Eight hundred eighty-six genes were exclusively regulated in MH only. Principal component analysis revealed a separated clustering of the three groups. The data pointed to an upregulation of many inflammatory mechanisms in MH including pathways which previously attracted relatively little attention in the setting of hypertensive kidney injury: Transcripts from all three complement activation pathways were upregulated in MH compared to NMH but not in NMH compared with controls; immunohistochemistry confirmed complement deposition in MH exclusively. The expression of chemokines attracting neutrophil granulocytes (CXCL6) and infiltration of myeloperoxidase-positive cells were increased only in MH rats. The data suggest that these pathways, especially complement deposition, may contribute to kidney injury under MH.In malignant hypertension, far more severe kidney injury occurs than in the “benign” form of the disease. The role of high blood pressure and the renin–angiotensin–aldosterone system is well recognized, but the pathogenesis of the renal injury of malignant hypertension (MH) remains incompletely understood. Using the rat model of two-kidney, one-clip renovascular hypertension in which some but not all animals develop MH, we performed a transcriptomic analysis of gene expression by RNA sequencing to identify transcriptional changes in the kidney cortex specific for MH. Differential gene expression was assessed in three groups: MH, non-malignant hypertension (NMH), and normotensive, sham-operated controls. To distinguish MH from NMH, we considered two factors: weight loss and typical renovascular lesions. Mean blood pressure measured intraarterially was elevated in MH (220 ± 6.5 mmHg) as well as in NMH (192 ± 6.4 mmHg), compared to controls (119 ± 1.7 mmHg, The most severe hypertension-induced kidney injury occurs in malignant hypertension.In a rat model of malignant hypertension, we assessed transcriptional responses in the kidney exposed to high blood pressure. A broad stimulation of inflammatory mechanisms was observed, but a few specific pathways were activated only in the malignant form of the disease, notably activation of the complement cascades.Complement inhibitors may alleviate the thrombotic microangiopathy of malignant hypertension even in the absence of primary complement abnormalities.The online version contains supplementary material available at 10.1007/s00109-021-02133-8. Arterial hypertension is one of the major risk factors for the development of cardiovascular disease . AdditioThe pathomechanistic factors for the development of malignant hypertension in contrast to the development of non-malignant arterial hypertension are only incompletely understood. In animal models, a marked and rapid rise of blood pressure appears to be a necessary condition . On the Here, we used a transcriptomic approach to elucidate specific alterations of gene expression of the kidney cortex in malignant versus non-malignant hypertension. We performed high-throughput RNA sequencing (RNA-seq) in a rat model of two-kidney, one-clip renovascular hypertension (2K1C) . Thirty-As described previously, the rat model of 2K1C was used to induce renovascular hypertension. Over a period of 35 days, only a part of rats spontaneously developed malignant hypertension (MH) after clipping of the left renal artery with a silver clip of 0.2 mm internal diameter . MH animGlobal gene expression in the non-clipped right kidney was assessed in sham, MH, and NMH animals using mRNA-seq analysis . To evalPrincipal component analysis (PCA) revealed a separated clustering of the three study groups Fig. . This obIngenuity pathway analysis  was used for further in silico network and pathway analysis of differentially expressed genes. Disease-specific comparison of MH and NMH animals revealed “inflammatory response” as the most significantly altered signaling network based on the associated number of differentially regulated genes Table . AccordiBased on these findings, a further assessment of inflammatory cells in the kidney was performed. Using immunohistochemistry, more cytotoxic T-cells were found in the kidneys of MH animals compared to controls Table , while nRenal expression levels of the chemokines CC-chemokine ligand 2 (CCL2), CC-chemokine ligand 7 (CCL7), and C-X-C motif chemokine ligand 6 (CXCL6) were significantly increased in the kidney of MH compared to NMH and sham animals Table . CC-ChemIn the group of cytokines, interleukin-10 (Il-10), leukemia inhibitory factor (LIF), and tumor necrosis factor-alpha (TNF-α) showed a significant expressional induction in MH compared to NMH and controls Table . InterlePearson’s correlation coefficient was used to quantify the association between selected molecular markers of inflammation and inflammatory cells Table . CCL2 poA broad consistence was detected between RT-PCR and RNA-seq when comparing the expression changes of these candidate genes, except for CCL5  kidney because this kidney displays the characteristic vascular lesions of malignant hypertension. We observed the most prominent upregulation of gene expression in functional pathways related to processes of inflammation and cell infiltration. This result did not come as a surprise, as an inflammatory response in kidneys exposed to high blood pressure has been well recognized for decades in this animal model , 19 as wPerhaps the most intriguing finding was the increased local expression of pathway components associated with complement activation. The similarity of renal vascular lesions observed in malignant hypertension to the ones seen in complement-mediated hemolytic-uremic syndrome has often been noted , and disOur findings contrast with some animals studies including the report of Cole et al.  who did A number of chemokines known to attract mononuclear cells were induced by renovascular hypertension and even more increased in the malignant form of the disease, notably CCL2 and CCL7. This observation as well as the corresponding increase of M1 macrophage infiltration was to be expected from previous reports from the same model . Others We did not observe a marked difference of T-cell infiltration between malignant and non-malignant hypertension, somewhat to our surprise. However, this absence of a difference should not be misunderstood to militate against the role of lymphocytes for the development of high blood pressure in angiotensin II-dependent forms of hypertension, an issue, which has attracted great interest in recent years –35. We fFurther, we noted a markedly increased expression of the chemokine CXCL6, which is known to attract neutrophil granulocytes, accompanied by increased expression of E-selectin . TherefoOur study has several limitations. First, the study groups MH and NMH might also be regarded as two extremes of a continuous spectrum rather than two distinct clinical courses. Data obtained from PCA as well as the fact that the same intervention by 2K1C induces significantly different courses of pathology supports the classification of MH and NMH animals as two distinct categories. Furthermore, comparisons between two extremes of a spectrum might still point to pathways associated with more severe hypertensive damage. Second, renal alterations in MH animals were only assessed at one time point. This does not allow to discriminate if the observed alterations are cause or effect of malignant hypertension. Our data are fully compatible with the notion of a threshold pressure which might trigger the observed transcriptional changes . Blood pAll procedures performed on animals were done in compliance with the DIRECTIVE 2010/63/EU of the European Parliament and were approved by the local government authorities . Animal experiments were reported with adherence to the ARRIVE guidelines .Rats were housed in a room maintained at 22 ± 2 °C, exposed to a 12 h dark/light cycle. The animals were allowed unlimited access to chow  and tap water. Two-kidney, one-clip renovascular hypertension (2K1C) was induced in male Sprague–Dawley rats  weighing 150–170 g by placing a silver clip of 0.2 mm internal diameter around the left renal artery through a flank incision under isoflurane anesthesia as previously described , and [MH + NMH] vs. sham. Results from significance tests were corrected for multiple testing (Benjamini-Hochberg).RNA-seq was performed in MH  repository under the accession number (pending).p value < 0.01 were analyzed. By the comparison with the current Ingenuity knowledge base significantly altered networks, upstream regulators and central candidate genes were extracted.In silico network and pathway analysis was performed using Ingenuity Pathway Analysis software, Version 52,912,811 . Differentially expressed genes with log2 fold change (LFC) > ± 2 and a corrected Tissue was processed as described previously . In summT method as specified by the manufacturer . Primer pairs used for experiments are shown in supplementary table Renal and myocardial tissue was homogenized in RLT buffer reagent  with an ultraturrax for 30 s, total RNA was extracted from homogenates by RNeasy Minicolumns (Qiagen) according to the manufacturer’s protocol, and real-time RT-PCR was performed. First-strand cDNA was synthesized with TaqMan reverse transcription reagents  using random hexamers as primers. Reactions without Multiscribe reverse transcriptase were used as negative controls for genomic DNA contamination. PCR was performed with an ABI PRISM 7000 Sequence Detector System and TaqMan or SYBR Green Universal PCR Master Mix (Applied Biosystems), as described previously . All samp < 0.05. Pearson correlations were used to assess associations between selected molecular markers of inflammation and inflammatory cells. Strength of Pearson’s correlations was graded according to the following pattern: r = 0.0–0.19 “very weak,” r = 0.2–0.39 “weak,” r = 0.4–0.59 “moderate,” r = 0.6–0.79 “strong,” and r = 0.8–1.0 “very strong.” Statistical significance was set at p-values < 0.05 [Data are expressed as means ± standard error of the mean (SEM). Normality was tested using the Shapiro–Wilk test. Subsequently, to assess differences between sham, NMH, and MH animals, one-way analysis of variance (one-way ANOVA), followed by Bonferroni post hoc test or, where appropriate, Kruskal–Wallis, followed by Dunn’s test, was performed using IBM SPSS 21 . Results were considered significant at s < 0.05 .https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE154019.Raw data for RNA-seq supporting this study are publicly available in the Gene expression Omnibus  repository at Supplementary file1 (DOCX 15465 KB)Supplementary file2 (DOCX 19 KB)Below is the link to the electronic supplementary material.


