Background and Objectives: Calcifying fibrous tumor (CFT) in the stomach is extremely rare and is easily misdiagnosed as a gastrointestinal stromal tumor (GIST). This study aims to determine the best method to differentiate between gastric CFT and GIST after a systemic review and meta-analysis. Materials and Methods: A systematic search of articles using electronic databases  was conducted and resulted in 162 articles with 272 CFT cases published from January 1988 to September 2019. Results: Of these cases, 272 patients, 60 patients with gastric CFT  were analyzed. The mean tumor size was 2.4 cm in patients with gastric CFT. Both endoscopic ultrasound (EUS) and computed tomography (CT) findings revealed well-defined (100% vs. 77.8%), heterogeneous (100% vs. 77.8%), iso-hypoechoic (71.4% vs. 33.3%), and calcified (85.7% vs. 77.8%) lesions, respectively. The majority of patients (53.3%) were symptomatic, with the most common symptom being abdominal discomfort (55.6%). None of the patients with gastric CFT showed recurrence after treatment, and most patients received nonendoscopic treatment . Both age and tumor size were statistically significant in patients with gastric CFT than GIST . The ratio of children among patients with CFT (5%) and GIST (0.05%) was also significantly different (p = 0.037). The calcification rates of gastric CFT had significantly higher calcification rates than GIST on images of EUS and CT . Conclusions: Compared with patients with GIST, patients with gastric CFT were younger, had smaller tumor size, and were symptomatic. Furthermore, gastric CFT was well-defined, heterogeneous in the third layer, and had high calcification rates on the images. A submucosal tumor (SMT) is a term used by endoscopists to depict any protuberance with intact mucosa. The etiology of most SMTs cannot easily be determined by esophagogastroduodenoscopy (EGD), computed tomography (CT), magnetic resonance image, or barium radiography . HoweverThere are no original studies regarding the comparison of CFT and GIST until now. Gastric CFT has been only infrequently discussed and sparsely investigated in the literature. Whether it could be differentiated from GIST remains uncertain, especially in preoperative surveys. Therefore, this study evaluates the clinical characteristics, including age, tumor size, stomach layer, symptoms, treatment choice, and gastric CFT imaging findings from the literature search, and compared these data with GIST.Our study followed the methods used in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Eligibility criteria were specified clearly to ensure that studies were selected in a systematic and unbiased manner. We included case series studies and retrospective cohort studies. The patient population was defined as adults or children (≤18 years old) diagnosed with CFT in any part of the stomach. A search was conducted to identify studies that involved patients with CFT in the stomach. Additionally, studies had to include CFT found at autopsy.We identified studies by searching electronic databases and then consulting with experts in the field. The search was performed using multiple databases, including PubMed (1988 to September 2019), EMBASE (1990 to September 2019), and LILACS (1987 to September 2019). A proficient research librarian provided the following predefined list of search terms and medical subject headings: calcifying fibrous tumor, calcifying fibrous pseudotumor, fibrous pseudotumor, childhood fibrous tumor with psammoma bodies, children fibrous tumor with psammoma bodies, pediatric fibrous tumor with psammoma bodies. No language restrictions were imposed on these searches.A double review process was applied to review the abstracts of all citations verified in the searches. After duplicate outcomes were removed, potentially relevant articles were included based on their full text. Additional studies were obtained from references of the selected articles. Controversial results were resolved by consensus among the senior authors (J-GP). Only studies fulfilling the eligibility criteria were included in this systematic review.The intended summary measure of treatment or imaging findings might have differed from that used in some studies. Therefore, we prespecified the summary measure of treatment and imaging findings. We divided these treatments into four categories: intervention (endoscopic treatment), diagnostic treatment , minor operation (resection), and major operation . For imaging findings with different interpretation results, all the image findings were re-evaluated by our radiologist. Additionally, calcification was divided into two groups in CT: macrocalcification  and microcalcification .t-tests were performed. Differences were assessed by the chi-squared test or Fisher’s exact test. A p-value of <0.05 was considered statistically significant. SPSS 19.0 statistical software  was used to perform all statistical calculations.Continuous variables were expressed as valid percentages and mean values with the standard deviation. For univariate analyses, n = 113), cases with gastric CFT but not the primary lesion (n = 2), articles not obtainable (n = 2), and articles not published in English (n = 15). No randomized controlled trial was included in the review. Finally, 30 full-text articles [A total of 306 records were identified . Three aish n = 1. No randlish n = . No randarticles ,32,33,34n = 5) and case reports (n = 25). A total of 60 patients with gastric CFT were evaluated in this study, ranging from 5–77 years. In most cases, the follow-up was conducted for >six months.Most eligible studies (85%) were published in the last decade. The designs of the studies we included were retrospective studies (p < 0.001). Fifty-eight cases mentioned the size of the tumor with a mean tumor size of 2.4 cm, which, compared with GIST, was also statically significant (p < 0.001). Three cases (5%) were children, and the ratio was significantly different from GIST (0.5%) [p = 0.037) (The mean age was 49.2 ± 13.9 years. The age distribution compared with GIST is shown in T (0.5%)  (p = 0.0= 0.037) .n = 32, 53.3%). Thirteen patients mentioned the period of symptoms, and three of them were acute, and 10 were chronic. Ten patients had ≥two symptoms, seven patients had double symptoms, and three patients had triple symptoms. Therefore, a total of 45 symptoms were analyzed. The most common symptom was abdominal discomfort . This symptom was followed by abdominal pain (17.8%), and abdominal distention (8.9%). The distribution of the leading symptoms is shown in Seven different leading symptoms for gastric CFT were detected. Most patients were symptomatic . Five patients’ tumors were in the mucosa/muscularis mucosa, eight patients’ tumors were in the muscularis propria, and two patients’ tumors were in the serosa  were in the body of the stomach. Thirty-four patients mentioned the layer of the tumor in the stomach. There are five distinct layers of the stomach on endoscopic ultrasound (EUS). Most tumors were located in the submucosa (e serosa .n = 7) were heterogeneous and well-defined. Most patients had tumors that were iso-hypoechoic (71.4%) and acoustic shadowing (71.4%)  .Fourteen patients received CT, and five patients were excluded . The tumors of the remaining nine patients were mostly were well-defined (77.8%), heterogeneous (77.8%), homo-hyperdense (66.7%), and with calcification (77.8%). In patients with calcification, most (85.7%) were macrocalcification  .p < 0.001)  had calcification. The overall calcification rate was 85.7% . We comp< 0.001) .n = 23, 46%), followed by intervention (36%), a major operation (12%), and diagnostic treatment (8%). More than half the patients  received nonendoscopic treatment.A total of 50 patients mentioned the choice of treatment . Most patients received a minor operation (n = 7/7), iso-hypoechoic , and calcification ; (ii) the most common findings in CT were well-defined , heterogeneous , homo-hyperdense , and calcification ; (iii) most patients  were symptomatic with a leading symptom of abdominal discomfort; (iv) most patients  received nonendoscopic treatment; (v) all patients (n = 60) did not recur after treatment; and (vi) CFT is statically different from GIST in age, size, and imaging calcification rate. Thus, CFT should be differentiated from GIST from clinical characteristics.Our study is the first to discuss gastric CFT as a differential diagnosis of GIST. We systematically reviewed the size, symptoms, imaging findings, and treatments of gastric CFT. We conducted a systemic search of the articles and reviewed 30 publications. We found that (i) the most common findings in EUS were heterogeneous . The high ratio of children ratio with CFT may be because of genetic and/or embryologic factors. Fukunaga et al. discovered a diploid DNA in a 20-year-old female patient [In our study, the ratio of children with CFT was 5%, which was statically different from GIST. One pooled population-based cohort study of GIST included 3480 patients with 0.37%, 14.9%, and 84.7% of ages 20, 20–50, and over 50 years, respectively . HoweverTumor size was significantly different between gastric CFT and GIST. This difference may be because gastric CFT has a benign character and grows slowly . Most paDiagnostic methods include EUS, CT, fine-needle aspiration (FNA), and mucosal biopsy. Clinical diagnosis of CFT is challenging; however, some of these diagnostic methods may be helpful. EUS may help to differentiate CFT from GIST. CFT consists of hyalinized collagenization with scattered calcifications consistent with the most common findings in EUS (heterogeneous and iso-hypoechoic) rather than anechoic or hyperechoic in malignant GIST . MoreoveThe overall calcification rate of gastric CFT was 85.7% in this study, and all were macrocalcifications (on CT). However, macrocalcification in GIST is extremely rare; only a few case reports are published ,42. TherThe diagnostic yields of FNA in GIST are correlated with tumor size. The diagnosis of large gastric GIST in EUS-guided Trucut punch biopsies or EUS–FNA reached 50–70% . In smalA frozen biopsy could not diagnose GIST; however, it could differentiate CFT from GIST. The cytomorphology of GIST is predominantly spindle cell (70%) or epithelioid (20%) . In thesFinally, we suggested ESD for the treatment of gastric CFT. ESD appears to be a feasible and safe procedure in SMT . In 2013n = 1/28), which was higher as compared to the endoscopic therapy (0%). In general, gastric CFT is a rare and benign tumor that can be easily removed by a simple excision procedure [Occasionally, it is difficult to identify the exact resection area using conventional or laparoscopic surgery. Moreover, these surgeries may have operative complications, such as celialgia . In thisrocedure . A totalCurrently, limited knowledge is available for gastric CFT owing to the low number of reported cases (hundreds). There are a few limitations of this study that need to be addressed. Since no retrospective or prospective study was performed to compare the diagnosis between gastric CFT and GIST, the study and control groups may not have had adequate homogeneity. Moreover, only seven and nine patients were included in the EUS and CT image analysis, respectively, due to which selection bias could not be avoided. Additionally, since no study was performed to compare the choice of treatment in gastric CFT, the treatment suggestion was expert opinion. This study did not review non-English studies, and a total of 15 non-English articles (mostly in Japanese) were excluded. The retrospective nature of such studies makes them particularly susceptible to selection bias regarding the choice of patients that received interventions. In other words, patients that are diagnosed with gastric CFT but did not receive the intervention are not reported. Thus, making it difficult to determine the actual tumor size and demographics of gastric CFT.Furthermore, no information is available regarding the exact rate of calcification for GIST. The calcification rate of GIST used in this study was approximately 3.6%, which was calculated on the basis of the information collected from relevant articles. Thus, there might be a discrepancy in the actual calcification rate of GIST and the data used for comparison with gastric CFT in this study.In daily clinical practice, GIST is the most common SMT encountered by gastroenterologists and surgeons. The frequency of patients suffering from gastric CFT is comparatively less. Our detailed analysis suggests that a complete examination, including EUS and CT, should be performed for the cases of SMT that are suspected to be associated with GIST. This is particularly important for SMT cases involving children, middle-aged individuals (mean: 50 years old), small tumor sizes (~2 cm), third layer SMT observed in EUS, and calcification in EUS or CT. Further, these evaluations might provide additional information that will assist in distinguishing gastric CFT from GIST. In suspected cases of gastric CFT, a frozen biopsy performed during the endoscopic procedure might be helpful in differentiating a benign fibrous lesion from a spindle-cell lesion, except for the lesions that are large and the available sections might not be correct representatives. The management of such lesions depends on the final pathological diagnosis. The present study highlights the suitability of ESD/EFR in the diagnosis and differentiation of gastric CFT from GIST and treatment of gastric CFT regardless of the tumor size.In conclusion, knowledge regarding certain patient characteristics, particularly age, tumor size, symptoms, imaging findings, and pathology, will be instrumental in distinguishing gastric CFT from GIST. Such a differential diagnosis prior to surgery will be helpful for gastroenterologists and surgeons in preventing excess surgery, especially in cases involving small tumor sizes, young age, submucosal lesion, and macrocalcification in CT images. Alternatively, a frozen biopsy might be helpful for diagnosis, except in cases where the lesions are large and the sections may not be representative. Such cases are managed depending on the final pathological diagnosis. We recommend the use of ESD for the differential diagnosis and treatment of gastric CFT, which will get low cost, less morbidity and mortality, non-invasive nature of ESD, less rate of complications, better quality of life observed in patients undergoing ESD.


