SBP Group Research Articles

Intensive Home Blood Pressure Lowering in Patients with Advanced CKD

Optimal blood pressure (BP) targets in advanced CKD are controversial. More intensive BP lowering in the setting of advanced CKD is thought to be associated with risk of acute kidney injury, hyperkalemia, and ESKD. We aimed to conduct a pilot trial of intensive BP control to determine if lower SBP targets can be safely achieved for patients with CKD through titration of BP medications using in-home measured BP. Non-blinded randomized controlled trial. 108 patients with advanced CKD (eGFR ≤30 mL/min/1.73 m2) and hypertension. Participants were randomized either to a target home SBP goal of <120 mmHg (N=66) or a less intensive SBP goal (N=42). Antihypertensive medications were titrated to achieve the target home SBP range in the first 4 months of the study and maintained until the end of the study. Home BP was measured using a wireless Bluetooth-enabled monitor that transmitted readings to providers in real-time. The primary efficacy outcome was the difference in achieved clinic SBP between the two study arms from months 4-12. Safety outcomes included hyperkalemia, a composite outcome of falls or syncope, and onset of need for dialysis or kidney transplantation. The mean clinic SBP at month 12 was 124.7 mmHg in the intensive SBP group vs. 138.2 mmHg in the less intensive SBP group. Averaged over months 4-12, the achieved mean clinic SBP in the intensive SBP arm was 11.7 mmHg (95% CI 7.5 to 16 mmHg, p<0.001) lower than the mean SBP achieved in the less intensive SBP arm. Primary safety outcomes were not statistically significantly different between the two arms (all p>0.05). Small sample size which may limit our ability to detect clinically significant differences in rates of adverse outcomes; single-center design. A clinic SBP goal of <120 mmHg is feasible to achieve with the help of real-time home BP monitoring and appears to be safe in this study population with advanced CKD. Larger trials to determine optimal BP targets in advanced CKD and the risks and benefits associated with more intensive BP control are warranted.

Association of office blood pressure with ischemic and bleeding events in patients undergoing percutaneous coronary intervention

Optimal blood pressure (BP) for patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains unclear. This study aims to identify the optimal BP by investigating the association between average office BP and future clinical events in patients undergoing PCI. Consecutive patients undergoing PCI from 2012 to 2016 were included. They were divided into five groups according to the average follow-up BP after discharge. The co-primary outcomes were net adverse clinical events (NACE) and major adverse cardiac and cerebrovascular events (MACCE) up to 5 years. NACE was defined as a composite of MACCE (all-cause death, non-fatal myocardial infarction (MI), non-fatal stroke, or any revascularization) or major bleeding. A total of 2845 patients were included, and among them, 787 (27.7%) experienced the NACE during the follow-up period. Patients in the highest SBP group (adjusted hazard ratio [HR] 1.495, confidence interval [CI] 1.189–1.880) and lowest SBP group (adjusted HR 1.625, CI 1.214–2.176) had a significantly higher risk of 5-year NACE. Similar associations were observed between SBP and the risk of MACCE, and similar results based on DBP categories were also observed. There was a J-curve relationship between SBP and DBP with respect to 5-year NACE and MACCE. The nadir point of risk for NACE and MACCE was found at 121.4/74.8 and 120.4/73.7 mmHg. In patients underwent PCI, there is a significant correlation between office BP level and clinical events, indicates the importance of efforts for optimal BP control to reduce ischemic and bleeding events.Trial registration: HanYang University Medical Center (HYUMC) Registry, NCT05935397.

Cumulative Blood Pressure Load and Incident CKD

The association of long-term cumulative blood pressure (BP) loads with the risk of incident chronic kidney disease (CKD) remains a matter of debate. This study investigated this association among healthy Korean adults with normal kidney function. Prospective cohort study. We analyzed 5,221 participants without CKD in the Korean Genome and Epidemiology Study. Cumulative systolic and diastolic BP (SBP and DBP) loads were calculated as the ratios of the areas under the curve (AUC) for SBP≥120mm Hg or≥80mm Hg for DBP divided by the AUC for all SBP or DBP measurements during the exposure period. These AUCs were categorized into 4 groups: group 0 (reference), cumulative BP load of 0 and groups 1-3, tertiles of cumulative BP loads. Primary end point was incident CKD defined as a composite of an estimated glomerular filtration rate (eGFR) below 60mL/min/1.73m2 or proteinuria greater than 1+on dipstick examination for at least 2 consecutive measurements≥90 days apart. Multivariable Cox proportional hazards regression to estimate the independent association of cumulative BP loads with incident CKD. Higher cumulative SBP and DBP loads were associated with an increased risk of incident CKD (HR, 1.23 [95% CI, 1.12-1.35] for SBP; and HR, 1.14 [95% CI, 1.04-1.26] for DBP loads for each 1.0-unit greater load). Compared with SBP group 0, groups 2 and 3 were associated with 1.94- and 1.89-fold greater risk of incident CKD. Compared with DBP group 0, groups 2 and 3 were associated with 1.42- and 1.54-fold greater risks. These associations of high cumulative BP loads with an increased risk of incident CKD remained consistent even in the subgroups not taking antihypertensive agents or without prior hypertension diagnosis. The assessment of CKD outcomes relied on eGFR and spot urine tests. These findings highlight the association between high cumulative SBP and DBP loads and the occurrence of CKD, even in individuals with normal BP levels. Although hypertension is a major risk factor for chronic kidney disease (CKD), most studies have focused on single-point blood pressure (BP) measurements. To explore the association between long-term cumulative BP load and the development of CKD, 5,221 Korean adults with normal kidney function were included in this study. Cumulative systolic BP and diastolic BP load both exhibited a significant association with an increased risk of incident CKD. Notably, the association of cumulative BP loads with elevated risk of incident CKD was evident also in individuals who were not taking antihypertensive agents or who had no previous history of hypertension. These findings underscore the importance of managing long-term exposure to high BP, even in individuals with normal BP levels.

