Non-steroidal anti-inflammatory drug (NSAID)—exacerbated respiratory disease (NERD) is an adult-onset inflammatory condition of the upper and lower airways. It is characterized by the co-existence of asthma, nasal polyposis, and hypersensitivity to NSAIDs. Over one-fourth of patients also have symptoms of chronic middle-ear infection. The clinical course of NERD is often severe and generally requires multimodal treatment with recurrent surgical measures. Studies presenting the disease burden and subjective symptom control of NERD are limited. In this qualitative questionnaire study, we present the clinical characteristics of asthma, nasal polyposis, NSAID intolerance and possible recurrent or chronic middle-ear infection of 66 confirmed NERD patients treated at our tertiary referral center between January 2016 and May 2017. Additionally, we present the patient-reported disease control of asthma, nasal polyposis, and middle-ear symptoms on a four-category Likert scale. The proportion of NERD patients with recurrent or chronic middle-ear infection was 18%. The proportion of good or very good subjective disease control was 83% for asthma, 58% for nasal polyposis, and 33% for chronic middle-ear infection, if present. Chronic middle-ear infection is common among NERD patients and should more often be recognized as part of the entity. Together with nasal polyposis, chronic middle-ear infection seems to affect patients more than asthma. The patient's perspective of disease control should be considered when planning the interdisciplinary follow-up and treatment of NERD. Non-steroidal anti-inflammatory drug (NSAID)—exacerbated respiratory disease (NERD) is an adult-onset inflammatory disease of the upper and lower respiratory mucous membranes characterized by the co-existence of asthma, nasal polyposis, and hypersensitivity to NSAIDs. The spectrum was originally described by Samter and Beers . It was It has been suggested that the prevalence of NERD in the general population is 0.3–0.9%. The prevalence is higher among patients with asthma 7%), chronic rhinosinusitis with nasal polyps 10%), or severe asthma 15%) (% (5), an%, chroni%, or sevShared decision-making with patients and adequate symptom-control achievement are listed as key components of precision medicine , 17, a cIn this study, we assessed the patient-reported control of asthma, nasal polyposis, and chronic middle-ear infections in NERD. In addition, we explored the extent of chronic middle-ear infection among NERD patients.Helsinki University Hospital (HUH) is a tertiary referral center that provides health care services for 1.67 million citizens. The HUH electronic patient records cover all medical specialties, excluding primary health care.We conducted a retrospective database search for patients with ICD-10 diagnoses of asthma  and nasal polyposis  between January 2016 and May 2017. The patient charts were manually reviewed to identify patients with a clinical history and symptoms of NSAID intolerance. Aspirin challenge was not required. A questionnaire, study description, informed consent form and prepaid return envelope were sent to the patients with suspected NERD. The non-respondents were re-approached once. Patients returned the questionnaires between April 2018 and May 2019. We analyzed all the returned questionnaires.The patients were first asked to confirm that they had diagnoses of asthma, nasal polyposis, and NSAID intolerance. Only patients confirming these conditions were included in the study. The questionnaire was divided into sections covering the medical history of asthma and NSAID intolerance and the medical and surgical history of nasal polyposis. In addition, one section contained questions about a possible adulthood history of chronic or recurrent middle-ear infections. At the end of each section, the respondents were asked to self-assess the current clinical control of asthma, nasal polyposis, and middle-ear symptoms. The disease control was assessed by a four-category qualitative Likert scale. The categories were “very good,” “good,” “poor,” or “very poor.” The middle category of “neither good nor poor” was eliminated to avoid a non-response option . The queP-value of <0.05 was considered statistically significant. Descriptive statistics were used for means, medians, and ranges.The associations between patient characteristics and clinical variables were calculated using Fisher exact tests. A The diagnoses of asthma, NSAID intolerance, and nasal polyposis were made in a short time span. The median time span was 4 years and the average was 6 years. When taking into account only the mean contraction ages, the first diagnosed condition was asthma, followed by NSAID intolerance and nasal polyposis. However, considerable variation existed in the order and timing of the separate conditions for individual patients. Six patients (9%) received all three diagnoses in the same year. The median age of onset for asthma was 33. The majority (94%) of the patients used inhaled corticosteroids. Less than half (38%) took leukotriene modifiers regularly, and only two (3%) had biological medical therapy. Two-thirds (64%) had needed peroral corticosteroid treatment either continuously or as a course in the past 5 years. The average number of required corticosteroid courses was seven. More than half of the patients  reported a positive family history of asthma.The median age of onset of nasal polyposis was 34. The majority (88%) used topical nasal steroids regularly. Of these, 23 (35%) used corticosteroid drops and the remainder nasal sprays. Nearly all (95%) had undergone surgical removal of nasal polyps, and the average number of reported operations was six. More than half (59%) had needed a course of oral corticosteroids in the past 5 years, on average seven times. One-fifth  reported a positive family history of nasal polyposis.The median age of onset of NSAID intolerance was 35. The reported aspirin- or NSAID-related symptoms included the worsening of asthma (38%), breathing difficulties (86%), swelling, itching, or irritation of the oral or pharyngeal mucous membranes (42%), skin symptoms (21%), and other symptoms (32%), including nasal congestion and discharge, sneezing, worsening of polyps, eye irritation, nausea, abdominal pain, and swelling of the face. Three patients (5%) reported anaphylaxis. No-one reported skin symptoms exclusively caused by NSAID, which makes NSAID-related urticaria unlikely. Thirty patients (45%) had undergone an aspirin challenge. Twenty-three patients (35%) had undergone aspirin desensitization between 1999 and 2018. Twelve of the desensitized patients (52%) reported relief of symptoms, including the reduced growth of nasal polyps, less nasal congestion and discharge, and less shortness of breath and asthma-related symptoms. Two of the challenged but not desensitized patients reported anaphylaxis on NSAID exposure. Aspirin treatment (250 mg) was used by five patients (8%) at the time of inquiry, which is less than half of those who had undergone successful desensitization with relief of their symptoms. Less than one tenth  reported a positive family history of NSAID intolerance.p = 0.0205). The number of infections in the past 5 years varied from two to over ten. The majority  had undergone adulthood myringotomy from one to five times. Over half  had had tympanostomy tubes inserted from one to eight times in adulthood. Six patients (50%) reported a history of adulthood tympanic membrane perforation and five reported a current tympanic membrane perforation. Two of the middle-ear symptomatic patients  had hearing aids, whereas two of the remaining non-ear-symptomatic patients  had hearing aids, all bilateral.About one-fifth  of the patients reported recurrent (more than twice a year) or chronic (more than 2 months) adult-onset middle-ear infection. The median age of onset was 37 years. Almost all  of the ear-symptomatic patients were women  reported the disease control of asthma they had experienced to be good or very good. Only 12% (8/66) reported poor or very poor asthma control. Twelve patients (18%) had had asthma for over 30 years, and four of these reported poor disease control.p = 0.001).In contrast to the reports on asthma, only slightly over half  regarded polyp control to be good or very good. The corresponding figure for poor or very poor polyp control was 38% (25/66). Compared to asthma control, the difference is statistically significant  regarded the control of their middle-ear symptoms as poor or very poor, and only one-third  as good or very good.The aim of the treatment of NERD is to achieve adequate control of symptoms and to minimize the effect of the disease on the quality of life , 19. ThiThe females outnumbered the males by 61% in the whole study group and by 92% in the middle-ear infection subgroup. This corresponds to earlier studies , 8, 10. The diagnostics and treatment of NERD patients were heterogenous. Less than half were diagnosed with aspirin challenge or treated with aspirin desensitization even though the desensitized patients seemed to also benefit from the treatment. Only a few were on aspirin treatment after desensitization. The use of leukotriene modifiers was reported by less than half of the respondents. Only two were undergoing biological anti-immunoglobulin-E (IgE) treatment for asthma, and none were undergoing biological treatment for nasal polyposis, despite recurrent courses of corticosteroids and numerous surgical procedures for nasal polyp control. Biological monoclonal antibody medication for severe nasal polyposis is a relatively recent therapeutic option , and theStudies presenting the clinical control and disease burden of NERD are limited , 20, 24,Studies of middle-ear symptoms associated with NERD are scarce and their impact on the patient's quality of life is not well-documented . In our This study has some limitations. The data were collected through a database search for ICD-10 diagnosis codes for asthma and nasal polyposis. Thus, we may have missed some patients without a registered diagnosis, and the total number of patients might be higher. Moreover, the data were collected in a university tertiary care center, excluding primary health care, which might have led to the relatively high 44% prevalence of NERD among our asthma and nasal polyposis patients compared to the 30% prevalence described earlier .The study design relied on information collected from the patients, thus posing the risk of reporting bias. Furthermore, we did not require a positive aspirin challenge for the diagnosis of NERD. Instead, intolerance was based on registered symptoms from aspirin intake on patient charts and the patient's subjective confirmation of intolerance. However, previous studies have shown that the clinical history of NSAID intolerance appears to be reliable , 5, 26.Recently, some studies have shown that the type of inflammation varies between NERD patients , 28. DueNERD is a chronic inflammatory systemic condition and the diagnoses of upper and lower respiratory tract disorders are often made close to each other, albeit usually on separate occasions and by different specialists. There is a risk of missing the overall picture of a patient's condition, leading to a delay in the diagnosis of NERD. This is harmful, considering the multimodal therapy and commonness of chronic middle-ear infection and the interventions required to control nasal and middle-ear symptoms. Lack of structured care recently emerged in a comprehensive register study, and patients have also complained about this , 29. TheAccording to our findings, nasal symptoms together with chronic middle-ear infection seem to affect patients more than asthma. Whether this is due to the inadequate use of medication or more severe disease remains to be evaluated. The patient's perspective of disease control should be taken into account when planning the follow-up and treatment of NERD. Middle-ear symptoms, although not an official component of the triad, deserve adequate evaluation and treatment and should be taken into account when considering treatment4 with biologics.The datasets presented in this article are not readily available because of patient confidentiality. Requests to access the datasets should be directed to the corresponding author.The studies involving human participants were reviewed and approved by Helsinki University Hospital Ethics Committee (HUH/3078/2017). The patients/participants provided their written informed consent to participate in this study.LH, AL, TK, and RS contributed to conception and design of the study and revised the manuscript critically for important intellectual content. RS screened manually the electronic patient records. AL drafted the questionnaire. AS and LH organized the database. LH performed the statistical analysis and drafted one picture of the manuscript. AS wrote the first draft of the manuscript. All authors have read and approved the submitted version.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.