Increasing evidence have indicated the relationship between intestinal dysbiosis and hypertension. We aimed to evaluate the effect of the electroacupuncture (EA) on intestinal microbiota in patients with stage 1 hypertension.93 hypertensive patients and 15 healthy subjects were enrolled in this study. Applying a highly accurate oscillometric device to evaluate the antihypertensive effect of EA. 16S rRNA sequencing was used to profile stool microbial communities from Healthy group, Before treatment (BT) group and After treatment (AT) group, and various multivariate analysis approaches were used to assess diversity, composition and abundance of intestinal microbiota.Firmicutes and lower Bacteroidetes abundance were observed in the BT group compared to the Healthy group. And EA treatment significantly decreased the Firmicutes/Bacteroidetes ratio compared to the BT group. Moreover, at the genus level, there was an increased abundance of Escherichia-Shigella in patients with hypertension, while Blautia were decreased, and EA reversed these changes.In this study, EA significantly decreased the blood pressure (BP) of hypertensive patients. Higher abundance of Our study indicates that EA can effectively lower BP and improve the structure of intestinal microbiota which are correlate with the alteration of blood pressure by electroacupuncture.Trial registration: Clinicaltrial.gov, NCT01701726. Registered 5 October 2012, https://clinicaltrials.gov/ct2/show/study/NCT01701726 Hypertension is China's leading cause of cardiovascular diseases (CVD), including stroke, heart failure, coronary heart disease . BecauseExcept for heredity and environment, intestinal microbiota has increasingly been recognized as a main risk factor for hypertension. Changes in composition and dysbiosis of intestinal microbiota were observed in multiple hypertensive patients and animals . ResearcA total of 108 subjects were enrolled:93 hypertensive patients and 15 healthy. All patients received EA treatment. Among them, 29 of whom had feces collected before and after treatment. 15 normal people were also collected feces after enrollment. The study protocol was approved by Sichuan Regional Ethical Review committee of the Teaching Hospital of Chengdu University of Traditional Chinese Medicine (2012KL-003) and conformed to the ethical guidelines of the 1975 Declaration of Helsinki. Patients of essential hypertension were included and clear diagnosis according to the seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. Study participants were recruited from the third teaching hospital of Chengdu University of Traditional Chinese Medicine and its surrounding communities. Participants were enrolled if they fulfilled the following criteria: without aAfter inclusion, patients received 18 sessions of acupuncture treatment (3 times weekly for 6 weeks). Each session lasted 30 min. We chose bilateral acupoints of taichong (LR3), taixi (KI3), renying (ST9), neiguan (PC6) according to traditional Chinese medicine theory and based on review of the literature. Disposable stainless-steel needles were used in acupuncture treatments. Insertion was followed by stimulation performed by lifting and thrusting the needle combined with twirling and rotating the needle sheath to produce the sensation known as deqi .In addit24 h ambulatory blood pressure recordings were obtained by a highly accurate oscillometric device  within 24 h before acupuncture treatment and the second day of the final treatment respectively. The TM-2430 monitor measures blood pressure automatically, on the same principle as the conventional mercury sphygmomanometer, with a cuff and a microphone. The interval between measurements can be preselected, and BP readings are recorded on a data processor. Blood pressure measurements were taken automatically every 15 min from 8 AM to 10 PM and every 30 min from 10 PM to 8 AM. If a reading were considered faulty by the device, it was programmed to remeasure, which helped to avoid missing a measurement. The data from the device were then downloaded onto a computer for subsequent analysis. Before the study started, the investigators were trained for the appropriate use of the BP measurement device used in the study, and had to demonstrate proficiency according to the manufacturer’s instruction.A total 73 Stool samples were collected, of which 15 samples were from healthy, 29 samples were collected before acupuncture treatment and 29 samples were collected at the second day of the final treatment. Fecal genomic DNA was isolated from stool samples by using a QIAamp DNA Stool Mini Kit  according to the kit protocol with modifications. The quality of extracted genomic DNA was checked by using the 2% agarose gel, and the DNA concentrations were determined with QuantiFluor™-ST Handheld Fluorometer with Blue Channels . The extracted DNA was stored at − 20 °C.Bacteria within each sample were identified via 16S rRNA Sequencing. PCR amplification for the V4 hypervariable regions of the bacterial 16S rRNA gene was performed using the 515F forward (5′-GTGCCAGCMGCCGCGGTAA-3′) and 806R reverse (5′-GGACTACHVGGGTWTCTAAT-3′) primers. Nextera XT V2 index kit Sets A and B were used to barcode PCR products and the AMPure XP bead system  was used for purification. Barcoded DNA underwent quantification, normalization and pooling to develop sequencing libraries which were then sequenced on the Illumina MiSeq platform . The Quantitative insights Into Microbial Ecology (QIIME) v1.9.1 analysis tool was used to join and de-multiplex forward and reverse sequences. Using the Silva reference database, the open reference operational taxonomic unit (OTU) picking method was used for taxonomic assignments with a pairwise identity threshold of 97%. Prior to downstream analysis, the OTU table was rarefied to 3000 sequences/sample with no samples removed in this step. These OTUs were analyzed by global parameters (described below) including determination of diversity, evenness, richness, and relative abundance of the bacteria identified in each sample.www.majorbio.com). Chao1, Ace, Simpson and Shannon index were used for comparison of alpha diversity. Principle coordinates analysis (PCoA) (Bray–Curtis dissimilarity index) and partial least squares discriminant analysis (PLS-DA) were used to visualize the change of distribution patterns. The unpaired two-tailed t-test was used for comparisons between Healthy and Hypertension. The paired t-test was used for comparisons between BT group and AT group. Spearman’s correlation coefficients were used to assess bivariate relationships. All results with P < 0.05 between groups were considered statistically significant.Paired t-test were performed to compare the baseline and post-treatment blood pressure. 