#730 Dialysis-induced changes in systolic, diastolic, and pulse pressure in maintenance hemodialysis patients

Abstract Background and Aims Hemodialysis (HD) therapy has a strong impact on cardiovascular function in both the short and long term. In the short term, the dialysis-induced changes in blood volume directly affect the arterial blood pressure (BP), frequently leading to intradialytic hypotension or hypertension, both associated with adverse outcomes. The aim of this study was to investigate the dialysis-induced changes in systolic (SBP), diastolic (DBP), and pulse pressure (PP) in maintenance HD patients and to assess their relationship with pre-HD BP. Methods 197 maintenance HD patients were studied during the middle dialysis session of the week. The mean pre-dialysis fluid overload was 2.0 ± 1.6 L (calculated as the difference between the pre-dialysis body weight and the target weight). All HD sessions lasted approximately 4 h and were performed using mainly low-flux dialyzers. SBP and DBP were measured pre-HD and post-HD using a sphygmomanometer. PP was calculated as SBP minus DBP. The patients were divided into two groups: A) patients with an intradialytic decline in SBP (∆SBP &amp;lt;0), and B) patients with an increase or no change in SBP during HD (∆SBP ≥0). Paired data were compared using the Student's t-test. Correlations between variables were assessed using Spearman's rho (ρ). Results During HD, SBP decreased in 120 (61%) patients (in 20 cases by more than 30 mmHg), remained unchanged in 11 (6%) patients, and increased in 66 (33%) patients (in 13 cases by more than 20 mmHg). DBP decreased in 94 (48%) patients, remained unchanged in 46 (23%) patients, and increased in 57 (29%) patients. In 76 (39%) patients both SBP and DBP decreased, whereas in 33 (17%) patients both SBP and DBP increased. In group A (n = 120), SBP, DBP, and PP decreased by 21 ± 16 mmHg (P &amp;lt; 0.001), 8 ± 11 mmHg (P &amp;lt; 0.001), and 13 ± 14 mm Hg (P &amp;lt; 0.001), respectively. In group B (n = 77), SBP, DBP, and PP increased by 12 ± 10 mmHg (P &amp;lt; 0.001), 4 ± 11 mmHg (P &amp;lt; 0.001), and 8 ± 13 mmHg (P &amp;lt; 0.001), respectively. Pre-HD SBP was 144 ± 23 mmHg in group A and 128 ± 25 mmHg in group B (P &amp;lt; 0.001). Pre-HD DBP was 80 ± 15 mmHg in group A and 68 ± 11 mmHg in group B (P &amp;lt; 0.001). In all patients combined, ∆SBP was similarly correlated with pre-HD SBP and pre-HD DBP (ρ = −0.42 in both cases, P &amp;lt; 0.001), whereas ∆DBP was more strongly correlated with pre-HD DBP (ρ = −0.52, P &amp;lt; 0.001) than with pre-HD SBP (ρ = −0.22, P &amp;lt; 0.01). ∆SBP was correlated with ∆DBP (ρ = 0.55, P &amp;lt; 0.001) and highly correlated with ∆PP (ρ = 0.78, P &amp;lt; 0.001). According to linear regression, SBP tended to increase during HD in patients with pre-HD SBP &amp;lt;118 mmHg (Fig. 1A), whereas DBP tended to increase in patients with pre-HD DBP &amp;lt;68 mmHg (Fig. 1B). Conclusions Patients with dialysis-induced decline in SBP (group A) had a significantly higher pre-HD BP (both SBP and DBP) compared with patients with an increasing or stable SBP (group B). This suggests that a high decline in SBP during HD appears to be more likely in patients with elevated pre-HD BP and that HD appears to have a pressure-normalizing effect in such patients. Similarly, a dialysis-induced increase in SBP or DBP appears to be more likely in patients with low values of pre-HD SBP or DBP, respectively.

ASSOCIATION BETWEEN OFFICE BLOOD PRESSURE AND LONG-TERM CLINICAL EVENTS IN PATIENTS WITH CORONARY ARTERY DISEASE AFTER PERCUTANEOUS CORONARY INTERVENTION

Objective: The optimal blood pressure (BP) target for patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains unclear. This study aimed to identify the optimal BP target by investigating the association between average office BP and future clinical events after PCI in patients with CAD. Design and method: Consecutive patients undergoing PCI from 2012 to 2016 were included. They were divided into five groups according to the average follow-up BP after discharge. The co-primary outcome was major adverse cardiac and cerebrovascular event (MACCE: all-cause death, non-fatal myocardial infarction, non-fatal stroke, or any revascularization) and net adverse clinical events (NACE: MACCE, or major bleeding) up to 5 years. Results: A total of 2,845 patients were included in the analyses, and among them, 787 (27.7%) experienced the NACE during the follow-up period. Patients in the highest SBP group (adjusted hazard ratio [HR] 1.495, confidence interval [CI] 1.189–1.880) and lowest SBP group (adjusted HR 1.625, CI 1.214–2.176) had a significantly higher risk of 5-year NACE. Similar associations were observed between SBP and the risk of MACCE, and similar results based on DBP categories were also observed. There was a J-curve relationship observed between SBP and DBP with respect to 5-year NACE and MACCE. The nadir point of risk for NACE and MACCE was found at 121.4/74.8 and 120.4/73.7 mmHg. Conclusions: In patients underwent PCI, there is a significant correlation between office BP level and clinical events, which indicates the importance of efforts for optimal BP control to reduce ischemic and bleeding events.