Mineralocorticoid receptor antagonists (MRAs) and sodium–glucose cotransporter-2 (SGLT2) inhibitors reduce the risk of kidney failure in chronic kidney disease (CKD). We performed an analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial by baseline conventional MRA (spironolactone and eplerenone) prescription.2; urinary albumin-to-creatinine ratio 200–500 mg/g), with or without type 2 diabetes, were randomized 1:1 to dapagliflozin 10 mg or placebo, once daily. The primary outcome was a composite of sustained ≥50% eGFR decline, end-stage kidney disease, or kidney or cardiovascular (CV) death. A prespecified kidney-specific secondary outcome was as the primary outcome but without CV death. Hyperkalemia (serum potassium ≥6.0 mmol/l) was an exploratory end point. Time-to-event analyses  assessed dapagliflozin versus placebo in patient subgroups defined by baseline conventional MRA use.Participants with CKD . The effect of dapagliflozin on the primary outcome was consistent in participants prescribed  and not prescribed  MRAs. This consistency was maintained for the kidney-specific outcome. The effect of dapagliflozin on hyperkalemia  was consistent among those prescribed  and not prescribed  MRAs. Adverse events (AEs) leading to discontinuation and serious AEs were similar between treatment groups, regardless of baseline MRA prescription.A total of 229 of 4304 DAPA-CKD participants (5.3%) were receiving conventional MRAs at baseline (dapagliflozin Dapagliflozin was similarly safe and efficacious in reducing major adverse kidney outcomes in participants with CKD who were or were not prescribed MRAs at baseline. Page 371See Commentary on Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have been the mainstay of treatment for the prevention of kidney failure in patients with CKD over the last 2 decades. However, despite use of these agents, the risk of kidney failure remains high. New therapeutic options to slow progressive loss of kidney function in patients with CKD with and without diabetes have emerged.,,MRAs reduce albuminuria in patients with CKD, but clinical trials to establish their effects on major kidney outcomes were lacking until recently.The DAPA-CKD trial enrolled patients treated with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers and also allowed treatment with conventional MRAs (spironolactone and eplerenone). We report the efficacy and safety of dapagliflozin in patients with CKD who were or were not treated with MRAs in DAPA-CKD.,2, and urine albumin-to-creatinine ratio (UACR) 200 to 5000 mg/g were eligible for participation. All participants used a stable dose of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for ≥4 weeks unless medically contraindicated. Use of conventional steroidal MRAs (spironolactone and eplerenone) was permitted. A complete list of inclusion and exclusion criteria and the trial protocol have been previously published.DAPA-CKD was a randomized, double-blind, placebo-controlled, multicenter clinical trial. The design and main results have been published previously.2 confirmed by a second measurement after at least 28 days), or death from a kidney or CV cause. A secondary, kidney-specific end point was defined in the same way as the primary end point but excluding CV death. The 2 other secondary end points were heart failure hospitalization or CV death, and all-cause mortality. Change in eGFR slope was prespecified as an exploratory efficacy end point. All efficacy end points were adjudicated by a masked, independent event adjudication committee, except for the quantitative assessments of eGFR-based end points—50% eGFR decline, eGFR <15 ml/min per 1.73 m2, or eGFR slope—which were obtained from our central laboratory.The primary composite end point was time to 50% decline in eGFR (confirmed by a second measurement after at least 28 days), onset of kidney failure  regression stratified by randomization factors (diabetes status and UACR), adjusting for baseline eGFR. We analyzed the effects of dapagliflozin on the mean on-treatment eGFR slope by fitting a two-slope mixed effects linear spline model (with a knot at week 2) with a random intercept and random slopes for treatment. Details of the analytical approach have been published previously.Out of 4304 participants, 229 (5.3%) were treated with conventional MRAs at baseline; 109 were assigned to dapagliflozin and 120 to placebo . Compare, P-interaction = 0.59) (P-interaction = 0.96)  compared with those not treated  a. Simila = 0.96) a and b.  = 0.96) a. The be = 0.96) a.Figure 2/yr, 95% CI 0.7–3.3)   a and tho = 0.48) b. Effect = 0.48) a and 3b.P-interaction = 0.96).With respect to safety, serious AEs were more frequently reported in participants treated with MRAs compared with those not treated with MRAs at baseline, but this was true for both the dapagliflozin and placebo groups. The incidence of AEs leading to study drug discontinuation or serious AEs did not differ between dapagliflozin and placebo groups and was similar in participants treated and not treated with MRAs at baseline . The effWe demonstrated that the benefits of dapagliflozin in patients with CKD with and without type 2 diabetes on the primary composite and other kidney end points were consistent in patients who were or were not treated with conventional steroidal MRAs at baseline. The safety and tolerability of dapagliflozin was also consistent irrespective of MRA use. These data suggest that the kidney protective effects of both drug classes are possibly complementary and support future trials to prospectively assess the efficacy and safety of combination therapy with SGLT2 inhibitors and MRAs.,post hoc analysis from the FIDELIO-DKD trial demonstrated that finerenone compared with placebo reduced UACR in patients treated with SGLT2 inhibitors at baseline  and in those not treated .The nephroprotective effects of SGLT2 inhibitors and MRAs can be explained through common and distinct mechanistic pathways. Both classes of agents exert hemodynamic effects and result in a reduction in intraglomerular pressure, which likely contributes to long-term stabilization of kidney function.MRAs increase serum potassium concentration and the risk of hyperkalemia. These effects are more pronounced in patients with CKD and heart failure, who may be most apt to benefit from these therapies. In contrast, SGLT2 inhibitors reduce the risk of hyperkalemia. For example, in patients with type 2 diabetes and CKD participating in the CREDENCE trial, canagliflozin reduced the risk of investigator-reported hyperkalemia-related AEs, initiation of potassium-sparing medications, and serum potassium concentrations ≥6.0 mmol/l.This study has some limitations. There were relatively few participants treated with MRAs at baseline, which limits the precision of the effect estimates. In addition, we were unable to assess the effect of initiation of combination therapy because participants were on a stable dose of MRAs before enrolment into the trial. As a result, we were unable to test the hypothesis that dapagliflozin in combination with MRA treatment results in additive or synergistic effects. Nevertheless, the nearly identical effect sizes suggest that there are independent effects of both agents in this population.In conclusion, in patients with CKD with and without type 2 diabetes, the effects of dapagliflozin in reducing the incidence of the primary composite and composite kidney end points, and of attenuating the decline in eGFR slope, were present in patients treated or not treated with MRAs at baseline. These findings support assessment of combination therapy with MRAs and SGLT2 inhibitors in future clinical trials.MP, PV, and NJ have nothing to declare. BVS, AML, and CDS are employees and stockholders of AstraZeneca. GMC has received fees from AstraZeneca for the DAPA-CKD Trial Steering Committee, research grants from the National Institute of Diabetes and Digestive and Kidney Diseases, support for research staff attending meetings from Amgen, participated in data safety monitoring boards for Angion, Bayer, and Recor, is on the board of directors for Satellite Healthcare and on trial steering committees for Akebia, Gilead, Sanifit, and Vertez, and holds stock options with Ardelyx, CloudCath, Durect, DxNow, Miromatrix, Outset, and Unicycive. JJVM has received payments to his employer, Glasgow University, for his work on clinical trials, consulting, and other activities from AstraZeneca, Cytokinetics, KBP Biosciences, Amgen, Bayer, Theracos, Ionis Pharmaceuticals, Dalcor Pharmaceuticals, Novartis, GlaxoSmithKline, Bristol Myers Squibb, Boehringer Ingelheim, Cardurion, and Alnylam, and has received personal lecture fees from Abbott, Alkem Metabolics, Eris Life Sciences, Hickma, Lupin, Sun Pharmaceuticals, Medscape/Heart.org, ProAdWise Communications, Radcliffe Cardiology, Servier, and the Corpus. RC-R is a member of the Executive Committee of the DAPA-CKD study and has received grants/contracts from GlaxoSmithKline and Novo Nordisk, consulting fees from Boehringer Ingelheim and Chinook, and payment/honoraria as a speaker or advisor from Boehringer Ingelheim, Amgen, Janssen, and Novo Nordisk. PR has received honoraria to Steno Diabetes Center Copenhagen for steering group membership and/or lectures and advice from AstraZeneca, Novo Nordisk, Bayer, and Eli Lilly; advisory board participation from Sanofi Aventis and Boehringer Ingelheim; and steering group participation from Gilead. RDT is a member of the Executive Committee of the DAPA-CKD study, has received consulting fees from Boehringer Ingelheim, Reata Pharma, and Chinook and payment/honoraria from Medscape and Medical Education Resources, participated in advisory boards for Bayer and Vifor and on data monitoring committees for Akebia and Otsuka. DCW has received consultancy fees from AstraZeneca and personal fees from Bayer, Boehringer Ingelheim, Astellas, GlaxoSmithKline, Janssen, Napp, Mundipharma, Reata, Vifor Fresenius, and Tricida. HJLH has received funding/honoraria and consulting fees to his institution for Steering Committee membership and/or advisory board participation from AstraZeneca (DAPA-CKD study), AbbVie, Travere Pharmaceuticals, Janssen, Gilead, Bayer, Chinook, Merck, and CSL Pharma, consulting fees from Boehringer Ingelheim and Novo Nordisk, honoraria for lectures from AstraZeneca, and participated in advisory boards for Mitsubishi Tanabe and Mundipharma.