16S rRNA gene sequencing data was analyzed on the free online platform of Majorbio Cloud Platform  and diastolic blood pressure (DBP) were higher in the patients with hypertension, as shown in Table Among 397 patients screened, P < 0.001, P < 0.01, P < 0.05). While DBP and dDBP (daytime diastolic blood pressure) decreased significantly after EA treatment . nDBP (nighttime diastolic blood pressure) did not show any difference before and after treatment (P = 0.051).After the six-week EA treatment, the blood pressure of patients differed significantly Table . SBP . Each sample was normalized to an equal sequencing depth and clustering. After filtering the low abundant < 0.1%) OTUs, 870 OTUs were obtained at a 97% similarity level, from which 16 phyla, 30 classes, 55 orders, 98 families, 294 genera and 554 species were detected. Good's coverage was 99.82%, indicating the sequences identified in this study could represent the majority of bacterial sequences present in the samples. Although rarefaction curves of numbers of observed OTUs per sample suggested new bacteria would be expected with additional sequencing  and Chao1/Ace (species richness) index between the Healthy group, BT group and AT group Fig. : Fig. S2A Venn diagram was used to show the number of common and unique OTUs, thus intuitively describing sample similarity and overlap. The unique OTUs in the Healthy, BT, and AT groups were 10, 75 and 12 respectively. The common OTU number in three groups was 570, accounted for 92.08%, 68.75% and 74.51% of the total number of OTUs in the Healthy group (619), BT group (829) and AT group (765) Fig. a. 5 phylFirmicutes and Bacteroidetes were showed significant dissimilarities among three groups. Higher abundance of Firmicutes (P < 0.05) and lower Bacteroidetes abundance (P < 0.05) were observed in the BT group compared to Healthy group. And EA treatment significantly decreased the relative abundance of Firmicutes (P < 0.01) compared to BT group. Moreover, compared to Healthy group, the ratio of Firmicutes to Bacteroidetes was significantly increased in the BT group (P < 0.001) and reduced in acupuncture group (P < 0.05)  Fig. a.Fig. 4IBifidobacteriaceae and Lachnospiraceae. Bifidobacteriaceae in BT group decreased compared to the Healthy group(P < 0.05). In addition, lower Lachnospiraceae abundance were observed in the Healthy group compared to the BT group (P < 0.05).At the Family level Fig. c, differBlautia and Escherichia-Shigella. The relative abundance of Blautia in the BT group was significantly decreased compared to the Healthy group (P < 0.01), but increased after EA treatment (P < 0.05). In contrast, BT group showed greater abundance of Escherichia-Shigella than that in the Healthy group (P < 0.05) and EA treatment (P < 0.05) decreased the abundance of Escherichia-Shigella.At the genus level Fig. d, differf_Streptococcaceae  and g_Escherichia-Shigella  showed positive correlations with DBP. In addition, the negative correlations were observed for g_Lachnoclostridium  and g_Eubacterium hallii  with SBP. Moreover, g_Blautia were simultaneously found significant negative correlation with SBP  and DBP .We further assessed the correlation between the 10 most prevalent bacteria at family- and genus-level and blood pressure Fig. . The f_SFirmicutes and Bacteroidetes changed in the patients before treatment, while EA significantly reduced Firmicutes abundance and the ratio of Firmicutes to Bacteroidetes. Moreover, EA increased the relative abundances of Blautia and reduced that of Escherichia-Shigella compared with BT group. Therefore, we suggest that the mechanism of reducing blood pressure by EA might be closely related with structural changes of gut flora.There is convincing evidence suggesting that balance of intestinal microbiota is an important factor in hypertension although the mechanism is complex and in part unknown –23. In tP < 0.001) and DBP . This finding was similar with a randomized, controlled, assessor-blinded pilot trial to assess the effects of acupuncture on prehypertension and stage 1 hypertension, in which SBP was reduced 5.7 mmHg [This study showed that EA treatment at the aucpoints of taichong (LR3), taixi (KI3), renying (ST9) and neiguan (PC6) significantly decreased the SBP -salt hypertensive mice) [Firmicutes and a lower abundance of Bacteroidetes were exhibited in individuals with stage 1 hypertension compared to healthy group. These findings were in agreement with the findings of Nosheen et al., who have demonstrated higher Firmicutes/Bacteroidetes ratio in patients with grade 3 hypertension [In addition, our data showed that EA decreased the ratio of ysbiosis . The altrtension , 32, 33.ectively . Same reectively . In the ve mice) –37. In ortension . Thus, tBlautia and Escherichia-Shigella at genus level. Blautia is a group of bacteria that produces multiple SCFAs, including acetate [Blautia has been detected in hypertensive patients with preeclampsia compared to healthy, pregnant control subjects [Blautia was also negatively correlated with systolic BP in spontaneously hypertensive rats and healthy male volunteers [Blautia in EA group may be closely related to decreased blood pressure. Escherichia-Shigella is a group of gram-negative bacteria containing lipopolysaccharides (LPS) in their cell walls [Escherichia-Shigella after EA treatment may suggest an improvement inflammatory status of the host.Moreover, we observed the regulation of EA on  acetate , propion acetate , succina acetate . SCFAs a acetate , 41. Ace acetate . Another acetate . In addi acetate –44. Lowesubjects , which wlunteers , 47. In ll walls . It is kll walls , which ill walls –51. Bomfll walls , 52 descll walls . In thisF_Streptococcaceae,g_Eubacterium hallii and g_Lachnoclostridium were observed correlation with blood pressure. Gut Streptococcaceae is also associated with inflammatory bowel disease [Streptococcus from gut might involve in the formation of atherosclerotic plaque microbiota [Eubacterium hallii is a common member of the adult gut microbiota that can produce butyrate from lactate and acetate, and convert 1,2-propanediol to propionate [Eubacterium hallii increased energy expenditure and fecal butyrate concentrations, thus modifying bile acid metabolism of db/db mice. Lachnoclostridium, a species belonging to Lachnospiraceae, was also a butyrate-producing bacterium [We also identified a significant correlation between BP values and 5 microbial taxa in the family at genus level.  disease  and live disease . Moreovecrobiota . Eubacteopionate , 58. Udaopionate  demonstracterium , which cacterium .Ruminococcaceae, Clostridiales  were higher in non-treated hypertensive (SBP:153.1 ± 14.6) than normotensive (SBP:109.7 ± 7.1) [Clostridia in hypertensive rats in the colonic microbiota [Ruminococcaceae and Clostridiales should be enough attention in hypertensive patients.In addition, we noticed an interesting phenomenon that hypertensive patients seem to produce more types of bacteria, although the abundance of these bacteria is very low. Further analysis showed that most of these bacteria belong to rtension . Another7 ± 7.1) . An animcrobiota . TherefoAs to the underlying mechanism or the target of acupuncture, neuroendocrine immunity system may be considered as an important pathway. As we mentioned, the association between intestinal microbiota and the host are complex and bi-direction. On the one hand, intestinal bacteria can modulate the host by producing a wide range of metabolites  and by their own component. Some of these metabolites and the bacterial components are risk markers for hypertension, inflammation and metabolic syndrome. On the other hand, the metabolism of host can regulate the microbiota in gut. For instance, the colonocyte metabolism works as a control switch, mediating a shift between homeostatic and dysbiosis communities . Also, sThere were several limitations in this study. Firstly, we did not observe the long-term effect of EA on hypertension and intestinal microbiota. A study has reported that the antihypertensive effect of acupuncture could be decreased with the elapse of time . AnotherThe present study shows that electroacupuncture can effectively lower blood pressure and improve the structure of intestinal microbiota which are correlate with the alteration of blood pressure by EA. These findings could inspire future research for understanding the mechanism underlying the therapeutic effects of acupuncture on hypertension.Additional file 1: Fig. S1 Alpha diversity rarefaction curves of samples based on species-level OTUs.Additional file 2: Fig. S2 Analysis of principal coordinate analysis (PCoA) with the bray_curtis distance matrix on the OTU level.Additional file 3: Table S1. Unique OTUs in BT group.


