Due to the various clinical and pathological manifestations of kidney involvement in lymphoproliferative disorder (LPD), the whole spectrum of kidney disease in LPD is still unclear, and data on kidney prognosis is scarce.We retrospectively reviewed the renal pathology profiles from January 2010 to December 2021, and 28 patients with B-cell LPD combined with intact renal biopsy data were included.There were 20 men and eight women aging 41 to 79 years at the time of renal biopsy (median age 62 years). According to hematological diagnosis, patients were classified into four groups: chronic lymphocytic leukemia (CLL) , Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) , Other non-Hodgkin’s lymphomas (NHL) , n=2; mucosa-associated lymphoid tissue (MALT) lymphoma, n=4; Low grade B-cell lymphoma, n=1), and monoclonal gammopathy of undetermined significance/monoclonal gammopathy of renal significance (MGUS/MGRS) . Median serum creatinine (Scr) level was 129  umol/L. Eight patients (29%) were presented with acute kidney injury (AKI), and five patients (18%) required hemodialysis upon admission. Twenty-three patients (82%) presented with proteinuria , 11(39%) of whom had the nephrotic syndrome. Interstitial malignant infiltration was the most frequent renal lesion (n=6). Eight patients underwent immunohistochemistry of renal tissues, of which three patients  had confirmed lymphoma infiltrates, and the infiltrating cells in the remaining five patients  were considered unrelated to lymphoma. The most common glomerular diseases were renal amyloidosis (n=4) and membranous nephropathy (n=4). Only 20 patients were treated, 13 of whom were treated with rituximab separately or in combination. The median follow-up time was 11 months. Of these, six had achieved hematological response, complete response in five cases. Eight had achieved renal response. At the end-of-study visit, four patients died and two progressed to end stage kidney disease (ESKD).In conclusion, the clinicopathological spectrum of renal involvement in BLPD is diverse. Renal biopsy and immunohistochemistry are required for early diagnosis and prognostic assessment. Chronic B-cell lymphoproliferative disorder (B-CLPD) is a group of mature B-cell clonal proliferative disorders characterized by clonal proliferation of mature lymphocytes in the peripheral blood/bone marrow and diagnosed by morphological, immunophenotypic and cytogenetic features of the peripheral blood/bone marrow. It includes chronic lymphocytic leukemia (CLL), multiple myeloma (MM), Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL), and other non-Hodgkin’s lymphomas (NHL) . Kidney Majority of the kidney involvement in LPD were associated with pathogenic monoclonal immunoglobulin which were mainly observed in patients with indolent B-cell lymphoma or monoclonal gammopathy of undetermined significance (MGUS). The physicochemical properties of the secreted monoclonal immunoglobulin (MIg) instead of tumor masses lead to the disorders . RecentlDue to the various clinical and pathological manifestations of kidney involvement in LPD, it is difficult for clinical diagnosis and subsequent treatment, and therefore the prognosis is unsatisfactory , 10. TheWe retrospectively reviewed the renal pathology profiles at the renal department of the First Affiliated Hospital of Nanjing Medical University from January 2010 to December 2021, and 28 patients with B-LPD combined with intact renal biopsy data were included . InclusiAll patients underwent a complete clinical and laboratory workup, including a thorough hematological examination, serum and urine protein electrophoresis, immunochemical characterization of the monoclonal component, and a bone marrow biopsy with aspiration. Conventional cytogenetic analysis was performed as part of the clinical workup for bone marrow aspirate with standard methods in the clinical laboratories. Mutations in myeloid differentiation primary response 88 (MYD88) whole exons were assessed on bone marrow aspirate or peripheral blood samples using the previously-described allele-specific polymerase chain reaction  or the S2 and proteinuria <0.5 g/d; partial response by a ≥50% increase in eGFR or reduction in proteinuria by 50% with stable renal function for patients with baseline eGFR >60 ml/min per 1.73m2. ESKD was defined as the initiation of maintenance dialysis or kidney transplantation.eGFR was calculated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation . NephrotAll kidney biopsy samples were subjected to light microscopy, immunofluorescence microscopy and electron microscopy (EM). Samples were parceled and sectioned at 2 mm, followed by periodic acid-Schiff (PAS), Masson or periodic acid-silver methylamine (PASM) staining. The slices were stained systematically with Congo red and checked under polarized light. For immunofluorescence, frozen sections of 3 mm were stained for ɑ, γ, μ heavy chain, κ and λ light chain , C3, C4 and C1q  by using polyclonal isothiocyanate fluorophore conjugates. Bone marrow smears or biopsies were performed on all patients. Immunohistochemical studies were performed on kidney and bone marrow biopsy samples using anti-CD20, CD19, CD3 and anti-CD38 antibodies .The clinical characteristics of all 28 patients were summarized in Bone marrow biopsy was performed in all patients. According to hematological diagnosis, patients were classified into four groups: CLL , WM/LPL , Other-NHL  lymphoma, n=4; Low grade B-cell lymphoma, n=1), and MGUS/MGRS  (Four of the eight WM/LPL patients were detected positive for the myeloid differentiation primary response 88 (MYD88) mutation by genetic testing. Recently the MYD88 mutation has been emerged as a hallmark of WM/LPL, implicating in its diagnosis, management, and treatment .1 patienOf 28 patients with available data, 15 had an apparently indolent disease without infiltration of hematopoietic tissues. The median serum light chain ratio was 1.64 . Among nine patients testing with free light chains, all had abnormal free light chain ratios. In 13 patients (46%), the hematological diagnosis preceded renal manifestations, within a mean time of 36 months. Of these, four had received chemotherapy at the 21, 42, 44, and 83 months, respectively, before the diagnosis of kidney disease. Attention needs to be paid to a patient whose kidney disease was diagnosed 3 months before the diagnosis of hematological disease.Serum immunofixation electrophoresis was conducted in 22 patients, and a serum MIg was detected in 13 cases (59%). The isotype was IgM , IgG , and IgA  respectively. The LC isotype was κ in 32% of cases.At the time of kidney biopsy, median serum creatinine (Scr) level was 129  umol/L. Eight patients (29%) were presented with AKI, and five patients (18%) required hemodialysis upon admission. Twenty-three patients (82%) presented with proteinuria , 11(39%) of whom had the nephrotic syndrome. Eight patients (29%) had microhematuria. In the other-NHL group, none were identified with AKI, mainly presenting with proteinuria. Renal ultrasound revealed morphologic abnormalities in one patient (4%), with kidney enlargement  and membranous nephropathy . A patient with MGUS had primary membranous nephropathy with positive serum anti-phospholipase A2 receptor (PLA2R) antibodies and diffuse granular deposits of anti-PLA2R antibodies in the basement membrane detected by immunofluorescence. Two patients were diagnosed with cryoglobulinemic glomerulonephritis , one of which was the type I IgM-κ cryoglobulinemic glomerulonephritis. The renal pathology of WM was a typical type of MPGN, with heavy hyperplasia and lobularity of the mesangial cells by light microscopy, and IgM-κ deposition in the mesangial region by immunofluorescence. Electron-dense deposits were found in the subendothelial, mesangial, and basement membrane region by electron microscope (EM)  and membranous nephropathy, respectively. Of the remaining 18 patients, 10 were receiving rituximab-based therapy regimen and two patients were treated with ibrutinib , followed by DLBCL (20%) . HoweverMGUS is a low-grade B-LPD manifested by monoclonal protein <3 g/dl and bone marrow plasma cells <10%. Kidney disease has been reported as a common complication of MGUS and the pathological pattern was mainly determined by the physicochemical properties of the pathogenic MIg rather than its concentration . In the C3 glomerulonephritis is a typical MGRS-related disease primarily caused by dysregulation of the alternative complement pathway. Recent studies have reported an unusually high prevalence of MIg and TMA in patients with C3 glomerulonephritis compared to the age-matched general population , 30. In Currently, MIg-related glomerulonephritis has been widely studied, but the association between non-MIg-associated glomerulonephritis, such as FSGS, diabetic nephropathy, and B-LPD has not reached consistent results , 36. It It has been reported that 80% of lymphomas invading the kidney presenting as AKI, but limited studies elaborated on the type of B-cell lymphoma . In one Previous studies found that the most common lesions involving the kidney in BLPD were lymphoma malignant infiltration in renal tubulointerstitial, severe infiltration of tumor cells, combined with acute tubular necrosis, which may lead to severe renal involvement , 26. JavThe study population size was too small to statistically assess the prognostic impact of chemotherapy on B-LPD related kidney damage. Three patients died within 4 months after the diagnosis of kidney disease, suggesting that the survival rates of patients with kidney diseases may be very low. However, three of the five patients who achieved hematological response developed renal response, indicating that early introduction of chemotherapy specifically targeting potential B cell clones may have the potential to prolong the survival time of patients. In this study, one patient with WM combined with cryoglobulinemic glomerulonephritis was prescribed with ibrutinib after unremarkable regimen of rituximab, cyclophosphamide and dexamethasone) (RCD). And the patient got off dialysis and achieved renal remission in a very short time. Further well-planned large