Abstract 17555: Are Intermittent BP Control and Patient Complexity Barriers to Antihypertensive Treatment Intensification for Uncontrolled BP?

Background: Antihypertensive (AH) therapeutic intensification (TI) is the exception even when systolic blood pressure (SBP, mmHg) is ≥160. Adults with hypertension (HTN) often have multiple chronic conditions (CCs) and wide intra-individual BP variability. Patient complexity and intermittent control to &lt;140/&lt;90 may contribute to low rates of AH TI. Methods: The study included 119,260 adults 18-85 years with a HTN diagnosis and ≥3 encounters with BP values in the past 2 years (01/01/20-12/31/22). SBP on the last recent visit, number (n) and percent (%) of patients by SBP group on the last visit, number of Elixhauser chronic conditions (ECC), % of visit in the past 2 years with BP &lt;140/&lt;90, and % of last visits with AH TI (addition of a new BP med class) are provided in the Table. Results: The main results are shown in the Table. The rate of TI correlated with the % of visits with uncontrolled BP in the past 2 years when controlling for number of CC (partial r=0.046, p&lt;0.0001) and inversely with CC when controlling for SBP (partial r = -0.039, p&lt;0.0001). Adjusted odds ratios (OR) for percent of visits controlled and TI was 1.697 (95% CI [1.577, 1.826]) when controlling for age, SBP, and number of chronic conditions. OR was 0.933 (95% CI [0.925, 0.942]) for number of chronic conditions and TI, controlling for SBP and % visits controlled. Conclusion: Hypertension control varies, even among groups with last SBP &lt;120 or ≥160. In fact, BP in adults with last SBP ≥160, BP was &lt;140/&lt;90 on nearly one third of visits in the prior two years, which may contribute to the fact that TI occurred on only one in four visits in this group. However, patient complexity (ECC) was not a barrier to TI in this patient cohort.

Diagnostic Value of Ascitic Endocan Levels in the Diagnosis of the Spontaneous Bacterial Peritonitis

Abstract Background Spontaneous bacterial peritonitis (SBP) is a serious complication of liver cirrhosis and is defined as infected ascites in the absence of any recognizable secondary cause of infection. One of the possible mechanisms of developing Spontaneous bacterial peritonitis is bacterial translocation. Aim of the Work The aim of this study is to assess the role of ascitic endocan levels in the diagnosis of SBP in decompensated cirrhosis. Patients and Methods 90 cirrhotic patients with ascites were included in the current study and divided into 2 groups: SBP group with positive ascites culture or with an AF PMNL count ≥ 250/mm3 included 45 subjects. Non SBP group with negative ascites culture or with an AF PMNL count &amp;gt; 250/mm3 included 45 subjects. In the SBP group, the mean age was 58.77 years with male predominance (68.8%).As regard to Non SBP group, the mean age was 59.31 years with male predominance 57.8%. Results There was a statistical significant difference in between SBP group and Non-SBP group as regard to Platelets, ALT, ascetic Total leucocyte count, Protein and LDH. The most common presentation in SBP group was Upper GIT bleeding and Abdominal pain and the most common organism detected in the culture of ascitic fluid Escherichia coli (80%) followed by Streptococcus viridans (15.5%). Ascitic Endocan level was significantly higher in SBP group than Non-SBP group with P &amp;lt; 0.001. The sensitivity and specificity of Ascitic Endocan in detection of SBP were 84.85% and 82.69% respectively. There was a positive significant correlation in between Ascitic Endocan level and ALT, AST, bilirubin, CRP, Child class, MELD score, Blood Leukocytes and TLC (cell/mm3) in ascitic fluid in SBP group. The significant predictors of bad outcome in patients with SBP were higher ascitic fluid Endocan level, CRP and higher Glucose in ascitic fluid (mg/dl) levels Conclusion High Ascitic endocan level is common in cirrhotic patients with SBP than in Non-SBP and that means Ascitic endocan is related to the severity of the disease. Ascitic endocan level is an independent risk factor for SBP. High Ascitic endocan level is a significant predictor of bad outcome in patients with SBP. Therefore, measurement of Ascitic endocan level provide a new strategy to more aggressive treatments for high-risk groups. Ascitic endocan level could be used as an inflammatory biomarker for the prognosis of patients with SBP

The Study of the Diagnostic Value of Ascetic Fluid C-Reactive Protein, Calprotectin and Calprotectin–Ascetic Albumin Ratio