The biomarker fibroblast growth factor-23 (FGF-23) has been associated with increased cardiovascular morbidity and mortality in both patients with and without type 2 diabetes. The aim of this study was to evaluate the relationship between FGF-23 and cardiac structure, function and perfusion in patients with type 2 diabetes and normal or mildly impaired kidney function. Furthermore, to investigate the association between FGF-23, anti-diabetes therapy and the classic complications and risk factors associated with type 2 diabetes.2 were excluded.In this cross-sectional study, 246 patients with type 2 diabetes underwent echocardiography and advanced cardiac magnetic resonance imaging to assess left ventricular (LV) structure and function. In addition, myocardial blood flow (MBF) during rest and pharmacological stress (adenosine 140 µg/kg/min) were evaluated in 183 of the patients. Patients with eGFR < 60 ml/min/1.73 m2 = 0.11) and increased E/e* . FGF-23 was lower in patients receiving glucagon like peptide-1 (GLP-1) analogues (71 (57–86) vs. 80 (60–98) ng/L, P = 0.01) than in those who did not receive GLP-1 analogues.Median (Q1–Q3) FGF-23 was 74 (58–91) ng/L. Patients with FGF-23 above the median had lower MBF during stress  and lower overall myocardial perfusion reserve (MPR) . LV mass  and E/e*  were higher in patients with FGF-23 above the median. In a linear model adjusted for age, sex, eGFR and hypertension, increasing FGF-23 was associated with decreased MPR (P < 0.01, RIn patients with type 2 diabetes and normal or mildly impaired kidney function, increased levels of FGF-23 are associated with impaired cardiac diastolic function and decreased MPR, caused by a decrease in maximal MBF during stress. Use of GLP-1 analogues is associated with decreased levels of FGF-23.Clinical trial registrationhttps://www.clinicaltrials.gov. Unique identifier: NCT02684331. Date of registration: February 18, 2016 The link between type 2 diabetes and cardiovascular disease is well established. In patients with type 2 diabetes, the risk of developing coronary artery disease (CAD), heart failure, and cardiovascular death is significantly increased compared to those without type 2 diabetes , 2. The 2 (contraindication to the contrast agent gadolinium) were excluded from the original study cohort. In patients with chronic kidney disease, FGF-23 can rise to very high levels. To reduce the risk of confounding, we further excluded patients with eGFR < 60 ml/min/1.73 m2 in this study, and only examined those with normal or mildly impaired kidney function. Prior to participation, all patients gave written informed consent. All patients underwent clinical examination including evaluation of diabetes complication status, echocardiography, CMR and blood- and urinary sampling. Information regarding patient medication, history of smoking, coronary artery disease, hypertension and duration of diabetes were collected from the electronical patient journal or reported by the patients themselves. Hypertension was defined as clinical blood pressure > 140/90 mmHg after 10 min of rest or as an active prescription of antihypertensive medication. Coronary artery disease was defined as angiographically verified coronary stenosis, previous myocardial infarction/percutaneous coronary intervention/coronary artery bypass graft or ischemic lesions on late gadolinium enhancement (LGE) CMR. Albuminuria was defined as a urinary albumin/creatinine ratio (UACR) > 30 mg/g and retinopathy was evaluated from the patients’ latest fundus photography, routinely performed in the diabetes outpatient clinic. Autonomic nervous function was evaluated using orthostatic blood pressure measurements and beat-to-beat variation. Autonomic neuropathy was diagnosed in patients with a decrease of 25 mmHg or more in the orthostatic systolic blood pressure measurement [The study was conducted at the Department of Cardiology and Endocrinology, Slagelse Hospital, and at the Department of Radiology, Næstved Hospital, Denmark. It was approved by the local ethics committee, Region Zealand, Denmark (SJ-490) and complied with the declaration of Helsinki. Detailed information about the study design and study cohort has previously been published . In shorsurement  or with surement . Periphe1 maps were acquired at similar positions as the perfusion sequences, using a breath-held Shortened Modified Look-Locker Inversion (ShMOLLI) recovery sequence. Native T1 mapping was performed prior to the stress perfusion scan; post-contrast T1 mapping was performed 10 min after contrast injection and just before the rest perfusion scan. LGE images were acquired using a phase sensitive inversion recovery reconstruction sequence. LGE images were acquired from the entire LV short axis stack and from the two-, three- and four-chamber views LGE lesions were considered positive if present in 2 or more views.2D Echocardiography was performed on a GE healthcare Vivid E9 cardiovascular ultrasound system, using a GE Vivid S5 probe. CMR was performed on a 1.5 T scanner  with spine- and cardiac coil, electrocardiographic gating and patients in the supine position. Detailed information about image acquisition and CMR sequence parameters has previously been published . Left ve1 map. The non-linear response of signal intensity to contrast agent concentration was corrected for based on the baseline signal intensity and T1 data [1 times and hematocrit values as previously described [CMR scans were analyzed with cmr42® . LV ejection fraction (LVEF), LV end-diastolic volume (EDV), LV end-systolic volume (ESV), LV stroke volume (SV), LV ejection fraction (LVEF), LV mass and LA max volume were analyzed as previously described . Quantif T1 data . Data we T1 data  was perf T1 data , was calescribed . ECV wasPatients had blood sampling performed just prior to the CMR scan. Following initial handling, the blood samples were immediately transferred to 1 ml cryotubes and stored at −80 °C for future usage. After a single freeze–thaw cycle, FGF-23 was analyzed on EDTA-plasma samples using a chemiluminescence immunoassay (CLIA) on a fully automated chemiluminescence analyzer, the Liaison XL .2-test or Fisher’s exact test, as appropriate. The general linear model was used for analysis of explanatory variables. Distribution of FGF-23 was skewed and logarithmically transformed for linear correlation. A two-tailed P-value < 0.05 was considered statistically significant. Statistical calculations were made in SAS Enterprise Guide v. 7.15 .Normally distributed continuous variables are expressed as mean ± SD and categorical variables as percentages. Skewed variables are expressed as median and interquartile range (IQR). Depending on the distribution, continuous variables were compared using an unpaired two-tailed student’s t-test or Mann–Whitney U test, and categorical variables were compared using the χ2 were excluded, leaving 246 patients in the final study cohort. Myocardial perfusion was measured in 183 of the 246 patients. In the entire cohort, FGF-23 ranged from 18.9 to 219.4 ng/L with a median level of 74 (IQR 58–91) ng/L.In total, 273 patients with available FGF-23 measurements were included in the original study cohort. Twenty-seven patients with eGFR < 60 ml/min/1.73 mClinical characteristics of patients with FGF-23 below and above the median are presented in Table FGF-23 was significantly lower in patients treated with both GLP-1 analogues and insulin only or as combination therapy. Treatment with sodium-glucose cotransporter 2 (SGLT-2) inhibitors as monotherapy or in combination with GLP-1 analogues or insulin were not associated with any significant changes in FGF-23 concentrations. Table 2 = 0.11, P < 0.001)  . MPR and E/e* remained significantly associated with FGF-23 when the model was adjusted for age, sex, eGFR and known hypertension (P < 0.01 for both), whereas UACR lost its significance after adjustment. LV mass was not significantly associated with FGF-23 in a linear model.In a linear model, increasing FGF-23 was associated with decreased MPR In conclusion, increased levels of circulating FGF-23, in patients with type 2 diabetes and normal to mildly impaired kidney function, is associated with impaired cardiac diastolic function and decreased myocardial perfusion reserve, caused by a decrease in maximal myocardial blood flow during pharmacological vasodilator stress. Peripheral neuropathy is associated with higher concentrations of circulating FGF-23, whereas patients treated with GLP-1 analogues or insulin have lower levels of circulating FGF-23. Our results support a relationship between FGF-23 and imaging markers of diabetic cardiomyopathy, and FGF-23 has previously been proposed as a potential predictor of cardiovascular disease in patients with diabetes . These f


Effective control of blood pressure is necessary to avert the risk of cardiovascular diseases from uncontrolled hypertension. Despite evidence on the benefits of hypertension control, rates of control in Ghana remain low. This study assessed the patient-level factors that influence hypertension control among adults in Accra, Ghana.A total of 360 hypertensive patients from two hospitals in Accra, Ghana were enrolled in the study. Patient socio-demographic characteristics were tabulated and associations between patient characteristics and hypertension control were estimated using chi-square tests and logistic regression.Less than a quarter of the patients had a controlled blood pressure. The patient’s sex [AOR = 3.53 ], senior and junior high school [AOR = 2.64 (95% CI 1.40–6.66_] and AOR = 3.06 (95% CI 1.03–6.67)] and presence of a comorbidity [AOR = 2.41 ] predicted BP control among patients. Dyslipidaemia  an increased pill burden, and length of diagnosis of 2–5 years (AOR = 0.27 (0.1–0.73)] however, were associated with reduced BP control [AOR = 0.32(95% CI: 0.18–0.57)]. The majority of patients reported forgetfulness, side effects of medication and high pill burden as reasons for missing their medications.Knowledge of hypertension among patients is low. Sex, formal education and the presence of comorbidity and more specifically dyslipidaemia influences blood pressure control. High pill burden and 2–5 years since diagnosis negatively affects the attainment of blood pressure control. Hypertension is recognized as a public health issue worldwide. Despite the global policy agenda set to address this challenge, blood pressure control remains elusive and hypertension is the leading cause of cardiovascular disease (CVD) worldwide –4. AlthoUnlike more developed countries of the world, low and middle-income countries (LMICS) continue to experience significant mortalities from infectious diseases . The epiIn Ghana, the Ghana Health Service (GHS) 2014 Annual Report attributed the highest outpatient cases between 2011 and 2014 to hypertension. Within that same period, the Greater Accra and Ashanti region recorded the highest number of diagnosed cases of hypertension totalling 152,545 and 140,947 respectively. In Ghana, 63% of women and 86% of men that are hypertensive reported being unaware of their condition according to the Ghana Demographic Health Survey 2014 . As a prDespite the existence of extensive evidence on the benefits of hypertension treatment, control has been unsatisfactory , 11, 12.Control rates of hypertension vary widely across and within populations. Various studies have reported rates of 32.9–49% among similar population groups , 16–18. The Seventh Report of the Joint National Committee (JNC 7) recommends that all patients be classified as normal (120/< 80), pre-hypertensive (120–80 – 139/89), or hypertensive based on the level of the systolic and/or diastolic Blood Pressure (BP). Hypertension control is therefore achieved when a hypertensive individual attains blood pressure targets of less than 140/90 mmHg. For patients with co-morbidities such as diabetes and/or CKD, targets are set even lower at < 130/80 mmHg for beneficial treatment outcomes .Target 6 of the nine endorsed global NCDS targets, call for member states to achieve a 25% reduction in elevated blood pressure within their specific settings . ReducinThis was a cross-sectional survey of adult hypertensive patients attending two hospitals in the Greater Accra Region of Ghana.A total of 360 participants were interviewed in this study – 213 from the first and 147 from the second hospital respectively. Only adult subjects were included in the study (18 years and above).Inclusion