prospective studies of the efficacy of ibrutinib on lymphoma concurrent with kidney disease may get more useful and reliable information.In conclusion, the clinicopathological features of renal involvement in B-LPD are diverse and complex. MIg-associated kidney disease has been relatively well studied previously, whereas less attention has been drawed on non-MIg-associated glomerulonephritis which requires distinction from primary to secondary forms. Renal biopsy and immunohistochemistry examination have the necessity for early diagnosis and prognostic assessment. Additionally, for MGRS early and proper diagnosis is essential to maximize the chance of disease-modifying treatments targeting a monoclonal Ig-producing proliferation. Further large, randomized controlled, prospective studies are still needed to ascertain the short- and long-term efficacy of kidney lesions on MGRS.The original contributions presented in the study are included in the article/The study was reviewed and approved by ethics committee of the First Affiliated Hospital of Nanjing Medical University (2022-SR-083).GN designed the research and contributed to the writing. LS analyzed the data and performed statistical analysis. CZ, YY, HM, ZW, and JL reviewed the manuscript. CX and SD conceived, coordinated the study, and had responsibility for its final content. BZ is the guarantor of this work who had complete access to all the data in the study and takes ultimate responsibility for the study design and integrity of data analysis. All authors contributed to the article and approved the submitted version.This work was supported by grants from the National Natural Science Foundation of China , the Natural Science Foundation of Jiangsu Province , the China Scholarship Council , Chinese Society of Nephrology , “PRO•Run” Fund of the Nephrology Group of CEBM(KYS2021-03-02-14 to BZ), Project of clinical capability improvement of the First Affiliated Hospital of Nanjing Medical University(to SD), the Clinic Research Center of Jiangsu Province (No. BL2014080) and the Priority Academic Program Development of Jiangsu Higher Education Institutions.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. 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During anesthesia, noncritical patients are routinely monitored via noninvasive cuff-based blood pressure (BP) monitors. Due to the noncontinuous nature of the monitoring, the BP values of the patient remain unavailable between consecutive cuff measurements, carrying the risk of missing rapid and sudden variations in BP. We evaluated the added value of using a photoplethysmography (PPG)-based continuous BP measurement device in addition to the standard cuff-based monitoring in a cohort of 40 patients in comparison with the current approach, in which only intermittent cuff-based measurements are available. When using a three-minute cuff measurement interval, using the PPG-based BP measurement in addition to the cuff-based monitor reduced the error (mean ± SD) of systolic (SBP) and mean (MBP) BP from 2.6 ± 19.6 mmHg and 1.2 ± 13.2 mmHg to 0.5 ± 11.2 mmHg and 0.0 ± 8.1 mmHg, respectively. Error grid analysis was also used to assess the improvement in patient safety. The additional use of the PPG-based BP measurement reduced the amount of data falling into higher risk categories. For SBP, points falling in the significant-, moderate-, and low-risk categories decreased from 1.1%, 8.7%, and 19.3% to 0.0%, 2.3%, and 9.6%, respectively. Similar results were obtained for MBP. These results suggest that using a PPG-based BP monitor—in addition to the standard cuff-based monitor—can improve patient safety during anesthesia induction, with no additional sensor needed. The routine monitoring of patients during anesthesia relies on the use of an oscillometric brachial cuff to measure arterial blood pressure (BP) . This teAn arterial catheter allows for continuous BP me and is known as the gold standard technique. However, due to its invasiveness, it is associated with various complications  ,10,11,12Continuous techniques using digital cuffs have been proposed, but they require specific devices and are limited in their applications; additionally, they can sometimes be unpleasant for the awake patient and raise questions about their accuracy and precision compared with the invasive gold standard that remains available .Over the last two decades, several techniques based on photoplethysmography (PPG) have opened new perspectives . Most ofAdding PEP to PTT involves a slight, clinically acceptable bias; the arrival of the pulse wave is detected at the periphery using a PPG-based device, such as a pulse oximeter. In addition, various studies have demonstrated feasible collection of the necessary variables during anesthesia induction ,18.In our study, we aimed to demonstrate that PAT-based continuous blood pressure measurement is a possible and accessible solution that can improve anesthesia safety compared with the use of a brachial cuff.www.clinicaltrials.gov on 11 January 2016. The informed consent of all enrolled patients was acquired. This sample of patients was collected by Ghamri et al. to study the determination of BP variations from the PPG waveform [The study was approved by the local ethics committee (CER-VD n° 327/15) and was registered under the number NCT02651558 at waveform .Forty patients aged ≥ 18 years undergoing elective surgery necessitating general anesthesia for ENT or neurosurgery with IBP monitoring were recruited. The recruitment took place in 2017 at Centre Hospitalier Universitaire Vaudois (CHUV), and exclusion criteria were patient refusal, inability to consent, and arterial disease leading to an AP difference (>15 mmHg on SAP or >10 mmHg on DAP) between both arms .On the day of surgery, diuretics, angiotensin II receptor blockers and angiotensin-converting enzyme inhibitor therapy were suspended.The patients were monitored  and connected to a Philips IntelliVue MP50 monitor . AP measurement was provided by the insertion of a 20-gauge, 4.5 cm length arterial catheter  in the left or right radial (38 patients) or femoral artery (2 patients). In the case of radial artery catheterization, a fingertip was placed on the contralateral hand for PPG data acquisition.Continuous IBP was recorded at induction of general anesthesia for 9–19 min with ixTrend express software version 2.1.0 .General anesthesia was induced by propofol (2–3 mg/kg), fentanyl (1–2 μg/kg) or continuous remifentanil infusion (0.1–0.5 μg/kg/min), and rocuronium (0.6 mg/kg). Maintenance of anesthesia was provided by continuous propofol infusion (6–12 mg/kg/h) and hemodynamic support by boluses of ephedrine (5–10 mg) or phenylephrine (50–100 μg) or continuous norepinephrine infusion (0.02–0.2 μg/kg/min) .Demographic values such as sex, age, height, weight, American Society of Anesthesiologists (ASA) score, comorbidities, site of catheterization, hypertension medication, and the type of surgeries were recorded.We referred to the sample size estimation by Ghamri et al. , who colAll signals were postprocessed and analyzed using MATLAB version 2020b . The raw pulse oximeter PPG signal and the arterial line signal were aligned in time through cross-correlation. The latter was acquired in synchronization with the ECG signal, making all three signals synchronous. The obvious artifacts in the raw arterial line signal were visually identified and excluded. At each heartbeat, the PAT was estimated as the delay between the R-wave peak of the ECG signal and the minimum of the second time derivative of the PPG signal. A 20 s moving window was used to refine the value of the PAT by calculating it as the average of all individual PAT values in the previous 20 s, with prior removal of outliers using the median absolute deviation method [The transformation of the logarithmic PAT values to the estimated BP values was achieved by training a linear model in a leave-one-out manner for each patient. To that end, the first PAT and invasive BP value of each patient’s recording was subtracted from all the patient’s values as follows:By applying the leave-one-out procedure, the model used for a given patient was trained on all other patients in the dataset, except on the patient themselves. The model was a simple linear model with no intercept, meaning that it consisted of a slope parameter The addition of The agreement between analysis , by comphe error . Althoughe error . The errAs pointed out by Mukkamala et al. , the coralue see . Note thn = 38) or femoral (n = 2) catheter. Demographics, biometric characteristics, average BP values, and variability of the patients are shown in We present the results of an analysis of 40 patients with a radial  were rejected prior to analysis due to high within-window variability. The 40 trained linear models  resulted in an average (±SD) value of the The corresponding error grid analysis plots are shown in the same figures. The percentage of points falling in each risk category as a function of the recalibration interval is detailed in Anesthesia can expose patients to large and rapid variations in blood pressure that a single brachial cuff, due to the intermittent nature of the measurement. In our study, we demonstrated that PAT-based continuous blood pressure measurement allowed identification of inaccessible time points of blood pressure values compared with the use of a brachial cuff.Comparing our PPG-based approach .Using an automated and continuous PPG-based technique would be feasible and seems reliable enough to increase safety during anesthesia induction by avoiding the potentially dangerous “blind spot” inherent in using a single brachial cuff. It may provide inexpensive complementary data to add to the usual monitoring. Currently, all existing PPG-based techniques require calibration to be accurate; thus, a full replacement of the brachial cuff is not yet possible. BP measurement using PAT as proposed is not meant to replace the use of an arterial catheter but only to increase safety. Therefore, patients who are severely ill, unstable, or require continuous hemodynamic support with vasoactive drugs should remain monitored by invasive means.