For almost two decades, the management of patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) was based on the optimal glycemic and blood pressure control as well as on the adequate blockade of the renin-angiotensin-system. Over the past few years, sodium-glucose co-transporter 2 (SGLT-2) inhibitors and glucagone-like peptide 1 receptor agonists (GLP1-RAs) were added to our therapeutic armarhatum, offering promise for more effective mitigation of the substantial residual cardiorenal risk of these patients. Large randomized controlled trials (RCTs) designed to demonstrate the cardiovascular safety of SGLT-2 inhibitors and GLP1-RAs showed that these novel anti-diabetic medications improve cardiovascular outcomes in patients with T2DM. RCTs conducted specifically in CKD patients with or without T2DM demonstrated that SGLT-2 inhibitors were also effective in retarding the progression of kidney injury to end-stage kidney disease. The kidney protective effects of GLP1-RA are not yet proven, but RCTs are currently ongoing to investigate this crucial research question. In this article, we review the available clinical-trial evidence supporting the use of SGLT-2 inhibitors and GLP1-RAs for cardiorenal protection in patients with T2DM and CKD. We provide clinical practice recommendations for a personalized approach in the use of these novel therapies, according to the severity of CKD and the presence of other cardiometabolic risk factors. Compare2 and UACR of 200–5000 mg/g were randomized to dapagliflozin (10 mg/day) or placebo. Approximately one-third of study participants had non-diabetic CKD. Once again, DAPA-CKD was stopped early for reasons of efficacy. Over a median follow-up of 2.4 years, dapagliflozin provoked a 39% placebo-subtracted reduction in the primary outcome that was defined as the composite of sustained > 50% decline in eGFR, ESKD, or death from renal and cardiovascular causes  [Subsequently, the DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) was a trial that was designed to investigate whether the cardiorenal protection afforded by SGLT-2 inhibitors extends to patients across multiple CKD stages with or without T2DM . In thisThe consistency of the benefit of SGLT-2 inhibitors on cardiovascular and kidney failure outcomes was investigated in an updated 2021 meta-analysis of all 6 currently available phase 3 trials involving a total of 46,969 participants [Although SGLT-2 inhibitors were initially introduced for the management of hyperglycemia, these medications appeared to exert pleiotropic actions that extend above and beyond their glucose-lowering efficacy . In factDespite the fact that treatment with SGLT-2 inhibitors is typically well-tolerated, physicians should be aware of some side effects associated with their use in daily clinical practice ,12. Geni2 [Taken together, large trials conducted specifically in CKD patients with or without T2DM provided solid evidence that the addition of an SGLT-2 inhibitor to standard-of-care treatment, including a RAS-blocker, is effective in slowing the progression of kidney injury to ESKD and in improving cardiovascular outcomes. On this basis, the 2020 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend the initiation of SGLT-2 inhibitor therapy for cardiorenal protection in patients with T2DM and CKD, when the eGFR is >30 mL/min/1.73 mp-value for the interaction: 0.18). With respect to the kidney protective effects, compared with placebo, GLP-1 receptor agonists were associated with a significant 21% reduction in the occurrence of the composite outcome of new-onset macroalbuminuria, doubling of serum creatinine, sustained ≥ 40% decline in eGFR, renal replacement therapy, or death from renal causes  [GLP-1 receptor agonists are incretin drugs that improve glycemic control by enhancing glucose-dependent insulin secretion, delaying gastric emptying, and promoting satiety . Similar73–0.83) . However73–0.83) .2/year, respectively. Notably, treatment-induced improvement in the eGFR slope was greater in the subgroup of patients with eGFR < 60 mL/min/1.73 m2 than in those with preserved kidney function at baseline. Compared with placebo, therapy with semaglutide or liraglutide provoked a 14%  and 20%  reduction in the risk for sustained 40% and 50% declines in eGFR during follow-up, respectively [2 at baseline, the renoprotective benefit of GLP-1 receptor agonists was greater in magnitude  [Further insights on the kidney protective effects of GLP-1 receptor agonists were provided by a combined analysis of 12,637 patients with T2DM enrolled in the LEADER  and SUSTAIN-6  trials . From baectively . Similarctively) . Taken t2; 39% and 44% of participants had micro- and macroalbuminuria at baseline, respectively. Over 52 weeks of follow-up, eGFR remained stable with dulaglutide 1.5 mg and dulaglutide 0.75 mg but declined with insulin glargine. At the study-end, the albuminuria-lowering effect of dulaglutide 1.5 mg and dulaglutide 0.75 mg did not significantly differ from that of insulin glargine [The first trial to explore the safety and efficacy of GLP1-RAs in patients with T2DM and moderate-to-advanced CKD was the AWARD-7 (Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease) . In this2 and UACR ≥ 300 to <5000 mg/g or patients with eGFR ≥ 25 to <50 mL/min/1.73 m2 and UACR 100–5000 mg/g. These patients will receive optimized background therapy with maximal tolerated doses of a RAS-blocker. The prespecified primary efficacy endpoint was defined as the composite of persistent ≥ 50% decline in eGFR, ESKD, or death from renal and cardiovascular causes. Effects of semaglutide relative to placebo on the occurrence of non-fatal MI, non-fatal stroke, or cardiovascular death will be explored as a prespecified secondary efficacy endpoint [The effects of GLP1-RAs on “hard” kidney failure and cardiovascular outcomes, specifically in patients with T2DM and CKD are currently under investigation in the ongoing FLOW (A Research Study to See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney) trial . This phendpoint . The estAs in the case of SGLT-2 inhibitors GLP-1 receptor agonists represent an incretin-based class of anti-diabetic medications that also protect the heart and the kidney, a pleiotropic action that can only partially be explained by the treatment-induced improvement in glycemic control ,12,31. G2) plus at least one additional cardiovascular risk factor, were randomized in a 1:1:1 ratio to receive once-weekly injectable efpeglenatide at doses of 4 or 6 mg or placebo. Notably, randomization was stratified according to the use of an SGLT-2 inhibitor at baseline, a drug class that was administered in >15% of study participants as background anti-diabetic therapy [The mechanism of action of GLP-1 receptor agonists is complementary to that of SGLT-2 inhibitors and, therefore, combination therapy may offer an additive benefit on cardiovascular and kidney failure outcomes as compared with each therapy alone. Some evidence to support this therapeutic approach was recently provided by the AMPLITUTE-O trial (Effect of Efpeglenatide on Cardiovascular Outcomes) . In this therapy . Over a  therapy . In pres therapy , providiThe most frequent side effects associated with the use of GLP-1 receptor agonists are nausea, vomiting, and diarrhea ,31. Thes2) [Collectively, large-scale trials designed to demonstrate the cardiovascular safety of GLP-1 receptor agonists provided strong evidence that this drug class is effective in improving cardiovascular outcomes in patients with T2DM, a benefit that appears to be similar in magnitude with the cardiovascular risk reduction provoked by SGLT-2 inhibitors . Seconda2) . The str2) .For almost two decades, the management of patients with T2DM and CKD relied on the optimal glycemic and BP control, whereas RAS-blockade was the only guideline-based treatment proven to be effective in slowing the progression of kidney damage and in improving the risk for adverse cardiovascular events. SGLT-2 inhibitors and GLP-1 receptor agonists are two novel classes of anti-diabetic medications with pleiotropic effects that extend beyond their glucose-lowering efficacy. The beneficial effects of these agents on cardiovascular and kidney failure outcomes have substantially modified the therapeutic algorithm of T2DM in patients CKD , offerin


Background: Sepsis is a serious public health problem worldwide. Blood pressure is one of the indicators that is closely monitored in intensive-care units, and it reflects complex interactions between the internal cardiovascular control mechanism and the external environment. We aimed to determine the impact of indicators related to the ambulatory blood pressure on the prognosis of sepsis patients.Methods: This retrospective study was based on the Medical Information Mart for Intensive Care IV database. Relevant information about sepsis patients was extracted according to specific inclusion and exclusion criteria. Examined parameters included the average blood pressure, blood pressure variability (BPV), and circadian rhythm, and the study outcome was in-hospital death. We investigated the effects of these indicators on the risk of in-hospital death among sepsis patients using Cox proportional-hazards models, restricted cubic splines analysis, and subgroup analysis.Results: This study enrolled 10,316 sepsis patients, among whom 2,117 died during hospitalization. All parameters except the nighttime variation coefficient of the diastolic blood pressure (DBP) were associated with in-hospital death of sepsis patients. All parameters except for fluctuations in DBP exhibited nonlinear correlations with the outcome. The subgroup analysis revealed that some of the examined parameters were associated with in-hospital death only in certain subgroups.Conclusion: Indicators related to the ambulatory blood pressure within 24 h are related to the prognosis of sepsis patients. When treating sepsis, in addition to blood pressure, attention should also be paid to BPV and the circadian rhythm in order to improve the prognosis and the survival rate. Sepsis is a serious public health problem worldwide. In 2016, sepsis was redefined as a life-threatening infection combined with an acute increase in Sequential Organ Failure Assessment (SOFA) score of ≥2 Blood pressure is one of the indicators that is closely monitored in intensive-care units for both short-term (minutes to hours) and long-term (days to months) fluctuations. It reflects complex interactions between the internal cardiovascular control mechanism and the external environment. Blood pressure variability (BPV) reflects the degree of fluctuation of the blood pressure over a certain period of time The Medical Information Mart for Intensive Care IV (MIMIC-IV) is a large public database that records comprehensive clinical information about patients. We used this database to explore the impact of indicators related to the ambulatory blood pressure on the prognosis of sepsis patients in detail.The data used in this study were obtained from version 0.4 of the MIMIC-IV database. This is a large, single-center, and open-access database that includes data on 257,366 admissions from 196,527 patients admitted to Beth Israel Deaconess Medical Center from 2008 to 2019 We qualified to use the MIMIC-IV database after completing an online course from the National Institutes of Health and passing the examination on Protecting Human Study Participants (Record ID: 38455175).According to Sepsis 3.0 