The aim of the audit was to identify patients at risk of developing Metabolic Syndrome who are on Clozapine in the community. Anyone who has three of following attributes has Metabolic Syndrome. A large waist size (greater than 40 inches in men or 35 inches in women) ,high blood pressure (130/85 mm Hg or higher) ,high triglycerides — a form of fat in the blood (150 mg/dL or higher) ,high blood sugar (a fasting level of 100 mg/dL or higher).Patients receiving should be regularly monitored under clinical review particularly in relation to side effects of the drug and maintain minimum standards of review both physically and clinical investigations once a year .To measure the screening of central obesity, Blood Pressure, serum glucose levels and lipid profile in last one year.Data were collected from Blood results and electronic entries of patients who are on Clozapine in South Ceredigion Community Mental Team. There were 31 patients of which 20 were male and 11 were female patients. The age range was 31–66 years and average was 46 years.52% of the patients had obesity,34 % with Hypertension,50 %Dyslipidaemia and 43 % had Increased glucose tolerance. 80 % were only on clozapine,3% were on combined Amisulpride, 10% on combined on Ariprazole, 3 % on combined Quetiapine.Treatment of causes like making changing lifestyle changes, weigh reduction using health diet and to include regular physical activity. Reduce Abdominal Obesity and in possible provide nutritional intervention.


Hypertension is a kind of cardiovascular syndrome with the main clinical manifestation of continuous increase of systemic arterial blood pressure. Hypertension coexists with other cardiovascular risk factors and is an important risk factor for cardiovascular and cerebrovascular diseases. Acupuncture is an important part of Traditional Chinese Medicine intervention. The antihypertensive effect of acupuncture on hypertension is based on the neuroendocrine system, characterized by multichannel and multitarget. This study aims to provide latest and updated proof of systematic review to assess the effectiveness and safety of acupuncture for hypertension.We will systematically search 9 databases from their inceptions to February 2021. Only randomized controlled trials of acupuncture combined with western medicine in the treatment of hypertension will meet the inclusion criteria. The main outcome measures we focus on include clinical efficacy, syndrome efficacy, Traditional Chinese Medicine syndrome score, diastolic and systolic blood pressure changes, blood pressure variability, heart rate variability, pulse rate variability, and adverse reactions. The research screening, data extraction, and risk of bias assessment will be employed by 2 reviewers independently, and disagreement will be decided by a third senior reviewer. The Revman 5.3 software will be used for meta-analysis. The confidence of proof will be rated adopting grading of recommendations assessment, development and evaluation tool and methodological quality of this research will be assessed using assessment of multiple systematic reviews-2 and risk of bias in systematic reviews. The publication quality will be evaluated by preferred reporting items for systematic reviews and meta-analyses (PRISMA).This systematic review (SR) will provide evidence-based medical evidence for hypertension therapy by acupuncture combined with western medicine and we will submit the findings of this SR for peer-review publication.This SR will provide latest and updated summary proof for assessing the effectiveness and safety of acupuncture for hypertension.INPLASY 202150047 It can damage the structure and function of important organs, such as heart, brain, and kidney, and eventually lead to functional failure of these organs. Hypertension is an important risk factor for cardiovascular disease, end-stage kidney disease, and all-cause death.Hypertension, one of the most common chronic diseases, is a kind of cardiovascular syndrome with the main clinical manifestation of continuous increase of systemic arterial blood pressure. In 2018, European Society of Cardiology /European Society of hypertension guidelines and Chinese hypertension guidelines continue to follow the previous standards, defining hypertension as ≥ 140 /90 mm Hg.,7 Based on 140 /90 mm Hg, there were about 1.13 billion hypertensive patients in the world in 2015, and the prevalence of hypertension in adults was 30% to 45%. With the aging of the global population and the change of people's lifestyle, the prevalence of hypertension is still on the rise. It is estimated that there will be 1.5 billion hypertensive patients in the world by 2025. Studies have shown that the incidence rate of blood pressure in China has been increasing year by year, but the awareness rate, treatment rate, and control rate of hypertension patients are still at a low level. Hypertension has brought a heavy economic burden on the health of Chinese patients. A cohort study shows that about 750,000 cardiovascular deaths in Chinese people aged 35 to 79 are associated with uncontrolled hypertension.In 2017, American Heart Association /American College of Cardiology guidelines redefined the diagnostic criteria of hypertension, which defined hypertension as ≥ 130 /80 mm Hg. At present, more and more evidences support that abnormal sensitivity and reactivity of peripheral blood vessels and structural changes of vascular wall are the main pathogenesis of hypertension. Modern studies have confirmed that hypertension is the result of abnormal vascular changes. In the early stage of hypertension, the whole body is characterized by small artery spasm. Long-term high blood pressure causes arteriosclerosis, subintimal hyaline degeneration, and proliferation or hypertrophy of middle smooth muscle cells, resulting in wall thickening and lumen stenosis, accompanied by the decline of vascular function, maintaining and developing high blood pressure, and further leading to ischemic injury of important target organs, such as heart, brain, and kidney.At present, the etiology of hypertension is considered to be closely related to genetic factors, environmental factors, vasoactive substances, sympathetic nervous system, renin angiotensin system, nitric oxide synthase/nitric oxide, endothelin, and insulin. The revised version of Chinese guidelines for the prevention and treatment of hypertension in 2018 clearly points out that the fundamental goal of hypertension is to reduce the total risk of cardiovascular, cerebrovascular, renal, and vascular complications as well as death. The target of reducing blood pressure should be lower than 140 /90 mm Hg in general patients, and can be further reduced to less than 130 /80 mm Hg in tolerable patients and some high-risk and above patients. Meta-analysis showed that for every 10 mm Hg decrease in systolic blood pressure or 5 mm Hg decrease in diastolic blood pressure, the risk of major adverse cardiovascular events was reduced by 20%, and the risk of all-cause death was reduced by 10% to 15%. Therefore, the control of blood pressure is particularly important.Studies have shown that every 20 mm Hg rise in systolic blood pressure or 10 mm Hg rise in diastolic blood pressure will significantly increase the risk of cardiovascular disease. If the patient is diagnosed as high-risk and very high-risk, the drug treatment should be started immediately. At present, the main drugs for the treatment of hypertension include diuretics, calcium channel blockers, adrenergic receptor blockers, renin–angiotensin–aldosterone system inhibitors, and sympathetic nerve inhibitors. According to the overall risk and specific characteristics of patients and drugs, the corresponding drugs are selected for treatment.In the specific treatment, cardiovascular risk assessment should be carried out first. Lifestyle intervention is the basic treatment for hypertension. On the basis of improving lifestyle, patients whose blood pressure still exceeds 140 /90 mm Hg and/or the target level should be given drug treatment. However, in clinical practice, there are still some limitations and confusion, especially for the treatment of grade I hypertension, there is no clear evidence that drug treatment will bring obvious benefits. In addition, due to the unstable effect of antihypertensive drugs, side effects and drug resistance caused by long-term medication, the compliance of patients is greatly affected, and the control rate and standard rate of blood pressure are reduced.Modern medicine for the treatment of hypertension clearly points out that its fundamental goal is to reduce the total risk of cardiovascular, cerebrovascular, and renal complications and death, mainly through antihypertensive drugs to control blood pressure. It is an significant part of TCM in hypertension therapy. A large number of clinical studies have proved that acupuncture has the effect of reducing blood pressure, and has the advantages of small side effects, low cost, simple and easy to be accepted by patients. Acupuncture can adjust Yin and Yang of human body, dredge Qi, and blood of meridians, regulate the function of viscera, relieve symptoms, and play the role of treatment and health care by stimulating acupoints on the body surface of meridians and viscera.As an important part of Traditional Chinese Medicine (TCM) intervention, acupuncture therapy has the outstanding characteristics of noninvasive and non-gastrointestinal administration, and can be combined with internal treatment, but can make up for the deficiency of internal treatment. Studies have shown that acupuncture can improve the function of cerebral cortex, enhance blood circulation in the brain, make blood vessels dilate, and blood flow unobstructed, and its mechanism is mainly related to the regulatory effect of acupuncture on nerves, immunity, and body fluids. In addition, acupuncture can relax nervous state, achieve the balance of excitement and inhibition, thus alleviate dizziness and headache symptoms, improve sleep, and reduce blood pressure. Some studies have confirmed that the antihypertensive effect of acupuncture may be related to the regulation of the rostral ventrolateral medulla area, the final central pathway regulating cardiovascular activity, the regulation of vascular endothelial related active factors, and the direct regulation of renin and