GBA1 molecular sequencing and lyso-Gb1 quantification. Treatment decisions were based on symptoms, signs, and routine laboratory tests. We diagnosed 97 patients , both type 1 (n = 87), and neuronopathic (n = 10). The median (range) age at diagnosis was 22 (1–78), with 36 children. In 65 patients, GD-specific therapy was started with a median (range) lyso-Gb1, 337 (60–1340) ng/mL, significantly higher than in patients who did not go on to treatment, 153.5 (9–442) ng/mL. Using a receiver operating characteristic (ROC) analysis, a cutoff of lyso-Gb1 > 250 ng/mL was associated with treatment with a sensitivity of 71% and specificity of 87.5%. Predictors of treatment were thrombocytopenia, anemia, and elevated lyso-Gb1 (>250 ng/mL). In conclusion, lyso-Gb1 levels contribute to the medical decision related to the initiation of treatment, mainly among mildly affected newly diagnosed patients. For patients with a severe phenotype, as for all patients, the main value of lyso-Gb1 would be to monitor response to therapy. The variable methodology and differences in the units of lyso-Gb1 measurements between laboratories prevent the adaptation of the exact cut-off we found in general practice. However, the concept is that a significant elevation, i.e., a several-fold increase from the diagnostic lyso-Gb1 cutoff, is related to a more severe phenotype and, accordingly, to the decision regarding the initiation of GD-specific therapy.Glucosylsphingosine (lyso-Gb1), the deacylated form of glucocerebroside, was shown to be the most specific and sensitive biomarker for diagnosing Gaucher disease (GD). The aim of this study is to assess the contribution of lyso-Gb1 at the time of diagnosis for treatment decisions in naïve patients with GD. Newly diagnosed patients from July 2014 to November 2022 were included in this retrospective cohort study. The diagnosis was done by sending a dry blood spot (DBS) sample for  GBA1) contribute to a broad spectrum of phenotypes from a perinatal-lethal to an asymptomatic form, traditionally subdivided into three main types [Gaucher disease (GD), one of the most common lysosomal storage disorders, is caused by a mutant lysosomal enzyme β-glucocerebrosidase, leading to the storage of glucocerebroside. Over 860 variants within the glucocerebrosidase gene GBA contribuDespite being a rare disease, several therapeutic options are available for patients with type 1 GD. Three formulations of enzyme replacement therapy (ERT), all administered intravenously, usually once every two weeks, and two oral compounds of substrate reduction therapy (SRT) have been approved by the United States Food and Drug Administration (US FDA), European Medicines Agency (EMA), and major regulatory agencies . In addiGlucosylsphingosine (lyso-Gb1), the deacylated form of glucocerebroside, was shown to be the most specific and sensitive biomarker for the diagnosis of GD ,6. FurthGBA1 variants were significantly older, with higher hemoglobin levels and lower lyso-Gb1 compared to those with type 1 due to severe GBA1 variants and those with neuronopathic GD  of 2 (0–78) months after the time of diagnosis. Six of the 32 untreated patients were not started on treatment due to personal reasons, and two were lost to follow-up. Those cases were excluded from further analysis, leaving 24 untreated patients. Starting treatment was not associated with sex or age at diagnosis. Treatment was more commonly started in patients diagnosed with type 1 GD due to severe athic GD .For the 24 patients not needing GD-specific therapy during a median (range) follow-up of 3.75 (1.5–8.5) years, lyso-Gb1 at diagnosis was significantly lower compared to those starting treatment . Of thosIn order to determine the optimum lyso-Gb1 cut-off point for treatment initiation, we computed a receiver operating characteristic (ROC) curve using the “Youden” method . ROC cur9/L were treated, except for two. One child had a platelet count of 50 × 109/L but was otherwise asymptomatic (lyso-Gb1 37.5 ng/mL). A blood smear revealed platelet clumps. We estimated his platelet count to be >100 × 109/L. Another patient had a platelet count of 86 × 109/L and lyso-Gb1 > 250 ng/mL but was otherwise asymptomatic. Both had a mild genotype, i.e., homozygous for the N370S variant.All patients with a platelet count < 100 × 10All patients with hemoglobin < 11.5 g/dL were treated, except one child with hemoglobin 10.6 due to iron deficiency anemia.All patients with lyso-Gb1 > 250 ng/mL were treated, except four (three children) with a mild phenotype. Two adults with lyso-Gb1 < 100 ng/mL initiated therapy due to thrombocytopenia with pregnancy-related bleeding and thrombocytopenia with extensive splenomegaly. One child presenting with lyso-Gb1 < 100 ng/mL started ERT three years after diagnosis for short stature after being unresponsive to growth hormone and an increase in lyso-Gb1 to over 200 ng/mL.9/L. For lyso-Gb1 levels, we chose three categories: <100 ng/mL, between 100–250 ng/mL, and >250 ng/mL. The odd ratio (OR) with 95% CI for predicting treatment is presented in Using the likelihood ratio test, the best-fitting model included platelet count, hemoglobin levels, and lyso-Gb1 levels at diagnosis. With the aim of enabling a more practical model, we transformed the continuous variables into categorical ones. Anemia was defined as hemoglobin <11.5 ng/mL and thrombocytopenia was defined as platelet count <100 × 10In our study, we aimed to learn how lyso-Gb1 can contribute to treatment decisions in patients with GD by following a large cohort of patients newly diagnosed with GD, recording their treatment status, and their lyso-Gb1 levels. Although the lyso-Gb1 levels were significantly higher in patients who started treatment vs. those who remained untreated, it was not the only predictor for initiating therapy. High lyso-Gb1, i.e., several fold increase from the diagnostic cutoff lyso-Gb1 levels, was associated with the initiation of therapy.Thrombocytopenia and anemia are well-recognized hematological manifestations of GD which, when clinically significant, warrant the initiation of therapy. However, not all cases of anemia and thrombocytopenia in patients with GD are related to GD, and isolated cytopenia without other GD-related signs and symptoms should lead to further investigation . PseudotBased on our study, we believe that lyso-Gb1 levels should play an important role in treatment decisions. In contrast to the other biomarkers described in GD , lyso-GbAccording to the Centogene laboratory cutoff values, lyso-Gb1 levels above 6.8 ng/mL suggest GD . In our GBA1 genotypes and neuronopathic GD, were significantly younger compared to those with milder GBA1 genotypes, initiation of therapy was not associated with age. Therapy was started only for symptomatic children. Asymptomatic children may grow into asymptomatic adults who also would not need therapy [Interestingly, while the patients that were diagnosed with genetically severe disease, i.e., severe  therapy , but som therapy . Althoug therapy , we and  therapy  that may therapy . Thus, aNewborn screening programs for lysosomal diseases, including GD, are being developed worldwide, showing good feasibility ,23,24,25Initiation of therapy was not associated with sex. Our observation that ERT can prevent pregnancy-related complications  led us, Reviewing a consecutive cohort of patients who started therapy in the last eight years prompted us to update the 1998 Israeli MOH criteria for approval of ERT . The updIn the updated criteria, we have highlighted several important points. First, lyso-Gb1 levels are important mainly for patients with milder symptoms, asymptomatic patients with a family history of significant disease, and asymptomatic patients with severe genotypes. For symptomatic cases, therapy should start irrespective of lyso-Gb1 levels. Second, age by itself is not a criterion. Third, we added a new criterion for patients with GD needing myelosuppressive therapy who would benefit from GD-specific treatment due to the significant risk of infection and/or bleeding. Due to anecdotal cases of patients with GD and monoclonal gammopathy of unknown significance (MGUS) or multiple myeloma who responded to ERT/SRT ,30,31, tGBA1 mutations have a higher propensity to develop Parkinson's disease [Patients with type 1 GD and carriers of  disease . The curNewly diagnosed patients from July 2014 to November 2022 at the Gaucher Unit, Shaare Zedek Medical Center, were included in this retrospective cohort study. The diagnosis was done by sending a dry blood spot (DBS) sample for GBA1 molecular sequencing and lyso-Gb1 level. All samples were analyzed in Centogene GmbH, Rostock, Germany, as previously described . ClinicaWe used the median (range) for continuous variables to report summary descriptive statistics. For nominal data, we reported the absolute and relative frequencies. The Kruskal–Wallis H test was used to determine statistically significant differences between two or more groups of an independent variable on a continuous dependent variable. A chi-square test was used to compare categorical data. The optimal.cutpoints r program with the “Youden” method was used to calculate the optimal cut point for starting treatment and plotting the ROC curves. The AUC under the ROC curve results are considered excellent for AUC values between 0.9–1, good for AUC values between 0.8–0.9, fair for AUC values between 0.7–0.8, poor for AUC values between 0.6–0.7, and failed for AUC values between 0.5–0.6 . A logisOur study proved the important role of lyso-Gb1 levels in the treatment decisions of patients with GD. The contribution is mainly among mildly affected newly diagnosed patients, i.e., initiation of therapy when the levels are highly elevated or rapidly progressive. The challenge of initiating GD-specific therapy in pre-symptomatic children is going to become even more relevant when newborn screening for lysosomal diseases becomes widely used, and the dependency on predictive biomarkers will be all the more critical.


ECHO) has been widely adopted to screen for pulmonary hypertension (PH), but there is still a high proportion of overestimation or underestimation of sPAPECHO. We therefore aimed to explore the accuracy and influencing factors of sPAPECHO with right heart catheterization (RHC) as a reference.Noninvasive assessment of pulmonary artery systolic pressure by Doppler echocardiography (sPAPECHO), and sPAPECHO. With mPAP ≥ 25 mm Hg measured by RHC as the standard diagnostic criterion of PH, the ROC curve was used to compare the diagnostic efficacy of sPAPECHO with other TR-derived parameters. The ratio (sPAPECHO–sPAPRHC)/sPAPRHC was calculated and divided into three groups as follows: patients with an estimation error between − 10% and + 10% were defined as the accurate group; patients with an estimated difference greater than + 10% were classified as the overestimated group; and patients with an estimation error greater than − 10% were classified as the underestimated group. The influencing factors of sPAPECHO were analyzed by ordinal regression analysis.A total of 218 highly suspected PH patients who underwent RHC and echocardiography within 7 days were included. The correlation and consistency between tricuspid regurgitation (TR)-related methods and RHC results were tested by Pearson and Bland–Altman methods. TR-related methods included peak velocity of TR (TR Vmax), TR pressure gradient (TR-PG), TR mean pressure gradient (TR-mPG), estimated mean pulmonary artery pressure , best diagnostic efficiency (AUC = 0.98), and lowest bias  compared with other TR-related methods. Ordinal regression analysis showed that TR signal quality, sPAPRHC level, and pulmonary artery wedge pressure (PAWP) affected the accuracy of sPAPECHO (P < 0.05). Relative to the good signal quality, the OR values of medium and poor signal quality were 0.26  and 0.23 , respectively. Compared with high sPAPRHC level, the OR values of low and medium sPAPRHC levels were 21.56  and 5.13 , respectively. The OR value of PAWP was 0.94 . TR severity and right ventricular systolic function had no significant effect on the accuracy of sPAPECHO.sPAPECHO, had comparable and good efficiency in PH screening. To make the assessment