Abstract Background Cirrhosis represents the final common histological pathway for a wide variety of chronic liver diseases. Cirrhosis is defined histologically as a diffuse hepatic process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodule. Some patients with cirrhosis are completely asymptomatic and have a reasonably normal life expectancy Aim of the Work The aim of the study is to evaluate the usefulness of Ascetic Fluid Calprotectin and CRP for the diagnosis of SBP.In addition, we will evaluate Ascetic fluid calprotectin-toalbumin ratio in the diagnosisof SBP. and to identify a clinically useful cut-off level that can be used for future development of an important clinical, and time saving for the diagnosis of SBP Patients and Methods This case control study was conducted at Ain Shams University Hospital and Theodorbilharz Reaserch institute to evaluate the usefulness of ascetic fluid calprotectin, CRP and calprotectin-to-albumin ratio for the diagnosis of SBP and to identify a clinically useful cut-off level that could be used for future development of an important clinical and time saving method for diagnosis of SBP. Fifty cirrhotic patients with ascites were divided into two groups; group 1 (non SBP control group) that included 25 patients with cirrhotic ascites without SBP and group 2 (SBP group) that included 25 patients with cirrhotic ascites with SBP. Results Regarding demographic data; statistical analysis of current results showed that there was no statistically significant difference between the two groups regarding mean age 60.20±8.86 compared to 63.04±6.86 (p = 0.211) and sex 12 patients (48%) and 13 patients (52%) were female and male, respectively compared to SBP Group were 14 patients (56%) and 11 patients (44%) were female and male respectively with (p = 0.478). Regarding ascetic fluid biochemical; statistical analysis of current results showed that there was a statistically significant difference between two groups according to AF CRP, AF Calprotectin, Calprotectin-Albumin Ratio and AF TLC (p &amp;lt; 0.05). The highest value was found in SBP Group (21.09±15.86), (196.72±135.00), (379.60±354.71) and (756.04±513.50) compared to Non SBP Group (8.73±7.04), (119.30±111.31), (187.83±186.07) and (196.00±105.99) respectively. While, there was no statistically significant difference between two groups according to AF Albumin and Neutrophil%, with p-value (&amp;gt;0.05 NS). Conclusion In cirrhotic patient with ascites, AF CRP, AF Calprotectin and Calprotectin –Ascetic Albumin ratio were useful and sensitive diagnostic parameters and seem to provide a satisfactory diagnostic accuracy in diagnosis of spontaneous bacterial peritonitis. The sensitivity and specifity of AF calprotectin is higher than AF CRP and AF calprotectin albumin ratio in diagnosis spontaneous bacterial peritonitis cases. There was significant positive correlation between AF Calprotectin and AF CRP and AF calprotectin albumin ratio among patient with spontaneous bacterial peritonitis. If no contraindications, AF CRP, AF Calprotectin and Calprotectin –Ascetic Albumin ratio measurements could be used for diagnosis of SBP with high diagnostic and accurate value.

879-P: Cardiorenal Outcomes Associated with the Use of Dapagliflozin Compared with DPP-4 Inhibitors as Add-on Treatment in Uncontrolled DM2 Patients with Failure to Previous Treatment—A Retrospective, Real-Life Evaluation in México

Mexico is one of the three countries in Region of Americas with the highest prevalence (14.4%) of DM. We conducted a retrospective study in Mexico and compare Dapagliflozin effect in cardio-renal outcomes and metabolic control compared to DPP4-inhibitors (DPP4i) as added-on therapy in T2DM patients with failure to previous medications. Objectives: Compare proportion of patients achieving HbA1c below 7%, first appearance of eGFR below 60 ml/min, renal replacement therapy, heart failure hospitalization and death by the end of the 156-week observation period from index date. Inclusion Criteria: T2DM subjects ≥18 years old with failure to any previous antidiabetic medication and HbA1c% ≥7 that started Dapa or DPP4i as add-on to other antidiabetic drugs from August 2014 to December 2019. Statistical Methods and Analysis: A propensity score matching model (nearest neighbor algorithm) was used. Results: Of 1800 subjects, 267 met statistical matching criteria. There were no differences in basal characteristics of age, SBP, Creatinine Clearance, but DAPA group had higher basal HbA1c (8.54±1.45 vs 8.16±1.43, p&amp;lt;0.01). Patients in Dapa compared to DPP4i achieved A1c ≤7% in 49.8% vs 20% (p&amp;lt;0.01) by week 156. Creatinine clearance between groups favored DAPA after week 52 (76.07±18.52 vs 86.40±21.27, p&amp;lt;0.01), and persisted through week 156 (68.19±19.4 vs 88.45±19.73, p&amp;lt;0.01). By week 52, Incidental CKD was present in 5.8% of Dapa group and in 14.8% of DPP4i group, p=0.013 (OR 0.607, 95% IC 0.409-0.901), and by week 156 6.5% DAPA vs 27.6% DPP4i, p&amp;lt;0.01 (OR 0.275, 95% IC 0.191-396). There were no differences in HF hospitalizations. Conclusion: In patients with uncontrolled T2DM who have failed to previous antidiabetic therapies, the add-on of dapagliflozin significantly provides reductions of HbA1c, microalbuminuria and reduces the risk of CKD compared to DPP4i add-on. Disclosure D.Espinoza-peralta: None. S.C.Juarez-comboni: Employee; AstraZeneca. A.M.Rodríguez: Employee; AstraZeneca. J.Hernandez-alarcon: None. I.N.Lopez: None. J.Cetina-canto: None. M.E.Búrquez-gonzález: None. P.V.Paul: None. G.A.Bustamante: None. J.Garnica cuellar: None. L.G.Mireles-zavala: None.

Predictors of response to radiation therapy and of progression to multiple myeloma in patients with solitary bone and extramedullary plasmacytomas