criteria, sepsis is defined as a suspected or confirmed infection plus an acute increase of >2 points in the SOFA score The outcome of this study was in-hospital death, and cases in which no death was observed during hospitalization were considered censored. Follow-up began at the time of a sepsis diagnosis and ended at the time of in-hospital death or discharge. The survival time was calculated in days.We noninvasively recorded SBP, diastolic blood pressure (DBP), and mean blood pressure (MBP) for the first 24 h after the diagnosis of sepsis. Considering that a patient may have their blood pressure measured more than once during the same hour, we used hourly averages. Daytime blood pressure was measured from 8:00 to 22:00, and nighttime blood pressure was measured from 22:00 to 8:00 the next day. The examined parameters included the following: (1) average blood pressure indicators: mean values of SBP, DBP and MBP over 24 h  and their corresponding daytime values  and nighttime values ; (2) BPV indicators: standard deviations of SBP, DBP, and MBP over 24 h  and their corresponding daytime values  and nighttime values ; coefficients of variation of SBP, DBP, and MBP over 24 h  and their corresponding daytime values  and nighttime values ; and (3) circadian rhythm indicators: fluctuation in SBP  and fluctuation in DBP .Any indicators that might confuse the relationship between examined parameters and outcome were adjusted as covariates in the subsequent analyses. These covariates included the following: (1) demographic indicators: age, gender, ethnicity, and body weight; (2) comorbidity indicators: Charlson Comorbidity Index, myocardial infarct, congestive heart failure, cerebrovascular disease, renal disease, mild liver disease, severe liver disease, uncomplicated diabetes, complicated diabetes, and malignant cancer; (3) laboratory test indicators: lactate, creatinine, and white blood cells; (4) disease severity scores: SOFA score and Acute Physiological Score III (APSIII); and (5) treatment-related indicators: use of mechanical ventilation, vasopressor, and continuous renal replacement therapy (CRRT). For indicators measured multiple times during hospitalization, we analyzed the first measurements made after the diagnosis of sepsis.SBP, DBP, and MBP are dynamic parameters, and some measured values will inevitably be missed at certain time points. In order to reduce the selection bias caused by the exclusion of too many cases with missing information, we used the Amelia package of R software to impute the missing values by the incorporation of polynomials of time to fit a model to predict missing values. The approach used meant that values observed close to the time point of a missing value greatly influenced the calculation of the missing value, while those that were not close had lower weights in the calculation model The average blood pressure indicators were divided into three categories according to the diagnostic criteria for hypertension: hypotensive group , normal blood pressure group , and hypertensive group . BPV and circadian rhythm indicators were divided into four categories according to their respective quartiles.The Kolmogorov-Smirnov test was used to determine whether the continuous variables were normally distributed. If they were, mean and standard-deviation values were used to describe the distribution, and Student's t test was used to analyze differences between groups. If continuous variables were not normally distributed, median and interquartile-range values were used, and differences between groups were analyzed using the Mann-Whitney U test. Categorical variables were expressed as frequency and percentage values, and intergroup differences were analyzed using the chi-square test or Fisher's exact test, as appropriate.The examined parameters were first analyzed as continuous variables, and Cox proportional-hazards models with unadjusted and adjusted covariates were constructed to analyze the relationships between the examined parameters and in-hospital death. The examined parameters were then analyzed as categorical variables, and Kaplan-Meier curves were drawn to show the survival of patients in different groups, while the log-rank test was used to analyze survival differences between groups. Similarly, Cox proportional-hazards models with unadjusted and adjusted covariates were also constructed. In addition, we added cross-product terms of examined parameters and stratification variables  This study enrolled 10,316 patients with sepsis, among whom 2,117 died during hospitalization. The median [interquartile range] follow-up time was 10 The results of the constructed Cox models are presented in Table The Kaplan-Meier curves of all examined categorical variables are shown in Figure The Cox models revealed that before adjusting for covariates, SBPmean, SBPmeanD, and SBPmeanN indicated that the hypotensive group had a higher risk of in-hospital death than the normal blood pressure group, while the hypertensive groups had a lower risk. However, after adjusting all covariates, only the hypotensive group had a significantly higher risk. DBPmean, DBPmeanD, MBPmean, MBPmeanD, and MBPmeanN showed similar results, but DBPmeanN showed a significant increase in risk of in-hospital death only in the hypotensive group before adjustment, while the difference was not statistically significant after adjustment.SBPsd, SBPsdD, and SBPsdN values in quartile 2 (Q2), quartile 3 (Q3), and quartile (Q4) did not differ from the values in quartile 1 (Q1) before adjustment, and all showed a significantly lower risk after adjustment. SBPcv, SBPcvD, and SBPcvN showed a significantly higher risk only in Q4 before adjustment. However, after adjustment, SBPcv showed a significantly lower risk in Q2 and Q3, SBPcvD showed a significantly lower risk in Q3, and SBPcvN showed a significantly lower risk in Q3 and Q4.SBPF showed a significantly lower risk in Q3 than in Q1 before adjustment, with no significant difference observed after adjustment. DBPF showed a significantly lower risk in Q3 and Q4 than in Q1 before adjustment, but only in Q3 after adjustment.The subgroup analysis revealed that MBPmeanD, MBPmeanN, DBPcvD, and MBPcvD interacted with age, and that MBPmean, MBPmeanN, SBPcv, and SBPcvN interacted with gender. Further stratified analysis showed that MBPmeanD and MBPmeanN had an effect on in-hospital death only among those aged ≥65 years, while DBPcvN and MBPcvD only had an effect among those aged <65 years. Moreover, the effects of MBPmeanN, SBPcv, and SBPcvN were only seen in males, while the effect of MBPmean was more pronounced in males Table .The results of the RCS analysis in Figure SBPsd and SBPsdN showed U-shaped relationships with in-hospital death, with a change point at around 20 mmHg. SBPsdD showed a W-shaped relationship, with change points at around 10, 15, and 20 mmHg, and significant negative and positive correlations were found when the value was lower than 10 mmHg and higher than 20 mmHg, respectively. DBPsd and DBPsdD showed roughly U-shaped relationships, with a change point at around 15 mmHg. DBPsdN showed an inverse N-shaped relationship, with change points at 8 and 15 mmHg. As DBPsdN increased, the risk of in-hospital death first increased and then decreased. MBPsd, MBPsdD, and MBPsdN showed U-shaped dose-response relationships with the outcome, and the change point was at about 15 mmHg.SBPcv, SBPcvD, and SBPcvN showed U-shaped relationships, with a change point at about 0.15. DBPcv showed a W-shaped relationship, with change points at about 0.15, 0.2, and 0.25, while DBPcvD and DBPcvN showed U-shaped relationships, with a change point at about 0.2. The dose-response relationships of MBPcv, MBPcvD, and MBPcvN with the risk of in-hospital death were roughly U-shaped, with a change point at about 0.2.SBPF showed an inverse N-shaped relationship with the outcome, with change points at around -5% and 5%, and a significant negative correlation below -5%. DBPF was associated with the risk of in-hospital death, but no significant nonlinear relationship was observed. The negative correlation was more obvious at values below 0%.Further interaction analyses Figure  showed tBPV is a very complicated life phenomenon that is affected by numerous factors Our analyses of Cox proportional-hazards models showed that SBPmean, SBPmeanD, and SBPmean values <90 mmHg; DBPmean, DBPmeanD, and DBPmeanN values <60 mmHg; and MBPmean, MBPmeanD, and MBPmeanN values <70 mmHg within 24 h are related to a poor prognosis in patients with sepsis. Further RCS analysis showed that SBP, DBP, and MBP had nonlinear relationships with in-hospital death, with change points at 110, 60, and 70 mmHg, respectively. Below the change points, the mortality rate decreased as the blood pressure increased. The underlying mechanism is that blood pressure is lowered due to cytokines and inflammatory substances in patients in the early stage of sepsis Our results indicate that variations in SBP, DBP and MBP are associated with mortality regardless of whether they occur over the entire day, during daytime, or during nighttime. In the RCS analysis, SBPsd, DBPsd, and MBPsd showed U-shaped relationships with in-hospital death, with change points at 20, 15, and 15 mmHg, respectively. The coefficients of variation of SBP and MBP showed U-shaped relationships with in-hospital death, and the change points were at around 0.15 and 0.2, respectively. A W-shaped relationship was observed between DBPcv and in-hospital death, and DBPcvD and DBPcvN showed U-shaped relationships with in-hospital death. SBPF had an inverse N-shaped relationship with the risk of in-hospital death, and a negative correlation with the risk of in-hospital death was obvious below -5%. DBPF was related to the risk of in-hospital death, and a negative correlation was obvious below 0%. Healthy people exhibit obvious circadian rhythms in the blood pressure The subgroup analysis revealed interactions of DBPsdD, DBPcvD, and MBPcvD with age. Blood pressure is greatly affected by age, with elderly patients having reduced blood vessel elasticity due to problems such as atherosclerosis and vascular sclerosis, allowing the above interactions to occur Most previous studies have focused on the effects of blood pressure and its variability in patients with hypertension or in healthy people on the heart, brain, and other organs, with few studies investigating the effects of blood pressure and its variability on prognosis in sepsis patients Of course, this study was also subject to certain limitations. First, it had a retrospective design, and the MIMIC-IV data coming from a single center may have resulted in selection bias. These two aspects restrict the ability to extrapolate our results, and so they need to be validated in a prospective cohort from multiple centers. Second, imputing missing values will lead to a certain degree of information bias. Third, some potential confounding factors such as the specific dosage of vasopressor were not taken into account due to the limitations of the database. Fourth, the present research would have benefited from a more regular measurement of blood pressure.Indicators of the ambulatory blood pressure measured within 24 h are related to the prognosis of sepsis patients. When treating patients with sepsis, in addition to measuring blood pressure, attention should be paid to their BPV and circadian rhythm indicators in order to improve the prognosis and the survival rate.