of sPAPECHO more accurate, attention should be paid to TR signal quality, sPAPRHC level, and PAWP.In this study, we found that all TR-related methods, including sPAP ECHO), and pulmonary artery systolic pressure (sPAPECHO). The current guidelines recommend TR Vmax to avoid additional error in the estimated right atrial pressure (RAP) [ECHO has also been shown to be a reliable method [ECHO is superior to other parameters in determining the probability of PH. sPAPECHO can also provide valuable information for evaluating treatment response and even predicting prognosis [ECHO [ECHO is under/overestimated. Based on clinical experience and review of previous literature, we assumed that right ventricular systolic function, pulmonary artery pressure level, TR severity, and signal quality would affect the accuracy of sPAPECHO. In addition, as an important parameter to distinguish pre- and post-capillary PH, pulmonary artery wedge pressure (PAWP) was also included in the analysis to examine whether there would be any difference in the accuracy of sPAPECHO. Therefore, the first aim of this study was to compare the efficiency of sPAPECHO and other parameters in PH screening, while the second aim was to find influencing factors that account for the inaccuracy of sPAPECHO.Right heart catheterization (RHC) is recognized as the gold standard for measuring pulmonary artery pressure, but its invasiveness limits its general applicability. Doppler echocardiography (DE) can noninvasively assess pulmonary artery pressure by peak velocity of tricuspid regurgitation (TR Vmax) and its derived parameters, including TR pressure gradient (TR-PG), TR mean pressure gradient (TR-mPG), estimated mean pulmonary artery pressure (mPAPre (RAP) . Furtherre (RAP) . As the e method ; howeverrognosis , 5; howeis [ECHO . To evalBetween October 2015 and October 2020, a total of 430 patients admitted to our center with known or suspected PH were evaluated. The inclusion criteria were age ≥ 18 years and the interval between echocardiography and RHC ≤ 7 days. The exclusion criteria were as follows: lack of TR, pulmonary artery stenosis or right ventricular outflow tract stenosis, poor image quality not suitable for analysis, ventricular septal defect, or patent ductus arteriosus. Patients’ demographic and clinical data were obtained from the electronic medical records. The institutional review board of the China–Japan Friendship Hospital waived the need for written informed consent as the study involved the retrospective analysis of clinically acquired data. The data underlying this article will be shared upon a reasonable request to the corresponding author.Baseline assessment of the eligible patients included WHO functional class, the level of N-terminal pro B-type natriuretic peptide (NT-proBNP), and a 6-min walk test (6MWT).RHC), and PAWP were recorded at end-expiration at baseline over at least three heart cycles. Cardiac output (CO) was obtained using Fick’s method. Pulmonary vascular resistance (PVR), cardiac index, stroke volume, pulse pressure, and diastolic pressure gradient were calculated using standard formulas. Pulmonary artery pressure was classified into low, medium, and high levels according to the tertiles of sPAPRHC.Hemodynamic measurements were performed with a 7F Swan-Ganz catheter Philips Allura X-PER FD20 flat-plate angiography system (Baxter Inc.). The system was zeroed and referenced at patients’ heart level as previously described [2. TR-mPG was obtained by tracing the time–velocity integral of TR. sPAPECHO and mPAPECHO were calculated by adding the estimated RAP to TR-PG and TR-mPG, respectively. RAP was divided into three categories  based on the inferior vena cava (IVC) diameter and its respiratory variation [ECHO–sPAPRHC)/sPAPRHC was calculated and divided into three groups as follows: patients with an estimation error between − 10% and + 10% were defined as the accurate group; patients with an estimated difference greater than + 10% were classified as the overestimated group; and patients with an estimation error greater than − 10% were classified as the underestimated group. The severity of TR was classified into three grades by comprehensively evaluating the regurgitation jet area and vena contracta (VC) width. The mild group was defined as jet area < 5 cm2, VC TR ≤ 3 mm; the moderate group as jet area 5–10 cm2, 3 mm < VC TR < 7 mm; and the severe group as jet area > 10 cm2, VC TR ≥ 7 mm. TR signal quality was classified into three types according to the extension of the signal for more than half of the systole and well-defined border. Good signal quality was defined as the one that met both criteria. Medium signal quality met only one of these criteria, while poor signal quality did not meet any of the criteria [ECHO measurements, a total of 34 randomly selected examinations were analyzed twice by the first investigator at a 1-week interval and once by the second investigator.Echocardiographic images were acquired using a GE Vivid E95 machine  equipped with M5S phased-array transducers. Analysis was performed independently by two blinded investigators using EchoPAC software . Two-dimensional echocardiography and Doppler echocardiography (DE) were performed based on current guidelines. TR-PG was calculated from the TR Vmax obtained from continuous-wave Doppler by the simplified Bernoulli equation: TR-PG = 4 (TR Vmax)ECHO and other TR-related methods. The influencing factors of sPAPECHO were analyzed by ordinal regression analysis. The intraclass correlation coefficient was used to determine inter- and intra-observer reproducibility for sPAPECHO from 34 randomly selected patients using an identical cine-loop for each view. For all statistical tests, a P value < 0.05 was used to indicate significance.Standard statistical software  was used for the statistical analysis. Data are expressed as mean ± standard deviation for quantitative variables with normal distribution, or as median (interquartile range) for variables not complying with normal distribution. The correlation and consistency between TR-derived parameters and RHC results were tested by Pearson and Bland–Altman methods. With mPAP ≥ 25 mm Hg measured by RHC as the standard diagnostic criterion of PH, a receiver operating characteristic (ROC) curve was used to compare the diagnostic efficacy of sPAPA total of 218 patients were finally identified and analyzed, as shown in Fig. ECHO was 0.988 (95% CI: 0.977–0.994), and the intraclass correlation coefficient for intraobserver reproducibility of sPAPECHO was 0.992 .The intraclass correlation coefficient for interobserver reproducibility of sPAPECHO, and sPAPECHO, showed a positive correlation with related RHC results . Bland–Altman analysis demonstrated low bias between RHC and echocardiographic results, with wide limits of agreements  was lower than that of TR-PG . The mean deviations of mPAPECHO and TR-mPG from mPAPRHC were −2.6 mm Hg (95% limits of agreement: −26.3 to +21.1 mm Hg) and 3.3 mm Hg (95% limits of agreement: −20.1 to +26.7 mm Hg), respectively.All of the TR-derived parameters, including TR Vmax, TR-PG, TR-mPG, mPAPlts Fig. . sPAPECHnts Fig. . The biaECHO had better predictive efficiency and sensitivity for determining the possibility of PH than other TR-related methods, including TR Vmax, TR-PG, TR-mPG, and mPAPECHO (Table P > 0.05). Using Youden index quantification, the optimal cutoff value for our cohort was 49.5 mm Hg for the sPAPECHO method with a sensitivity of 94.9% and a specificity of 85.7%.The ROC analysis showed that sPAPHO Table , but theRHC was divided into three levels according to its tertiles . The low-level group was defined sPAPRHC less than 63 mm Hg. Patients with sPAPRHC between 63 mm Hg and 85 mm Hg were considered the medium-level group, while patients with sPAPRHC higher than 85 mmHg were classified as the high-level group. The univariate ordinal analysis demonstrated that RV WT, FAC, TR signal quality, sPAPRHC level, RAP, PVR, PAWP, and mPAP were associated with the inaccuracy of sPAPECHO estimation (Table RHC level significantly affected the accuracy of sPAPECHO (P < 0.05). Relative to good signal quality, the OR values of medium and poor signal quality were 0.26  and 0.23 , respectively. Compared with high sPAPRHC level, the OR values of low and medium sPAPRHC levels were 21.56  and 5.13 , respectively. The OR value of PAWP was 0.94 . In contrast, TR severity and RV systolic function parameters  did not remain in the final equation.There were 79 patients 36.2%) in the overestimated group, 81 patients (37.2%) in the accurate group, and 58 patients (26.6%) in the underestimated group. sPAP% in the ECHO, have comparable and good efficiency in PH screening. (2) The assessment of sPAPECHO would be more reliable after taking TR signal quality, sPAPRHC levels, and PAWP into account.Key findings of our study are as follows: (1) All TR-related methods, including sPAPECHO showed comparable efficiency to other TR-related methods in PH screening. Compared with mPAPECHO, sPAPECHO is more convenient to measure. As a derived variable of TR Vmax, sPAPECHO did not amplify measurement errors in assessing pulmonary artery pressure as indicated by the current guidelines; on the contrary, it showed better sensitivity while maintaining similar specificity. Relative to TR Vmax, TR-PG, and TR-mPG, sPAPECHO contains more information from RAP, which may account for its better accuracy and lower bias. RAP elevates with the increase of RV overload [ECHO also supported that RAP is of additional diagnostic value in predicting PH. Compared with mPAPECHO, sPAPECHO has the advantage of being simple and convenient. Taken together, sPAPECHO can be a convenient and effective measurement for clinical application in PH screening.In our study, sPAPoverload , so it ioverload . Hellenkoverload  on mPAPEECHO [ECHO, because interpretation error of peak velocity is further amplified by the square of the Bernoulli equation. We also found that good signal quality could bring overestimation of sPAPECHO for some cases. In our cohort, sPAPECHO was still overestimated in 41% of the patients who obtained good signal quality of TR. After further analysis, we found that the lower sPAPRHC level and PAWP were significantly associated with the overestimation of sPAPECHO in patients with good signal quality. This phenomenon suggests that we cannot simply rely on good signal quality, and attention should also be paid to sPAPRHC level and PAWP because they both affect the accuracy of sPAPECHO.First, our findings confirmed previous reports that the TR signal quality would affect the accuracy of sPAPECHO . Poor siRHC level on the accuracy of sPAPECHO, Groh et al. [ECHO tends to be underestimated at a high sPAPRHC level. We assumed that the coupling mechanism between RV contractility and its load may account for this phenomenon. When sPAPRHC mildly elevates during the initial phase of PH, RV coupling could be maintained by enhanced RV contractility [RHC by DE is relatively reliable. However, as PH progresses and RV uncoupling occurs, CO would decrease and RV preload would increase, along with elevated RAP, so the right atrioventricular pressure gradient would decrease, and DE would underestimate sPAPRHC. sPAPRHC level may affect the accuracy of sPAPECHO through the coupling mechanism between RV contractility and its load. This finding suggests that we should synthesize more echocardiographic signs when evaluating the efficacy of PH, because the decrease in sPAPECHO at this time is not necessarily a result of disease improvement, but may also be a sign of underestimation of sPAPECHO caused by RV decoupling.Second, as for the effect of sPAPh et al.  found thactility , 14, andECHO due to the higher PAWP may be related to the lower threshold in post-capillary PH patients. Amsallem et al. [ECHO threshold for PH diagnosis, which is consistent with our findings. The optimal cutoff value of our cohort was 49.5 mm Hg, which is higher than the cutoff values in previous studies that had focused on post-capillary PH patients with higher PAWP [RHC and sPAPECHO. They speculated that elevated left atrial pressure can be transmitted to the right atrium via the shared interatrial septum as well as through