criteria: Hypertensive patients who have been on treatment for not less than a year.Exclusion criteria: Pregnant women, patients who were taking drugs that could increase blood pressure and patients diagnosed with psychiatric conditions were excluded from the study.A list of hypertensive patients given appointments for each day was obtained from the records department of both facilities. Numbers were assigned to the individuals on the list. The numbers were randomly selected using the Excel random number generation. An average of 50 to 60 patients was booked for each clinic day for both facilities with the facility with a higher caseload contributing 30–35 per day.A written informed consent (signed or thumb printed) was obtained from each participant Respondents who were unable to read, write or sign nominated an independent witness to attest to the consent process. Data was collected using a structured questionnaire composed of four different sections  and the associated medications. Information about the taking of non-prescribed drugs was also obtained. A final knowledge score was obtained for each respondent out of 13. The categorisation of knowledge was based on a tercile distribution. The respondents were scored on their knowledge of a normal adult blood pressure and the number of causes and complications of hypertension they knew of. Scores of 9–13 (representing the upper third) were considered as having “Good knowledge”, scores of 5–8 (representing the middle third) were categorized as “Moderate knowledge” and scores of 1–4 (representing the lower third) were categorized as “Poor knowledge”.The next section assessed patients’ perceptions about the control status of their hypertension as well as their perception of the efficacy of antihypertensive medications being taken. The final section sought to assess patient level factors such as adverse effects experienced from the use of antihypertensive medication, high pill burden /polypharmacy, cost of medications, forgetfulness, and belief in divine intervention or belief in being cured of hypertension.The developed questionnaire was reviewed by subject matter experts for face and content validity for readability, clarity and comprehensiveness. Minor revisions were necessary. The tool was further revised, and pretested among hypertensive patients reporting for blood pressure management at a facility that served a similar population to the study areas. This was to determine performance in the field as planned .2 and fishers exact where appropriate. The hypertension control status of each patient was determined by calculating the average of all SBP and DBP readings recorded. Binary logistic regression was conducted on socio-demographic and patient level factors to determine their influence on hypertension control. All predictor variables were entered in the regression model at once. Blood pressure control in logistic regression was coded as 0 for poor control and 1 for optimal control. All analyses were conducted in STATA and statistical significance was set at a 95% confidence interval.Cross-tabulations of patient socio-demographic variables, factors influencing hypertension control were undertaken. A descriptive analysis was conducted using Pearson’s χEthical clearance was sought from the Ghana Health Service Ethical Review Committee with approval number (GHS-ERC: 037/12/17). Permission to conduct research at Ghana Health Service facilities was also sought from the Regional Directorate of Ghana Health Service, Greater Accra region and subsequently from the Municipal Directorates of both facilities.A total of 360 patients participated in the study. All participants resided in urban areas and were native Ghanaians. By sex, 105 males and 255 females were interviewed with the mean age of 61.9 (± 10.7) with ages ranging from 27 to 94 years. More than half of the respondents were aged over 61 years. Respondents were mostly married, and few had attained tertiary education (4.7%) . Table Less than a quarter of patients achieved hypertension control 23.3%). Various socio-demographic characteristics were assessed against hypertension control. By sex, among female respondents, 69 (27.1%) had achieved hypertension control and 15 (14.3%) of male respondents had achieved hypertension control. This association was found to be significant (.3%. Varip < 0.006). Table Assessing patients by comorbidity showed that 18% of patients who had no comorbidities had achieved hypertension control. However, more patients with some comorbidity had achieved hypertension control (23.3%). Among patients with dyslipidaemia, 8.9% had controlled hypertension ] compared to those who took 1 to 2 pills. (Table The findings of this study are indicative both of low knowledge of hypertension and blood pressure control among patients. Factors that were significantly associated with BP control were sex, education and the presence of comorbidity. Females achieved BP control more than their male counterparts, a finding in congruence with recent evidence from the Ghanaian setting , 20. ThiAlthough knowledge of hypertension in this study was critically lower than available estimates, it is inconsistent with reports indicating poor knowledge of hypertension among Ghanaians , 21, 26.In this study, blood pressure control was positively associated with junior high and secondary education compared to those with no formal education. A finding in contrast to recent district-level findings in Ghana but indicative of opportunities for health education among patients that have attained at least junior secondary education .A larger proportion of patients in this study with comorbidities did not achieve BP control. It is plausible, that comorbid patients, may have encountered challenges in observing the treatment for blood pressure control. This finding is similar to reported studies that highlight reduced BP control among patients with dyslipidaemia , 33. It Among patients who report taking 3–4 blood pressure pills per day, the observed reduction in control may be a result of the challenges of high pill burden. Similar results from more developed settings showed that patients who were on three or more antihypertensive pills were likely to miss their medication or have a treatment gap compared to those who were being treated on two pills . AlthougThe reported reasons for missed medications highlighted forgetfulness as the prime cause. For adult patients, it is plausible that forgetfulness is due to the competing psychosocial demands of daily life. Medication side effects, high pill burden, cost of medication, belief in divine intervention, belief that one is cured and distrust of orthodox medicine were reasons given by respondents for poor adherence. These reasons are nonetheless similar to those identified in a Nigerian study on hypertension medication adherence .Our study is not without limitations. First, information concerning knowledge and management of hypertension was self-reported lending itself to recall and information bias. All other patient history and comorbidity was reviewed from records. This study also does not control for the different treatment types being used by participants on treatment. We recommend that physician-patient communication on the importance of treatment for the control and improvement in the condition must be encouraged to foster awareness and adherence. There is also a need for treatment guidelines with an emphasis on the use of polypills to reduce pill burden and improve blood pressure control.This study concludes that knowledge of hypertension among patients is low. Although sex, formal education and the presence of comorbidity and more specifically dyslipidaemia influences blood pressure control. High pill burden negatively affects the attainment of blood pressure control. The study also adds to the growing body of evidence highlighting the consistently low rates of hypertension control in Ghana over the last decade .Additional file 1. English questionnaire developed for the study.


Artificial intelligence (AI), as an advanced science technology, has been widely used in medical fields to promote medical development, mainly applied to early detections, disease diagnoses, and management. Owing to the huge number of patients, kidney disease remains a global health problem. Challenges remain in its diagnosis and treatment. AI could take individual conditions into account, produce suitable decisions and promise to make great strides in kidney disease management. Here, we review the current studies of AI applications in kidney disease in alerting systems, diagnostic assistance, guiding treatment and evaluating prognosis. Although the number of studies related to AI applications in kidney disease is small, the potential of AI in the management of kidney disease is well recognized by clinicians; AI will greatly enhance clinicians' capacity in their clinical practice in the future. Kidney disease is a major public health problem in part because of its common etiology caused by diabetes, hypertension, obesity, and aging; the incidence of these conditions is increasing. According to the Global Burden of Diseases, Injuries, and Risk Factors Study 2015, 750 million people worldwide suffered from kidney disease AI is a science of computer simulated thinking processes and human behaviors, which involves computer science, psychology, philosophy and linguistics. In 2016, Alphago 3-0 won a professional human Go player. It was the first computer program that defeated a world champion of Go, clearly revealing the potential that AI will bring technological advances in the era. The continued rapid growth in computer-processing power over the past two decades, the availability of large data sets and the development of advanced algorithms have driven major improvements in machine learningElectronic medical records (EMR) provide large-scale and real-world clinical data, which is the basis for developing AI technology in the clinic. It is challenging for humans to directly analyze these massive data; this is not only because of the massive time required and cares needed to avoid human errors but also the ability to derive the insights or information in depth. Clearly, AI technology holds nonparallel advantages over humans in these domains A non-systematic review of the literature was performed by screening PubMed up to 1st of August 2019. Using the search terms including "artificial intelligence", "machine learning", “artificial neuron networks”, “deep learning”, "kidney Disease", "chronic kidney disease" , "acute kidney Injury" and “nephrology”.Literature was derived from English articles or articles that could be obtained with English abstracts. Studies of human dataset were included. References were also identified from the bibliographies of identified articles and the authors' files.Early prediction of deterioration can play an important role in supporting health care professionals, as an estimated 11 percent of hospital deaths follow a failure to promptly recognize and treat deteriorating patients It is reported that AI technology has an advantage in warning of critical illness, such as acute kidney injury (AKI) The traditional linear models require the statistical assumption of a liner relationship between the covariates and the risk of morbidity, and are often overfitting and multicollinearity. Machine learning approaches were introduced for better or comparable predictive ability than statistical analysis to predict postoperative outcomes. AI may offer opportunities for identifying patients at risk within a time window that enables early treatment Tomaše et al. build a model which can predict 55.8% of all inpatient episodes of AKI, and 90.2% of all AKI that required subsequent administration of dialysis by AI in 703,782 adult patients There are also reports of AI applications in alerting the occurrence of CKD. A pilot program using e-technologies to detect CKD was conducted in Australia . The software was built on algorithms trained to identify at-risk patients and to order a relevant screening test for CKD In addition, AI has also been studied in the early warning of complications of CKD. Galloway et al. reported that using only 2 ECG leads, a deep-learning model detected hyperkalemia in patients with renal disease with an AUC of 0.853 to 0.883. The application of artificial intelligence to the ECG may enable screening for hyperkalemia of CKD patients. However, the study is