angiotensin.Currently, a number of clinical trials have shown that acupuncture has good clinical efficacy and safety for the treatment of hypertension.Systematic review (SR) is a kind of literature synthesis method, aiming at a specific clinical problem, systematically and comprehensively collect the current published or unpublished studies, use the strict evaluation methods of evidence-based medicine and clinical epidemiology, screen out the literatures that meet the quality standards, and carry out qualitative or quantitative combined analysis to get the best comprehensive conclusion at present. Currently, although several SRs have addressed this issue, however, its effectiveness is still inconclusive and none of them have further evaluated the effectiveness and safety of acupuncture for hypertension after more new randomized controlled trials (RCT) have been published. Therefore, this study aims to provide latest and updated evidence of systematic review to evaluate the effectiveness and safety of acupuncture for hypertension and provide reliable evidence for clinical practitioners.Previous studies have reported that acupuncture combined with western medicine can be used to the treatment of hypertension.22.1This systematic review and meta-analysis aims to evaluate the effectiveness and safety of acupuncture combined with western medicine in the treatment of hypertension.2.2https://inplasy.com/?s=202150047) and will be reported according to Preferred Reporting Item for Systematic Review and Meta-analysis Protocols (PRISMA-P) guidance.This SR has been registered on International Platform of Registered Systematic Review and Meta-analysis Protocols ,Cochrane Central Register of Controlled Trial, ovid, Web of Science, China National Knowledge Infrastructure, WangFang Database, Chinese Science and Technology Periodical Database, SinoMed. The language is limited to Chinese and English. In addition, we will also supplement the search for the following clinical trial registration platforms to confirm ongoing and completed RCTs: Clinical Trials.gov trials registry, Chinese Clinical Trial Registry, Current Controlled Trials, WHO clinical trials registry, The Australian New Zealand Clinical Trials Registry and Centre Watch. The retrieval time range is from their inceptions of each database to March 2021. Grey literature will also be searched to avoid omission. We will also manually search the references of published SR and related professional journals. In addition, we will consult experts in relevant fields to determine the completed but unpublished literature. The search strategy in PubMed can be found in Supplemental Digital Content  and it will be adjusted according to the characteristics of each database.2.5We will use EndNoteX 8.0 software to manage the retrieved literature. First, the retrieved literatures will be selected by 2 researchers independently according to the inclusion and exclusion criteria, and the full text of the literatures meeting the criteria will be downloaded for further screening. The researchers will record the literature excluded in this process and provide reasonable reasons. Details of the selection process will be presented in the PRISMA flow chart Fig. .Two researchers will extract information from the included eligible studies using a predetermined form. The key information extracted includes funding, participants , interventions , controls , outcomes  and study design . If required information is not reported, we will try to request it from the corresponding author of the studies.Divergence in the process of literature selection and information extraction will be solved through discussion or judged by a third senior researcher. If the included RCTs have missing data, we will contact the corresponding authors. If missing data are unobtainable, intention-to-treat analysis will be conducted and sensitivity analysis will be performed to address the potential impact of missing data, which will be discussed if necessary.2.6Cochrane risk of bias assessment tool version 2.0 (RoB 2.0) will be used to assess the risk of bias of RCTs. We will evaluate the risk of bias in RCT from 5 domains, namely “risk of bias arising from the randomization process,” “risk of bias due to deviations from the intended interventions,” “missing outcome data,” “risk of bias in measurement of the outcome,” “risk of bias in selection of the reported result.”Each domain contains several signal questions and the evaluator may answer “probably yes,” “probably no,” “no,” “no information” according to the content of clinical study. According to the evaluation results of 5 areas, the overall risk of bias may be “low risk,” “possible risk,” and “high risk.”In addition, we will use the modified Jadad scale to evaluate the quality of the included studies. We will evaluate 4 aspects, namely “randomization,” “concealment of allocation,” “double blinding,” “withdrawals and dropouts.” According to the scoring principle, 1 to 3 scores will be considered as low-quality literature, and 4 to 7 scores as high-quality literature.This process will be evaluated independently by 2 researchers, during which disagreement will be solved through discussion or judged by a third senior researcher.2.7I2 values will be applied to measure the inter-study heterogeneity. When the P value of Q test >.1 and I2<50%, heterogeneity is acceptable and a fixed effects model will be applied. If P value of Q test <.1 and I2>50%, heterogeneity is significant and we will use subgroup analysis, meta regression analysis, and sensitivity analysis to explore the causes, if still unable to find, we will use random effect model to estimate or descriptive analysis. Binary variables will be expressed using the risk ratio with 95% confidence interval and continuous variables by the weighted mean difference with 95% confidence interval. We will use the method of eliminating low-quality research according to the risk of bias assessment results and replacement effect model to conduct sensitivity analysis to judge the robustness of the conclusion. If the number of included studies is more than 10, we will use inverted funnel plot to detect potential publication bias. Besides, Peters regression test will be applied for binary variables, and Egger for continuous variables to provide quantitative evidence of any publication bias.The Revman 5.3 software will be used for perform meta-analysis. The Q test and 2.8 Five factors may downgrade the level of evidence, namely “inconsistency,” “imprecision,” “limitations/risk of bias,” “publication bias,” and “indirectness.” The overall quality of evidence may be rated as “high,” “moderate,” “low,” or “very low.” This process will be performed independently by 2 reviewers, during which disagreement will be solved through discussion or judged by a third senior reviewer.We will use Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to evaluate the confidence of outcome estimates.2.9 and Risk of bias in systematic reviews (ROBIS) will be used to evaluate the methodological quality of this study. Furthermore, we will use PRISMA  to assess the reporting quality of this research. We will calculate kappa statistics to understand the consistency of assessments by AMSTAR-2, ROBIS, and PRISMA between 2 reviewers. Kappa 0.6 to 0.8 will be regarded as “substantial agreement” and 0.8 to 1.0 as “almost perfect agreement.” This process will be conducted independently by 2 researchers, and disagreement will be decided through discussion or by a third senior researcher.Assessment of multiple systematic reviews-2 (AMSTAR-2)2.10This systematic review and meta-analysis will be reported according to Reporting Items for Systematic Reviews and Meta-analyses of Acupuncture: the PRISMA for Acupuncture Checklist.This systematic review will not require ethical approval because there are no data used in our study that are linked to individual patient data. In addition, findings will be disseminated through peer-review publications.2.111.This research will be the latest and updated SR to summarize the relevant proof of acupuncture combined with western medicine for the treatment of hypertension.2.GRADE system will be applied to rate the confidence of evidence in this proof.3.AMSTAR-2, ROBIS, and PRISMA will be used to evaluate the methodological quality and reporting quality of this research.4.The search language is limited to Chinese and English, which may lead to omission.5.This study will use a variety of ways to conduct a comprehensive search of potential RCTs.6.This study will evaluate the results of different methods for the treatment of hypertension through autonomic nervous function evaluation indicators.7.Due to the limitation of team members, we will only search Chinese and English electronic database.3 The antihypertensive effect of acupuncture on hypertension is based on the neuroendocrine system, characterized by multichannel and multitarget. The comprehensive effect of acupuncture overcomes the shortcomings of single way of action and narrow indications of western medicine. We should further study and explore the antihypertensive effect of acupuncture, and establish a scientific evidence system of acupuncture in the treatment of hypertension, so as to provide a basis for the comprehensive treatment of hypertension in clinic.Human blood pressure regulation is mainly divided into short-term regulation and long-term regulation. Short-term regulation refers to the immediate regulation of blood pressure changes in a short period of time, mainly through neural regulation. The long-term regulation is mainly accomplished by the renal-body fluid control system, in which the renin–angiotensin system is the most important factor. The central nervous system regulates blood pressure by regulating sympathetic and parasympathetic nerves and their related neurotransmitters.WS and XJ conceived and designed this protocol. WS drafted this article. HXJ and CJ reviewed and edited this article.Conceptualization: Sihan Wang, Xu Jiatuo.Formal analysis: Sihan Wang, Xu Jiatuo.Funding acquisition: Ji Cui, Xiao-Juan Hu.Investigation: Sihan Wang.Methodology: Sihan Wang, Xu Jiatuo, Ji Cui.Project administration: Sihan Wang, Xu Jiatuo, Ji Cui, Xiao-Juan Hu.Supervision: Xiao-Juan Hu.Writing – original draft: Sihan Wang.Writing – review & editing: Sihan Wang, Xu Jiatuo, Ji Cui, Xiao-Juan Hu.