pericardial constraint and limit TR velocities, thereby also affecting the accuracy of sPAPECHO. Until now, the mechanism by which PAWP affects the accuracy of sPAPECHO is still unclear, so more multicenter studies are needed to validate this deduction. Based on the above findings, we think that the accuracy of sPAPECHO would be improved if combined with the assessment of left ventricular filling pressure by echocardiography. Although RHC is the gold standard for PAWP or left ventricular filling pressure, whether PAWP is elevated can be assessed by indirect signs of echocardiography, such as the ratio of mitral E peak velocity and averaged e’velocity (E/e'm ratio), TR Vmax, and left atrium volume index. Echocardiologists can synthesize such information to determine whether patients have PAWP elevation, to assess the sPAPECHO and the possibility of PH more reasonably.Third, we found that echocardiography tended to underestimate pulmonary artery pressure when PAWP increased. We speculated that the underestimation of sPAPm et al.  found thher PAWP , 17. Preher PAWP  also fouECHO. Hioka et al. [ECHO. Our study differed from other studies in that the TR severity did not significantly affect the accuracy of sPAPECHO. It should be noted that only 9.6% of patients in our cohort had severe TR, which was in line with the actual clinical situation that severe TR only appears in the minority of patients. However, in patients with mild or moderate TR, we could also obtain good signal quality and estimate sPAPECHO appropriately (Fig. ECHO is not as significant as that of TR signal quality.Furthermore, there is no consensus as to how TR severity would interfere with the accuracy of the sPAPa et al.  reporteda et al.  reportedely Fig. . TR seveECHO. Theoretically, RV systolic function would gradually decrease [ECHO.We found that none of the RV systolic parameters had a significant impact on the accuracy of sPAPdecrease , but RV decrease . TherefoRHC level, and PAWP into the assessment of sPAPECHO would improve its accuracy and avoid overly invasive examination.Finally, incorporating TR signal quality, sPAPThis study has several limitations. First, this was a retrospective study with a small sample size. Although 90.5% of our patients had PH, and in 47.7% of them, PH was due to chronic pulmonary thromboembolism, the sample size of other types of PH was relatively small. Thus, we could not give specific suggestions for each type of PH. Second, we included patients who had undergone RHC and echocardiography within 7 days due to the restriction of clinical actual conditions. However, the average interval time was 3 days in this study, and the majority of patients had pre-capillary PH, which indicated that the patients’ hemodynamics was relatively stable and did not change dramatically during this short time. Furthermore, contrast microbubbles were not adopted to enhance the tricuspid regurgitation jet for patients with mild regurgitation or poor signal quality. Finally, the single-center nature of the present study limited generalization.ECHO, had comparable and good efficiency in PH screening. To make the assessment of sPAPECHO more accurate, attention should be paid to TR signal quality, sPAPRHC level, and PAWP.In this study, we found that all TR-related methods, including sPAP


During carotid endarterectomy (CEA) surgery, blood pressure management is particularly important to prevent cerebrovascular and cardiac complications. Ephedrine is a commonly used vasopressor, however, we report the case of a patient with unusually severe blood pressure elevation following intravenous ephedrine administration during CEA.A 72-year-old man diagnosed with right proximal internal carotid artery stenosis underwent CEA under general anesthesia. After declamping the common carotid artery, blood pressure rapidly increased by 125 mm Hg (from 90 to 215 mm Hg) after ephedrine (4 mg) was administered, but the heart rate was stable.There was an ordinal increase in blood pressure after the same small dose of ephedrine was administered at the early stage of the surgery. And the surgical approach was difficult because he had a high location of carotid bifurcation and a prominent mandibular angle. Because of the anatomical proximity of the cervical sympathetic trunk to the carotid bifurcation and the particularly complicated surgical process in the present case, we postulate the reason for this adverse reaction as transient sympathetic denervation supersensitivity.Perdipine (0.5 mg) was administered repeatedly to reduce blood pressure.After surgery, he was diagnosed with right hypoglossal nerve palsy, and no other abnormal signs were found.This case highlights the need for caution in the use of ephedrine, which is commonly used in CEA surgery, wherein blood pressure management is particularly important. Although it is a rare and unpredictable case, α-agonists are considered safer in situations where sympathetic supersensitivity is possible. Moreover, a carotid atheroma located in the area of the carotid sinus and surgical manipulation of the carotid arteries disrupt the carotid baroreceptor mechanism, resulting in blood pressure fluctuation during CEA surgery. Notably, perioperative hemodynamic instability can directly or indirectly influence cerebrovascular and cardiac morbidity and mortality in patients undergoing CEA owing to their coexisting disease and the nature of the surgical procedure, such as carotid cross-clamping and revascularization of the carotid stenosis area.Carotid endarterectomy (CEA) is a preventative surgery for decreasing the subsequent risk of fatal or disabling stroke in patients with significant carotid stenosis. Arterial pressure is often difficult to control in patients undergoing CEA because of the relatively high incidence of coexisting coronary artery disease, hypertension, and diabetes mellitus.Herein, we report the case of a patient with unusually severe blood pressure elevation following intravenous ephedrine administration during CEA despite an ordinal response to ephedrine 90 minutes earlier. We postulate the reason for this as transient sympathetic denervation supersensitivity.A 72-year-old man diagnosed with right proximal internal carotid artery stenosis at a routine health checkup was scheduled to undergo CEA Fig. . He had 2 partial pressure of 35 to 45 mm Hg with an O2/air mixture. The blood pressure after the induction of anesthesia was 114/46 mm Hg, with a heart rate of 57 beats/min, and an invasive catheter was inserted into the left radial artery for blood pressure monitoring. The blood pressure decreased during dissection of the muscle, and intravenous ephedrine (4 mg) increased the systolic blood pressure from 99 mm Hg to 120 mm Hg. Blood pressure was maintained between 124 and 147 mm Hg during dissection. The patient had a prominent mandibular angle and a complex neurovascular anatomy, and his carotid artery bifurcation was located at the C2 to C3 level, which is a high level; therefore, the surgical approach was difficult. To access the carotid artery, hypoglossal nerve traction was unavoidable. Two hours after starting the surgery, carotid clamping was performed, and blood pressure at this time was 120 to 140 mm Hg without the administration of a vasoactive drug. After declamping the common carotid artery, the systolic blood pressure and heart rate decreased to 90 mm Hg and 56 beats/min, respectively. Ephedrine (4 mg) was administered intravenously with the expectation of a 20-mm Hg increase in systolic blood pressure, as previously observed; however, the systolic blood pressure markedly increased to 215 mm Hg and the heart rate increased to 65 beats/min. At that time, the propofol concentration was 3.0 μg/mL, remifentanil concentration was 3.0 ng/mL, the patient state index was 32%, and the train-of-four value was 0. There was no evidence of ephedrine misdosage, light anesthesia level, or insufficient neuromuscular blockade. The surgery was stopped, and intravenous perdipine (0.5 mg) was administered repeatedly. The systolic blood pressure was restored to 100 mm Hg, but after resuming surgery, intravenous phenylephrine infusion had to be started to maintain systolic blood pressure at 110 to 125 mm Hg. The cerebral oximeter value was 60 to 62% on the right and 65 to 67% on the left. Immediately following surgery and restoration of patient consciousness, neurologic examination was performed. The patient’s tongue deviated to the right side, and no other abnormal signs were found. He was diagnosed with right hypoglossal nerve palsy, which resolved 3 months later. The patient was concerned about postoperative complications related to cerebrovascular and cardiac morbidity due to large fluctuations in blood pressure during surgery; however, the related prognosis was fortunately good.Before surgery, his systolic blood pressure was 137 to 149 mm Hg and his heart rate was 60 to 71 beats/min in the hospital ward. Upon arrival in the operating room, his blood pressure was 132/72 mm Hg and his heart rate was 78 beats/min. Baseline cerebral oximeter value was 52% on the right and 60% on the left. General anesthesia was induced with a target-controlled intravenous infusion of propofol and remifentanil. Tracheal intubation was performed after administering rocuronium (50 mg) intravenously. General anesthesia was maintained with propofol (target effect-site concentration: 3–4 μg/mL) and remifentanil (target effect-site concentration: 3.5–4.5 ng/mL) to achieve a bispectral index of 40 to 55. Ventilation was controlled to achieve an end-tidal CO Hypertension commonly occurs after CEA surgery because of surgically-related baroreceptor dysfunction, which not only predisposes the patient to hemorrhage and myocardial ischemia but can also lead to cerebral hyperperfusion. Therefore, to prevent the occurrence of these complications, it is necessary to avoid developing hypertension after revascularization.A common practice after revascularization during CEA is to maintain systolic blood pressure at <160 mm Hg or within 20% of the preoperative baseline value.,6 This indirect action can lead to the development of tachyphylaxis following the depletion of noradrenaline from nerve terminals. Thus, it should be noted that in the present case, the systolic blood pressure increased by approximately 20 mm Hg after the intravenous administration of 4 mg ephedrine at the early stage of surgery, but 90 minutes later, it rapidly increased by 125 mm Hg (from 90 to 215 mm Hg) after the same small dose of ephedrine was administered. It is also noteworthy that ephedrine, which is often used as a vasopressor in CEA surgery, can cause this reaction. Initially, we suspected a dosing error of ephedrine; therefore, we checked the remaining ephedrine dose and the syringe used, which confirmed that only 4 mg of ephedrine had been administered. The depth of anesthesia and the degree of the neuromuscular blockade was ruled out as other factors that could cause a rapid increase in blood pressure, and there was no new surgical stimulus that was very painful.In the present case, the patient’s systolic blood pressure decreased to 90 mm Hg after revascularization, thus necessitating the intravenous administration of 4 mg ephedrine to increase the blood pressure. Ephedrine is a sympathomimetic drug that stimulates both α- and β-adrenergic receptors by the endogenous release of norepinephrine, thereby increasing blood pressure, cardiac output, and stroke volume. In addition, the surgical approach was difficult in the present case because of the complex neurovascular anatomy encompassing the ansa cervicalis, hypoglossal nerve, and facial vein. Because of the high bifurcation and prominent mandibular angle, in addition to the abovementioned factors, traction of the hypoglossal nerve was unavoidable during surgery, and as concerned, symptoms of ipsilateral hypoglossal nerve palsy appeared after surgery. Among the structures surrounding the carotid artery bifurcation, the cervical part of the sympathetic trunk lies embedded in the posterior wall of the carotid sheath. Because of its anatomical proximity to the carotid artery bifurcation and the particularly complicated surgical approach in the present case, it is possible that the sympathetic nerve received direct compression or traction force during the surgical procedure or ischemic damage due to injury of the blood vessels it supplies.The carotid artery bifurcation was located at the level of the C2 to C3 vertebral body junction in the present case. The high location of carotid artery bifurcation is associated with difficult surgical access in CEA. To determine the reason for the abnormal reaction to ephedrine administration in the present case, we referred to reports of ephedrine adverse reactions in patients with Parkinson disease.