Introduction: Radiation therapy (RT) plays an important role in treating Solitary Extramedullary (EMP) and Solitary Bone (SBP) Plasmacytomas. The objective of this study is to review the effectiveness of RT in locally controlling the disease and looking at factors that predict progression to Multiple Myeloma (MM) in the PET scan-era. Methods: We performed a retrospective analysis of consecutive plasmacytoma patients (pts) treated at our high-volume center. We identified 94 pts, of which 62 were diagnosed with SBP and 32 with EMP, without evidence of MM at diagnosis (end-organ damage, >10% bone marrow involvement, >1 plasmacytoma). We identified 94 total pts, largest series to date in the literature, treated with RT (no pts received systemic therapy) between January 1, 2000, through December 31, 2020. Of the 94 pts, 62 were diagnosed with SBP and 32 with EMP, without evidence of MM at diagnosis (end-organ damage, >10% bone marrow involvement, >1 plasmacytoma). We utilized radiographic staging including PET scans and clinical assessments to determine patient outcomes. Outcomes include initial radiographic responses using the European Expert Panel Response Criteria, local control (LC), overall survival (OS), and progression to MM. Kaplan-Meier was used to assess LC and OS. Univariable analysis was done using age, sex, race, plasmacytoma type (EMP vs. SBP), PET scan at staging versus other modalities, first post-RT response (CR, no CR), Pre-RT SUV of lesion, RT dose (≥45 Gy) and overall response to RT (if CR was achieved). Results: Patient and treatment characteristics are summarized in table 1. 24 (66%) EMPs and 54 (84%) SBPs received a radiation dose ≥45 Gy. After excluding 8 patients who were lost to follow up, 81% of patients with EMPs and 81% with SBPs achieved complete response (CR) with a median time to CR being 11 months (range 0.53–38.9) for EMP and 8 months (range 0.6–89.2) for SBP. All pts achieving a CR were treated with doses ≥40 Gy. Only 1 (3%) EMP and 2 (3%) SBPs had an in-field failure after CR. The 5-year OS was 68% for EMPs and 94% for SBPs [p = 0.007]. Out of 94 pts, 19 died, and cause of death was not related to the plasma cell neoplasm in 7 EMP pts. The 5-year rate of progression to MM was 28% in the EMP group, and 64% in the SBP group [p = 0.006], with progression-free survival (PFS) of 61% In the EMP group and 35% in the SBP group [p = 0.041]. On univariate analysis, sex, age, RT dose (<45 Gy, ≥45 Gy), staging PET, location [EMP vs. SBP] and achieving a CR after RT (at first post-RT response and CR at any time) were analyzed. Pts with EMP were at significantly lower risk for progression to MM (HR 0.3, 95% CI: 0.2, 0.8; p = 0.009) Additionally, Pts with CR on first post-RT imaging were at lower risk for progression to MM (HR 0.6, 95% CI: 0.3, 1.0, p = 0.05). Conclusion: Our data indicates that definitive RT for EMP and SBP can provide excellent LC. Progression to MM remains the main problem and is more common among pts with SBP, which is concordant with previously published literature. Keyword: Multiple Myeloma Conflicts of interests pertinent to the abstract. B. Imber Honoraria: GT Medical Technologies

Association Between Admission Systolic Blood Pressure and Cardiovascular Events in Acute Myocardial Infarction Patients with Different Left Ventricular Ejection Fractions.

Among patients with acute heart failure, left ventricular ejection fraction (LVEF) is closely related with admission blood pressure. However, it is unclear whether the systolic blood pressure is associated with the LVEF in acute myocardial infarction (AMI) patients. we evaluated the predictive value of admission SBP in AMI patients with different LVEF status. Data were from our hospital database bank. 4114 patients were included in this analysis. Patients were divided into 2 groups according to their LVEF in the first echocardiography record after admission. Patients were categorized into 4 groups (SBP 90-99 mm Hg, SBP 100-119 mm Hg, SBP 120-139 mm Hg, and SBP ≥140 mm Hg) based on SBP level at admission. The mean age was 64.9 ± 12.5 years and 28% were female. For patients of LVEF < 50% in the lowest SBP group (SBP 90-99 mm Hg), the incidence of in-hospital cardiovascular death was significantly higher than other SBP groups (reference: SBP 90-99 mm Hg) (adjusted OR = 0.267, 95% CI: 0.113-0.728 for SBP 120-139 mm Hg, P =.004 and OR = 0.241, 95% CI: 0.089-0.651 for SBP ≥ 140 mm Hg, P =.005). Patients of LVEF ≥50% in the highest SBP group (SBP ≥ 140 mm Hg) were at higher risk of cardiogenic mortality during long-term follow-up (reference: SBP ≥140 mm Hg) (adjusted HR = 0.313, 95% CI: 0.489-0.962 for SBP 100-119 mm Hg, P <.001, HR = 0.701, 95% CI: 0.488-0.987 for SBP 120-139 mm Hg, P =.003, and HR = 0.554, 95% CI: 0.198-0.837 for SBP 90-99 mm Hg, P =.001). SBP 90-99 mm Hg were associated with increased in-hospital cardiovascular death in AMI population with LVEF < 50%, and SBP > 140 mm Hg were associated with increased long-term cardiovascular death in AMI subjects with LVEF >50%.

Effects of Shenling Baizhu powder on pyrotinib-induced diarrhea: analysis of gut microbiota, metabonomics, and network pharmacology

BackgroundShenling Baizhu Powder (SBP) is a traditional Chinese medicine (TCM) prescription, which has the good efficacy on gastrointestinal toxicity. In this study, we used gut microbiota analysis, metabonomics and network pharmacology to investigate the therapeutic effect of SBP on pyrotinib-induced diarrhea.Methods24 Rats were randomly divided into 4 groups: control group, SBP group (3.6 g/kg /bid SBP for 10 days), pyrotinib model group (80 mg/kg/qd pyrotinib) and pyrotinib + SBP treatment group. A 16S rRNA sequencing was used to detect the microbiome of rat fecal bowel. Metabolic profiles were collected by non-targeted metabolomics and key metabolic pathways were identified using MetaboAnalyst 5.0. The antitumor effect of SBP on cells treated with pyrotinib was measured using a CCK-8 assay. Network pharmacology was used to predict the target and action pathway of SBP in treating pyrotinib-related diarrhea.ResultsIn vivo study indicated that SBP could significantly alleviate pyrotinib-induced diarrhea, reaching a therapeutic effect of 66.7%. SBP could regulate pyrotinib-induced microbiota disorder. LEfSe research revealed that the SBP could potentially decrease the relative abundance of Escherichia, Helicobacter and Enterobacteriaceae and increase the relative abundance of Lachnospiraceae, Bacilli, Lactobacillales etc. In addition, 25-Hydroxycholesterol, Guanidinosuccinic acid, 5-Hydroxyindolepyruvate and cAMP were selected as potential biomarkers of SBP for pyrotinib-induced diarrhea. Moreover, Spearman's analysis showed a correlation between gut microbiota and metabolite: the decreased 25-hydroxycholesterol in the pyrotinib + SBP treatment group was negatively correlated with Lachnospiraceae while positively correlated with Escherichia and Helicobacter. Meanwhile, SBP did not affect the inhibitory effect of pyrotinib on BT-474 cells and Calu-3 cells in vitro. Also, the network analysis further revealed that SBP treated pyrotinib-induced diarrhea through multiple pathways, including inflammatory bowel disease, IL-17 signaling pathway, pathogenic Escherichia coli infection and cAMP signaling pathway.ConclusionsSBP could effectively relieve pyrotinib-induced diarrhea, revealing that intestinal flora and its metabolites may be involved in this process.