To exam the associations between the use of sodium glucose co-transporter 2 inhibitor (SGLT2i) and the risk of lower limb complications, and to analyze the associated factors.Clinicaltrial.gov were searched from the inception to November 2020. Randomized controlled trials of SGLT2i conducted in population containing diabetic patients with reports of amputation, peripheral arterial disease (PAD) and diabetic foot (DF) events were included. Random-effect model, fixed-effect model and meta-regression analysis were accordingly used.Pubmed, Medline, Embase, the Cochrane Center Register of Controlled Trials for Studies and The numbers of SGLT2i users versus non-SGLT2i users in the analyses of amputation, PAD and DF were 40,925/33,414, 36,446/28,685 and 31,907/25,570 respectively. Compared with non-SGLT2i users, the risks of amputation and PAD were slightly increased in patients with canagliflozin treatment . Meta-regression analyses indicated that greater weight reduction in SGLT2i users was significantly associated with the increased risks of amputation , PAD  and DF . Lower baseline diastolic blood pressure , more systolic blood pressure reduction  and more diastolic blood pressure reduction  were significantly associated with the increased risks of amputation, PAD and DF respectively in patients with SGLT2i treatment.The risks of amputation and PAD were slightly increased in patients with canagliflozin treatment. Reductions in body weight and blood pressure were associated with lower limb complications in patients with SGLT2i treatment. Sodium-glucose cotransporter 2 inhibitor (SGLT2i) is an effective hypoglycemic agent in the management of type 2 diabetes (T2D), with significant improvements in glycemic control and favorable cardiovascular/renal benefits . HoweverRecently, several systematic reviews and meta-analyses have re-evaluated the association between SGLT2i and amputation, which indicated that SGLT2i was not associated with the increased risk of amputation , 6. HoweMoreover, the explanations for the increased risk of amputation observed in patients with canagliflozin treatment are not definite. One hypothesis emphasized the hemodynamic effects of diuresis and blood pressure reduction within canagliflozin treatment. Similar effects were also found in diuretics, which might worsen the peripheral perfusion and in turn increase the risk of lower limb amputation in patients with T2D . HoweverTherefore, we designed and performed an updated meta-analysis using data from randomized controlled trials (RCTs) of SGLT2i conducted in population containing diabetic patients, to hopefully produce a comprehensive safety evaluation on amputation, PAD and DF in patients using SGLT2i, and more importantly, to assess the association between altered hemodynamic status (diuresis and blood pressure reduction) and the risk of lower limb complications in SGLT2i users. Our study aims to provide state-of-the-art evidence-based guidance for appropriate clinical application of SGLT2i especially in patients at high risk of lower limb complications.Clinicaltrial.gov from the inception to November 2020. The search terms were as follows: type 1 diabetes (T1D); T2D; SGLT2i; cardiovascular outcome trial (CVOT); renal outcome trial (ROT); efficacy; safety; placebo controlled; RCT. The search strategies were as follows: (1) “T1D or T2D” and “CVOT or ROT” and “SGLT2i”; (2) “T1D or T2D” and “efficacy or safety” and “SGLT2i” and “RCT”; (3) “T1D or T2D” and “placebo controlled” and “SGLT2i” and “RCT”. The searching results from two investigators were checked together to form the final database for study selection. Reference lists of relevant articles were also screened in order not to miss any possibly eligible study.According to recommendations from the Cochrane Handbook for Systematic Reviews for meta-analysis, two independent investigators (NL and XZ) conducted systematic searches respectively for RCTs of SGLT2i in Pubmed, Medline, Embase, the Cochrane Center Register of Controlled Trials for Studies and The inclusion criteria for eligible studies were as follows: (1) RCTs conducted in population containing diabetic patients; (2) RCTs with reports of PAD, amputation and DF events; (3) RCTs with SGLT2i and placebo or non-SGLT2i active control in different treatment arms. The exclusion criteria for the meta-analysis for SGLT2i treatment were as follows: (1) RCTs without diabetic patients at all; (2) RCTs without reports of PAD, amputation and DF event.clinicaltrial.gov website with unique registered RCT number if the data was absent in both articles and supplementary materials. PAD is defined as the narrowing or blockage of the vessels that carry blood from the heart to the legs. The pre-specific PAD events included in this meta-analysis were as follows: arterial thrombosis limb, arterial stenosis limb, ischemic limb pain, iliac artery stenosis, iliac artery occlusion, iliac artery embolism, femoral artery occlusion, femoral arterial stenosis, extremity necrosis, intermittent claudication, peripheral arterial occlusive disease, peripheral artery occlusion, peripheral artery ischemia, peripheral artery stenosis, peripheral artery thrombosis, peripheral artery circulatory failure and leg ischemia. We addressed discrepancies by inviting a third investigator (FL) to join the discussion, and resolved disagreements by consensus.Two investigators (NL and XZ) abstracted data of all studies, including the publication infomation, study design, treatment arms, study duration, baseline characteristics, efficacy endpoints such as HbA1c change, weight change and blood pressure change etc., lower limb complication event, and assessed the qualities of the included studies. Another two investigators (CL and WY) checked the abstractions and assessments for accuracy. The risk of bias was evaluated using the Cochrane risk of bias tool. PAD, amputation and DF events would be extracted from 2 statistics were used to evaluate the between-study heterogeneity, when an I2 value > 50% indicating high level of heterogeneity. Fixed-effects model was used for low level of heterogeneity and random-effects model was used for high level of heterogeneity. Meta-regression analyses were performed to evaluate the associations between different potential associated factors and the risks of PAD, amputation and DF. Publication bias was assessed via funnel plot tests. Statistical significance was considered at P < 0.05.Continuous outcomes were evaluated by computing the weighted mean differences (WMDs) and 95% confidence intervals (CIs). Categorical outcomes were evaluated by computing the odd ratios (ORs) and accompanying 95% CIs. Higgins IStatistical analyses were primarily performed by using the STATA statistical software package  and the Review Manager statistical software package . Analyses were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for conducting and reporting meta-analyses of RCTs.In total, there were 39 RCTs of SGLT2i treatment included in our study, among which 31 RCTs, 15 RCTs and 19 RCTs were included in the analyses for PAD, amputation and DF respectively  , the risk of PAD  and the risk of DF  , might give us the hints. GLP-1RA, enhances glucose-dependent insulin secretion, inhibits glucagon secretion, slows gastric emptying, and reduces food intake , 16. UnlBlood pressure is another indicator for the hemodynamic status. Our study showed that baseline diastolic blood pressure, greater systolic blood pressure reduction and greater diastolic blood pressure reduction were significantly associated with increased risks of amputation, PAD and DF respectively in SGLT2i users. Blood pressure, as an important vital sign, could also reflect the peripheral perfusion status. Greater blood pressure reduction could be a result of reduced intravascular volume. As is mentioned earlier, the use of thiazide diuretics might increase the risk of lower limb amputation in patients with T2D . The antIt is noted that SGLT2i may also increase diet and water intakes as compensatory feedbacks in response to glycosuria and diuresis. Compensatory increased sugar intake has been reported in patients with T2D under dapagliflozin treatment . HoweverBased on the above analyses, we proposed that, in patients with high risk of lower limb complications, loss of intravascular volume at the early phase with SGLT2i treatment, reflected as diuresis-mediated weight reduction and blood pressure reduction, may contribute to first ischemic damage for the extremities in these patients. Continuous weight reduction at the later phase with SGLT2i treatment would further facilitate the blood pressure reduction and worsen the insufficient distal perfusion, which might contribute to the gradual development of PAD. Surgical removals might be eventually required in some extremely severe cases.Furthermore, according to our meta-analysis, typical volume depletion indicators such as hematocrit, hemoglobin, were not associated with the increased risks of amputation and PAD. Such inconsistence might be due to the limited available data for the variables mentioned above. However, in patients with mild to moderate loss of body fluid, we assumed that weight reduction and blood pressure reduction rather than typical volume depletion manifestations, could still be observed. Thus, such subclinical volume depletion in patients at high risk requires attention as well.Our study showed that the risks of amputation was only slightly increased in patients with canagliflozin treatment, but not in other subtypes of SGLT2i. It was proposed that partial inhibition of SGLT1 of canagliflozin might be associated with this subtype difference in inhibiting selectivity . HoweverActually, SGLT2i is a revolutionary antidiabetic agent which develops a novel treatment pattern for patients with diabetes. The clinical benefits from SGLT2i are much more than sorely improved glycemic control. SGLT2i confers more favorable pleiotropic effects on body weight, alanine aminotransferase and eGFR changes, potentially improving patients’ cardiometabolic disease risk when achieves hypoglycemic effects comparable to antidiabetic agents like dipeptidyl peptidase-4 inhibitor (DPP-4i) . MoreoveIn fact, SGLT2i is generally well tolerated in patients with diabetes. But the enhanced precaution action may further reduce the potential risk during the SGLT2i treatment course for patients susceptible to lower limb complications. Our study indicates that the amplitudes of reductions in body weight and blood pressure are associated with risks of lower limb complications, which calls for an additional attention to the alterations in body weight and blood pressure, two common indicators easy and feasible to monitor during the SGLT2i treatment. In studies in which canagliflozin was not included, SGLT2i were associated with lower risks of chronic heart failure and adverse lower limb events compared with DPP4i among patients with T2D and PAD in real-world practice . It mighThere were some limitations in our studies. First, although there were adjudication committees for cardiovascular and renal endpoints in CVOTs and ROTs, and for important adverse events like urinary tract infection in efficacy and safety evaluation trials, there was no adjudication committees specially designed and set up for relevant lower limb complications in these RCTs. But as large event-driven RCTs, CVOTs and ROTs were basically with proper study design and reliable data assessments. The consistent results from CVOT and ROT strata enhance the creditability of our primary conclusion. Second, the definitions of PAD vary from trial to trial. To minimize the bias, we have unified the inclusion criteria of pre-specific PAD events and strictly stick to it during the data extraction. Moreover, several important data were not commonly reported in the published trials, including hematocrit, smoking status and previous PAD or amputation history. Actually, we did collect the available data about these alternative hemodynamic indicators and independent risk factors, and conducted the corresponding analyses. However, due to the limited data, we did not observe any significant association. Further analyses are still needed to validate and improve the hemodynamic hypothesis in the future.According to our meta-analysis, compared with non-SGLT2i users, the risks of amputation and PAD were slightly increased in patients with canagliflozin treatment. Greater reductions in body weight and blood pressure might be associated with the increased risk of lower limb complications in SGLT2i users. Monitoring body weight and blood pressure reduction might be an important risk precaution action for patients at high risk of lower limb complications during the SGLT2i treatment course. It might help the health care professionals achieve a safe application of SGLT2i in the clinical settings.Additional file 1: Figure S1. Flowchart of included randomized controlled trials of SGLT2i treatment. Figure S2. The funnel plot of included randomized controlled trials of SGLT2i treatment in amputation analysis. Figure S3. The funnel plot of included randomized controlled trials of SGLT2i treatment in PAD analysis. Figure S4. The funnel plot of included randomized controlled trials of SGLT2i treatment in DF analysis. Table S1. The baseline characteristics of included trials of SGLT2i treatment. Table S2. The risk of bias for included trials of SGLT2i treatment. Table S3. Body weight and blood pressure reductions in patients with SGLT2i treatment.