–11 These reports indicated that cardiac sympathetic nerve denervation can occur in patients with Parkinson disease, resulting in excessive cardiovascular responses to sympathomimetic drugs; this condition is known as cardiac sympathetic denervation supersensitivity. Its mechanism of action could be explained by an absence of norepinephrine uptake or an increased density of β-adrenergic receptors in postsynaptic membranes.Although cardiac autonomic innervation is highly variable and its anatomy remains controversial, the cervical sympathetic trunk is generally known to provide postganglionic cardiac sympathetic innervation.,13 Therefore, we speculated that in the present case, a severe intraoperative reduction in the sympathetic pathway activity to the heart may have caused transient hypersensitivity.Unlike the cases of Parkinson disease, in the present case, it is difficult to believe that the sympathetic nerves were bilaterally damaged simultaneously considering that our patient had undergone right carotid artery surgery. However, the inference that hypersensitivity to ephedrine was the cause of the marked increase in blood pressure in our patient is supported by the following observations: there was an ordinal increase in blood pressure after the same small dose of ephedrine was administered at the early stage of the surgery; other factors that could cause a rapid increase in blood pressure at the time could be excluded; and this event occurred immediately after the major surgical procedure of the carotid artery. In addition, the fact that only the blood pressure increased and the heart rate did not change significantly is unusual, which is similar to the findings observed in the patients with Parkinson disease. and first-bite syndrome; however, the present case exhibited no symptoms of these conditions. Hence, we believe that there was an ischemic event in the cervical sympathetic trunk during the surgical procedure that drastically reduced sympathetic postganglionic signaling to the heart, but the ischemia did not cause postoperative neuronal palsy sequelae.Possible complications caused by sympathetic nerve injury during neck surgery include postoperative Horner syndrome In the present case, blood pressure decreased immediately after it had markedly increased earlier. Therefore, phenylephrine was continuously administered, and no particular adverse reactions were observed; this finding is similar to other cases in which sympathetic denervation supersensitivity was reported. Thus, this type of vasopressor, which does not stimulate the heart, was considered to be safer in this case.Among the vasopressors commonly used during surgery, phenylephrine and vasopressin are selective α-adrenergic receptor agonists that increase total peripheral vascular resistance and have no direct effect on cardiac contractility.Adverse reactions caused by the administration of ephedrine, which is commonly used during surgery, can cause serious problems in CEA surgery, wherein blood pressure management is particularly important. Although it is a rare and unpredictable case, α-agonists are considered safer in situations where sympathetic supersensitivity is possible.Conceptualization: Hyunjee Kim, Jeong Eon Kim.Supervision: Taeyoung Yu.Writing – original draft: Hyunjee Kim, Jeong Eon Kim.Writing – review & editing: Hyunjee Kim, Jeong Eon Kim.


Background: Allergen-specific immunotherapy is currently the only disease-modifying treatment for allergic asthma, and it has been shown to improve control of asthma while reducing both drug use and asthma exacerbations. However, its effects on lung function—especially its long-term effects—remain controversial. We aimed to identify factors associated with a possible beneficial effect of allergen-specific immunotherapy on lung function in asthma by retrospectively evaluating the long-term changes in lung function in children with asthma who received house dust mite subcutaneous immunotherapy (HDM-SCIT). Methods: We enrolled children with asthma who had undergone HDM-SCIT for more than 1 year. Clinical information and lung function measurements were retrieved from the electronic chart system. To characterize the trajectory of lung function change, we performed linear regression analysis to evaluate the maximal expiratory flow at 50% of the forced vital capacity during two periods: before and during HDM-SCIT. Slopes from a least-squares regression line for the two periods, i.e., S1 before HDM-SCIT and S2 during HDM-SCIT, were compared. The subjects were then classified into two groups: an improving group (Group I) defined as S2 − S1 > 0, and a declining group (Group D) defined as S2 − S1 < 0. The clinical factors at the start of HDM-SCIT were compared between the two groups. Results: A total of 16 patients were analyzed. Eight patients were classified into each of Group I and Group D. The mean ages were 10.5 and 11.8 years, and the mean treatment periods were 4.1 and 3.9 years. Group I had a significantly lower blood eosinophil count and a significantly higher HDM-specific IgE level than Group D. Logistic regression showed a strong relationship between those two markers and the lung function trajectory. Conclusion: Control of the blood eosinophil count in highly HDM-sensitized patients may increase the beneficial effect of HDM-SCIT on lung function. Asthma is a heterogeneous inflammatory disease characterized by bronchial hyperreactivity and airflow obstruction. In allergic asthma, respiratory symptoms and underlining airway inflammation are triggered by allergen exposure. House dust mite (HDM) is the most common and important allergen , especiaThe efficacy of AIT for lung function in asthma, however, is yet to be established ,8. In a Recent cohort studies demonstrated that low childhood lung function or low acquired lung function in early adulthood has lifelong consequences, including the risk of developing COPD ,11,12,13Here, we investigated long-term changes in lung function in children and adolescents with asthma who underwent HDM-SCIT. Since AIT has not shown a uniformly beneficial effect on lung function, we hypothesized the existence of a subtype of patients who benefit from AIT or factors associated with a favorable outcome. To test that hypothesis, we compared the baseline factors between patients whose long-term lung function improved during HDM-SCIT and those whose function did not improve.Dermatophagoides pteronyssinus) and a history of HDM-related symptoms such as a cough or wheezing upon exposure to a “dusty environment”. The patients were eligible if they had valid spirometry data at 5 or more time-points during the pre-SCIT period of at least 6 months so that changes in lung function could be compared before and during the treatment. SCIT was performed using a standardized HDM extract  as rush immunotherapy followed by a monthly maintenance protocol, as reported elsewhere [We enrolled children and adolescents <18 years of age with HDM-allergic asthma who underwent HDM-SCIT for ≥1 year at Mie National Hospital. Allergy to HDM was confirmed on the basis of a positive test for specific IgE (sIgE) to HDM , and predicted values of the parameters were obtained using equations based on the height and age of Japanese children . Since SThe baseline clinical data at the start of SCIT were compared using the chi-squared test for categorical variables and the Mann–Whitney U test for continuous variables. A logistic model for predicting a favorable lung function trajectory (Group I) was constructed using variables that were significantly different by univariate analyses. We report the adjusted probabilities of the outcome, the odds ratio (OR), and the 95% confidence interval (CI) based on the model. Goodness-of-fit was tested using the Hosmer–Lemeshow test, and the area under the receiver operating characteristics (ROC) curve for predicting a favorable trajectory was obtained. Wilcoxon’s rank-sum test was used to compare changes in the ICS dose during SCIT. Statistical analyses were performed with GraphPad Prism 9 .A total of 16 patients were eligible for the study, and we analyzed 1158 spirometric measurements after excluding 7 outliers out of the total 1165 by the ROUT method with a false discovery rate <1% . Table 1The clinical characteristics, lung function, and laboratory data at the start of SCIT were compared between the two groups . The meaLung function at the last observation point were also compared . IncreasBased on the above results, we constructed a logistic regression model for predicting a favorable lung function trajectory (Group I) using the eosinophil count and HDM-sIgE level at the start of HDM-SCIT . The preBecause SCIT is not recommended in patients with poorly controlled asthma, all the subjects were under good control at the start of HDM-SCIT. At the last observation point during the treatment period, asthma control remained good in all of the patients based on the international guideline . HoweverThe benefit of AIT for lung function in allergic asthma has not been established, possibly because of heterogeneous study patient populations. In this study, we sought to identify factors that relate to a beneficial effect of HDM-AIT on lung function. For evaluation of lung function, we focused on the longitudinal changes rather than measurement results at the last observation of AIT since lung function measurements at single time-points often fluctuate in children, and the long-term trend may better represent outcome. We found that a low peripheral blood eosinophil count and a high HDM-sIgE level at the start of the treatment were independently associated with an improved lung function trajectory in children and adolescents with HDM-allergic asthma. Why would a lower peripheral blood eosinophil count be associated with a favorable lung function trajectory? Eosinophils contribute to the pathogenesis of asthma by causing chronic airway inflammation , and a hHigher levels of HDM-sIgE were also associated with a favorable HDM-SCIT outcome. For AIT, it is essential that the treatment be specific for the allergen that is causing the symptoms . In thisAn additional important finding in this study was that the ICS dose was significantly lower  after abIn addition, it is noteworthy that the median dose of ICS was lower after HDM-SCIT not only in Group I but also in Group D . It may be that if the higher dose were maintained  until thThis study has at least four limitations. First, the number of the subjects was too small. A much larger number is necessary to confirm the statistical difference observed in the study. However, we were able to observe the patients for changes for up to 7–8 years, and the findings from this long-term observation can be analyzed in a further RCT. Second, this was a retrospective observational study, without controls. Randomized placebo-controlled trials to exclude confounding factors that may impact the long-term effect of AIT need to be performed. Third, this study’s total observation period, although around 7 to 8 years, was not long enough. As stated above, the clinical impact of lung function decline becomes evident when children and adolescents reach older adulthood ,11,12,13This study identified two markers that seem to predict a beneficial effect of HDM-SCIT on lung function of children and adolescents with asthma. The predictive power of a lower peripheral blood eosinophil count may indicate the importance of control of airway inflammation for achieving the most benefit from the treatment. Similarly, the predictive power of a high HDM-sIgE level may underscore the importance of allergen specificity in considering AIT.


