Asthma exacerbation is defined as an acute attack of shortness of breath with more than 25% decrease in morning peak flow compared to the baseline on 2 consecutive days, which requires immediate standard therapy. The majority of asthmatic patients are considered to be steroid-sensitive; however, corticosteroid-resistant asthma is a subset of asthma with poor response to corticosteroids and is responsible for frequent hospital admissions. In this study we aimed to compare the effects of two enhancing strategies, the nebulized ketamine and IV magnesium sulfate, in treatment of severe steroid resistant asthma.This double-blind randomized clinical trial was conducted on patients who presented to a referral clinic in Alborz, Iran. Using random allocation, patients were divided into two groups. The first group was treated with nebulized ketamine and the second group was treated with intravenous magnesium sulfate. Peak expiratory flow rates were assessed before the intervention, 30 and 60 min after the intervention and compared with the aid of SPSS software.4 groups, there was no statistically significant difference across both groups.The Peak expiratory flow rates before the intervention, 30 min and 60 min after the intervention was statistically significantly different in both ketamine and magnesium sulfate groups. Peak expiratory flow rates change between 0 and 60 min were 29.4 and 15.2% in the ketamine and magnesium sulfate group respectively. Although the ketamine group showed much higher increase in mean PEFR compared to the MgSOOur study concluded that combined with standard therapy, both ketamine and IV magnesium sulfate are effective agents in the improvement of PEFR in patients with acute severe asthma that failed to respond to traditional therapies. However, there were no statistically significant difference between the two groups. Asthma is a heterogenous chronic respiratory disease usually characterized as reversible airflow obstruction that presents with symptoms including shortness of breath, wheezing and cough caused by airway hyperresponsiveness to stimuli . The pat2-adrenergic agonists. However, corticosteroid-resistant asthma is a subset of asthma with poor response to corticosteroids and is responsible for frequent hospital admissions in approximately 5–10% of asthmatic patients [The majority of asthmatic patients are considered to be steroid-sensitive, which is defined as achievable disease control with the aid of glucocorticoids and βpatients . The exapatients –10.For steroid-resistant asthma, second-line pharmacological therapies are currently being tested. They consist of steroid-sparing medications including magnesium sulfate, parenteral beta-2 agonist, intravenous (IV) aminophylline, or ketamine. However, there is no consensus regarding their therapeutic benefits and superiority. Ketamine for instance, is a sedative/analgesic agent mainly used for procedural anesthesia. However, its putative beneficial effects in bronchospasm management of SR asthma are less clear. Limited studies have shown promising results regarding its effects on bronchodilation and treatment of recurrent SR asthma due to its sympathomimetic properties, particularly in children . IntraveThis randomized double blind clinical trial was conducted on patients who referred to emergency department of Shahid Rajaei Educational and Medical Center, Alborz, Iran from 2019 to 2020 with the chief complaint of severe asthma exacerbation*. Also, all patients who were aged between 18 and 65 years and patients who showed resistance to corticosteroids as a treatment for asthma exacerbation, were included in this study. Furthermore, patients who had the history of ketamine and sulfonamide sensitivity reaction in addition to the patients who did not consent were excluded from the study. The sample size was calculated to be 35, in which Zα =1.96, Zβ = 0.85, S = 62, d = 42 :*Severe asthma defined as failure to improve symptoms, blood oxygen saturation and persistent respiratory distress (peak expiratory flow < 50%) following first-line regimen administration. As we mentioned before, the first-line treatment options include IV hydration, oral/IV corticosteroids, nebulized beta-2 adrenergic  and muscarinic anticholinergics.4 was infused intravenously over a period of 20 min. Patients of both groups were assessed for PEFR 30 min and 60 min after the intervention by a peak flow meter  after a deep inhalation with the same measurement technique.Patients were chosen to be in the ketamine and magnesium sulfate groups based on a 1:1 allocation using block randomization method and GraphPad Software. Both groups received primary treatments at first and patients in the ketamine group received nebulized ketamine (0.1–0.3 ml/kg); for patients in the magnesium sulfate group 2 g of MgSOData were entered to version 25 of SPSS software for final analysis. Quantitative variables were reported as mean ± SD and qualitative variables were reported as numerical (percentage) data. The Anderson-Darling test was used for assessing the normality of data. Considering the normality of data based on the Anderson-Darling test, two-way repeated measures ANOVA was used for analyzing PEFR changes between two groups. Furthermore, independent t-test was used for measuring the differences of PEFR between two study groups.4. There