, 2103 individuals were linked to administrative data; of these individuals, 1292 had a common GN and were included in our main analyses . Of the The most frequent GN was IgA nephropathy , with pauci-immune glomerulonephritis being second most common . This was true across all time periods in the study. Patients with a diagnosis of LN tended to be younger, whereas patients with pauci-immune GN tended to be older. Patients with IRGN and pauci-immune GN had the lowest median estimated glomerular filtration rate (eGFR) at the time of biopsy, whereas patients with membranous nephropathy and focal segmental glomerulosclerosis (FSGS) had the highest median urine albumin-to-creatinine ratio (ACR). Patients with IRGN had the highest number of comorbidities. The baseline characteristics of the patients with common GNs are presented in Supplemental Figure 1. The IRGN group presented with the highest rate of kidney failure, with 70.3% progressing to kidney failure over a median of 3.9 years of follow-up. In contrast, the membranous nephropathy group had the lowest risk of kidney failure, with 13.4% progression to kidney failure over a median of 5.9 years of follow-up.The Kaplan-Meier curves for kidney failure are shown in Compared with the reference group of IgA nephropathy, FSGS , IRGN , membranous nephropathy , and minimal change disease  were associated with a lower risk kidney failure, following adjustment for age, sex, baseline eGFR, and urine ACR. Increasing urine ACR  was associated with a higher risk of kidney failure. Predictors for kidney failure and mortality are summarized in Supplemental Figure 2. The IRGN had the highest risk of all-cause mortality, with 42.3% of patients dying over a median of 3.9 years of follow-up, whereas IgA nephropathy had the lowest risk of all-cause mortality (18.1%) over a median of 5.7 years of follow-up. After adjustment for age, sex, baseline eGFR, and urine ACR, a diagnosis of IRGN  and increasing age  were associated with a higher risk of mortality. Conversely, higher baseline eGFR  was associated with a lower risk of mortality.The Kaplan-Meier curves for all-cause mortality are shown in Supplementary Table 6.The most frequent broad diagnostic category was proliferative glomerulonephritis , with nonproliferative glomerulonephritis being second most common . This was true across all time periods in the study. Patients with a diagnosis of hereditary kidney disease tended to be younger, whereas patients with a deposition disease tended to be older. Patients with diabetic nephropathy, vascular disease, and tubulointerstitial disease had the lowest median estimated glomerular filtration rate (eGFR) at the time of biopsy, whereas patients with deposition diseases had the highest median urine ACR. Patients with diabetic nephropathy had the highest number of comorbidities, whereas patients with hereditary diseases had the least. The baseline characteristics of the patients are presented in Of the broad categories, the diabetic nephropathy group presented with the highest rate of kidney failure, with 74% progressing to kidney failure over a median of 4.5 years of follow-up. In contrast, of those with a diagnostic biopsy, the nonproliferative glomerulonephritis group had the lowest risk of kidney failure, with 29.9% progression to kidney failure over a median of 5.8 years of follow-up. Deposition diseases were associated with the highest risk of all-cause mortality, with 58.5% of patients dying over a median of 2.8 years of follow-up.2628 we adopted a novel method for data extraction using a natural language processing algorithm, demonstrating the feasibility of the creation of such a registry without an exhaustive chart review of potentially thousands of patients. Although natural language processing software has been used for data extraction from pathology reports in oncology,2931 to our knowledge this is the first application of such software for data extraction from kidney biopsy pathology reports. Our methods could serve as a model to other centers looking to create a similar registry with high-quality data, without an in-depth manual review of potentially thousands of biopsy reports.We describe the creation of a comprehensive clinicopathologic registry of biopsy-proven kidney diseases, with an emphasis on glomerular diseases. While the concept of a kidney biopsy registry is not new, with many such registries described in the literature, Such