Background: Kidney failure is a common public health problem around the world. The vast majority of kidney failure cases in Sub-Saharan African nations, including Ethiopia, go undetected and untreated, resulting in practically certain mortality cases. This study was aimed primarily to model the time to (right and left) kidneys failure in the patients at Adama Hospital Medical College using the copula model.Study design: A retrospective cohort study.Methods: The copula model was used to examine join time to the right and left kidneys failure in the patients by specifying the dependence between the failure times. We employed Weibull, Gompertz, and Log-logistic marginal baseline distributions with Clayton, Gumbel, and Joe Archimedean copula families.Results: This research comprised a total of 431 patients, out of which, 170 (39.4%) of the total patients failed at least one kidney during the follow-up period. Factors such as sex, age, family history of kidney disease, diabetes mellitus, hypertension, and obesity were found to be the most predictive variables for kidney failure in the patients. There was a 41 percent correlation between the patients’ time to the right and left kidneys failure.Conclusion: The patients’ kidney failure risk factors included being a male, older adult, obese, hypertensive, diabetic and also having a family history of kidney disease. The dependence between the patient’s time to the right and left kidneys failure was strong. The best statistical model for describing the kidney failure datasets was the log-logistic-Clayton Archimedean copula model. Kidney failure  is an irreversible condition in which one or both kidneys fail to filter waste materials from the blood adequately.2on the other hand. Kidney failure has increased in frequency and prevalence in the last ten years, and this trend is projected to continue.3 In 2016, the United States Renal Data System stated that the kidney failure incidence rates in Taiwan, the United States, the Jalisco region of Mexico, and Thailand were 493, 378, 355, and 346 per million populations per year, respectively.4 According to the 2019 Global Renal Health Atlas, 14.5 million people worldwide have kidney failure, and due to the economic, social, and political problems, just 5.4 million of them get treated. Furthermore, each year, over two million people die as a result of a lack of access to healthcare.5 Kidney failure is a common public health problem around the world, with a growing incidence and prevalence on one hand, and high costs and poor outcomes6 Patients with kidney failure in Africa have the lowest access to the renal replacement therapy, and just nine to 16 percent of them are treated, and the treatment rates in Central and Eastern Africa are estimated to be as low as one to three percent because of the high cost.7 Most of the kidney failure cases in Sub-Saharan African nations, including Ethiopia, go undetected and untreated, resulting in practically certain mortality cases.8 Ethiopia has a high prevalence of renal disease, which has risen to 12.2 percent in recent years due to an increase in diabetes and hypertension.9 According to World Health Organization (WHO) data, published in April 2011, kidney illness claimed the lives of 12 038 Ethiopians, accounting for 1.47 percent of all death cases. According to a study conducted at Adama Hospital Medical College in 2016, 27.40% of 500 patients with end-stage renal disease, died10 of this disease. In Africa, kidney illness is at least three to four times more common than in developed countries.11 These types of events are linked because they are from the same subject12 and studying such data necessitates some model parameters on the temporal dependence on the bivariate event endpoint.13 Traditional survival analysis techniques assume that the survival times of the different subjects are independent. However, as a pair of kidneys share the same biological gene, the patients’ times to the right and left kidneys failure, are not independent of each other. When the event times are dependent on a survival study, completing the analysis using methods based on the independent assumptions leads to inaccurate estimates. In medical studies, it is usual to record two event times for each patient, such as the failure times of the paired human organs.14 and deals with two events per subject and dependency between the failure times. This study was aimed primarily to investigate the relationship between a patient’s time to the right and left kidneys failure, as well as the influence of the variables on the dependent structure. As a result, we used the copula model which includes the influence of variables on the failure times in the presence of dependence Adama Hospital Medical College was the site of the research. Hailemariam Mamo Memorial Hospital and Adama Referral Public Hospital were the hospital’s two prior names in the past. It is one of Ethiopia’s first medical hospitals, located in Adama, in Oromia region, 100 km southeast of Addis Ababa. Because of its location, patient load, and staff capacity, the hospital was promoted to a medical college in 2003 E.C. In this study, a retrospective investigation was carried out. Data were gathered from the patients’ medical records from January 1, 2015, to January 30, 2020, by the health professionals. All kidney disease patients who had registered at Adama Hospital Medical College were included in the study. There were a total of 431 patients considered. The response variables were the patients’ times to the right and left kidneys failure, which were measured over a few days. The starting point was the date on which the kidney disease patients were admitted to the hospital. The study came to an end when the kidney disease patient died or when the study period concluded on January 30, 2020. During the study, one of the following four scenarios might occur in a patient: a)  both of the patient’s kidneys were failing, b)  only the patient’s right kidney was failing, c)  only the patient’s left kidney was failing, or d)  neither of the patient’s kidneys were failing. In the kidney failure dataset, the times to the right and left kidneys failure in the patients could not be precisely observed, leading to bivariate censored data. Right bivariate censored data occurs when the study ends before the occurrence of one or both events. Death, dropout, referral to another facility, or the termination of the research were all the reasons for censorship. By the way, sex, smoking status, family history, age, alcohol consumption, diabetes mellitus, hypertension, anemia, and obesity were all the explanatory variables.2 and had provided complete information in their registration log books or on their patient identity cards were considered eligible for the trial. Patients who did not provide enough information on one of the critical factors in their registration books or on their identity cards were not eligible. Patients who were born with only one kidney or who were born with two kidneys but only one of them worked were also excluded from the study. Patients who had a GFR of less than 60 mL/min/1.73mT1i,T2i) and , i = 1, 2, 3,…, n denotes the bivariate failure times and censoring times for the ith patients, respectively. Then for each patient, we observe Thecopula model was used to examine the bivariate event times (join time to the right and left kidneys failure) in the patients by specifying the dependence between the failure times. First, let us show the notation for bivariate time to event data. Assume that there are n patients. Let  is used to show the dependency structure between the times to the right and left kidneys failure in the patients. The copula uniqueness is for the fact that it models two marginal distributions and their dependence separately, allowing the marginal models to be flexible and the covariate effects to be easily interpreted.16 The Archimedean copula family, which is one of the most common copula families because of its flexibility and simplicity,17 is one of the most popular copula families for bivariate events data. Clayton, Gumbel, and Joe are the most commonly employed Archimedean copula models in the survival analyses. Copula has provided unified statistical methodologies and flexible survival models. The copula parameter  for a Clayton copula is given as 18when η→0 Similarly, for Gumbel Copula,19η ≥1 and are independent when =1. For a Joe copula16, τ is given by the below equation, and meaning times to bivariate events are positively associated when η ≥ 1 and are independent when η = 1. Kendall’s tau (τ) is the most commonly utilized measure of the dependence degrees/levels between bivariate event times in practice. Kendall’s tau is just a function of  It is required to design a regression model for the margins to analyze the influence of the variables on the patients’ time to kidney failure. Proportional hazards models (Weibull and Gompertz), as well as proportional odds (Log-logistic) models are supported by the marginal models. Generally, the marginal survival model in terms of the hazard function is given by: λ0j is the baseline hazard function for the jth margin, Zji is the covariate for the ith patient, and jth margin and β are the coefficient of the covariates. We used Clayton, Gumbel, and Joe Archimedean copula families with Weibull, Gompertz, and log-logistic marginal baseline distributions. Where21 Akaike information criterion (AIC) and Bayesian information criterion (BIC) are useful to choose the best fitting copula. AIC and BIC are given by: Several model selection procedures have been proposed for the copula-based time to events endpoints models. Where, k is the number of parameters estimated by the model; n is the number of observations and 22 The plot should resemble a straight line if the baseline marginal distribution assumption holds constant. The scatter plot of the joint survival distribution or scatter plot of the bivariate event times are used to check the adequacy of the Archimedean copula families.23 If the scatter plot is condensed, the given Archimedean copula family fits the kidney failure datasets well. R. software (version 4.0.5) with the “CopulaCenR” package was used for the data analysis.17 Regardless of which type of the model is fitted and how the variables are selected to be in the model, it is important to evaluate how well the model fits the data. To check the adequacy of the marginal baseline distribution, the Weibull is plotted by the log of the cumulative hazard with the logarithm of time; the Gompertz is plotted by the log of the hazard with the time, and the log-logistic is plotted by the log-failure odd with the log time. This research comprised a total of 431 patients. Out of which, 170 (39.4%) of the patients failed at least one kidney during the follow-up period. Furthermore, 51 (11.8%), 43 (10%), and 76 (17.6%) patients were found to have failed only their right, left, or both kidneys, respectively, whereas 261 (60.6%) were found to have not failed both kidneys during the follow-up period . The entP values less than 25% were considered for multi-variable analysis.18 In the univariable analysis covariates like sex, family history, age (56 years and older), diabetes mellitus, hypertension, anemia, and obesity were signiﬁcant at 25% level of signiﬁcance in all models. However, residence, smoking status, and alcohol consumption were not signiﬁcant at 25% level of signiﬁcance, and they were excluded from the multivariable analysis. By the way, univariable and multi-variable analyses were applied. In univariable analysis, the model which contains each covariate at a time was ﬁtted to determine variables that have the potential for being included in the multivariable analysis. Covariates in the univariable analysis with  The Weibull, Gompertz, and log-logistic were used for the parametric marginal baseline distribution; and Clayton, Gumbel, and Joe Archimedean copula families were used in the multivariable survival analysis. The log-logistic-Clayton Archimedean copula model’s AIC and BIC values were 789.20 and 4297.55, respectively, which were the lowest among all models. In addition, the model had a higher Final joint maximum log-likelihood value of -2121.48. As a result, the most efficient model for describing the kidney failure datasets was the log-logistic-Clayton Archimedean copula model. With the Clayton Archimedean copula model, the measure of the parameters’ dependence was at the highest level when we assumed the log-logistic marginal distribution (0.41), followed by the Weibull marginal distribution (0.40) .