Chronic rhinosinusitis with polyposis (CRSwNP) is a multifactorial naso-sinusal inflammatory disease that affects 2–4% of the adult population. It highly affects the patient quality of life (QoL) in many levels making it a public health issue. The management of CRSwNP is based on a detailed clinical history, a complete endoscopic examination and a precise computed tomographic (CT) analysis. The aim of this study is to evaluate the prevalence and severity of the various CRS clinical manifestations as well as to highlight the potential relationship between symptom scores, asthma and ESS outcomes.A retrospective cohort study was performed in the 20 August hospital, between January 2017 and December 2018, on patients diagnosed with CRS according to guidelines recommendations, and were beforehand refractory to initial medical therapy and elected to FESS. The patients were divided into two groups, the first group (G1) of patients with asthma and the second (G2) without asthma in order to expose an eventual significant difference in the improvement of symptoms after surgery. The Sino Nasal Outcome Test-22 (SNOT-22) was used to evaluate QOL.A total of 100 patients participated in the study with an average age of 44.53 years. The sex ratio was 1.04 (51% men). Asthma was present in 48% of patients while 20% of patients were intolerant to aspirin with a significant difference between the asthmatic and non-asthmatic group (p < 0.05). It appears that asthma was not objectively correlated with a higher Lund Mackay radiological score (p > 0.05). A higher significant improvement was observed between preoperative and postoperative SNOT-22 scores in group with asthma [42.7 ± 16.3 versus 11.8 ± 9.1] and in group without asthma [38.3 ± 15.1 versus 10.5 ± 14.2].Asthma in CRS is an additional symptom in these patients, mainly reflected in the subset of nasal symptoms in SNOT-22. However, it did not significantly affect the quality of life of the CRSwNP population. •Chronic rhinosinusitis with polyposis highly affects the patient quality of life in many levels making it a public health issue.•The aim of this study is to highlight the potential relationship between symptom scores, asthma and ESS outcomes.•SNOT-22 scores were significantly reduced in the postoperative period in the asthma and non-asthma groups, with no significant difference between the 2 groups. It constitutes a major health problem, since its prevalence reaches 4% of the general population, and its high cost and drop in individual production due to increased absenteeism and the deterioration of the quality of life (QoL) ,2. Its mSNOT22 represents a clinical means that reflects the degree of severity of the disease as well as its impact on the mood and well being.Endoscopic endonasal surgery ESS is the most preferred treatment for the CRS forms resistant to medical treatment, it is based on the theory that the diseased nasal mucosa can restore its function after improving ventilation and drainage .The aim of this study is to evaluate the prevalence and severity of various clinical manifestations of CRS as well as to expose the potential relationship between symptom scores, asthma and outcomes following ESS and to analyse the positive effects of ESS on clinical symptoms and QoL. We hypothesized that the patients without asthma may have lower baseline symptom scores than those with asthma.2A cohort study was fulfilled in the otorhinolaryngology departement of the 20 August hospital between January 2017 and December 2018.A serie of 100 adult patients undergoing ESS for medically refractory CRS formed the study group, with 30 patients lost to follow-up. CRS was refractory if symptoms persisted after a minimum of six weeks of treatment which includes antibiotics, topical corticosteroids and antihistamines. Asthma and aspirin intolerance were systematically sought. Preoperatively, the patients were clinically examined and evaluated according to the SNOT22 clinical score. This questionnaire was self-administered in the standard fashion with 22 items graded on a 6-point scale ranging from 0 (no problem) to 5 (problem as bad as can be) with a maximum score of 110 [The study population underwent ESS with a standard technique. The extent of surgery was determined by the severity of disease and extent of involvement of sinuses as per the preoperative CT scan and nasal endoscopy.The patients were followed up postoperatively with a control at 3 months and at 6 months to determine the effect of asthma on outcomes of ESS on CRS, based on endoscopic examination and SNOT22 scoring.The study population was divided into 2 groups, the first one (G1) of patients with asthma and the second (G2) of patients without asthma in order to show the presence or not of a significant difference in the improvement of symptoms after surgery.t-test. All significance tests used a two-sided P-value of 0.05.Data management and analysis were performed using IBM SPSS Statistics for Windows, version 25.0.0 . Categorical data were summarized as frequencies, and cross-tabulations and ×2 tests for significance made comparisons across allocated groups. Continuous variables were summarized as the mean and range, and comparisons between groups were made using the independent samples The study was reported in line with the STROCSS criteria . And regEthical approval has been exempted by our institution.33.1A total of 100 patients were enrolled in our study. The sex ratio M/F was 1.04 (men: 51%) and the mean age was 44.53±10 years.Asthma was presented in 48% of patients while, 20% of patients were intolerant to aspirin. Most of the patients (77%) had never been operated on for endoscopic sinus surgery ESS for CRSwNP, and only 20% of cases presented recurrences, and 3% of them were operated on more than 2 times. The average time between symptoms and the first consult was 5 years with extremes ranged from 6 months to 10 years. Bilateral permanent nasal obstruction was the main symptom in all patients, the rhinorrhea was watery in 35%, purulent in 16%, bloody in 1% while it was absent in 48% of the cases and hyposmia was present in 68% of cases.The average SNOT 22 score was 41.03, with extremes of 5–69 .Table 1CMost of the patients (84%) did not respond to a well-conducted medical treatment based on short-course oral corticosteroid therapy and topic corticosteroid therapy for at least 3 months, whether or not combined with antibiotic therapy.3.2The CT scan of paranasal sinus was performed in 75% of patients. The average Lund-Makay score was 16.8 with extremes of 2–24, the score was ≥15 in 34 cases (45.3%) and ≤14 in 41 patients (54.7%). It also showed anatomical variants, since 4% of patients had a procidence of the optic nerve and carotid canal.3.3trans-ethmoid sphenoidotomy in 60% of the casess, associated with a lower turbinectomy in 2% of cases.All patients underwent an endoscopic sinus surgery ESS with polypectomy combined with a middle meatotomy. Anterior and posterior ethmoidectomy were performed in 85% of the cases, a The result after ESS were evaluated with SNOT22 at three and six months .Table 2E3.4In our series we did not have major complications and postoperative synechiae was the most common problem, encountered in 12 (12%) patients. These were easily cleared by systematic postoperative outpatient care with meticulous cleaning of the nasal cavity. Minor complications like nasal bleeding were occasionally encountered in eight (10%) patients who were treated conservatively with packing and did not require blood transfusion.4Chronic rhinosinusitis with polyposis (CRSwNP) is a multifactorial naso-sinusal inflammatory disease that occurs in 2–4% of the adult population . It is oIn our serie, asthma was present in 48% of the patients which is similar to the literature, where it varies between 20 and 60% . FemalesThe association with asthma is not in itself a factor of clinical severity of naso-sinusal polyposis ,12. In oWidal Syndrome should be checked in all patients with nasosinusal polyposis. Aspirin intolerance, found in more than half of all patients (CRSwNP) associated with asthma, was a provider of a clinically more severe polyposis ,16. ReceMedical treatment remains the reference treatment. As asthma associated with CRSwNP is highly eosinophilic, anti-leukotriene (Montelukast), anti-IgE  and anti IL-5 (Mepolizumab and reslizumab) treatments have shown promising results for both asthma and polyposis-sinus ,19.FESS was introduced in the 1960s by Professors Messerklinger and Wigand. It was popularised in Europe by Stammberger, then in North America by Kennedy . ESS is A number of disease specific questionnaires have been developed to evaluate quality of life. SNOT-22 is the most widely used and validated questionnaire ,26. We aThe CRSwNP has already been associated with poorer outcomes and reduced quality of life. Further analysis of the CRSwNP population did not find a significant association between atopy and measures of quality of life. Thus, the presence of atopy in CRSwNP appears to have no significant impact on the symptom burden of CRSwNP ,28.In our study, we observed that SNOT-22 scores were higher in the preoperative period, then reduced significantly in the post-operative period in the asthmatic and non-asthmatic group without significant difference at the 3rd month and the 6th month respectively (p > 0.05).This study has several limitations that should be acknowledged. The sample size was small; 30 patients were lost to follow-up, and the conclusions cannot be taken for granted.But the strengths of this study include the presence of a control group, the use of a properly adapted and validated assessment instrument, the assessment of results done from the standpoint of the patient, and a follow-up to 6 months. Furthermore, surgeons were blinded for preoperative SNOT-22 score.This study has served as a guideline for further research in the future and cannot be generalised to the entire current FESS population. More extensive studies will be needed.5Asthma in CRS causes an additional symptom in these patients, which is mainly reflected in the subset of nasal symptoms in SNOT-22. However, it did not significantly affect the quality of life of the CRSwNP population.Although there has been major advances in this field, there is still a lack of consistent evidence to reach firm conclusions about the relationship between CRS and asthma. Research on the basic pathophysiology of the nose and demonstration of the unified airway concept are mandatory. Clarification is also required concerning whether CRS management affects other comorbid lower airway diseases. A collaboration between otorinolaryngologist and pneumologist is necessary for a global and adequate management of the asthmatic patient with naso-sinusal polyposis.This research did not receive any specific grant(s) from funding agencies in the public, commercial, on non-for-profit sectors.This research did not receive any specific grant(s) from funding agencies in the public, commercial, on non-for-profit sectors.Lahjaouj Meryem: study concept and acquisition of data.Laachoubi Mohammed: Corresponding author, writing the paper.El bouhmadi Khadija: writing the paper.Youssef Oukessou: study concept.Sami Rouadi: supervision.Reda Abada: revising the paper.Mohamed Roubal: revising the paper.Mohamed Mahtar: final approval.Researchregistry: 6522.Laachoubi Mohammed.Written informed consent was obtained from the patient for publication of this research study. A copy of the written consent of each patient is available for review by the Editor-in-Chief of this journal on request.Not commissioned, externally peer-revieweedThe authors declare no conflicts of interest for this article.