broad, yet high-quality data capture is a relatively unique feature of our registry, and only described in a handful of registries internationally. The nature of the clinical data linkage, combined with the method of data extraction from pathology reports, contributes to a highly sustainable registry requiring minimal long-term maintenance to ensure data quality. This is important, as lack of sustainability was quoted as the most common concern amongst GN registry operators in an international questionnaire.We describe the data linkage of pathological data from all biopsies completed in Manitoba over a 20-year period with a robust set of clinical and administrative databases that contain complete information regarding medication prescriptions, laboratory data, hospitalizations and other healthcare utilization as well as vital statistics.3336; such an increase has been described previously. In addition, since 2002, all renal biopsy processing and reporting in Manitoba has been centralized in a core renal pathology service in one department, supported by a recognized specialist renal pathologist. This subspecialty model of pathology reporting facilitates communication between the reporting pathologist and clinicians, provides for the necessary detailed clinicopathologic correlation, and greatly improves the quality of renal biopsy reporting. This improved renal pathology service likely also contributed to the significant increase in biopsy incidence since 2002. However, our current biopsy rate appears largely similar to other regions, suggesting the current physician practice pattern is not significantly different from other centers and therefore not a likely source of bias in our registry. We also observed a striking risk of kidney failure and mortality associated with biopsy-proven infection-related glomerulonephritis, which is out of keeping with the published literature.39 This may reflect a selected population, as those with IRGN and a benign course may not be biopsied and simply managed expectantly. Nonetheless, given that our current biopsy rate is similar to other locations, this bias would likely apply to all cohorts described in the literature, and therefore further research in our cohort is required.We noted several important observations in the epidemiology of glomerular disease in Manitoba in the last 2 decades. First, we observed an almost 3-fold increase in biopsy incidence over the course of the study period. This is likely multifactorial and reflects improved access to biopsy, and possibly a change in physician practice. This is not necessarily surprising, given the advancements in the understanding of the benefits of biopsy in both risk stratification and treatment selection in GN41 we observed a very high kidney failure risk for patients with LN. The reasons for this are not immediately clear, but the relatively low eGFR and higher age at diagnosis raise the possibility that patients are being biopsied later in their disease course, especially considering patients with LN are typically younger than patients with lupus without LN and develop LN soon after diagnosis.42 This is further supported by the fact that most patients with lupus who have clinically apparent kidney involvement are not biopsied in our center. In patients diagnosed with IgA nephropathy, we observed a similarly striking kidney failure risk of 45% over a median 5.7 years of follow-up compared with 27.7% described in the Toronto cohort and 12% in the VALIGA cohort over similar follow-up duration. When comparing with these cohorts, our cohort was typically older, with much lower eGFR at biopsy, suggesting patients may be identified later in their disease course. With 25% of patients having an eGFR of less than 18 mL/min at biopsy, it is possible that biopsies are occurring later due to late referral. It is also possible that many patients were not biopsied earlier in their disease course due to a lack of concrete evidence regarding the use of immunosuppressive therapy for the treatment of IgA nephropathy, and that therefore a biopsy would not necessarily change management; this will likely change with the publication of more recent trials demonstrating a benefit of corticosteroids or other immunosuppressives.47 Nonetheless, more research is required to understand the factors influencing the high rate of kidney failure in this group.Compared with the published literature,49 Programs such as