Predictors of Response to Radiation Therapy and of Progression to Multiple Myeloma in Patients with Solitary Bone and Extramedullary Plasmacytomas

Purpose/Objective(s): Radiation therapy (RT) plays an important role in treating Solitary Extramedullary (EMP) and Solitary Bone (SBP) Plasmacytomas. The objective of this study is to review the effectiveness of RT in locally controlling the disease and looking at factors that predict progression to Multiple Myeloma (MM) in the PET scan-era. Materials/Methods: We performed a retrospective analysis of consecutive plasmacytoma patients (pts) treated at our high-volume center. We identified 94 pts, of which 62 were diagnosed with SBP and 32 with EMP, without evidence of MM at diagnosis (end-organ damage, >10% bone marrow involvement, >1 plasmacytoma). We identified 94 total pts, largest series to date in the literature, treated with RT (no pts received systemic therapy) between January 1, 2000, through December 31, 2020. Of the 94 pts, 62 were diagnosed with SBP and 32 with EMP, without evidence of MM at diagnosis (end-organ damage, >10% bone marrow involvement, >1 plasmacytoma). We utilized radiographic staging including PET scans and clinical assessments to determine patient outcomes. Outcomes include initial radiographic responses using the European Expert Panel Response Criteria, local control (LC), overall survival (OS), and progression to MM. Kaplan-Meier was used to assess LC and OS. Univariable analysis was done using age, sex, race, plasmacytoma type (EMP vs. SBP), PET scan at staging versus other modalities, first post-RT response (CR, no CR), Pre-RT SUV of lesion, RT dose (≥45Gy) and overall response to RT (if CR was achieved). Results: Patient and treatment characteristics are summarized in table 1. 24 (66%) EMPs and 54 (84%) SBPs received a radiation dose ≥45Gy. After excluding 8 patients who were lost to follow up, 81% of patients with EMPs and 81% with SBPs achieved complete response (CR) with a median time to CR being 11 months (range 0.53-38.9) for EMP and 8 months (range 0.6-89.2) for SBP. All pts achieving a CR were treated with doses ≥40Gy. Only 1 (3%) EMP and 2 (3%) SBPs had an in-field failure after CR. The 5-year OS was 68% for EMPs and 94% for SBPs [p=0.007]. Out of 94 pts, 19 died, and cause of death was not related to the plasma cell neoplasm in 7 EMP pts. The 5-year rate of progression to MM was 28% in the EMP group, and 64% in the SBP group [p=0.006], with progression-free survival (PFS) of 61% In the EMP group and 35% in the SBP group [p=0.041]. On univariate analysis, sex, age, RT dose (<45 Gy, ≥45 Gy), staging PET, location [EMP vs. SBP] and achieving a CR after RT (at first post-RT response and CR at any time) were analyzed. Pts with EMP were at significantly lower risk for progression to MM (HR 0.3, 95% CI 0.2, 0.8; p=0.009) Additionally, Pts with CR on first post-RT imaging were at lower risk for progression to MM (HR 0.6, 95% CI 0.3, 1.0, p=0.05). Conclusion: Our data indicates that definitive RT for EMP and SBP can provide excellent LC. Progression to MM remains the main problem and is more common among pts with SBP, which is concordant with previously published literature. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Appreciation of an alternative: Dutch alumni look back on their science master, a work-based learning vs a research-oriented approach

The Science, Business and Policy Program (SBP) of the University of Groningen has been a work-based learning program for science master students since two decades. This program, a direct consequence of the Bologna declaration of education in Europe, has a distinctive position in European science curricula. Here, we use a web-based survey (N = 242), comparing alumni perceptions on the SBP program (N = 111) with a research oriented master (ROM, N = 131). Alumni from both programs predominantly had a content-driven motivation to choose for either the ROM or SBP format. For SBP alumni, this preference was also inspired by the master’s focus on society and a career outside academia. We assessed self-perceived learning outcomes using an extended version of the Science Student Skills Inventory. Both groups were positive about the academic level of their program. Scientific content knowledge and practical research skills were perceived as sufficient by both groups, although significantly higher in the ROM group. Both groups were equally positive about obtained skills in academic reasoning and would have preferred more disciplinary content knowledge. The SBP group perceived their skills on teamwork, multidisciplinary working, leadership, ethical thinking and project work to be significantly higher compared to ROM alumni. The SBP group felt significantly more prepared for a career outside academia and the ROM group for a career in academia. Relatively the ROM group missed career preparation. Both specific work-based learning and classical research approaches were seen as valid ways to obtain a high-quality, science master level, although for different career ambitions.