η) was significant, implying that the times to the right and left kidneys failure were dependent. The Kendall’s tau (τ), revealed a strong correlation between the times to the right and left kidneys failure in the patients (τ = 41%)  .2) were 50% more than for non-obese patients . The odds of kidneys failure for the male patients were 45% more than for the female patients . The odds of kidney failure for patients with a family history of kidney diseases was 53% more than patients without a family history of kidney diseases . The odds of kidney failure for the patients aged 56 years and older were 90% more than those patients aged less than 35 . The odds of the kidney failure for hypertensive patients were twice of the patients who did not have hypertension . The odds of kidney failure for a diabetic patient was 53% more than for non-diabetic patients . The odds of kidney failure for obese patients  had a higher risk of kidney failure, which was consistent with the previous research.32 This could be due to the fact that the additional weight causes the kidney to work harder and filter wastes at a higher rate than usual. This additional work raises the risk of kidney disease over time. Diabetic individuals were shown in this study to be more likely to have kidney failure, which agreed with the previous research.34 This could indicate a problem with blood glucose (sugar). High blood sugar levels destroy the kidney’s millions of microscopic filtration units over time. As a result, kidney failure can occur. Furthermore, hypertension was found to be a determining prognostic factor for kidney failure in the patients in this investigation. Hypertensive patients were more likely to have kidney failure, according to the study. This could be related to the fact that uncontrolled high blood pressure can constrict, weaken, or stiffen the arteries near the kidneys over time. And then, these arteries will be unable to carry enough blood to the renal tissue due to their impairment. This result was also in accordance with the previous studies.37 Age factor was found to be a major predictor of kidney failure in the study. According to the study, the likelihood of kidney failure was higher among elderly patients than others. This could be because as people get older, their kidneys tissues shrink, and their ability to function declines. This is consistent with an earlier research. The advanced statistical copula model was used in this work, which was particularly intriguing when event times’ endpoints were dependent. Despite the strengths, there were also significant limitations to this study. Due to the use of the secondary data, socio-demographic characteristics such as marital status, occupation, religion (particularly), and the patients’ educational levels were not included in this study because they were not recorded. The best statistical model for describing the kidney failure datasets was the log-logistic Clayton Archimedean copula model. The patients’ kidney failure risk factors included being a male, older adult, obese, hypertensive, diabetic, and also having a family history of kidney disease. The dependence between the patient’s time to the right and left kidneys failure was strong. Since hypertension, diabetes, and obesity were all risk factors for kidney failure, so lowering blood pressure, lowering sugar levels, and losing weight may help to prevent kidney failure. Because the failure of one kidney predicts the failure of the other, it is preferable to treat the failed one before it worsens.The prevalence of at least one kidney failure was 39.4%. Hypertensive patients were more likely than non-hypertensive patients to have kidney failure. The times to (right and left) kidneys failure were highly correlated.  The authors gratefully acknowledge Adama Hospital Medical College for the provision of the data. The authors declare that there was no conflict of interest in this study. Ethical approval was obtained from the Institutional Research Ethics Review Committee of the Jimma University College of Natural Sciences. A letter of support was written to Advanced Healthcare Management Corporation (AHMC). The authors submitted an official letter to AHMC. After clarifying the purposes of the study, the secondary data were obtained from all subjects and/or their legal guardian(s) for the participated cases who were children under 16. All methods were carried out following the relevant guidelines and regulations. Respondents had the right not to participate or withdraw from the study at any stage. There was no direct fund for this study.


We discuss a case in which urinary L‐FABP measurements were used to manage a 46‐year‐old male patient receiving V‐A ECMO support. His mean blood pressure was ≥75 mmHg for the first 24 h after the initiation of V‐A ECMO, and he experienced a rapid decrease in urinary L‐FABP levels. Measurement of urinary L‐FABP levels can aid in indicators of circulation and management of V‐A ECMO. Urinary L‐FABP levels may reflect a slight shortage of intravascular volume. And this study is suggested that urinary L‐FABP may be more sensitive than lactate in controlling intravascular water balance. V‐A ECMO management includes echocardiographic assessments of cardiac function and evaluations of the peripheral circulation based on venous oxygen saturation, lactate levels, regional cerebral oxygen saturation, and central venous pressure. ECMO flow rates exceeding cardiac output result in low pulse pressure, leading to low mean blood pressure. Thus, the mean blood pressure is also used to manage organ perfusion and peripheral circulation during ECMO support.Generally, urinary liver‐type fatty acid‐binding protein (L‐FABP) is a useful clinical marker in the monitoring of chronic kidney disease (CKD).Herein, we discuss a case in which urinary L‐FABP measurements were used during V‐A ECMO management.2Here, we describe a 46‐year‐old male patient who had collapsed at home in the presence of a close relative, who called for an ambulance and started resuscitation maneuvers until the arrival of the medical team. He has no medical history. The monitor waveform showed ventricular fibrillation requiring three defibrillation shocks, endo‐tracheal intubation, and transport to our hospital. Extracorporeal cardiopulmonary resuscitation was initiated on arrival due to the onset of refractory ventricular fibrillation. The interval between the onset of cardiac arrest and V‐A ECMO cannulation was 45 min. After starting V‐A ECMO, defibrillation was performed once. The monitor waveform became pulseless electrical activity (PEA).Electrocardiographic changes and increased levels of creatine kinase‐muscle/brain (CK‐MB) were suggestive for myocardial infarction Table . An emerFigure On hospital day 5, the patient was weaned off V‐A ECMO without deterioration of urinary L‐FABP levels, lactate levels, or mean blood pressure. On hospital day 6, he was weaned off IABP without changes in mean blood pressure or lactate levels. Thereafter, although the mean blood pressure remained unchanged, urinary L‐FABP levels temporarily increased, following which they decreased again. During the same period, the daily fluid balance was negative on consecutive days. During treatment in the ICU, UN and Cre values were within normal ranges. On hospital day 8, he could follow instructions and was weaned off mechanical ventilation and extubated on hospital day 10. On hospital day 13, he was discharged from the ICU and transferred to the general ward. On hospital day 24, no neurological sequelae were noted, and he was discharged from our hospital with independent gait.3Urinary L‐FABP is used to monitor CKD and predict the onset of acute kidney injury. Like the lactate value, it is also used to determine microcirculatory disturbances.During ECMO, the mean blood pressure is often maintained at ≥65 mmHg. However, there are no clear criteria for the index value, and the target value varies across institutions. Although one report suggested a higher survival rate among patients managed with a target mean blood pressure of 70–80 mmHg,Our patient's mean blood pressure was ≥75 mmHg for the first 24 h after V‐A ECMO initiation, and he experienced rapid decreases in both urinary L‐FABP and lactate levels. In this case, the target mean blood pressure was 70 mmHg, and weaning from V‐A ECMO was eventually successful.In patients managed with a mean blood pressure of ≥70 mmHg who exhibit normal lactate levels, temporary increases in urinary L‐FABP occurred following extubation, as observed in our patient. One possible explanation is that the daily fluid balance was adjusted between −500 and −5000 ml during this period to improve systemic edema. Therefore, the volume of fluid replacement is maintained at the minimum level to ensure a relatively higher urinary output. In general, variation in the UN/Cre ratio is one way of measuring the degree of intravascular dehydration. However, there was no significant increase in the ratio during this period. Thus, urinary L‐FABP levels may reflect a slight shortage of intravascular volume that is not reflected by lactate levels and UN/Cre ratio. We believe that the measurement of L‐FABP is one of the useful tests that can determine the fluid balance of critically ill patients.On the contrary, urinary L‐FABP measurement has a defect. Since urinary L‐FABP levels are measured from urine samples, they cannot be used for patients undergoing dialysis or those with anuria in the early stage of shock. And Lactate levels detected by blood gas tests can be measured within 1 min, whereas urinary L‐FABP measurements take 10 min. For this reason, urinary L‐FABP is not an emergency indicator that requires results within minutes.We routinely measure urinary L‐FABP in critically ill patients treated with ECMO. Circulatory management is performed by comprehensively examining parameters such as lactic acid level and blood pressure, and urinary L‐FABP. Unfortunately, urinary L‐FABP failed to prove to be more sensitive than traditional hemodynamic indicators such as lactate and mean blood pressure. But urinary L‐FABP is measured from urine samples. As a strength of the current inspection, urinary L‐FABP is to be a non‐invasive hemodynamic indicator compared with lactate as determined by blood tests. It also may be useful as an index of hemodynamics in the progression of anemia or in patients without invasive arterial pressure measurements.4Our findings suggest that urinary L‐FABP can be used as a hemodynamic indicator for managing patients receiving V‐A ECMO support and it can be used equivalently to conventional hemodynamic indicators such as lactate and mean blood pressure. And this study is suggested that urinary L‐FABP may be more sensitive than lactate in controlling intravascular water balance. But, since it is a case study, it is necessary to accumulate and investigate cases in the future.RI wrote and drafted the manuscript. SY and YM measured urinary L‐FABP and lactate levels. YN, HS, MW, TY, and MH drafted the manuscript. All authors read and approved the final manuscript.This research did not receive any specific grant from funding agencies in the public, commercial, or not‐for‐profit sectors.The present study was approved by the Toho University Medical Center Omori Hospital Ethics Committee. Informed consent was obtained from participants or their family members prior to enrollment and after receiving written explanations about the aims and procedures used in the study .Written informed consent was obtained from the patient for publication of this case report.