Kidney Check, which aims to screen, triage, and treat populations at high risk of kidney disease in Canada, deserve ongoing support and funding to improve kidney failure and mortality risk due to diabetic nephropathy.Although not an immune-mediated glomerular disease, it is important to note that in our cohort, a biopsy diagnosis of diabetic nephropathy was associated with a high risk of kidney failure. Although these patients presented with low eGFR and significant albuminuria, it is also important to consider the selection bias associated with biopsy-proven diabetic nephropathy, as this typically suggests a population behaving in a manner out of keeping with typically progressing diabetic kidney disease, and thus may be at higher risk of kidney failure than those who are not biopsied. Nonetheless, it highlights an urgent need for earlier diagnosis and intervention, especially with the advent of new, efficacious therapies for preventing chronic kidney disease progression in diabetes.Our data are hypothesis-generating with respect to quality indicators, namely, prescription of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) as well as statins. Although it is possible that many patients were not prescribed these medications due to low eGFR or side effects, such as hyperkalemia in the case of ACE inhibitors and ARBs, or myopathy in the case of statins, this finding may serve as a target for future quality improvement initiatives in our institution.Our registry has several strengths. First, we describe a novel method of data extraction accompanied by robust data quality checks, which could serve as a model for other institutions interested in creating a glomerular diseases or kidney biopsy registry. This method contributes to the sustainability of the registry going forward and allows cases to be added as they are diagnosed. Our registry contains robust pathological data along with comprehensive clinical and administrative data, facilitating future research in patients with GN. We also have a long period of follow-up, allowing for identification of trends in disease incidence but also outcomes such as mortality and kidney failure. making this a unique cohort that has yet to be described in the GN literature. In addition, kidney biopsy registries such as ours are subject to a selection bias, which affects not only disease incidences but also interpretation of outcome data, as such patients were biopsied while others were not. However, it would seem logical that patients who are biopsied have the most clinically significant disease, consistent with standard international practice. Furthermore, although our data capture is robust, data that are now indispensable in risk stratification for treatment of certain diseases, such as Oxford scores in IgA nephropathy, or phospholipase A2 receptor (PLA2R) antibody status in membranous nephropathy, are not available for many patients owing to their time of implementation in clinical care. Fortunately, these data are captured in the most recent patients and will be collected in all future patients enrolled in the registry.Our registry also has limitations. Our study is single-center, with a relatively small number of biopsies per year as compared with other published registries. However, we captured all biopsied patients in a region with a diverse population, approximately 18% of which is Indigenous,The Manitoba Glomerular Diseases Registry is a clinicopathologic registry created using novel data extraction techniques and capturing the spectrum of biopsy-diagnosed kidney diseases in Manitoba with a focus on glomerular disease. This registry will facilitate future research into epidemiological trends, clinical outcomes, and utilization of health services for patients with GN, including exploring the relationship among socioeconomic status, rurality, and the development of certain glomerular diseases, and will serve as a model for creation of similar registries in other institutions and health systems. Future endeavors also include creating a prospective database with biospecimens that can be linked with biopsy reports and administrative data for further understanding of disease pathways in this population.Click here for additional data file.Supplemental material, sj-docx-1-cjk-10.1177_20543581231178963 for The Development of a Comprehensive Clinicopathologic Registry for Glomerular Diseases Using Natural Language Processing by Bryce Barr, Oksana Harasemiw, Ian W Gibson, Olivier Tremblay-Savard and Navdeep Tangri in Canadian Journal of Kidney Health and Disease