Predictors of Response to Radiation Therapy and of Progression to Multiple Myeloma in Patients with Solitary Bone and Solitary Extramedullary Plasmacytomas

<h3>Purpose/Objective(s)</h3> Radiation therapy (RT) plays an important role in treating Solitary Extramedullary (EMP) and Solitary Bone (SBP) Plasmacytomas. The objective of this study is to review the effectiveness of RT in locally controlling the disease and looking at factors that predict progression to Multiple Myeloma (MM) in the PET scan-era. <h3>Materials/Methods</h3> We performed a retrospective analysis of consecutive plasmacytoma patients (pts) treated at our high-volume center. We identified 99 pts, of which 64 were diagnosed with SBP and 35 with EMP, without evidence of MM at diagnosis (end-organ damage, >10% bone marrow involvement, >1 plasmacytoma). We identified 99 total pts, largest series to date in the literature, treated with RT between January 1, 2000, through December 31, 2020. We utilized radiographic staging including PET scans and clinical assessments to determine patient outcomes. Outcomes include initial radiographic responses, local control (LC), overall survival (OS), and progression to MM. Kaplan-Meier was used to assess LC and OS. <h3>Results</h3> Patient and treatment characteristics are summarized in table 1. 24 (69%) EMPs and 54 (84.4%) SBPs received a radiation dose ≥45Gy. 74% (n=26, 5 pts were lost to follow up [FU]) of EMPs and 78% (n=50, 3 pts were lost to FU) of SBPs achieved completed response (CR) with a median time to CR being 7.7 months (0.1-38.9) for EMP and 15.46 months (0.6-89.2) for SBP. All pts achieving a CR were treated with doses ≥40Gy. Only 1 (3%) EMP and 2 (3%) SBPs had an in-field failure after CR. The 2-year OS was 68% for EMPs and 98% for SBPs [p=0.004]. Out of 99 pts, 14 died, and cause of death was not related to the plasma cell neoplasm in 5 EMP pts. The 2-year rate of progression to MM was 15% in the EMP group, and 33% in the SBP group [p<0.001]. On univariate analysis, baseline SUV and size, location [EMP vs. SBP] and achieving a CR after RT were analyzed. Pts with SBP were at higher risk for progression to MM [p<0.05]. <h3>Conclusion</h3> Our data indicates that definitive RT for EMP and SBP can provide excellent LC. Progression to MM remains the main problem and is more common among pts with SBP, which is concordant with previously published literature.

Alterations of gut microbiota in cirrhotic patients with spontaneous bacterial peritonitis: A distinctive diagnostic feature.

BackgroundSpontaneous bacterial peritonitis (SBP) is a severe infection in cirrhotic patients that requires early diagnosis to improve the long-term outcome. Alterations in the gut microbiota have been shown to correlate with the development and progression of liver cirrhosis. However, the relationship between SBP and gut microbiota remains unknown.MethodsIn this study, we applied 16S rRNA pyrosequencing of feces to ascertain possible links between the gut microbiota and SBP. We recruited 30 SBP patients, 30 decompensated cirrhotic patients without SBP (NSBP) and 30 healthy controls. Metagenomic functional prediction of bacterial taxa was achieved using PICRUSt. ResultsThe composition of the gut microbiota in the SBP patients differed remarkably from that in the NSBP patients and healthy individuals. The microbial richness was significantly decreased, while the diversity was increased in the SBP patients. Thirty-four bacterial taxa containing 15 species, mainly pathogens such as Klebsiella pneumoniae, Serratia marcescens and Prevotella oris, were dominant in the SBP group, while 42 bacterial taxa containing 16 species, especially beneficial species such as Faecalibacterium prausnitzii, Methanobrevibacter smithii and Lactobacillus reuteri, were enriched in the NSBP group. Notably, we found that 18 gene functions of gut microbiota were different between SBP patients and NSBP patients, which were associated with energy metabolism and functional substance metabolism. Five optimal microbial markers were determined using a random forest model, and the combination of Lactobacillus reuteri, Rothia mucilaginosa, Serratia marcescens, Ruminococcus callidus and Neisseria mucosa achieved an area under the curve (AUC) value of 0.8383 to distinguish SBP from decompensated cirrhosis.ConclusionsWe described the obvious dysbiosis of gut microbiota in SBP patients and demonstrated the potential of microbial markers as noninvasive diagnostic tools for SBP at an early stage.

Severe Pulmonary Bleeding after Assist Device Implantation: Incidence, Risk Factors and Prognostic Impact.

Background: Continuous flow left ventricular assist devices (CF-LVAD) improve survival in patients with advanced heart failure but confer risk of bleeding complications. Whereas pathophysiology and risk factors for many bleeding complications are well investigated, the literature lacks reports about pulmonary bleeding. Therefore, it was the aim of the present study to assess incidence, risk factors, and clinical relevance of pulmonary bleeding episodes after LVAD implantation. Methods: We retrospectively analyzed our institutional database of 125 consecutive patients who underwent LVAD implantation between 2008 and 2017. Demographic and clinical variables related to bleeding were collected. The primary endpoint was incidence of severe pulmonary bleeding (SPB). Results: Nine out of 125 patients suffered from SPB during the postoperative course (7.2%) 11 days after surgery in the median. None of them had a known history of lung disease or bleeding disorder. History of prior myocardial infarction (0% vWD. 42.2%, p = 0.012) and ischemic cardiomyopathy (25.0% vs. 50.0%, p = 0.046) were less frequent in the SBP group. Concomitant aortic valve replacement was more common in the group with SPB (33.3% versus 7.0%, p = 0.034). Surgical (blood loss 9950 vs. 3800 mL, p = 0.012) as well as ear-nose-throat (ENT) bleedings (33% vs. 4.6%, p = 0.015) were observed more frequently in patients with SPB. SPB was associated with a complicated postoperative course with a higher incidence of acute kidney failure (100% versus 36.7%, p = 0.001) and delirium (44.4% versus 14.8%, p = 0.045); a higher need for red blood cell (26 packs versus 7, p < 0.001), fresh frozen plasma (18 units versus 6, p = 0.002), and platelet transfusion (8 pools versus 1, p = 0.001); longer ventilation time (1206 versus 171 h, p = 0.001); longer ICU-stay (58 versus 13 days, p = 0.002); and higher hospital mortality (66.7% vs. 29%, p = 0.029). Conclusion: SPB is a rare but serious complication after LVAD implantation and is significantly associated with higher morbidity and mortality. The pathophysiology and potential risk factors are unknown but may include coagulation disorders and frequent suctioning or empiric bronchoscopy causing airway irritation.