Chronic kidney disease (CKD) is an increasing global health burden. Current treatments for CKD include therapeutics to target factors that contribute to CKD progression, including renin–angiotensin–aldosterone system inhibitors, and drugs to control blood pressure and proteinuria control. Recently, associations between chronic disease processes and the human microbiota and its metabolites have been demonstrated. Dysbiosis—a change in the microbial diversity—has been observed in patients with CKD. The relationship between CKD and dysbiosis is bidirectional; gut-derived metabolites and toxins affect the progression of CKD, and the uremic milieu affects the microbiota. The accumulation of microbial metabolites and toxins is linked to the loss of kidney functions and increased mortality risk, yet renoprotective metabolites such as short-chain fatty acids and bile acids help restore kidney functions and increase the survival rate in CKD patients. Specific dietary interventions to alter the gut microbiome could improve clinical outcomes in patients with CKD. Low-protein and high-fiber diets increase the abundance of bacteria that produce short-chain fatty acids and anti-inflammatory bacteria. Fluctuations in the urinary microbiome are linked to increased susceptibility to infection and antibiotic resistance. In this review, we describe the potential role of the gut, urinary and blood microbiome in CKD pathophysiology and assess the feasibility of modulating the gut microbiota as a therapeutic tool for treating CKD. Chronic kidney disease (CKD) is a growing healthcare burden affecting about 13.4% of the population worldwide . In adulCurrent treatments for CKD include renin–angiotensin–aldosterone system inhibitors and drugs to control blood pressure and proteinuria. An increasing number of studies suggest that the composition of the microbiome has a key role in maintaining health. The human microbiome is the collection of all microbial DNA in the human body, which is distributed in various body parts as; skin, gastrointestinal, urinary tract, respiratory tract, and oral cavity . These mp-cresyl sulfate are associated with renal fibrosis, endothelial dysfunction, a decline in the estimated glomerular filtration rate (eGFR), cardiovascular complications, and increased mortality and morbidity in CKD  . The undBifidobacterium and Lactobacilli are negatively correlated with CKD progression and long-term survival  and healthy individuals , interleukin (IL)-6, and thiobarbituric acid-reactive substances .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. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


After working in the isolation ward, nurses reported malaise  more often than paramedics . The risk of ill-being in nurses was approximately nine times higher than in paramedics  and increased with the age of the subjects . Conclusion: FFP2/FFP3 filter masks did not worsen blood oxygenation in medical staff caring for patients isolated due to SARS-CoV-2 in the ICU. The presence of subjective symptoms such as fatigue may be due to lack of adequate hydration.The dynamically changing epidemiological situation caused by the SARS-CoV-2 virus is associated with the increased burden and fatigue of medical personnel. The aim of the study was to evaluate: (1) oxygen and carbon dioxide blood pressure and saturation levels in medical personnel caring for patients isolated due to SARS-CoV-2 in ICUs; (2) adverse symptoms reported by medical personnel after leaving the isolation zone. Design: A Prospective Cohort Study. Methods: The project was implemented in the first quarter of 2021. Medical personnel working with patients isolated due to SARS-CoV-2 in the ICU of three hospitals were eligible for the study. The participants of the study were subjected to two analyses of capillary blood by a laboratory diagnostician. Results: In the studied group of medical personnel (n = 110) using FFP2/FFP3 masks, no significant differences ( The dynamically changing epidemiological situation caused by the SARS-CoV-2 virus is associated with the increased workload and fatigue of medical personnel. Prolonged use of personal protective equipment (PPE) may contribute to this. Particularly vulnerable groups, due to the time they must spend in PPE, are nurses working in the intensive care unit for patients infected with SARS-CoV-2 and the paramedics who support them ,2. TransThe purpose of this study was: (1) to evaluate the levels of oxygen and carbon dioxide pressure and saturation in arterialized capillary blood collected from medical personnel caring for patients isolated due to SARS-CoV-2 in the ICU; (2) to evaluate the adverse symptoms reported by medical personnel after leaving the isolation zone.This was a prospective cohort study that included 110 medical staff caring for patients isolated due to SARS-CoV-2 in the ICU of three hospitals in Poland. The study was approved by the Bioethics Committee of University of Rzeszow. The authors followed the guidelines of the Declaration of Helsinki  and STROBE  . The resThe study involved nurses and paramedics who: gave informed consent to participate in the study; worked in a hot (contaminated) zone for a minimum of 2 h ; worked The study did not include nurses and paramedics who: did not agree to participate in the study; worked in the cold zone; worked shifts for less than 1 h; used a surgical mask; had a history of respiratory diseases.2, 75–100 mmHg; PaCO2, 35–45 mmHg; HCO3−, 22–28 mmol/l; O2sat, 70–95%; BE +/− 2.5 mmol/L [Two capillary blood samples were taken from the subjects for Capilar Blood Gases Test. The first blood sampling was performed before securing the medical personnel with personal protective equipment. The second blood sampling was performed immediately after completion of the isolation care . Each ti5 mmol/L . ParticiData collection included: age, body weight, body height, gender, profession, co-morbidities, time of working in an isolation ward, number of times entering the isolation ward, type of medical protective mask, adverse events connected with work in an isolation ward.The primary outcomes included the assessment of oxygen and carbon dioxide pressure and saturation levels in arterialized capillary blood. The secondary outcomes were the assessment of adverse symptoms reported by medical staff after leaving the isolation zone.The minimum size of the sample was determined a priori with G*Power . Given an effect size of 0.3333 with a minimum of 90% power, the minimum number of participants was calculated as 97 with a 5% type 1 error.p values being below 5% were taken as statistically significant for two-sided tests. Statistical calculations were performed in STATISTICA v.13 (TIBCO Software Inc. (2017), Kraków, Poland).Continuous quantitative variables were characterized as medians and quartiles, while qualitative variables were presented as counts of each level with corresponding percentages. Quantitative variables were compared between dependent groups (Before vs. After) by Wilcoxon probability tests (Wilcoxon tests) due to the lack of normal distribution of these variables in both groups. Normal distribution of quantitative variables was determined by the Shapiro–Wilk test. The chi-square test or Fisher’s test was used to compare qualitative variables between the study groups. Effects of age, gender, body weight, body height, smoking, time of working in an isolation ward, and profession on the physical symptoms (expressed as a dichotomous variable: no and yes) were tested in a univariate logistic regression model . The p = 0.0001). All subjects were protected with PPE, with 29% wearing a mask with an FFP2 filter, 27% of subjects wearing a half-face mask with an FFP3 filter, and 44% of subjects wearing a full-face mask with an FFP3 filter. The exact characteristics of the study group are presented in Sixty-three (57%) nurses and 47 (43%) paramedics were enrolled in the study. The median age of the subjects was 28 years, median height was 170 cm, and median weight was 70 kg. Thirty-eight percent of the subjects reported that they smoked cigarettes, while 4% of the subjects reported having a cardiovascular disease. Capillary blood analysis was performed in 62% of the subjects after one entry into the isolation zone, in 31% of the subjects after two entries, in 6% of the subjects after three entries, and in only one subject after four entries into the isolation zone. The median time spent in isolation was 240 min. Of note, during the entire observation period there was a significant difference between nurses and paramedics in terms of their time of working in an isolation ward  vs. 180 ; Z = 3.83; p > 0.05) between individual parameters. Medians of pO2 (75.45 mmHg vs. 76.10 mmHg), pCO2 (37.70 mmHg vs. 37.90 mmHg), and SaO2 (96.25% vs. 96.0%) were similar. Variables such as gender, occupation, smoking, type of mask used, and number of entries into the ICU (one entry vs. more than one entry) also had no effect (p > 0.05) on blood gas results.p = 0.00002). In univariate logistic regression analysis, the risk of malaise in nurses after exiting the isolation zone was approximately nine times higher than in paramedics  (p = 0.000016.Twenty-nine percent of subjects reported adverse symptoms after leaving the isolation zone. The most common complaints were fatigue and drowsiness . Nurses to 26.8)  and incrto 26.8) . Nurses 2) pressure, and oxygen level (SpO2) were measured at the end of six 10-min phases: sitting quietly and walking briskly without a mask, sitting quietly and walking briskly with a fabric mask, and sitting quietly and walking briskly with a surgical mask. An expected and intended increase in heart rate was observed when walking without a mask compared to sitting without a mask, while no effect on ventilation was observed [2 concentration and oxygen saturation were observed [p = 0.031). This study highlights that a significant proportion of nurses and physicians were dehydrated at the beginning and end of their medical shift professionals’ attitudes towards the importance of hydration for health, well-being, and productivity. Respondents from Mediterranean countries, i.e., Italy, Spain, and Greece, believed that a good hydration strategy was a key aspect in counteracting dehydration, while respondents from Germany and the UK considered it less important. The study did not consider whether this was due to differences in climate or culture [The results of this study suggest that FFP2/FFP3 filter masks have no effect on blood oxygenation in medical personnel caring for patients isolated due to SARS-CoV-2 in the ICU. The most common adverse reactions reported by medical personnel after leaving the isolation zone were fatigue and drowsiness. The frequency of adverse symptoms depended on age and occupation, with nurses more likely to report adverse symptoms than paramedics. One must bear in mind that paramedics in Poland, though fully qualified to provide diagnostic, treatment, and prophylactic services, especially in acute life-threatening situations across patients of all ages, have limited responsibilities in the ICU settings. Due to legal constraints, they are allowed to perform various tasks only with direct supervision of registered nurses as far as the intensive care environment is concerned. Based on current scientific evidence, the wearing of PPE, including face shields or goggles, face masks, barrier aprons or coveralls, and gloves is recommended when caring for patients with COVID-19. The use of masks is thought to reduce the spread of SARS-CoV-2 but is also a frequently cited concern for inadequate gas exchange . In our observed . Similarobserved . Studiesobserved ,14 showeobserved . The anaobserved . Long woobserved ,18. In aDue to technical limitations, we could not measure hematocrit and glucose levels, and there was no possibility of immediate gasometry assessment after leaving the isolation zone due to the necessity to undress in compliance with the sanitary regime. The type of activities performed during the stay in the ward was not analyzed, and each time they could significantly differ in terms of effort and intensity. Other potential factors influencing mental and physical well-being, such as food and fluid intake or sleep deprivation, were not taken into account.FFP2/FFP3 filter masks did not impair blood oxygenation in medical personnel caring for patients isolated due to SARS-CoV-2 in the ICU. Adverse effects of being in the isolation zone were related to the profession and age of the medical staff.In the short term, maintaining adequate hydration can help prevent dehydration, which can cause headaches, dizziness, fatigue, fainting, rapid heartbeat, and other symptoms . The imp