Ventriculoperitoneal shunt (VPS) with adjustable differential pressure valves are commonly used to treat infants with hydrocephalus avoiding shunt related under- or overdrainage. The aim of this study was to analyse the influence of VPS adjustable differential pressure valve on the head circumference (HC) and ventricular size (VS) stabilization in infants with post intraventricular haemorrhage, acquired and congenital hydrocephali.th and 75th. The patients were divided into two groups: infants with hydrocephalus due to an intraventricular haemorrhage (IVH-H), and infants with hydrocephalus due to other aetiologies (OAE-H).Forty-three hydrocephalic infants under 6 months old were prospectively included between 2014 and 2018. All patients were treated using a VPS with adjustable differential pressure valve. HC and transfontanelle ultrasonographic VS measurements were regularly performed and pressure valve modifications were done aiming HC and VS percentiles between the 252O in the IVH-H group comparing to 5 cm H2O in the OAE-H group (p = 0.013).The mean of pressure valve modification was 3.7 per patient in the IVH-H group, versus 2.95 in the OAE-H group. The median of last pressure valve value was higher at 8.5 cm HOptimal VPS pressure valve values could be extremely difficult to settle in order to gain normalisation of the HC and VS in infants. However, after long term follow up (mean of 18 months) and several pressure valve modifications, this normalisation is possible and shows that infants with IVH-H need a higher pressure valve value comparing to infants with OAE-H. The treatment of children hydrocephalus is one of the most common pediatric neurosurgery procedures and several techniques are used in order to establish a cerebral spinal fluid (CSF) dynamics balance in the brain. Generally it has to be distinguished between an occlusive and a communicating hydrocephalus with or without malabsorption. Since newborn infants are not often to be considered for endoscopic third ventriculostomy –7, VPS i2O and a fixed gravitational unit at 20 cm H2O. Indication for VPS insertion was crucially analysed taking into account several factors like signs of elevated intracerebral pressure, bradycardia, restlessness, shrill crying, vomiting as well as fast growing HC together with increased VS. In children with possible CSF access (e.g. with temporary CSF reservoir), analysis of CSF was performed to determined lower levels of protein and erythrocytes as well the absence of bacteria before VPS insertion to avoid VPS dysfunction or/and infection. Perioperative antibiotics were given following institutional standards. After surgery all patients received cranial and abdominal low dose radiographic control to exclude proximal and/or distal catheter misposition. At VPS implantation the standard pressure valve value was initially set to 5 cm H2O in almost all cases. Body weight, body height, HC and VS at birth as well at VPS insertion were documented. Measurements of HC and transfontanelle ultrasonography VS were prospectively performed with initial follow-up amounted at day 3, 5 and 7 after VPS implantation and continuously every 2 weeks in most of the cases. The end of the follow-up was determined once HC and VS percentile reached the range between 25th and 75th and stayed at this range during at least 3 months without any other additional pressure valve modification. Criteria for valve adjustments were based on significant drops or rises in the HC percentile and/or in VS. We used the HC growth curve of Fenton and collaborators for preterm children [th and 90th, the VPS valve pressure was 3 to 4 cm H2O down regulated and when between 90th and 75th down regulation of 2 cm H2O were performed. Similar was set for lower HC percentile and valve pressure was 3 to 4 cm H2O up regulated once HC percentile was between 5th and 10th and 2 cm H2O up regulated when HC percentile between 10th and 25th. No modifications were done when HC percentile represented between 25th and 75th. Only when VS was over 97th or under 3rd percentile, the valve pressure was carefully 2 cm H2O down or up regulated, respectively.The patients were divided into two groups: post intraventricular haemorrhage hydrocephalus , and infants with congenital or hydrocephalus due to other aetiology  and analysed