Overexpression of ascitic interleukin-35 induces CD8+ T cell exhaustion in liver cirrhotic patients with spontaneous bacterial peritonitis

Interleukin (IL) -35 induces immunotolerance by suppression of CD8+ T cells during chronic infections and cancers. In the present study, we amined to investigate the role of IL-35-mediated regulation of CD8+ T cells in patients with liver cirrhosis. Seventy-one patients with liver cirrhosis (46 patients with untainted ascites and 25 patients with spontaneous bacterial peritonitis [SBP]) and 22 controls were enrolled. Plasma and ascitic IL-35 levels were measured using ELISA. Peripheral and ascitic CD4+ and CD8+ T cells were purified to investigate their functional phenotypes. IL-35-stimulated CD8+ T cells were cultured with HepG2 cells in direct and indirect contact systems. Lactate dehydrogenase expression and cytokine secretion were measured to determine the cytotoxicity of CD8+ T cells. Plasma IL-35 was elevated in patients with liver cirrhosis, and ascitic IL-35 levels were higher in the SBP group than in the untainted ascites group. No significant differences in transcription factor expression or cytokine production in peripheral and ascitic CD4+ T cells were observed among groups. In the SBP group, ascitic CD8+ T cells expressed decreased cytotoxic molecules, along with the reduced secretion of interferon-γ and tumor necrosis factor-α when compared with the untainted ascites group. IL-35 stimulation suppressed ascitic CD8+ T cell cytotoxicity and cytokine production in both direct and indirect contact culture systems. This process was accompanied by decreased cytotoxic molecule expression and increased immune-checkpoint molecules in ascitic CD8+ T cells. The present findings revealed that overexpression of ascitic IL-35 dampened the cytotoxicity of CD8+ T cells in liver cirrhotic patients with SBP.

Association of peridialytic, intradialytic, scheduled interdialytic and ambulatory BP recordings with cardiovascular events in hemodialysis patients.

Ambulatory-BP-monitoring (ABPM) is recommended for hypertension diagnosis and management in hemodialysispatients due toits strong association with outcomes. Intradialytic and scheduled interdialytic BP recordings show agreement with ambulatory BP. This study assesses in parallel the association of pre-dialysis, intradialytic, scheduled interdialytic and ambulatory BP recordings with cardiovascular events. We prospectively followed 242 hemodialysis patients with valid 48-h ABPMs for a median of 45.7months to examine the association of pre-dialysis, intradialytic, intradialytic plus pre/post-dialysis readings, scheduled interdialytic BP, and 44-h ambulatory BP with outcomes. The primary end-point was a composite one, composed of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, resuscitation after cardiac arrest, hospitalization for heart failure, coronary revascularization procedure or peripheral revascularization procedure. Cumulative freedom from the primary end-point was significantly lower with increasing 44-h SBP (group 1, < 120mmHg, 64.2%; group 2, ≥ 120 to < 130mmHg 60.4%, group 3, ≥ 130 to < 140mmHg 45.3%; group 4, ≥ 140mmHg 45.5%; logrank-p = 0.016). Similar were the results for intradialytic (logrank-p = 0.039), intradialytic plus pre/post-dialysis (logrank-p = 0.044), and scheduled interdialytic SBP (logrank-p = 0.030), but not for pre-dialysis SBP (logrank-p = 0.570). Consideringgroup 1 as the reference group, the hazard ratios of the primary end-point showed a gradual increase with higher BP levels with all BP metrics, except pre-dialysis SBP. This pattern was confirmedin adjusted analyses. An inverse association of DBP levels with outcomes was shown with all BP metrics, which was no longer evident in adjusted analyses. Averaged intradialytic and scheduled home BP measurements (but not pre-dialysis readings) display similar prognostic associations with 44-h ambulatory BP in hemodialysis patients and represent valid metrics for hypertension management in these individuals.

The effect of different cleaning agents and resin cement materials on the bond strength of contaminated zirconia

The purpose of this study was to examine the effect of different cleaning methods and resin cements on the shear bond strength (SBS) of contaminated zirconia. A total of 92 disc-shaped zirconia specimens were contaminated with different procedures. Then, the specimens were grouped according to cleaning methods and resin cements: no cleaning + Variolink Esthetic DC (CNV ), no cleaning + Panavia V5 (CNP ), sandblasted + Variolink Esthetic DC (SBV ), sandblasted + Panavia V5 (SBP ), Ivoclean + Variolink Esthetic DC (ICV ), Ivoclean + Panavia V5 (ICP ), Katana Cleaner + Variolink Esthetic DC (KCV ), and Katana Cleaner + Panavia V5 (KCP ). Following an aging protocol in a 37°C for 1week, SBS analysis was performed with a universal test machine. For the surface topography and elemental analysis, scanning electron microscopy and energy-dispersive X-ray spectroscopy (EDS) were used. Significance was evaluated as p< .05 and p< .01. The highest SBS results were found in the SBP group, showing a statistically significant difference from all other groups (p <.05). For the same cleaning method, Panavia V5 showed statistically significantly higher SBS values than Variolink Esthetic DC (p< .01), except the CNP -CNV (p= .880) and KCP -KCV (p= .082) groups. The most detected surface elements by EDS were Zr, O, C, and N, respectively. The contaminated zirconia surfaces must be cleaned for successful adhesion. The use of phosphate-containing adhesives in combination with sandblasting will increase the adhesion strength, and universal cleaning agents can be a good alternative to sandblasting.