were not any significant differences between groups in terms of gender distribution . The mean of age in ketamine and MgSO4 groups was 39.4 ± 9.7 and 41.9 ± 11.5 respectively. Also, there were not any significant differences in the context of age between two groups .Seventy patients were enrolled in this study with mean age of 40.9 ± 10.6. There were 36 (51.43%) male subjects and 34(48.60%) females, which were divided into two groups of ketamine and MgSOn = 13). According to Table P-value < 0.001) . Accordingly, both groups showed significant reduction in hospital admission. However, there were no statistically significant difference between two groups (ketamine and MgSO4) in terms of rate of hospitalization . In the MgSO4 group, the mean value of PEFR in patients before the intervention was 332.85 ± 74.72. Moreover, the values of PEFR 30 min and 60 min after MgSO4 administration were 345.57 ± 71.80 and 356.28 ± 71.98, respectively . Although the ketamine group showed much higher increase in mean PEFR compared to the MgSO4 groups, there was no statistically significant difference across both groups   showed promising results in treatment of severe SR asthma. However, the PEFR improvements were not significant between the two groups. To the best of our knowledge, this is the first study which compares the effects of nebulized ketamine and magnesium sulfate in the SR severe asthma exacerbation.In the current study, the effects of ketamine and magnesium sulfate in the cases of steroid-resistant (SR) asthma were evaluated. This study reveals that nebulized ketamine can significantly improve PEFR in steroid resistant asthma exacerbation. Also, intravenous magnesium sulfate  after 30, and 60 min of ketamine administration. Additionally, administration of the nebulized form of ketamine has no influence on central respiratory response compared to the intravenous form of ketamine. Thus, using the nebulized ketamine seems to be the safer treatment option, since it lacks the respiratory depression side effect of IV ketamine.Ketamine is a rapid-acting phencyclidine derivative with analgesic, sedative, and anti-emetic properties . It can Accordingly, Betts et al. in 1971 demonstrated the effect of ketamine on asthmatic patient for the first time . In the 4 probably provides desirable results in severe SR acute asthma in adult patients treated with conventional bronchodilators. In addition, we concluded that 2 g IV MgSO4 administration through 30 to 60 min, reduces hospital stay and improves PEFR significantly. Rowe et al., observed the similar results regarding the effects of IV MgSO4 as an adjuvant therapy [Magnesium sulfate on the other hand, is a cellular hemostatic agent involved in histamine, and acetylcholine release leading to bronchodilation. It can also cause bronchial smooth muscle relaxation by interfering with calcium influx . The cur therapy . Previou therapy . However therapy . General therapy .The last-line pharmacologic treatment for SR asthma includes cyclosporine, dapsone, gold salts, intravenous immunoglobulin (IVIG), and hydroxychloroquine. However, the majority of these medications are associated with significant risk of side effects and there are limited studies confirming their safety and efficacy. For instance, Alexander et al.  conclude4 are highly effective in treatment of severe steroid-resistant asthma exacerbation in adults. Additionally, nebulized form of ketamine showed more desirable effects on improvement of respiratory function and decreasing hospital stay compared to IV MgSO4. However, these differences were not statistically significant.Overall, our study suggests that combined with standard therapy both ketamine and IV MgSO4.A potential limitation of this study is the lack of interfering factors such as duration of asthma, number of previous attacks, severity of previous attacks and comorbidities in the study. It would be useful for future studies to consider these factors. Methodological limitations were small sample size, and short follow-up time. Also, another limitation of this study might be the fact that magnesium sulfate was administered as a standard dose of 2 g intravenously compared to ketamine, which was administered through a dose-dependent fashion with a nebulizer. However, it must be taken into consideration that the role of inhaled magnesium sulfate in management of severe steroid-resistant asthma is not generally recommended, which was the main reason for the use of IV MgSO4. However, there were no statistically significant difference between the two groups.Our study concluded that combined with standard therapy, both ketamine and IV magnesium sulfate are effective agents in the improvement of PEFR in patients with acute severe asthma that failed to respond to traditional therapies. Also, our study demonstrated that both therapies are generally effective in relieving bronchospasm and increasing blood oxygen saturation in severe steroid-resistant asthmatic patients. Additionally, nebulized form of ketamine showed more desirable effects on improvement of respiratory function and decreasing hospital stay compared to IV MgSO