separately. The software used for statistical analysis was Statistical Package for the Social Sciences (SPSS). All values are given in percentage, mean, standard deviation, confidence interval at 95% (CI95), median and interquartile range (IQR). The comparison between groups was performed using ANOVA and Mann-Whitney U test and p values < 0.05 were considered statistically significant.This study was approved by the ethic committee Goethe-University Hospital, Frankfurt am Main which waved the need for parents or guardians consent. We included forty-three infants with hydrocephalus aged of one day to 6 months old in a prospective single-center study between 2014 and 2018. All patients were implanted with the Aesculap-Miethke-proGAV-shunt system, consisting of a ventricle and abdominal catheter, pumping-chamber reservoir, adjustable differential pressure valve ranging from 0 to 20 cm Hchildren , 27. We 95 0.7). The mean follow-up was 18.9 ± 14.2 months (CI95 4.3). The causes of hydrocephali were diverse. By far, the most frequent cause was due to intraventricular haemorrhage  at the initial VPS insertion was 2.1 ± 2.2 months (CI95 509.8) and 2919.1 ± 638.7 grams (CI95 276.2), respectively. The mean height at birth was 39.4 ± 7.5 centimetres (CI95 3.5) in the IVH-H infants and 48.5 ± 3.9 centimetres (CI95 1.7) in the OAE-H infants. All together the mean weight at birth of all 43 patients was 2354 ± 1061.3 grams (CI95 326.6) and the mean height at birth 44.3 ± 7.3 centimetres (CI95 2.3). The mean of head circumference in the IVH-H group was 28.6 ± 5.4 centimetres (CI95 2.5) compared to 35.5 ± 3.9 centimetres (CI95 1.7) in the OAE-H group and all together among the 43 patients 32.3 ± 5.8 centimetres (CI95 1.8).Hydrocephalus due to other aetiology (OAE-H) are described below and were grouped together to enable better assessment of the effectiveness of VPS therapy in managing children hydrocephalus. Among the 43 patients, 20  suffered from hydrocephalus after intraventricular haemorrhage (IVH-H) and 23  due to different aetiologies (OAE-H) including aquaeductal stenosis (n = 5), brain infection (n = 4), myelomeningocelia (n = 2), meningocelia (n = 1), spina bifida (n = 2), Dandy-Walker malformation (n = 2), Arnold-Chiari malformation type II (n = 1), Pfeiffer syndrom (n = 1), occlusive hydrocephalus (n = 3), malabsorptive hydrocephalus (n = 1) and one child developed hydrocephalus after severe intracerebral haemorrhage due to a brain infection . As to b95 0.7) in the IVH-H children versus 1.9 ± 2.8 months (CI95 1.2) in the OAE-H children. The mean weight at VPS insertion was 3287 ± 1142 grams (CI95 534.3) for infants with IVH-H and 4209.3 ± 1688 grams (CI95 730) for infants with OAE-H. The mean height at VPS insertion was 48.9 ± 7.7 centimetres (CI95 3.6) and 53.7 ± 7.5 centimetres (CI95 3.3), respectively. All together, at VPS insertion of all 43 patients, the mean weight was 3780.3 ± 1516 grams (CI95 467) and the mean height was 51.5 ± 7.9 centimetres (CI95 2.4). The mean HC for IVH-H infants was 34.8 ± 3.8 centimetres (CI95 1.8) and 39.5 ± 4.7 centimetres (CI95 2) for OAE-H and all together between all 43 patients was 37.4 ± 4.9 centimetres (CI95 1.5). The mean follow-up was 21.6 ± 16 months (CI95 7.5) for IVH-H infants versus 16.6 ± 12.3 months (CI95 5.3) for OAE-H infants  were initially treated through external reservoir before definitive VPS insertion and only 17% approximately (4 out of 23) in the OAE-H group. The mean age at VPS insertion was 2.2 ± 1.5 months ). The initial mean pressure valve value was 5.4 ± 1.27 cm H2O (CI95 0.59) with median and IQR of 5 (5–5) for the IVH-H group and 6.13 ± 2.53 cm H2O (CI95 1.09) also with median and IQR of 5 (5–5) for the OAE-H group  with median and IQR of 2.5 (1–5.25) and 2.95 ± 3.28 (CI95 1.41) with median and IQR of 2 (1–4), respectively. All together there was a mean of valve pressure modifications from 3.3 ± 3.15 (CI95 0.97) with median and IQR of 2 (1–5) in all 43 patients  and with median and IQR of 10 (8–10) and in 35% of the children with OAE-H with a mean value of 8.5 ± 1.19 cm H2O (CI95 0.99) and with median and IQR of 8.5 (7.75–9.25). In all 43 patients 49% valve pressures had to be up regulated with a mean of 9.28 ± 2.43 cm H2O (CI95 1.1) and with median and IQR of 9 (8–10). In the other hand, down regulation was performed in only 20% of IVH-H patients with mean value of 5 ± 2.82 cm H2O (CI95 4.5) and with median and