retrospective and need prospective testing. Additionally,the model is a screening test with low specificity, with upwards of 42% false-positive results, which may cause anxiety and inconvenience for patients.Besides, AI can also predict cost and mortality of patients. Lin et al. claimed that applying AI modeling could help to provide reliable information about one-year outcomes following dialysis in the aged and super-aged populations. They concluded that those with cancer, alcohol-related disease, stroke, chronic obstructive pulmonary disease (COPD), previous hip fracture, osteoporosis, dementia, and previous respiratory failure had higher medical costs and a high mortality rate Moreover, Eiichiro et al. identified factors of progressive CKD from healthy population at a health check point by using Bayesian network and artificial intelligence. They included hypertension, the time-series changes in the prognostic category of CKD, proteinuria and eGFR et al The high morbidity rate associated with kidney stone disease is one of the main concerns in healthcare systems. Kazemi Y et al. developed a model for the early detection of the type of kidney stone and the most influential parameters in 936 patients with nephrolithiasis. The final ensemble-based model (with an accuracy of 97.1%) could be safely applied to predict the chances of developing nephrolithiasis Whereas, the current studies are mainly retrospective analyses, and the applicability needs further verification. Moreover, it is reported that an ANN model using 3 variables did not perform better than a new regression model in improving GFR estimation Computer Aided Diagnosis (CAD) is a technology combined medical image and computer image processing to quantify and judge the characteristics of the focus, could assist clinicians to identify and analyze lesions timely and accurately Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common hereditary disease in kidney. It is characterized by progressive enlargement of the kidneys caused by progressive development of renal cysts, often accompanied by declining renal function It is often difficult for physicians to achieve preoperative differential diagnosis between renal cell carcinoma and some benign renal tumors by virtue of existing imaging techniques (including CT and MRI), such as adiposity angiomyolipoma Besides, Image genomics can complete genomic analysis in characterizing disease biology by extracting a large number of tumor image features through AI, and associating the image features with the underlying mutation status of tumors, molecular markers, underlying activated biologic pathways, or clinical outcomes by developing “association maps” between them What is more, Kuo et al. identified the CKD status defined by an eGFR of <60 ml/min/1.73 m2 based on 4,505 kidney ultrasound images by deep neural network (The AUC of the model is 0.904). A Pearson correlation coefficient of 0.741 and accuracy of 85.6% indicated the strong relationship between AI and creatinine-based GFR estimations Congenital abnormalities of the kidney and urinary tract (CAKUT) in children are a challenging task. A pre-trained deep learning model  is adopted for transfer learning-based feature extraction from 3-channel feature maps computed from ultrasound images. SVM classifiers are then built upon different sets of features, including the transfer learning features, conventional imaging features, and their combination. The AUC for classifiers built on the combination features were 0.92, 0.88, and 0.92 for discriminating the left, right, and bilateral abnormal kidney scans from controls with classification rates of 84%, 81%, and 87%; specificity of 84%, 74%, and 88%; and sensitivity of 85%, 88%, and 86%, respectively. It is suggested that the combination of transfer learning features and conventional imaging features yielded the best classification performance for distinguishing CAKUT patients from normal controls based on their ultrasound kidney images Renal interstitial fibrosis is an indicator of the presence and extent of chronic kidney disease. The standard quantitative method of visual evaluation is very important for the diagnosis of renal diseases. The Banff schema is one of the standards used for the renal allograft rejection grades classification. The visual scoring is subject to pathologists' intra- and inter-observer variability, may not be repeatable or reproducible. CAD can reduce the workload of pathologists, also has an advantage of precision and meticulousness. Wei et al.International Classification of Disease (ICD) codes is important for population health and cohort discovery when clinical information is limited. Sina Rashidian et al. used deep learning methods which based on demographics, lab results, and medications, as well as codes from previous encounters to model coder decision making. Three test cases were investigated including acute renal failure (ARF) and CKD, the AUC of predicting ARF and CKD were 0.9194 and 0.9424 separatelyGuidelines are the basis for decision-making, which are formulated through large-scale investigations. These guidelines are thus population-based and adjustments are needed using the guidelines on individual cases. Personalized and accurate treatment protocols are required. AI can analyze the association of treatment protocols and efficacy from a large number of patients, develop models based on efficacy and risk factors, guide the choice of treatment protocols, and improve clinical efficacy. Related studies on kidney disease are scanty, mainly in hemodialysis patients.Anemia is one of the main common comorbidities in patients undergoing hemodialysis. The incidence and severity of anemia are gradually increasing as renal function declining Substantial progress has been made in the application of computer-driven methods to provide erythropoietic dosing information for patients with anemia resulting from chronic kidney disease. Initial solutions were simply computerized versions of traditional paper-based anemia management protocols. True personalization was achieved through the use of advanced modeling techniques such as artificial neural networks, physiologic models, and feedback control systems Blood pressure (BP) and fluid volume are crucial points for patients undergoing hemodialysis. The prevalence of hypertension is 40-90% of patients with ESRD according to the BP definition used, the population selected, and the timing of measurement Dialysis is the main treatment for ESRD. Dialysis affects the patient's life in a wide range, and some patients cannot tolerate hemodynamic instability of intermittent dialysis, there are great expectations for the development of wearable artificial kidneys. Wearable dialysis devices can make the real-time analysis of equipment alarms, dialysis parameters, and patient-related data with a real-time feedback response. Martin et al. Robotics are also steadily being introduced in health care, especially in surgery, with systems such as the da Vinci® Surgical System that involves a magnified 3D high-definition computer vision system (part of it aided by ML) and tiny wristed instruments that bend and rotate more complexly than the human hand. An autonomous image-guided robotic needle insertion for blood draws and intravenous insertions has also been designed that combines robotics, AI, computer vision, and image technology Figure  77. It mAI can identify factors affecting prognosis by analyzing database, and develop models evaluating the relationship between factors and prognosis. In this section, we will summarize AI applications in evaluating prognosis involving several common kidney diseases.CKD-MBD is another common comorbidity in ESRD patients, which increases mortality. The serum concentrations of phosphate (P), calcium (Ca) or parathyroid hormone (PTH) are associated with negative outcomes. The three parameters, P, Ca, PTH, interplay of each other, but the relationship is non-linear. Classical statistical methods have no advantages on analyzing associations among variables non-linear but affected by non-trivial feedback loops. The machine learning seems to be a predictive analytic approach. To quantify the degree of association between the three parameters, Mariano et al developed a data analysis system by RF from 1,758 HD patients. Comparing with Classical statistical methods, the power of prediction of the new model was markedly increased IgAN is the most common primary glomerular kidney disease. About 20-40% of IgAN patients will reach ESRD within 10-20 years of diagnosis. Early prediction of ESRD is valuable. Liu et al. DKD is a common complication and a mainly cause of diabetes deaths. It is critical to identify the risk factors to stratify DKD risk to improve patient management. As early in 2013, Leung RK et al. used a multi-staged strategy based on machine learning and mathematical modeling to predict genotype-phenotype risk patterns in 119 DKD patients and 554 without DKD type 2 diabetic patients. They found out that age, age of diagnosis and lipid parameters were major clinical predictors while genetic polymorphisms related to inflammation and lipid metabolism were the most selected genetic predictors In 2018, Arianna et al. Kidney transplantation is another main treatment for ESRD. But only a few patients can receive kidney transplantation because the shortage of kidney and high technical requirements. Predicting the outcome of kidney transplantation is important to optimize transplantation parameters and modify factors related to recipient, donor, and transplant procedure. Lofaro et al. Several studies between 2008 and 2017 have demonstrated that although acute kidney injury is usually reversible, some patients may experience incomplete recovery of kidney function, while others subsequently develop accelerated loss of kidney function, resulting in an increased risk of chronic kidney disease 2+-EDTA carried the highest weights are predicting factors Norouzi et al. predicted renal failure progression in 465 CKD patients by using Integrated Intelligent Fuzzy Expert System and found out that the model could accurately (>95%) predict the GFR for sequential 6-, 12-, and 18-month intervals The study was carried out on a contemporary cohort of 27,615 US veterans with incident ESRD by implementing a random forest method on 49 variables obtained before dialysis transition to predict outcomes of 30-, 90-, 180-, and 365-day all-cause mortality after dialysis initiation. The results showed that the model provided C-statistics (95% CI) of 0.7185 (0.6994-0.7377), 0.7446 (0.7346-0.7546), 0.7504 (0.7425-0.7583), and 0.7488 (0.7421-0.7554) for predicting risk of death within the 4 different time windows It is noticeable that AI does not only play great role in Nephrology Figure , but als