Obesity has become a global epidemic problem affecting every system and is associated with many consequences including coronary artery disease, hypertension, diabetes mellitus, dyslipidemia, obstructive sleep apnea, and socioeconomic and psychosocial impairment. Laparoscopic sleeve gastrectomy is one of the best and most commonly done operations for weight loss. Elevated peak airway pressure and hypoxemia are common problems that anesthesiologists face during laparoscopic surgeries with conventional volume-controlled ventilation. This study aimed at the use of the prolonged I:E ratio as an alternative strategy to improve gas exchange and the respiratory mechanics of obese patients undergoing laparoscopic sleeve gastrectomy.n=26) and the VCV group (n=26). Respiratory parameters were adjusted as tidal volume (Vt) 8mL/kg ideal body weight, respiratory rate 12 breaths/min, positive-end expiratory pressure (PEEP) 0, fractional inspired oxygen (FiO2) 0.6, and I:E ratio 1:2 for the VCV group and 2:1 for the IRV group; hemodynamics and respiratory mechanics were monitored and recorded after intubation (0 min), before pneumoperitoneum (10 mins), and after pneumoperitoneum (20 mins), 30, 40, 50, and 60 mins. IRV significantly improves the respiratory mechanics during pneumoperitoneum in the form of decreasing the peak pressure (Ppeak) and plateau pressure (Pplat) and improving the dynamic compliance, but the mean pressure (Pmean) was increased; it also increased the partial pressure of oxygen  significantly. No statistical significance was found regarding the demographic data or the hemodynamics.The study was a prospective randomized controlled trial and was performed between April 2019 and March 2020. After the approval of the departmental ethical committee and the informed written consent had been taken from the patients, fifty-two obese patients undergoing laparoscopic sleeve gastrectomy were enrolled in this study. After endotracheal intubation, the patients were randomly divided into the IRV group (IRV is superior to conventional VCV in morbidly obese patients undergoing laparoscopic sleeve gastrectomy as it improves respiratory mechanics and oxygenation. The WHO categorizes obesity as grade I obesity , dyslipidemia, gastroesophageal reflux disease (GERD), anxiety, and depression  results in a cephalad shift of the diaphragm, which leads to a decrease in lung volume and atelectasis  or respiratory rate, as the high airway pressure may not allow a further increase in VT, and increasing the respiratory rate sometimes fails to correct hypercapnea. Thus, COProlongation of inspiratory to expiratory ratio has become an alternative strategy for improving gas exchange and respiratory mechanics. This strategy is used in surgical patients with reduced lung compliance due to surgical factors during general anesthesia as well as critical patients with acute respiratory syndrome  with inspiratory to expiratory (I:E) ratio of 2:1 could improve oxygenation as a primary outcome in morbidly obese patients undergoing laparoscopic sleeve surgery, and the effect of IRV on respiratory mechanics  and hemodynamics as a secondary outcome2, ASA II and III. We excluded patients with age more than 45 years and less than 21 years, BMI higher than 50kg/m2, ASA class IV, severe intraoperative bleeding affecting hemodynamics, and operations that extended more than 60 min. The 52 patients were randomly divided into 2 groups: IRV (n=26) and VCV (n=26).The study was a prospective randomized controlled trial and was performed between April 2019 and March 2020. After the approval of the departmental ethical committee and the informed written consent had been taken from the patients, we chose a total of 52 morbidly obese patients for a laparoscopic sleeve gastrectomy in reverse Trendelenburg position, from 21 to 45 years old, ranging BMI between 35 and 50 kg/m2 blockers ranitidine 50 mg. Monitoring, including electrocardiogram, invasive blood pressure, pulse oximetry, and venous access, was established. After preoxygenation for 3–5 min, anesthesia was induced with intravenous fentanyl 1–2 ug/kg lean body weight (LBW), propofol 2 mg/kg LBW given over 15 s, and atracurium 0.50 mg/kg ideal body weight (IBW), followed by paracetamol 10mg/kg IBW. After tracheal intubation using a direct laryngoscope, capnography was established and the lungs were ventilated with a Datex-Ohmeda Aespire anesthesia ventilator. Ventilation parameters were set as tidal volume 8 mL/kg ideal body weight, respiratory rate 12 breaths/min, 0 PEEP, fraction inspired oxygen (FiO2) 0.6, oxygen flow 2 L/min, inspiratory pause 10%, and an I:E ratio of 2:1 (in the IRV group) or 1:2 (in the control group). Anesthesia was maintained with 1.5–2.5 vol% end-tidal isofluorane to keep control of the hemodynamic response (blood pressure and heart rate) within a 25% range of the preoperative value. Trocars were placed in a supine position. Pneumoperitoneum tension was set at 15 mmHg. Lactated Ringer’s solution was infused at a rate of 6–8 mL/kg/h throughout the study. The same team of surgeons conducted the operations and were unaware of the patient’s study group. After surgery, all patients were extubated at the operation room and transferred to the post-anesthesia care unit.In the OR, all patients were premedicated with prokinetics intravenous metoclopramide 20mg and HLung mechanics readings including peak pressure (Ppeak), plateau pressure (Pplat), and mean airway pressure (Pmean) were recorded every 10 min till the end of the first hour; also, dynamic and static compliance of the respiratory system were calculated after intubation and every 10 min until the end of the first hour: static compliance = tidal volume/Pplat − PEEP and dynamic compliance = tidal volume/Ppeak − PEEP.Hemodynamic parameters, mean arterial blood pressure (MAP), and heart rate (HR) were monitored at the start and all through the procedure and recorded before anesthesia induction (T0), immediately after intubation (T1), before pneumoperitoneum (T2), after pneumoperitoneum (T3), and then every 10 to 60 min.every 10 min in the first hour for arterial oxygen tension .Arterial blood gas was analyzed using a blood gas analyzer at T0 and 2) as a primary outcome to compare the effect of the two methods of ventilation. Using two independent samples t test with expected large effect size (0.8), a level of significance of ≤0.05, and a power of 0.80, a sample size of at least 26 cases per group is needed. The patients were randomized using a random number table and the use of a closed envelope technique which was employed to allocate patients between the two groups.In this clinical trial, we have used oxygenation  version 22.0. Quantitative data were expressed as mean ± standard deviation (SD). Qualitative data were expressed as frequency and percentage.The following tests were used:t test of significance was used when comparing between two means.▪ The independent-samples χ2) test of significance was used in order to compare proportions between two qualitative parameters.▪ The chi-square P-value <0.05 was considered significant.P-value <0.001 was considered as highly significant.P-value >0.05 was considered non-significant.▪ Probability , and there was no statistically significant difference in the duration of surgery as shown in Table Statistical analysis for demographic data for the two groups revealed that there was no statistically significant difference  and T1 (just after intubation) , but starting from T2 (just before pneumoperitoneum) to T6 after (60 min), there was a statistically significant difference in PO2 between the two groups as seen in Table Regarding PORegarding the peak airway pressure, our study showed that there was a statistically significant difference between the two groups with generally lower peak airway pressure at the study group (IRV) than the control group (VCV) as shown in Table P-value <0.05) with lower plateau pressure in the study group than in the control group as shown in Table The results of the study including plateau pressure revealed a statistically significant difference between both groups through all times  with the study group higher than the control group as shown in Table As regards the mean airway pressure, this study revealed that there is a statistically significant difference between the two groups  between the two groups at all times as seen in Table In comparison with the results of this study as regards the dynamic compliance (CD), we observed a statistically significant difference . A person with a BMI of 20–25 kg/m2 is normal, whereas a BMI of 26–29.9 kg/m2 is called overweight. A patient with a BMI of 30–39.9 kg/m2 is defined as obese and is counted as extreme/morbid obese with a BMI > 40 kg/m2. An individual with a BMI > 50 kg/m2 is superobese, and if with a BMI > 60 kg/m2 is supersuperobese. The risk of developing obesity-related conditions is based on BMI, the higher the BMI, the higher the risk  by the height in meters squared   to the conventional volume-controlled ventilation with an I:E ratio of 1:2 in morbidly obese patients undergoing laparoscopic sleeve gastrectomy operations. The study reveals an increase in arterial PaO2 and mean airway pressure and a decrease in peak and plateau pressures, with no statistically significant changes in hemodynamics  did not affect hemodynamics (Sinha et al. To our knowledge, this study is the first to assess the inverse ratio volume control ventilation in bariatric surgery with reverse Trendelenburg position; all previous studies either used the pressure-controlled mode or just prolonged the I:E ratio; according to the metanalysis done by Souza et al., there is no advantage of PCV above VCV in morbidly obese patient ventilation.The limitations of our study is that detection of atelectasis was not included as oxygenation alone is not an indicator of atelectasis in pneumoperitoneumIn conclusion, this study found out that IRV of volume control mode is superior to conventional ratio VCV in morbidly obese patients undergoing laparoscopic sleeve gastrectomy as it increases the lung compliance, partial pressure of oxygen, and mean airway pressure together with a decrease in peak and plateau pressures.