IQR of 5 (4–6) and in 35% of the OAE-H patients with mean value of 2.62 ± 2.26 cm H2O (CI95 1.89) and with median and IQR of 4 (0–5). The rate of down regulation in all 43 patients was 28% with mean value of 3.41 ± 2.61 cm H2O (CI95 1.65) and with median and IQR of 3.5 (2.25–5). For 15% and 30%, respectively with a total of 23% for all 43 patients, the same initial valve pressure value was settled after modifications  with median and IQR of 8.5 (5–10) in the IVH-H group versus 5.56 ± 2.99 cm H2O (CI95 1.29) with median and IQR of 5 (4.5–8) in the OAE-H group. This difference was statically significant . The mean of last valve pressure value, including all 43 patients, was 6.74 ± 3.43 cm H2O (CI95 1.05) with median and IQR of 7 (5–9)  .2O (mean 8.1 cm H2O) in the IVH-H group and 5 cm H2O (mean 5.6 cm H2O) in the OAE-H group.The main findings of this study were that 84% of children with hydrocephalus treated with a VPS system with an adjustable pressure valve required pressure modification. Ninety percent of the infants with hydrocephalus due to intraventricular haemorrhage (IVH-H) needed pressure valve modifications comparing to 78% of the infants with hydrocephalus due to other aetiologies (OAE-H). The last and optimal median pressure valve value for which the patients presented a stable HC percentile was 8.5 cm HChanging the valve pressure value was made according to the HC and/or transfontanelle ultrasonography VS measurements. Most of the cases, HC measurement was a good indicator of under- and overdrainage during follow-up suggesting the required direction of valve pressure adjustment. However, we observed two cases of overdrainage leading to bilateral hygroma in asymptomatic children with stabilised HC percentile .This observation means that overdrainage is not necessarily accompanied with changes in HC measurements toward smaller value reinforcing the important role of transfontanelle cerebral ultrasonography. Therefore we recommend systematic follow-up period of at least 2 to 3 months after shunt insertion, even in absence of symptoms. Finally, the relatively small size and monocentric origin of patients sample as well as the follow up period have to be considered before making definitive conclusions. Despite these limitations, we believe that these results indicate that using an adjustable differential pressure valve presents the advantage of adjusting pressure as needed to efficiently manage hydrocephalus in children regardless aetiologies  and OAE-H (5.56 cm H2O), respectively at the end of follow up.(TIF)Click here for additional data file.S1 Data(XLSX)Click here for additional data file.


To investigate factors affecting the cardioprotective proprieties of dexmedetomidine in patients after pulmonary lobectomy.The data of 504 patients who received dexmedetomidine combined with general anesthesia and video-assisted thoracoscopic surgery (VATS) lobectomy in Shanghai Lung Hospital from April 2018 to April 2019 were analyzed retrospectively. Patients were divided into normal troponin group (LTG) and high troponin group (HTG) according to whether the postoperative troponin level was greater than 13. Ratio of systolic blood pressure greater than 180, heart rate greater than 110, the dose of dopamine and other drugs, the ratio of neutrophils to lymphocytes, postoperative visual analog scale (VAS) pain score and hospital stay were compared between the two groups.Preoperative systolic blood pressure, intraoperative maximum systolic blood pressure, intraoperative maximum heart rate, intraoperative minimum heart rate and N-terminal pro hormone brain natriuretic peptide (NT-proBNP) correlated with troponin values. The proportion of patients with systolic blood pressure greater than 180 in the HTG was higher than that in the LTG (p=0.0068), and the proportion of patients with heart rate greater than 110 was significantly higher in the HTG compared to the LTG (p=0.044). The ratio of neutrophils/lymphocytes in the LTG was lower than that in the HTG (P<0.001). At 24 and 48 hours after operation, the VAS score in the LTG was lower than that in the HTG. Patients with high troponin had longer hospital stay.Intraoperative systolic blood pressure, maximum heart rate, and postoperative neutrophil/lymphocyte ratio are important factors that affect the myocardial protection properties of dexmedetomidine and may affect the postoperative analgesia effect and the length of hospital