Introduction: Uncontrolled and inadequately managed asthma substantially reduces Quality of Life (QOL) and can lead to premature death. The aim of this study is to understand the role of montelukast in improving quality of life in asthmatic patients by comparing it with placebo.Methods: This prospective, single-arm, interventional study was conducted from September 2019 to February 2020 in the pulmonology outpatient department of a tertiary care hospital in Pakistan. All patients were prescribed montelukast (10 mg once daily).Results: At day 28, participants had a higher score on the Asthma Quality of Life Questionnaire-Standard (AQLQ-S) overall and in all sub-domains compared to day 0. The improvement was significant overall and for the sub-domains of symptoms, activity limitations, and environmental stimuli.Conclusion: Montelukast has an effective role in asthma control as well as in improving the quality of life in the Pakistani population. Asthma is characterized by an airway reaction leading to reversible airflow obstruction in association with airway hyper-responsiveness (AHR) and airway inflammation . Asthma Management of asthma is crucial. Inhaled corticosteroids (ICS) prove to produce promising results, however leukotriene receptor antagonists (LTRAs) are becoming more and more popular these days due to feasibility of use. LTRAs in contrast to ICS do not predispose the patient to long-term adverse effects . LTRAs hIn Pakistan, fewer studies have been conducted that study the role of montelukast in the management of asthma. Hence our aim is to study its role to help pulmonologists manage asthma effectively by reducing the morbidity and mortality of the disease.This prospective, single-arm, interventional study was conducted from September 2019 to February 2020 in the pulmonology outpatient department of a tertiary care hospital in Pakistan. Both male and female asthmatic patients who were older than 15 years were enrolled in this study. Patients who presented with acute exacerbations of asthma and those who had previously taken montelukast were excluded from the study. All patients were given montelukast (10 mg once daily). Compliant patients were defined as those who took montelukast for at least 21 days. The patients were instructed to bring their strips on follow-up to ensure compliance.A total of 156 participants were enrolled and were followed for four weeks. Patients who weren’t followed-up were not included in the analysis. A self-structured questionnaire was used to record the participant’s age, gender, duration of asthma, and symptoms. Quality of life was evaluated using the Asthma Quality of Life Questionnaire-Standard (AQLQ-S) on day 0 and day 60. AQLQ-S has 32 items assessing four domains: symptoms, activity, emotions, and environment control. A higher score means a higher quality of life . Data were processed through and analyzed using SPSS for Windows version 23.0 . AQLQ-S mean and standard deviation (SD) were calculated for continuous variables such as age and AQLQ-S. Frequency and percentage were calculated for categorical variables including gender, age, duration of asthma, and symptoms. A comparison was done for scores of AQLQ-S on days 0 and 60 using dependent T-test. P-values of less than 0.05 meant there is a difference between AQLQ-S score on day 0 and day 60 and that the null hypothesis is void.At the start of the study, 156 asthmatic patients were included. During the study, one (0.6%) patient stopped taking montelukast due to an adverse event and 21 (13.4%) participants were not followed-up. The study was completed by 134 (85.9%) participants, who were included in the final analysis. All these participants were compliant. The mean age of participants included in the analysis was 22 ± 8 years, of which 68 (50.7%) participants were men and 66 (49.3%) were women. Their disease characteristics are shown in Table 1At day 28, participants had a higher score on the Asthma Quality of Life Questionnaire-Standard (AQLQ-S) overall and in all sub-domains compared to day 0. The improvement was significant overall and for the sub-domains of symptoms, activity limitations, and environmental stimuli (Table Montelukast is a leukotriene receptor antagonist. It reduces leukotriene D4 (LTD4) levels in the respiratory tract by competetively binding to the cysteinyl leukotriene receptor (CysLT1). LTD4 is a potent broncho-constrictor and CysLT1 attracts inflammatory cells. Normally, the binding of CysLT1 with LTD4 leads to allergic and hypersensitivity reactions, therefore montelukast plays a vital role in the management of asthmatic patients .In this study, there was significant improvement in the Asthma Quality of Life Questionnaire-Standard (AQLQ-S) overall. Among sub-domains, all domains had improved significantly except emotional function. The result is comparable to previous studies. Baig et al. in their double-blind trial compared montelukast with placebo. They found overall significant quality of life improvement, like our study; however, in their study only the environmental stimuli sub-domain of AQLQ-S had significant improvement compared to placebo . StudiesIn an experimental, double-blind, crossover study, researchers gave 20 mg of montelukast two times a day for almost a week to a group of patients and compared the results with the patients taking placebo. They reported that the symptoms produced by leukotriene E4 (LTE4) were significantly improved in the patients taking montelukast . This stNevertheless, there are various studies that support montelukast in the management of acute exacerbation of asthma as well as chronic asthma of varying severity. Montelukast ameliorates inflammation of the respiratory tract, as well as improves the overall symptomatology of the asthmatic patients. From various data available and our research on this topic, we can safely conclude that pulmonologists should consider using montelukast in the management of asthma as an add-on therapy with ICS or LABA to improve the overall morbidity and quality of life in asthma patients. Other studies should be done to compare if montelukast can replace ICS or not, as ICS has some long term side-effects. More studies are required to study the effect of montelukast on the mortality of asthma patients.In this study, there was significant improvement in overall Asthma Quality of Life Questionnaire-Standard (AQLQ-S). Among sub-domains, environment functions, symptoms, and activity limitations had significant improvement. It is important to consider the impact on quality of life of various treatment options available for asthma. Our study, along with various global studies, shows that montelukast is effective in improving patients quality of life.


Dyslipidemia confers excess atherosclerotic cardiovascular risk in type 2 diabetes mellitus (DM) patients, and this requires prompt identification and management to reduce morbidity and mortality. This study assessed the prevalence and pattern of dyslipidemia in type 2 DM patients in Zaria, Northwestern Nigeria.This was a cross-sectional study of newly diagnosed type 2 DM patients at Ahmadu Bello University Teaching Hospital (ABUTH), Zaria. Demographic, clinical and laboratory data were extracted from the case notes of eligible patients and analyzed using STATA version 14. Continuous variables were presented as mean ± standard deviation (SD), or median and interquartile range (IQR) while categorical variables were as frequencies and percentages. Student t and chi-square tests were used to test for association at p < 0.05.A total of 322 subjects  with a mean age of 53.5 ± 10.8 years partook in the study. The prevalence of dyslipidemia was 69.3%. Mixed dyslipidemia of high triglyceride (TG) and high low-density lipoprotein cholesterol (LDL-C) was present in 41.0%; high TG and low high-density lipoprotein cholesterol (HDL-C) in 2.8%; and high LDL and low HDL in 2.5%. Atherogenic dyslipidemia, isolated hypercholesterolemia and isolated low HDL-cholesterol were present in 3.4%, 2.5% and 23.6% respectively. Dyslipidemia status was not associated with age, sex, duration of DM or hypertension, obesity, and mean fasting blood sugar (FBS) and 2-hour postprandial glucose.The prevalence of dyslipidemia is high in the newly diagnosed type 2 DM patients and therefore, initial management should incorporate measures to control dyslipidemia. Atherosclerotic cardiovascular diseases (ASCVD) defined as coronary heart disease, cerebrovascular disease, or peripheral arterial disease presumed to be of atherosclerotic origin represents the largest proportion of cardiovascular diseases (CVD), and is a leading cause of premature mortality and disability-adjusted life years (DALYs) globally -3. In 20Study area: this study was carried out at the Ahmadu Bello University Teaching Hospital (ABUTH), Zaria, Northwestern Nigeria. ABUTH is a 500-bed capacity hospital that provides services to patients from Northern Nigeria and the neighboring countries of Niger and Chad Republics.Study design: this was a cross-sectional study of newly diagnosed type 2 DM patients who attended the Endocrine and Metabolism Clinic of ABUTH from 1st January 2016 to 31st December 2017.Study population: subjects were newly diagnosed type 2 DM patients aged 30 years and above. Patients with gestational DM, steroid-induced DM, thyroid disease or secondary dyslipidemia were excluded from the study.Data collection: demographic, clinical and laboratory data were retrieved from the case notes of patients who satisfied the eligibility criteria. Demographic data retrieved were age and sex, while clinical and laboratory data were: height, weight, waist circumference, duration of DM, blood pressure, duration of hypertension, fasting and 2-hour postprandial blood sugar over the last 3 months, fasting cholesterol level, fasting triglyceride level, fasting low density lipoprotein, fasting high density lipoprotein.Dyslipidemia: this was defined as serum total cholesterol level ≥ 5.2mmol/L and/or serum LDL cholesterol ≥ 2.6 mmol/L, and/or serum triglyceride ≥ 1.7 mmol/L, and/or serum HDL cholesterol < 1mmol/L for men or < 1.3mmol/L for women [or women . Atherogor women . Non-HDLor women , and athor women ,24, wereHypertension: hypertension was defined as a blood pressure recording of ≥ 140/90 mmHg on more than 1 hospital visit or a documentation of treatment with anti-hypertensive medications [ications .Type 2 diabetes mellitus: this was defined as documentation of fasting blood sugar ≥ 7.0 mmol/L or 2h postprandial blood sugar ≥ 11.1 mmol/L for the first time in a patient, with or without classical symptoms of DM; or presentation for the first time with symptoms of hyperglycemic crises and a documented random blood sugar ≥ 11.1 mmol/L; and good glycemic target was defined as preprandial capillary plasma glucose between 4.4-7.2 mmol/L and 2h postprandial capillary plasma glucose < 10.0 mmol/L [0 mmol/L .Anthropometry: body mass index was classified as: normal (BMI 18.5-24.9), overweight (BMI 25.0-29.9), obesity (BMI ≥ 30) [MI ≥ 30) . TruncalMI ≥ 30) .Statistical analysis: data were coded and entered into STATA version 14  for analysis. Continuous variables with symmetrical distribution were expressed as means ± standard, while those with skewed distribution were expressed as median and interquartile range. Categorical variables were expressed as frequencies and percentages. Student t-test and chi-square test were used to test for association. Statistical significance was set at p < 0.05.Ethical approval: ethical approval for the research and permission for use of data was obtained from the Ahmadu Bello University Teaching Hospital Research Ethics Committee (ABUTH-REC). To maintain privacy and confidentiality, each patient was assigned a unique numerical identifier for tracking purposes only and data was retrieved anonymously.2 and 92.8 ± 13.1 cm respectively. The mean fasting blood sugar and mean 2-hour postprandial sugar were 7.9 ± 3.1 mmol/L and 10.7 ± 3.5 mmol/L respectively, and 227 (70.5%) of them were hypertensive. Other clinical characteristic such as mean fasting blood sugar, mean 2h postprandial blood sugar, median duration of diabetic mellitus, median duration of hypertension, and mean serum lipid levels of the patients are as shown in A total of 322 patients  with type 2 DM fulfilled the eligibility criteria and were included in the study. Their mean age was 53.5 ± 10.8 years while their mean body mass index and mean waist circumference were 27.8 ± 6.4 kg/mDiabetic dyslipidemia confers at least two-to-threefold excess risk for premature atherosclerosis of large- and medium-sized vessels, independent of other risk factors; and numerous large-scale epidemiological studies and well-controlled clinical trials have shown a well-established association between lipid disorders and cardiovascular risks -32. Dyslet al. [et al. [et al. [et al. [Atherogenic dyslipidemia of 3.4% in our patients signifies an increase in apolipoprotein B (ApoB), and a shift of LDL pool towards small, dense LDL that are cholesterol-ester depleted, and more atherogenic with higher risk for ASCVD ,46. Isolet al.  and Sang [et al. ; finding [et al. , Goel et [et al. , and Pok [et al.  show varThe study highlights the high prevalence of dyslipidemia in patients with type 2 diabetes mellitus attending clinic at ABUTH, Zaria, Nigeria with mixed dyslipidemia of TG and high LDL being the commonest pattern. This implies that many of the type 2 DM patients are at a higher risk of ASCVD. There is, therefore, the need to prioritize a comprehensive lipid care in the management of all type 2 DM patients.Diabetes mellitus and dyslipidemia are independent risk factors for atherosclerotic cardiovascular disease;Dylipidemia confers excess risk of adverse cardiovascular event in diabetes mellitus patients;Lipid management reduces cardiovascular events in both diabetic and non-diabetic patients.The prevalence of dyslipidemia in type 2 DM patients in Zaria is 69.3%;Mixed dyslipidemia of high triglyceride and high low-density lipoprotein was the predominant pattern of dyslipidemia.The authors declare no competing interests.