What is the incidence of impaired kidney function in adolescents with anorexia nervosa, and how does it correlate with body mass index and physiologic parameters of anorexia nervosa severity?In this case-control study of 395 adolescent patients with recent diagnosis of anorexia nervosa, impaired kidney function was found in 36.8%. Minimal heart rate and free triiodothyronine levels showed correlation with eGFR but not with admission body mass index.Results of this case-control study suggest that impaired kidney function may be a better parameter of anorexia nervosa severity than body mass index. Anorexia nervosa (AN) is a common psychiatric disorder associated with electrolyte imbalances and impaired kidney function, but their incidence and association with disease severity are unknown.To analyze kidney function in patients with AN and its association with body mass index (BMI) and physiologic parameters of disease severity.International Classification of Diseases, Ninth Revision. All patients were aged 9 to 18 years and hospitalized in the general pediatric ward between 2010 and 2019. BMI and estimated glomerular filtration rate (eGFR) were compared with age- and sex-matched controls hospitalized with other diagnoses.Single-center retrospective case-control study of recently hospitalized patients with a diagnosis of AN according to 2. Association between eGFR, BMI, minimal heart rate, and free triiodothyronine (T3) levels were determined using logistic regression.Impaired kidney function was defined as eGFR less than 90 mL/min/1.73 m2; nadir: 79.1 [8.5] mL/min/1.73 m2; latest: 97.7 [15.7] mL/min/1.73 m2; P < .001). Mean (SD) serum creatinine (SCr) to BMI ratio was higher in both anorexia groups compared with controls in impaired kidney function (4.9% [1.0%]), non–impaired kidney function (3.55% [0.84%]); and control groups (2.8 [1.1%]) (P < .001). There was no difference in admission BMI between anorexia groups with and without kidney function impairment. Mean (SD) free T3 levels  and mean (SD) minimal heart rate  were lower and hospital stay was longer  in the impaired kidney function group. The highest correlation was found between minimal heart rate and minimal eGFR .A total of 395 patients were included in the study group . Impaired kidney function was found in 36.8% (146 of 395). Mean (SD) eGFR decreased during hospitalization in the group with kidney function impairment (admission: 83 [10.9] mL/min/1.73 mImpaired kidney function in patients with AN is common and transiently worsens during hospitalization. SCr values probably underestimate the degree of kidney function impairment in AN. Results of this study found that patients with impaired kidney function had worse anorexia severity parameters unrelated to admission BMI. Therefore, kidney function impairment may be a better marker of anorexia severity. This case-control study assesses the prevalence of impaired kidney function in a cohort of pediatric patients with recent diagnosis of anorexia nervosa and examines the association of impaired kidney function with body mass index and disease severity. Kidney-related complications such as electrolyte disturbances, nephrocalcinosis and alterations in water metabolism are common. Acute and chronic kidney disease (CKD) are also described in patients with AN.2 Chronic hypokalemia, volume depletion, hypophosphatemia with rhabdomyolysis, and nephrolithiasis are potentially important factors in the development of CKD in patients with AN.5 However, the exact pathophysiologic mechanism of kidney function impairment is not well characterized and the main body of evidence for these phenomena is from studies performed more than 30 years ago.Anorexia nervosa (AN) is a common psychiatric disorder that disproportionately affects adolescents and young adults and is associated with high rates of morbidity and mortality. Its complications are associated with the combination of food restriction, weight loss, psychological stress, and the endocrinological and metabolic adaptations to this condition. The reduction of energy intake in patients with AN induces metabolic changes leading to different complications,7 of patients with long-standing AN and severe and irreversible kidney disease have been reported. Kidney histologic findings revealed hypertrophy of the juxtaglomerular apparatus, advanced glomerular collapse, and interstitial fibrosis, consistent with ischemic kidney injury.6 In another AN cohort,7 end-stage kidney disease was reported in 5.2% of the patients. However, these studies provide data on adults with long-standing (>20 years) AN. The incidence of impaired kidney function (IKF) at the time of AN diagnosis has not yet been determined. We hypothesized that IKF may be an important indicator of AN physiologic severity. The aim of the study was to determine IKF prevalence and its association with disease severity in a cohort of pediatric patients with recent diagnosis of AN.Previous case seriesnorexia nervosa, eating disorder, eating disorder, unspecified, loss of weight or bradycardia (n = 538). For the latter 2 diagnoses, medical records were investigated, and data from patients with other diagnoses, such as inflammatory bowel disease, cancer, or cardiac conductance abnormalities, were excluded.The Rabin-Schneider Institutional Review Board approved the study protocol. We performed a single-center retrospective study of data from all patients aged 9 to 18 years hospitalized in general pediatric wards at Schneider Children's Medical Center in Israel with a recent diagnosis of AN between 2010 and 2019. The ethics committee granted a waiver of informed consent. Hospital medical records were screened for patients with first-time hospitalization with a diagnosis of aDiagnostic and Statistical Manual of Mental Disorders (Fourth Edition)8 (before 2013) and Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (after 2013).9 The diagnosis was based on clinical interviews, patient observation, parental information, and medical evaluations by child psychiatrist or psychologist. Patients with AN are usually referred to a general pediatric ward in the Schneider Children's Medical Center when first diagnosed, for the purpose of acute medical stabilization for a serious decrease in weight or finding of severe bradycardia despite maximally intensive community-based care. Cases with AN hospitalized for other medical conditions were not included in the study group.Anorexia nervosa was diagnosed according to the criteria of the 10 and its correlation to body mass index (BMI) and physiologic parameters of AN severity . Assuming that eGFR calculation may underestimate the degree of GFR decrease (because of a discrepancy between the preserved height and decreased muscle mass in patients with AN) we also calculated the SCr/BMI ratio. For comparison of normal SCr and SCr/BMI ratio, a randomly selected group of age- and sex-matched patients with normal age- and sex-adjusted SCr values, hospitalized during the same period with other diagnoses  served as controls. The SCr was determined using the enzymatic assay. Missing data on height (n = 103) were approximated, based on the 50th percentile for age and sex, as height should not be depressed in short-term calorically restricted patients in this age range.The computerized medical record review included the estimated glomerular filtration rate (eGFR), calculated by serum creatinine (SCr) and height using the modified Schwartz equation,11 Pearson χ2 test or Fisher exact test (2-tailed) were used for analysis of between-group differences in discrete variables, and the analysis of variance was used for continuous variables. Pearson correlations were applied to assess for correlations between variables. Using those variables found to be significant (P < .10) on univariate analysis, we applied a stepwise logistic regression to determine those variables significantly associated with eGFR. We used analysis of variance with repeated measures to describe changes in SCr during hospitalization. A P value ≤.05 was considered statistically significant. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for case-control studies.Data were analyzed using BMDP software.P < .001).A total of 395 individuals were included in the study group and 495 were included in the control group. Mean (SD) age at hospitalization was 14.6 (2.2) years in the study group and 13.6 (2.6) years in the control group; 80.2% of the patients (397 of 495) were girls in the control group and 81.6% (298 of 395) were girls in the group with AN . Median 3 levels were slightly decreased , with 28% of patients with an FT3 value below normal. Mean (SD) SCr was in the normal range in the entire study group, but was higher in comparison with controls (0.68 [0.15] mg/dL vs 0.54 [0.14] mg/dL: P < .001), similar to minimal eGFR . The mean (SD) SCr significantly increased during hospitalization and then decreased to a lower than admission value in the AN group  (P < .001). Stepwise logistic regression comparing AN cases with controls revealed that SCr/BMI , age , sex , and minimum eGFR  had higher ORs than SCr or eGFR or admission BMI. These parameters yielded a receiver operating characteristics area under the curve of 0.84. Electrolyte abnormalities during hospitalization included hypophosphatemia (<2.5 mg/dL): 5 of 376 (1.3%), hypomagnesemia (<1.7 mg/dL): 1 of 281 (0.35%), hyponatremia (<135 meq/L): 11 of 378 (2.9%), hypokalemia (<3.5 meq/L): 13 of 389 (3.3%) available tests.Median length of hospitalization in AN group was 10  days, mean (SD) blood pressure (BP) on admission was 102.6 (11.0)/62.7 (9.6) mm Hg and mean (SD) heart rate (HR) on admission was 89 (11) beats per min. Mean (SD) minimal HR was 51.6 (15.8) beats per min. FTariance) . The SCr2. The latter (IKF) was found in 36.8% (146 of 395) of patients. The SCr changed substantially during hospitalization  in both IKF and non IKF groups. However, the mean values were higher in the IKF group   .P = .41). A significant difference between IKF and non-IKF groups was found in maximal SCr during hospitalization . Accordingly, there was a significant difference in mean (SD) minimal eGFR  and SCr/BMI  between IKF and non IKF groups. Mean (SD) eGFR decreased during hospitalization in the group with IKF for admission (83 [10.9] mL/min/1.73 m2) as well as latest . Mean (SD) SCr, eGFR, and SCr/BMI values were not only significantly different between the whole AN group vs controls .Comparison between IKF and non-IKF groups is presented in controls , but als3 levels, available for fewer patients in the AN group (n = 187), were lower in the IKF Vs non IKF group . A similar difference was seen for minimal mean (SD) HR . Length of hospitalization was longer in the IKF group .The FTP < .001), minimal HR , and diastolic and systolic blood pressure on admission independently estimated low vs normal eGFR, yielding an AUC of 0.89.We used stepwise logistic regression analysis for the cases group (n = 383), using eGFR above or below 89.9 mL per minute as a cut-off value. We found that SCr/BMI , higher than correlations between minimal HR and SCr/BMI . The FT3 levels also showed a significant correlation with minimal eGFR  similar to SCr/BMI . No correlation between minimal HR and BMI  or between HR and BMI percentile on admission  was seen .Using Pearson correlation, we found the strongest correlation between minimal HR and minimal eGFR , that reversed to normal by protein repletion.19 Children with calorie-protein malnutrition demonstrated significant reductions in GFR, RPF and filtration fraction.20 Reports on chronic tubulo-interstitial nephropathy in AN attributed it to chronic hypokalemia, acute kidney injury induced by rhabdomyolysis and glomerulosclerosis.23 Histopathologic changes in patients with long-standing AN associated with decreased eGFR and hypokalemia have been reported.24 In this cohort, there was no difference in admission BMI between IKF and non-IKF groups, but as mentioned, we describe these patients at the time of AN initial diagnosis in contrast to longer follow up periods described in the literature.The exact mechanism of kidney function impairment in AN is not well understood. Nutrition plays a substantial role in renal function.25 Bradycardia and hypotension are cardiovascular responses to starvation due to the profound parasympathetic predominance of low body weights or significant weight loss.26 In a retrospective study27 of children and teenagers with AN, low GFR was linked to low BMI and bradycardia. Dehydration was not solely responsible for renal impairment.27 In this cohort, bradycardia and low FT3 levels were more prominent in the IKF compared to non-IKF group. The strongest correlation was seen between minimal HR and minimal eGFR, higher than correlations between minimal HR vs SCr/BMI. FT3 levels showed a similar correlation with minimal eGFR and SCr/BMI. The length of hospitalization was longer in IKF group than in non-IKF group also indicating IKF as reflecting a more severe AN condition.Cardiovascular and endocrinological complications are common in AN, including impaired thyroid function. Total and free triiodothyronine levels are low, as an adaptive mechanism for conserving energy for vital functions, and normalize during weight gain.28 In addition, binging/purging subtype of AN may be more commonly associated with reduced kidney function.5 As this study was retrospective, we could not obtain data on either weight loss rate or the subtype of eating disorder.Correlation between degree of bradycardia and IKF shown in this cohort may be partly explained by hemodynamic changes due to increased parasympathetic activity and low cardiac outflow. In our study, no correlations between minimal HR and BMI, or between FT3 and BMI were seen. Median BMI percentile in this cohort was low but 40% of the AN cohort had a BMI percentile value above 40, reflecting the increased incidence of atypical AN, in which significant weight loss within the normal range occurs.Given the retrospective nature of this study, there was not sufficient information to fully characterize IKF associated conditions, including urine analysis, electrolyte abnormalities and kidney imaging. In addition, we had to approximate height data in part of the cases group. Serum cystatin C levels were not available. We could not obtain data on weight loss rate.In this study, IKF in patients with AN is common and worsens during hospitalization. SCr values may underestimate the degree of IKF. Patients with IKF had lower minimal HR and FT3 and longer hospitalization, without differences in admission BMI. Therefore, IKF may be a better marker of AN severity.