Portosystemic collateral vessels are a sign of portal hypertension in liver cirrhosis. Esophageal collateral veins (ECVs) are one major type of portosystemic collateral vessels, which increase the recurrence of esophageal varices and bleeding after variceal eradication. However, the risk factors for ECVs were still unclear.  We retrospectively screened cirrhotic patients who had contrast-enhanced computed tomography (CT) images to evaluate ECVs and upper gastrointestinal endoscopic reports to evaluate gastroesophageal varices at our department. Univariate and multivariate logistic regression analyses were performed to explore the independent risk factors for ECVs. Odds ratios (ORs) were calculated. Subgroup analyses were performed in patients with and without previous endoscopic variceal therapy which primarily included endoscopic variceal ligation (EVL) and endoscopic injection sclerotherapy (EIS). p = 0.026), previous EVL , platelet , and esophageal varices needing treatment (EVNTs) . The prevalence of ECVs was 60.8% (73/120) in patients undergoing EVL, 50% (10/20) in those undergoing EIS, and 47.5% (48/101) in those without previous endoscopic variceal therapy. The independent risk factors for ECVs were the use of nonselective beta-blockers  and EVNTs  in subgroup analyses of patients with and without previous endoscopic variceal therapy, respectively.  Overall, 243 patients were included, in whom the prevalence of ECVs was 53.9%. The independent risk factors for ECVs were hepatitis C virus infection (OR = 0.250,  The presence of ECVs should be closely associated with the severity of portal hypertension in liver cirrhosis. Risk of ECVs might be increased by previous EVL. Esophageal varices (EVs) are the most common collaterals in advanced cirrhosis that are located inside the esophageal lumen . BleedinEsophageal collateral veins (ECVs) refer to the portosystemic collateral vessels outside the esophageal lumen . Individk (2019) 35.In this single-center retrospective study, we screened cirrhotic patients who underwent both contrast-enhanced computed tomography (CT) and upper gastrointestinal endoscopy between December 2014 and May 2019. The data were derived from our prospectively established database collecting cirrhotic patients admitted to our department. This study was approved by the medical ethical committee of our hospital, and the approval number was The inclusion criteria were as follows: (1) patients were diagnosed with cirrhosis according to the medical history, clinical features, laboratory, and/or imaging results and (2) both endoscopic examinations and contrast-enhanced CT scans were performed at their admissions. Patients whose contrast-enhanced CT images were not well preserved were excluded.γγ-glutamine transferase (GGT), blood urea nitrogen, creatinine (Cr), sodium, potassium, prothrombin time (PT), activated partial thromboplastin time, and international normalized ratio (INR). EVL was performed by ligation device MBL-6-F . The drug used during EIS was polycinnamyl alcohol . We also recorded the use of nonselective beta-blockers (NSBBs) within 1 month before admission. The Child-Pugh and model for end stage of liver disease (MELD) scores were calculated as follows  + 3.78 × ln [TBIL (µmol/L) × 0.058] + 11.2 × ln(INR) + 6.43.Child-Pugh score = ALB score + TBIL score + INR score + ascites score + HE score. MELD score = 9.57 × ln [Cr . We were blind to endoscopic findings before analyzing the CT images. ECVs were defined as enhanced dilated vascular shadow surrounding the esophagus at the portal vein phases of contrast-enhanced CT images .As for the patients who underwent endoscopic variceal therapy, the endoscopic findings regarding EVs would be extracted, if endoscopic examinations were performed after contrast-enhanced CT scans during the same hospitalizations; by contrast, the endoscopic findings would not be extracted, if endoscopic examinations were performed before contrast-enhanced CT scans during the same hospitalizations. As for the patients who did not undergo endoscopic variceal therapy, the endoscopic findings regarding EVs would be extracted regardless of the order of contrast-enhanced CT and endoscopy. EVs needing treatment (EVNTs) include moderate and severe EVs that are diagnosed according to the Chinese consensus regarding management of gastroesophageal varices . In detaU test. Categorical variables were expressed as frequencies and percentages and compared by Chi-square tests. A two-sided p < 0.05 was considered statistically significant. Univariate and multivariate logistic regression analyses were used to identify the risk factors of developing ECVs. Variables with a p < 0.1 in univariate analysis were included in multivariate analyses. Only one of the variables with collinearity was selected in multivariate analyses. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed in patients with and without history of endoscopic variceal therapy. Statistical analyses were performed using the SPSS software version 20.0 .Continuous variables were expressed as mean ± standard deviation and median (range) and compared by using Mann–Whitney A total of 243 cirrhotic patients who underwent contrast-enhanced CT and upper gastrointestinal endoscopy at the same hospitalization were included . Among tp = 0.011) and levels of WBC (p < 0.0001), PLT (p < 0.0001), AKP (p = 0.014), and GGT (p = 0.042) and higher proportions of EVs (p < 0.0001), EVNTs (p = 0.002), and previous EVL (p = 0.044) and levels of INR (p = 0.005), PT (p = 0.005), and MELD score (p = 0.017) than those without ECVs (Patients with ECVs had significantly lower proportion of hepatitis C virus (HCV) infection , previous EVL , PLT , and EVNTs  were independently associated with ECVs  and levels of WBC (p = 0.036), PLT (p = 0.014), AST (p = 0.045), AKP (p < 0.0001), and GGT (p = 0.008) and higher levels of Cr (p = 0.010) and MELD score (p = 0.018)  .p = 0.042) was independently associated with ECVs  and PLT (p = 0.003) and higher proportions of EVs (p < 0.0001) and EVNTs (p = 0.002) and levels of INR (p = 0.007) and PT (p = 0.010)  .p = 0.006) was independently associated with ECVs (Univariate logistic regression analyses showed that ascites, PLT, EVs, and EVNTs were significantly associated with ECVs. Because there is a collinearity between EVs and EVNTs, only EVNTs were included in the multivariate analyses . Multivaith ECVs .The present study showed that HCV infection, a low PLT count, presence of EVNTs, and previous EVL were independently associated with ECVs in cirrhosis.EVL and EIS were the common endoscopic variceal therapy approaches for controlling variceal hemorrhage and preventing from first or recurrent bleeding from high-risk varices. Current guidelines recommend EVL as the preferred endoscopic therapy because EVL may be superior to EIS in terms of complications and patients' outcomes , 15. In NSBBs are recommended as another first-line therapy for preventing variceal bleeding in patients with high-risk varices because it could significantly reduce portal pressure , 19. BesEVs and ECVs, the common types of portosystemic collateral veins, were one of the common consequences of portal hypertension , 21. AccMost previous studies have suggested that the presence of ECVs may be associated with the recurrence of EVs . HoweverThere were several limitations in our study. First, this was a single-center retrospective study, in which selection bias and data missing were inevitable. Second, we employed CT scans, but not endoscopic ultrasonography. Thus, the types of ECVs could not be accurately classified. Third, CT images are not ideal in a few patients, in whom ECVs and EVs were not clearly distinguished on CT scans. Fourth, ECVs mostly appear as irregular blood vessel clusters on CT scans, so we cannot measure the diameter of ECVs and record the changes of ECVs.In conclusion, the presence of ECVs was closely associated with the severity of portal hypertension indicated by lower PLT count and EVNTs. Additionally, EVL might induce the development of ECVs; by comparison, EIS might be more effective for eliminating ECVs. Further prospective studies should be needed to confirm this finding.