stay. Dexmedetomidine is an α2 adrenergic receptor agonist with various pharmacological effects including analgesia and anxiolytic.This led to improved myocardial function and reduced cardiac ischemia-reperfusion injury. Studies have showed that dexmedetomidine protects the heart by inhibiting the expression of high mobility group box one and activating the cholinergic anti-inflammatory pathway.8In patients undergoing surgery, hemodynamic fluctuations caused by factors such as surgical stimulation and extracorporeal circulation can lead to adverse events such as aggravation of cardiac insufficiency, arrhythmia, and myocardial ischemia.Data of 825 patients who underwent thoracoscopic lobectomy in Shanghai Pulmonary Hospital from April 2018 to April 2019 were retrospectively analyzed. The data were obtained from the electronic medical record system of Shanghai Pulmonary Hospital. Of 825 patients, 535 underwent VATS lobectomy and were considered for the inclusion in the study.Thirty-one patients were excluded based on the following exclusion criteria:Any history of heart disease, including coronary heart disease, myocardial infarction, arrhythmia, cardiomyopathy, etc.Hypertension that fails to reach the target after drug treatment or untreated.For the remaining 504 patients, clinical indicators related to the troponin value were analyzed by regression analysis. Patients were then divided into normal troponin group (LTG) and increased troponin group (HTG) according to whether the postoperative troponin level was greater than 13 .The study was approved by the ethics committee of the hospital .The anesthesia regimen of all patients was dexmedetomidine combined with general anesthesia, and no pre-anesthetic medication was used before anesthesia. Patients fasted for 12 hours (water and food) before the operation. Venous access was established in the operating room, and vital signs were monitored. Each patient received a central venous catheter. Then, 1μg/kg of dexmedetomidine was injected intravenously within 10 minutes before induction of anesthesia, and maintained at a rate of 0.2 μg/ (kg·h). After induction of anesthesia, mechanical ventilation was done with endotracheal intubation: tidal volume (VT) 8-10 mL/kg, respiratory ratio 1:2, RR: 12-14 times/minute, and oxygen flow 2 L/min, with continuous injection of 3-6 mg/ (kg·h) propofol, 0. Anesthesia was maintained with 05-0.2 μg/ (kg·min) remifentanil and 1-2 μg/ (kg·min) cisatracurium. The depth of anesthesia is monitored by an anesthesia depth monitor. During the operation, blood oxygen saturation [Sp(O2)] was maintained at about 98%, PETCO2 at 35-45 mmHg (1 mmHg = 0.133 kPa), and Fi (O2) at 0. 8 to 1. 0. Propofol, cisatracurium, and remifentanil were discontinued 10 minutes before skin suture. When the patient resumed spontaneous breathing, consciously opened his eyes, and was conscious, the tracheal intubation was removed. Sp(O2) was maintained at > 95%, an analgesic pump  was used. Repeated doses of 0.5-2.5 mg neostigmine were injected intramuscularly or subcutaneously at appropriate intervals, with a daily dose range of 5-20 mg and analgesia for two days. Patients self-administered non-steroidal anti-inflammatory drugs (Celebrex) for two days. The following clinical indicators were compared between groups:The proportion of patients with intraoperative systolic blood pressure greater than 180 and heart rate greater than 110;-1 each time during anesthesia can increase heart rate and blood pressure. So we compared the amount of dopamine and other drugs used in anesthesia between the two groups;Intravenous injection of 1-2 μg·kgThe ratio of neutrophils to lymphocytes in blood samples of patients on the second day after surgery;The VAS score of postoperative pain,Total length of hospital stay including surgery duration.χ̅±S. The comparison between the groups was done by t-test. Within-group comparisons were made by the paired t-test; count data were expressed by case (%). Comparisons between groups were performed using the 2χ test. The correlation between the indicators was analyzed by multiple linear regression. P < 0. 