However, cardiac output was lower both at rest and during exercise, implying an elevated pulmonary vascular resistance (PVR) in DM + HC + CKD swine (153 ± 10 vs. 122 ± 9 mmHg∙L−1∙min∙kg). Phosphodiesterase 5 inhibition and endothelin receptor antagonism decreased PVR in DM + HC + CKD (− 12 ± 12 and − 22 ± 7 mmHg∙L−1∙min∙kg) but not in Healthy swine (− 1 ± 12 and 2 ± 14 mmHg∙L−1∙min∙kg), indicating increased vasoconstrictor influences of phosphodiesterase 5 and endothelin. Inhibition of nitric oxide synthase produced pulmonary vasoconstriction that was similar in Healthy and DM + HC + CKD swine, but unmasked a pulmonary vasodilator effect of endothelin receptor antagonism in Healthy (− 56 ± 26 mmHg∙L−1∙min∙kg), whereas it failed to significantly decrease PVR in DM + HC + CKD, indicating loss of nitric oxide mediated inhibition of endothelin in DM + HC + CKD. Scavenging of reactive oxygen species (ROS) had no effect on PVR in either Healthy or DM + HC + CKD swine. Cardiovascular magnetic resonance imaging, under anesthesia, showed no right ventricular changes. Finally, despite an increased contribution of endogenous nitric oxide to vasomotor tone regulation in the systemic vasculature, systemic vascular resistance at rest was higher in DM + HC + CKD compared to Healthy swine (824 ± 41 vs. 698 ± 35 mmHg∙L−1∙min∙kg). ROS scavenging induced systemic vasodilation in DM + HC + CKD, but not Healthy swine. In conclusion, common comorbidities directly alter pulmonary vascular control, by enhanced PDE5 and endothelin-mediated vasoconstrictor influences, well before overt left ventricular backward failure or pulmonary hypertension develop.Pulmonary hypertension is common in heart failure with preserved ejection fraction (HFpEF). Here, we tested the hypothesis that comorbidities  directly impair pulmonary vasomotor control in a DM + HC + CKD swine model. 6 months after induction of DM + HC + CKD, pulmonary arterial pressure was similar in chronically instrumented female DM + HC + CKD (The online version contains supplementary material available at 10.1007/s00395-021-00891-7. Pulmonary vascular disease (PVD) is prevalent in a large proportion of patients with heart failure with preserved ejection fraction (HFpEF); about one out of four patients meet the criteria of overt pulmonary hypertension (PH) in this population  pressure > 25 mmHg at rest), which is associated with increased mortality and cardiac hospitalization , 32, 60.Common comorbidities for cardiovascular disease, including diabetes mellitus (DM), hypercholesterolemia (HC), chronic kidney disease (CKD), are independently—but especially in combination—well-known risk factors for the development of HFpEF , 43. TheIn light of these considerations, we aimed to investigate the effects of a chronic pro-inflammatory state, induced by 5 months of DM, HC and CKD, on pulmonary microvascular and right ventricular (RV) structure and function. The effects of DM, HC and CKD on the systemic and pulmonary vascular function were assessed with a focus on endothelial dysfunction, and the balance between NO and ET, in chronically instrumented female swine with DM + HC + CKD at rest and during graded treadmill exercise , 55.All animal experiments were approved by the Animal Care Committee at the Erasmus University Medical Center  and in accordance with the “Guiding Principles in the Care and Use of Laboratory Animals” as approved by the National Research Council of the National Academies. 19 female Yorkshire × landrace swine (24 ± 1 kg) were included in the experimental group (DM + HC + CKD) while 18 healthy female Yorkshire × landrace swine of similar age and weight were used as controls .−1 per day i.v. on three consecutive days. The severity and stability of DM was monitored bi-weekly by measurements of blood glucose and ketone levels.The induction of risk factors in the DM + HC + CKD group has been described in detail elsewhere . Briefly−1), Sedazine  and atropine (2 mg) and artificially ventilated  isoflurane was added for anesthesia). CKD was produced by microembolization of the global right kidney as well as the lower pole of the left kidney. For this purpose, the renal arteries were catheterized under fluoroscopy guidance  with a Swan-Ganz catheter, inserted through a 9 F sheath in the right common carotid artery. Following inflation of the balloon to prevent back-flow into the aorta, 75 mg of polyethylene microspheres with a diameter of 38–42 μm  were infused in each kidney. The wound was closed and the animals were allowed to recover.2 weeks after DM induction, animals were sedated with intramuscular injection of a cocktail of Zoletil  supplemented with sodium chloride (20 g per day) was gradually introduced. The Healthy group continued to receive regular swine-chow. Animals were housed in pairs but were fed separately and had ad libitum access to drinking water.The animals were divided into two groups; one group  was chronically instrumented 5 months following induction of the risk factors, as described elsewhere , and ren−1) and antibiotic prophylaxis (25 mg∙kg−1 amoxicillin i.v.) for 7 days. All catheters were flushed daily with heparinized saline  to prevent the formation of blood clots and to ensure catheter patency  by a blinded observer and checked by a second blinded observer.B) receptor staining of the vascular endothelium was performed on 4 µm thick cryo-preserved lung tissue sections, . Arterioles ranging between 20 and 60 µm in diameter were selected and the lumen divided in four quadrants. Scores were given ranging from 0 (no ETB receptor staining in the endothelium) to 4 (endothelium completely stained for ETB receptor), by a blinded observer and checked by a second blinded observer. If more than half of the quadrant showed endothelial positive staining for the ETB receptor, the quadrant was scored positive.Endothelin B  staining on pressure fixated lung tissue in a semi-quantitative way by an experienced, blinded observer. If infiltrates were centered around pulmonary arteries and veins, the inflammation of the areas were scored from 0 to 4, 0—no inflammation; 1—partial diffuse inflammation; 2—generalized diffuse infiltration; 3—diffuse and focal dense infiltration and 4—strong focal dense infiltration. An area of at least 0.5 cmGene expression of several anti-oxidant enzymes, the endothelin system, endothelial and inducible NO synthase, and PDE5 was measured in snapfrozen lung tissue. Total RNA was isolated from bulk lung tissue samples. RNA purity and concentration were measured and cDNA synthesis  was performed using 500 ng RNA as input. Gene expression was analyzed on the CFX96 Real-Time PCR detection system  using the SensiMix SYBR-green supermix (Bioline). The genes investigated and the primers used are shown in Table Total endothelial NOS (eNOS), phosphorylated eNOS (Ser1177 site), vasodilator-stimulated phosphoprotein (VASP), phosphorylated VASP, eNOS monomer and dimer protein levels were determined in frozen, homogenized bulk pulmonary tissue samples. For detection of eNOS monomer and dimer fractions, low temperature SDS–PAGE in the absence of β-mercaptoethanol was performed as previously described . Briefly2 consumption indexed for body weight (BVO2) was computed by (cardiac output/body weight) × . SVR was calculated as mean arterial pressure/(cardiac output/body weight). Transpulmonary gradient (TPG) was computed by mean pulmonary arterial pressure − mean left atrial pressure. Pulmonary vascular resistance indexed for body weight (PVR) was computed by /(cardiac output/body weight). Ea was computed by mean pulmonary arterial pressure/(stroke volume/body weight). Compliance was computed by (stroke volume/body weight)/(systolic − diastolic pulmonary pressure). Data were tested for normality using the Shapiro–Wilk and Kolmogorov–Smirnov test. Data showing a normal distribution are presented as mean ± SEM, whereas data without normal distribution are shown as median [interquartile range (IQR)]. Statistical analysis of hemodynamic data was performed in SPSS Statistics 21.0 , using a two-way ANCOVA for treatment effects and between group differences, with BVO2 as covariate. Comparison of other variables between the two groups was performed by unpaired Student’s t test for parametric data or Mann–Whitney U test for non-parametric data. Statistical significance was accepted when P ≤ 0.05 (two-tailed), and P ≤ 0.10 (two-tailed) was accepted as a statistical trend.Off-line analysis of hemodynamics was performed using CODAS and Matlab. Hemodynamic data were averaged over 10 s. Body OAs shown in Table 2) was unaltered compared to Healthy swine   in DM + HC + CKD swine, particularly under resting conditions  and media-to-lumen ratio in vessels of ~ 80 µm diameter as well as muscularization of vessels ranging 10–30 µm in diameter were similar between Healthy and DM + HC + CKD  Fig. . RespiraVR) Fig. . Furtherons Fig. . This inA + Bi induced similar vasodilation of the systemic vasculature in DM + HC + CKD and Healthy swine , a measure of RV afterload was not changed in DM + HC + CKD Fig. . RV systP = 0.196) and the Fulton index  were unchanged. Additionally, capillary density was similar in both groups  The increase in PVR in response to NOSi was similar in DM + HC + CKD compared to Healthy swine, with unaltered eNOS protein, phosphorylation and uncoupling. Furthermore, eNOSi unmasked a vasodilator effect of subsequent ETA + Bi in Healthy swine, but not in DM + HC + CKD swine, consistent with the observed loss of pulmonary endothelial ETB receptors. (v) ROS scavenging did not induce pulmonary vasodilation in either DM + HC + CKD or Healthy swine. The implications of these findings are discussed below with a focus on PVD as an early complication of DM + HC + CKD.The present study tested the hypothesis that in a swine model with multiple comorbidities and left ventricular diastolic dysfunction, in the absence of overt left ventricular backward failure, multiple comorbidities result in functional pulmonary vascular alterations in exercising swine. The main findings were that (i) the combination of DM, HC and CKD resulted in increased systemic and pulmonary vascular resistance. (ii) The increase in pulmonary vascular resistance was principally due to changes in pulmonary vasomotor control in the absence of pulmonary vascular structural changes. (iii) ETHFpEF is a heterogeneous disorder resulting from various combinations of underlying comorbidities that is more prevalent in women , 43. To B receptors to vasoconstrictor ETA receptors is higher in women as compared to men, and ETA-mediated vasoconstriction is less pronounced in the forearm of women than men [One aspect of HFpEF that was not accounted for in the present study, is that HFpEF is predominantly present in older post-menopausal women. Indeed, sex-differences and sex-hormones are well-known to play a role in the regulation of vascular tone as well as in the development and progression of cardiovascular disease , and difthan men . Future The importance of early detection of PVD in various pathologies is increasingly recognized. In pulmonary arterial hypertension, the threshold for PH has recently