It's not uncommon for patients with end-stage renal disease (ESRD) to develop hypertension that is resistant to antihypertensive medications and volume control, making it a challenge to control blood pressure in those patients. In this article, we present a 71-year-old female with a history of ESRD on intermittent hemodialysis (IHD), who developed refractory hypertension despite the use of seven antihypertensive agents in addition to IHD. The patient underwent bilateral nephrectomy as a last resort therapy for managing resistant hypertension, which led to a significant improvement in blood pressure (BP) and decreasing the number and doses of antihypertensive agents. This article aims to raise the awareness and alertness of clinicians to the efficacy of bilateral nephrectomy as rescue therapy for refractory hypertension in hemodialysis patients. Chronic kidney disease patients are at risk of developing hypertension secondary to volume overload, sympathetic over-activity, activation of the renin-angiotensin system, arteriosclerosis, and noncompliance with antihypertensive medications. Some patients with end-stage renal disease (ESRD) on intermittent hemodialysis (IHD) are resistant to volume control and antihypertensive medications for the treatment of hypertension. A diagnosis of resistant hypertension (HTN) is made in these patients when the patient's blood pressure (BP) is uncontrolled in spite of the concurrent use of three antihypertensive agents of different classes or if BP is controlled with four or more medications  as compaIn rare cases of refractory hypertension in ESRD patients whose elevated BP is resistant to all interventions, including IHD medications and hemodialysis, bilateral nephrectomy is considered an effective method for the management of refractory hypertension in hemodialysis patients among other invasive and experimental lines of treatment .We present a 71-year-old female, with a past medical history of hypertension, hyperlipidemia, end-stage renal disease , renal artery stenosis  angiography in addition to mild to moderate spinal muscular atrophy (SMA) stenosis), age-associated arteriolosclerosis, pseudo-resistant hypertension , and medications noncompliance. The patient remained dependent on a nicardipine drip despite multiple regimen oral antihypertensives and daily four-hours hemodialysis sessions. Choices for the treatment of this patient's refractory hypertension were considered, including renal denervation and bilateral nephrectomy. Multiple disciplinary meetings of the patient's cardiologist, endocrinologist, nephrologist, and urologist were held and a decision was made to proceed with bilateral nephrectomy. The choice of renal denervation was deferred in this patient, as it’s an invasive procedure with unproven efficacy in the treatment of resistant hypertension.Bilateral nephrectomy took place with no major complication of the patient except for the transfusion of three units of packed red blood cells (RBCs) due to intraoperative bleeding. The patient was monitored in the coronary care unit (CCU) for one week after the procedure, remained dependent on the nicardipine drip, which tapered down until discontinued on Day 8 postop, with the SBP range between 160 and 180. The patient's BP continued to normalize afterward, over a period of three months, with previous and current SBP ranges listed in Table Resistant hypertension refers to elevated BP that is uncontrolled in spite of the concurrent use of three antihypertensive agents of different classes or if BP is controlled with four or more medications as compared to refractory hypertension when BP is uncontrolled despite using five or more drugs, including chlorthalidone and a mineralocorticoid receptor antagonist under the care of a hypertension specialist. Patients with resistant and refractory HTN are at risk of significant comorbid conditions, as one study showed that patients with resistant hypertension have a 32% increase in the risk of developing ESRD, a 24% increase in the risk of myocardial ischemia, a 46% increase in the risk of heart failure, a 14% increased risk of cerebrovascular events, and a 6% increased risk of mortality. Patients with chronic kidney disease are at risk of developing HTN, resistant HTN, and refractory HTN secondary to volume overload, sympathetic overactivity, activation of the renin-angiotensin system, and arteriosclerosis, with a prevalence of 50%-60% of ESRD patients on hemodialysis being hypertensive, and a prevalence of resistant hypertension of 33.4%, 28.9%, and 15.8% in chronic kidney disease with estimated glomerular filtration rate (eGFR) levels of <45 ml/min, 45-60 ml/min, >60 ml/min, respectively [Other secondary causes of resistant hypertension should be investigated before attributing it to chronic kidney disease and before proceeding with invasive management, including primary aldosteronism (10%-20% of resistant hypertension), renal artery stenosis secondary to fibromuscular dysplasia or atherosclerosis in older patients, or obstructive sleep apnea, with one study showing a 71%-85% prevalence of obstructive sleep apnea (OSA) in patients with resistant hypertension referred to in sleep studies [Controlling BP in patients with ESRD on dialysis decreases mortality secondary to cardiovascular events, as one study showed a decrease in cardiovascular events, mortality, and all-cause mortality in ESRD on dialysis and patients whose BP was controlled with antihypertensive therapy. After achieving optimal dry weight through dialysis by increasing dialysis time and decreasing dialysate sodium -10, antiIf the above regimen is ineffective, more invasive measures can be considered such as bilateral nephrectomy. Other experimental methods, including renal denervation and stimulation of carotid sinus baroreceptors, is being studied. Bilateral nephrectomy is the most effective intervention in reducing blood pressure in patients with resistant/refractory hypertension to any other therapy . It workOther invasive interventions for treating hypertension include renal denervation, by which catheter-based radiofrequency or ultrasound ablation of renal sympathetic nerves is done. Although this method is found effective in BP reduction in hypertensive patients, its role in treating resistant hypertension has not been established . ExperimAmong the invasive interventions in treating resistant hypertension in patients with end-stage renal disease on dialysis despite dietary and lifestyle modifications, including increased dialysis time, decreased sodium dialysate, and the administration of multiple antihypertensive agents, bilateral nephrectomy is the most effective measure for treating hypertension in terms of lowering blood pressure, improving the clinical picture and quality of life, and reducing the number and dosage of antihypertensive medications in these patients.


To the Editor:Eosinophilic airway inflammation is present in approximately half of patients with asthma, and it is particularly associated with asthma attacks. IL-5 is a major cytokine involved in eosinophil differentiation, proliferation, activation, and eosinophil-mediated inflammatory responses . Severe Pharmacodynamic studies of mepolizumab and benralizumab have only been undertaken over longer time periods, and their findings are difficult to compare, as baseline and change in blood eosinophils have been expressed differently –9. Theren = 6) for the treatment of poorly controlled eosinophilic asthma or commencing maintenance treatment with mepolizumab 100 mg subcutaneously (n = 6) or benralizumab 30 mg subcutaneously (n = 6) for poorly controlled severe eosinophilic asthma . We assessed blood eosinophil counts at baseline , at 2 and 4 hours after the first dose for all patients, and at 6, 8, 24, and 96 hours if the blood eosinophil count remained higher than 150 cells/μl. A 30-day blood eosinophil count was obtained for those who received the mepolizumab or benralizumab injection. There is no previous information on the onset of action of mepolizumab and benralizumab; however, the effect of prednisolone starts in about 2 hours, so we included the time points 2 and 4 hours, and later time points to show the predicted slower onset of mepolizumab. Hematological analysis was done by laboratory staff using an Abbott Architect ci8200 analyzer.This was a substudy of the Oxford Airways Study . The Oxford Airways Study is an observational study of patients with asthma and chronic obstructive pulmonary disease, which allows blood, sputum, and bronchoscopy sampling at stable state and during exacerbations, before and after clinical treatment. The main outcome of this substudy was time to reach a 50% reduction in blood eosinophil count after administration of mepolizumab, benralizumab, and prednisolone. Patients were recruited from the Oxford Special Airways Clinic. Inclusion criteria were having a known diagnosis of severe asthma and baseline blood eosinophil count above 300 cells/μl. Subjects who had taken prednisolone in the preceding 2 weeks or who were already on a biologic treatment were excluded. We recruited 18 patients who were either commencing prednisolone 30 mg daily for 5 days   and higher than in the prednisolone arm at 4 hours . The geometric mean (geometric SD) blood eosinophil counts 30 days after benralizumab and mepolizumab were 8 (2.8) and 92 (1.7) cells/μl, respectively (P = 0.002).Demographics, inhaled corticosteroid dose, lung function, baseline blood eosinophil count, and exhaled nitric oxide levels were not significantly different between groups . The meaoc test) . A bloodTo the best of our knowledge, this is the first study comparing the rate of depletion of blood eosinophils in the first 24 hours after treatment with mepolizumab and benralizumab. We found that, in contrast to mepolizumab, benralizumab caused rapid and near complete depletion of eosinophils with a speed of onset of effect very similar to that seen with oral prednisolone. The blood eosinophil count 30 days after the first injection was also significantly lower after benralizumab compared with mepolizumab. These findings are consistent with greater efficacy and a different mechanism of eosinophil depletion.Mepolizumab and benralizumab have proven and similar efficacy and safety in the longer-term treatment of severe eosinophilic asthma , 3, sugg