05 indicated statistical significance.SPSS 20.0 software was used to analyze the data. Normal distribution measurement data were expressed as Medical records of 634 patients were reviewed, including 534 cases of VATS lobectomy and 100 cases of non-VATS lobectomy. Of 534 VATS-lobectomy cases, 503 were included in this study, and 31 cases were excluded due to preoperative structural heart disease, history of myocardial infarction, history of coronary heart disease, etc. There were 438 cases in the LTG and 65 cases in the increased troponin group. There was no statistical difference in the general demographics such as age, sex ratio, height, and age between the two groups .We used multiple linear regression analysis to assess the correlation between troponin levels and other observed indicators. The analysis results showed that preoperative systolic blood pressure, intraoperative maximum systolic blood pressure, intraoperative maximum heart rate, intraoperative minimum heart rate, and NT-proBNP correlated with troponin values. The results are summarized in .The percentage of patients with intraoperative systolic blood pressure greater than 180 in the HTG was higher than that in the LTG (p=0.0068), and the proportion of patients with heart rate greater than 110 was significantly higher than that in the LTG (p=0.044). The results are shown in We compared the intraoperative doses of dopamine, atropine, esmolol, norepinephrine, and nicardipine between the two groups, and the results showed no significant inter-group difference . The ratThe postoperative analgesic effects in both groups were compared using the VAS score, as shown in The results of this study showed that intraoperative systolic blood pressure, maximum heart rate and postoperative neutrophil/lymph ratio were important factors affecting the myocardial protection proprieties of dexmedetomidine and may also affect the postoperative analgesic effect and the length of hospital stay. Dexmedetomidine is a more selective α2 receptor agonist than clonidine, and can reduce the release of excitatory transmitters from the central sympathetic nerve, and exert anxiolytic, sedative and analgesic effects.12The research of the clinical applications of dexmedetomidine mainly focuses on surgical anesthesia, postoperative sedation and analgesia, while its pharmacological effects are mainly manifested in the protection of nervous system, immune system, body inflammation and organ function. There are many factors in the perioperative period that may lead to myocardial injury.13Dexmedetomidine has a good protective effect on ischemia-reperfusion injury of various organs and tissues that is mainly related to the inhibition of lipid peroxidation mediated by oxygen free radicals. The study of Erer D et alThe excessive release of inflammatory factors is closely related to myocardial injury. Dexmedetomidine reduces oxidative stress and inflammatory response in surgical patients, improves immune function and reduces surgical complications. Intraoperative inflammation can also affect the protective effect of dexmedetomidine on the heart.17A meta-analysis by Wang et al19The results of our study also showed that the neutrophil/lymphocyte ratio of the patients with elevated troponin was higher than that of the patients with normal troponin. It shows that intraoperative inflammation can also affect the cardioprotective effect of dexmedetomidine. In addition, we observed increased postoperative pain scores and length of hospital stay in the HTG of patients. Our results indicate that increased blood pressure, increased heart rate and increased neutrophil/lymphocyte ratio during the operation may also affect the analgesic effect of dexmedetomidine.It is a retrospective study with a high variability in the number of patients in each group. We only analyzed one indicator, troponin, which may impact the validity of our conclusions on the cardioprotection proprieties of dexmedetomidine. In addition, there are many interference factors that were not evaluated in this study, such as patients were on remifentanil as well, which decreased blood pressure and heart rate with analgesic properties as well. The use of remifentanil can result in cardi-protection and decrease in troponin levels, but may potentially have an impact on the results.Intraoperative systolic blood pressure, maximum heart rate, and postoperative neutrophil/lymph ratio are important factors that affect the myocardial protection proprieties of dexmedetomidine and may affect the postoperative analgesia effect and the length of hospital stay.HL: Conceived and designed the study.HL, CL and HS: Collected the data and performed the analysis.HL, JL and HS: 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.