been lowered from 25 to 20 mmHg , as multIn our study, the relation between cardiac index and PA pressure was shifted upwards due to an increased TPG, and PVR was higher at all levels of exercise in swine with DM + HC + CKD as compared to Healthy swine at a time that left atrial pressure was not affected, suggesting microvascular alterations in the pulmonary vasculature. Interestingly, our data show that PVD, evidenced by the elevated PVR, is present even before the increase in SVR and the presence of left ventricular diastolic dysfunction resulting in overt elevations in left atrial pressure or PA pressure. However, already at this time point, a more generalized microvascular dysfunction is present as we have recently shown in this porcine model that coronary microvascular function is also impaired .The increased PVR was accompanied by higher circulating levels of TNF-α and ET-1, further reflecting inflammation and endothelial dysfunction. The higher PVR, in the absence of an increase in PA pressure, seems to be in contrast with the general assumption that HFpEF-PH progresses from isolated post-capillary PH due to left ventricular dysfunction, to pre- and post-capillary PH , 33. AltPVD is characterized by endothelial dysfunction, impaired pulmonary vasomotor control and vascular remodeling. Endothelial dysfunction involves an imbalance between the ET and NO pathways, which may alter pulmonary vascular control. In the current study, the endogenous vasodilator influence of NO was unaltered in the pulmonary vasculature as NOSi resulted in a similar vasoconstrictor response in DM + HC + CKD and Healthy swine. These data are consistent with previous findings from our laboratory, showing that the response to NOSi was maintained in swine with PVD secondary to myocardial infarction , 56 and Further downstream in the NO-pathway, PDE5i resulted in a pulmonary vasodilation in DM + HC + CKD and normalized PVR, whereas no effect of PDE5i was observed in Healthy swine. The absence of a pulmonary vasodilator effect of PDE5i in Healthy swine is different from previous observations in which we showed a modest pulmonary vasodilator effect of PDE5 inhibition in Healthy swine , 58. ThiConflicting results have been published with respect to the efficacy of PDE5 inhibition in HFpEF-PH, and recent meta-analyses concluded that there was no beneficial effect of PDE5 inhibition on pulmonary hemodynamics or exercise capacity , 8, althConsistent with the increased ET-dependent vasoconstrictor influence on the pulmonary vasculature, circulating ET-1 levels were higher in swine with DM + HC + CKD as compared to Healthy controls suggesting either increased production or impaired clearance. The elevated ET-levels in our swine model are in accordance with human studies, showing elevated plasma ET-levels in HFpEF-PH patients correlating with PA pressures , 41, 53,A and ETB receptors are expressed in the pulmonary circulation under both physiological and pathophysiological circumstances [A is only present on vascular smooth muscle cells, mediating vasoconstriction, whereas ETB is present on both the vascular smooth muscle cell and the endothelial cells, mediating vasoconstriction and vasodilation, respectively. The lack of effect of ETA + Bi in Healthy swine may be due to a balance between ETA and/or ETB-mediated vasoconstriction and ETB-mediated vasodilation [A + Bi [A and/or ETB receptor expression or function with age. Similarly, in pathophysiological circumstances, ETA and ETB protein expression may be altered and the interaction with the NO-cGMP pathway may be altered [A + Bi produced a greater reduction in PVR in swine with DM + HC + CKD, suggesting that the balance between the vasoconstrictor and vasodilator pathways is shifted towards vasoconstriction in the DM + HC + CKD swine, and consistent with a withdrawal of endothelial ETB influence. Indeed, immunohistochemical analysis showed reduced ETB receptor staining on the pulmonary endothelium in DM + HC + CKD swine. Immunohistochemical staining of ETA receptors failed due to lack of a porcine specific antibody suitable for immunohistochemistry. Furthermore, given the partial muscularization of the pulmonary arterioles, with few smooth muscle cells surrounding the lumen, it was not possible to reliably measure ETB receptor staining of the medial layer. Nevertheless, loss of endothelial ETB receptors may result in reduced ET-1 clearance [ETmstances . ETA is dilation . Althoug [A + Bi , 37, 38, [A + Bi . The rea altered , 63. In  altered  and pulm altered , ETA + Blearance , 14, theA+Bi. These data suggest that in Healthy swine, the vasoconstrictor effect of ET, mediated through activation of the ETA and/or ETB receptors on vascular smooth muscle cells is balanced by a vasodilator influence, through the endothelial ETB receptor with subsequent activation of the NO-cGMP pathway. NOSi abrogates this vasodilator action of ETB-activation, thereby unmasking a vasoconstrictor effect of ET in the Healthy pulmonary vasculature. Conversely, in swine with DM + HC + CKD, the effect of ETA + Bi was similar in the presence and absence of NOSi, consistent with a loss of endothelial ETB receptors, which was confirmed histologically. Our data imply that an imbalance in the contribution of ETA and ETB to pulmonary vasomotor control—specifically loss of ETB-mediated vasodilation—plays an important role in the increase in PVR in our model Below is the link to the electronic supplementary material.


Acute kidney injury after cardiac surgery is characterized by specific patterns of damage and recovery that are important to consider for management and outcome. The Kidney Disease: Improving Global Outcomes (KDIGO) classification covers only part of the conceptual framework and is thus insufficient for a comprehensive diagnosis. This review highlights the strengths and limitations of the recent criteria and provides an overview of biomarkers of cardiac surgery-associated acute kidney injury (CSA-AKI). The evolving understanding of CSA-AKI as a time-sensitive condition has increased the demand to enhance the diagnostic criteria and translate biomarkers into clinical practice. Acute kidney injury (AKI) is a common but still underrecognized complication, occurring in 10 to 15% of all hospitalized patients and in almost 60% of patients admitted to the intensive care unit . CardiovWhile the term “AKI” summarizes a syndrome of acute organ damage and dysfunction with various pathophysiologies, the subset occurring after cardiac surgery is specifically referred to as cardiac surgery-associated acute kidney injury (CS-AKI). Characterizing the different entities of AKI has become increasingly important, since emerging evidence suggests that each type has unique molecular and diagnostic features and requires differentiation in treatment .The majority of patients undergoing cardiac surgical procedures present with a range of predisposing factors and comorbidities, such as advanced age, insulin-dependent diabetes mellitus, heart failure, and chronic kidney disease. It is widely recognized that these conditions are strongly associated with an unfavorable renal outcome and should therefore be addressed by risk assessments . ClinicaExposure of this at-risk population to the noxious stimuli of cardiopulmonary bypass and ischemia-reperfusion injury following aortic cross-clamp might contribute to the development of CSA-AKI. Hypoxemia and the accumulation of metabolic products cause acidosis and cellular damage. Extracorporeal circulation is associated with significant hemodynamic alterations, renal hypoperfusion, and hemolysis . The infSeveral definitions of the condition formerly known as acute renal failure have limited the comparability of clinical outcome measures and the general provision of consensus recommendations. The first standardized definition of changes in kidney function, the RIFLE  classification, was introduced in 2004 and later advanced by the Acute Kidney Injury Network, resulting in the AKIN criteria in 2007 ,17. FinaNew insights have furthered our understanding of AKI as part of a continuum, ranging from a healthy state to chronic kidney disease. The spectrum of this conceptual framework covers subclinical damage preceding KDIGO stage 1 and embeds AKI persisting beyond 7 days within the category of Acute Kidney Disease and Disorders (AKD). While renal recovery in whole or in part may begin at any point within this timeline, the persistence or progression of disease may occur as well, eventually resulting in chronic kidney disease (CKD) after a duration of 3 months  19,20].,20.19,20This conceptual change increasingly challenges the biomarkers that are used to define AKI, since serum creatinine and urine output are of limited value in predicting recovery or the progression of disease and even less fit for detecting subclinical damage.Traditional renal biomarkers still continue to be the standard of care and remain indispensable for the assessment and monitoring of kidney function. Serum creatinine is ubiquitously accessible and changes are easily recognized and can even be integrated into electronic alerts for automated detection ,22. The P = 0.004). Moreover, 8.1% of patients who presented initially with decreased urine output alone developed chronic kidney disease at day 180, compared to 5.2% of patients without AKI. The authors concluded that a decreased urine output after cardiac surgery is associated with a worse long-term outcome  × [IGFBP7] that is commercially available in several European countries and was approved in 2014 by the Food and Drug Administration in the United States  × [IGFBP7] was also challenged for its variable diagnostic performances. Recently, Grieshaber et al. reported the results from a risk-score-guided observational trial with [TIMP-2] × [IGFBP7] measurements in high-risk patients among a cohort of 613 patients undergoing cardiac surgery. [TIMP-2] × [IGFBP7] was merely predictive of early AKI 24 h after surgery  .p < 0.0001). Additionally, high preoperative levels were associated with significantly reduced long-term kidney function and were reflective of AKI-to-CKD transition  × [IGFBP7]-guided implementation of a simple care bundle consisting of the optimization of volume status and hemodynamics, functional hemodynamic monitoring, the avoidance of nephrotoxic drugs, and the prevention of hyperglycemia effectively reduced the incidence of stage 2 and 3 AKI in comparison to the control group ; = 0.034) . This tr= 0.034) ,61,62. CA consensus statement by the Acute Disease Quality Initiative Consensus Conference on the implementation of biomarkers in clinical routine to prevent, diagnose, and manage AKI proposed an advanced staging system based on biomarkers of function and damage . In thisCardiac surgery-associated AKI features specific patterns of damage and recovery that go unrecognized by recent diagnostic criteria. The role of timing as a crucial factor in the management of CS-AKI demands enhanced criteria reflective of subclinical damage. Biomarkers of CS-AKI provide additional discriminative features and are on the threshold of finding their way into clinical practice.


The radiological or interventional use of contrast medium exposes patients to a risk of contrast-induced nephropathy. Pre-existing kidney failure is a major risk factor. Point-of-Care Capillary blood creatinine tests are promising; their speed might help to optimize treatment decisions and patient care in these situations.The objective of the present study was to assess the ability of a new point of care capillary blood creatinine test  to diagnose kidney failure, relative to a standard lab-based plasma creatinine assay. A total of 113 patients 33 women (29.2%) were included. The capillary blood creatinine concentration was significantly correlated with the plasma creatinine concentration in both men ] = 0.84 [0.75 – 0.89]; p<0.001) and women . The test’s diagnostic performance was satisfactory, its sensitivity was 70% [35 – 93] in women and 78% [52 – 94] in men, and its specificity was 91% [72 – 99] in woman and 93% [84 – 98] in men.Rapid Point-of Care Capillary creatinine test is an easy-to-use, accurate tool for detecting kidney failure before a patient is exposed to procedures involving contrast medium. The POC test performed less well in patients over the age of 75 and in patients with high plasma creatinine level The useThe prevention of CIN is mainly based on the removal of modifiable risk factors  and the identification of high-risk patients  . For exa2.2.1.We performed a prospective, single-centre study of routine clinical practice in the cardionephrology outpatient unit at Ambroise Paré University Hospital . Between October 2015 and June 2016, we included all consecutive patients aged 18 or over attending the outpatient unit for diagnostic and/or interventional procedures involving the injection of iodinated contrast agent  or for nephrological or cardiovascular examinations not involving the use of iodinated contrast agent. There were no exclusion criteria. The study’s primary objective was to evaluate the diagnosis of kidney failure on the basis of the capillary blood creatinine level (Ccap) versus the plasma creatinine level (Cpl) in consecutive patients attending the cardionephrology outpatient unit. The study’s secondary objective was to evaluate the diagnosis of kidney failure on the basis of the glomerular filtration rate calculated from the Ccap (eGFRcap) versus that calculated from the Cpl (eGFRpl) in the same patients.2.2.The Ccap was measured with a POC test  used routinely in the outpatient unit. After the patient had fasted overnight, a nurse collected a drop of capillary blood from the finger, placed it on the device’s test strip, and inserted the strip into the reader. The result (expressed in μmol/l) was given 25 seconds later. The assay method is based on the transformation of creatinine into hydrogen peroxide, as catalysed by three enzymes in the following reactions:® CREA, Ortho Clinical Diagnostics, Raritan, NJ, USA that had been calibrated with IDMS. The fasted patient’s blood sample was collected by venepuncture of the arm with a 22 gauge needle and sent to the hospital’s central laboratory. The laboratory estimated the eGFRpl from the plasma creatinine level, using the CKD-EPI equation.The hydrogen peroxide was then detected electrochemically; the redox reaction generates a current that is directly proportional to the creatinine concentration in the sample . Althoug2.3.2, according to the CKD-EPI equation. Quantitative variables were expressed as the mean ± standard deviation (SD), and qualitative variables were expressed as the frequency (percentage). The degree of correlation between the capillary blood measurements (Ccap and eGFRcap) and the plasma measurements (Cpl and eGFRpl) was assessed by calculation of Pearson’s correlation coefficient (r). The level of agreement between the capillary and plasma measurements was evaluated by calculation of the intraclass correlation coefficient (ICC) and graphically in a Bland-Altman plot.The thresholds for kidney failure were a creatinine level of 110 μmol/l for men and 96 μmol/l for women, and an eGFR below 60 ml/min/1.73mhttp://www.R-project.org.The performance indicators (Sensitivity (Se) and Specificity (Sp)) for the diagnosis of kidney failure on the basis of the capillary blood measurements (Ccap and eGFR cap) with the Stat Sensor X-press versus the plasma measurements (Cpl and eGFRpl) were calculated, and a receiver operating characteristic ROC curve was used to determine the eGFRcap threshold for a diagnosis of kidney failure. All statistical analyses were performed with R Core Team (version 3.2.3. 2013). R a language and environment for Statistical computing. R Foundation for Statistical Computing, Vienn, Austria. URL 3.3.1.2 in 79 patients (69.9%), between 30 and 60 ml/min/1.73m2 in 24 (21.2%), between 15 and 30 ml/min/1.73m2 in 6 (5.3%), and below 15 ml/min/1.73m2 in 4 (3.6%).A total of 113 patients (33 women (29.2%)) were included in the study. The median age was 67, and the mean ± SD age was 64.8 ± 14.4 overall, 64.9 ±17.1 for the women, and 64.8 ± 13.2 for the men. Thirty-one patients (27.4%) were over 75. The general characteristics of the study population are summarized in 3.2.Ccap was significantly correlated with Cpl in both men  and women  . Further3.3.There was a good degree of correlation between eGFRcap and eGFRpl  . Likewis3.4.2. This threshold gave a true positive rate of 80%, a false positive rate of 6.4%, and an area under the curve of 0.963. Seven patients were classified as false negatives , according to eGFRcap. Five of the seven were over the age of 75, and the other two were respectively 70 and 74 years old.The sensitivity [95%CI] for diagnosis of kidney failure using Ccap was 70% [35 – 93] in women and 78% [52 – 94] in men. The specificity was 91% [72 – 99] in women and 93% [84 – 98] in men. The sensitivity for diagnosis of kidney failure using eGFRcap was 80% [62 – 91], and the specificity was 92% [84 – 97]. A receiver operating characteristic curve analysis showed that the eGFRcap threshold for kidney failure was 60 ml/min/1.73m4.The Stat Sensor X-press POC capillary blood creatinine test can be easily used to diagnose kidney failure at the patient’s bedside prior to an examination involving an injection of iodinated contrast agent. The diagnostic sensitivity and specificity were 70–78% and 91–93%, respectively for women and men. Our study population was representative of patients at a high risk of developing CIN because they were elderly and had cardiovascular risk factors. The median age was 67, and a third of the patients were over 75. The performance of capillary creatinine measurements has been evaluated in several studies, the main results of which are summarized in 2=0.9328); again, however, there was negative bias (−30%) at higher creatinine values. The SD of the estimation was 20 μmol/l for Cpl values between 100 and 200 μmol/l. Our results are in line with these studies, i.e. a close correlation between Ccap and Cpl but notable bias at higher values of Cpl. However, the patients in whom notable bias was identified all had a Ccap value that enabled an unambiguous diagnosis of kidney failure and thus the adoption of the measures to prevent CIN. The significant bias in patients with late-stage kidney failure might be due (at least in part) to analytical interference by high blood concentrations of urea. In fact, urea is an intermediate product of the enzyme reaction used in the POC test device and inhibits the hydrolysis of creatinine into sarcosine and urea.The Nova StatSensor’s analytical performances have also been evaluated in a Canadian study  16]. Th. Th16]. In patients under the age of 75, the ability of Ccap and eGFRcap to diagnosing kidney failure prior to the performance of diagnostic and/or therapeutic procedures involving an iodinated contrast agent appears to be acceptable. In patients aged 75 and over, the diagnostic performance of Ccap or eGFRcap appears to be less good. However, this point should be confirmed in additional studies of a larger number of elderly participants; our sample size in this age class was low.5.Our study confirmed the value of a POC capillary blood creatinine test for diagnosing (at least in patients under the age of 75) kidney failure prior to the injection of iodinated contrast agent in an emergency setting – i.e. when the turnaround time for a lab assay is too long. The rapid, simple, reliable identification of patients with impaired renal function may have a significant impact in daily practice by enabling the implementation of preventive measures and thus limiting the risk of CIN. POC capillary blood creatinine test for is promising because it is an easy-to-use, accurate tool that gives quick results. Further studies in elderly populations are warranted because the false positive rate in this age class is still too high.