Endovascular treatment is standard of care for transplant renal artery stenosis (TRAS). No study has evaluated long-term outcomes compared between percutaneous transluminal renal angioplasty (PTRA) and PTRA with stenting (PTRAS). Accordingly, this study aimed to investigate the 1-year clinical success, and short- and long-term event-free survival between PTRA and PTRAS in patients diagnosed with TRAS at Thailand’s largest national tertiary referral center.This single-center retrospective study included kidney transplant patients treated for TRAS during January 2001 to June 2019. Clinical success was defined as (1) increase in estimated glomerular filtration rate (eGFR) > 15%, or (2) reduction in mean arterial pressure (MAP) > 15% with no decrease in antihypertensive medication, or no reduction in MAP or reduction in MAP < 15% with decrease in antihypertensive medication. Incidence of kidney transplant graft failure and transplant renal artery stenosis were also collected.. 77.4%, p = 0.845) and BP reduction  at 1 year were similar between the PTRA and PTRAS groups. Compared between PTRA and PTRAS, event-free survival for composite of kidney transplant graft failure or transplant renal artery restenosis was significantly higher for PTRAS at 1 year , but not significantly different at 10 years .Sixty-five cases of TRAS were identified from 1072 patients who underwent kidney transplantation. The majority (98.5%) had end-to-side anastomosis technique. Thirty-four patients had PTRA, while 31 patients had PTRAS. One-year clinical success according to renal outcome and BP reduction was 78.5% and 49.2%, respectively. Both renal outcome (79.4% vsWe demonstrated the 1-year clinical success, and short- and long-term event-free survival between PTRA and PTRAS in TRAS patients. One-year clinical success was found to be similar between groups. Event-free survival for composite of kidney transplant graft failure or transplant renal artery restenosis was significantly higher in PTRAS at 1 year, but similar between groups at 10 years.Trial registration Thai Clinical Trials Registry, TCTR20200626002. Registered 26 June 2020—Retrospectively registered, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trial search&smenu = fulltext&task = search&task2 = view1&id = 6441 Organ transplantation is an essential medical advancement that can help patients return to living a normal life. The number of patients being treated by kidney transplantation (KT) in Thailand is increasing . More thEven though PTRA/PTRAS in TRAS has been studied in some retrospective reviews and a meta-analysis , the outThis single-center retrospective cohort study enrolled TRAS patients who underwent PTRA or PTRAS treatment at the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand during the January 2001 to June 2019 study period. The protocol for this study was approved by the Siriraj Institutional Review Board (SIRB) (COA no. 289/2017). This study complied with all of the principles set forth in the Declaration of Helsinki (1964) and all of its later amendments. We sought out all patients aged > 15 years who had either or both of the following International Classification of Diseases (ICD-10) codes: (1) kidney transplant status (ICD-10 Diagnosis Code Z94.0) and/or (2) renovascular hypertension (ICD-10 Diagnosis Code I15.0) with ICD 9 CM code 3950 Angioplasty of other non-coronary vessel or ICD 9 CM 3990 Insertion of non-drug-eluting peripheral vessel stent. Medical records were reviewed. Patients with TRAS who underwent PTRA or PTRAS were included. Patients with primary allograft disease, urologic complication, or infection were excluded.We collected and recorded the patient clinical presentation that led to a diagnosis of TRAS. Non-invasive test , or magnetic resonance angiography (MRA) was used for the initial investigation. The Doppler diagnostic criteria for TRAS was peak systolic velocity (PSV) 200 cm/s or increase in PSV by 50% within stenotic segment or jet aliasing –11. The All invasive endovascular procedures were performed in an inpatient setting. Risk and benefit were discussed with the patient according to standard preoperative protocol. Ipsilateral common femoral artery puncture followed by selective renal angiogram was performed in the transplanted kidney to confirm a diagnosis of TRAS if the stenosis was greater than 50%. Digital subtraction angiography (DSA) criteria was defined ≥ 50% luminal narrowing –16. The The primary endpoint was one-year clinical success after PTRA/PTRAS, which was defined, as follows: (1) Increased estimated glomerular filtration rate (eGFR) > 15% within 1 year or (2) Reduced mean arterial pressure (MAP) > 15% with no decrease in antihypertensive medication, or no reduction in MAP or reduction in MAP < 15% with decrease in antihypertensive medication within 1 year. This primary endpoint was chosen according to prior publication , 13, 14.Kidney transplant graft failure was defined as failure of graft function for any reason that ultimately required renal replacement therapy and/or retransplantation  Transplat-test  or Mann–Whitney U test . Event-free survival was determined using Kaplan–Meier survival analysis. A p-value of less than 0.05 was considered statistically significant. All statistical analyses were performed using SPSS Statistics v.18.0 .Categorical data were presented as frequency and percentage, and continuous variables were reported as mean ± standard deviation for normally distributed data or as median and interquartile range  for non-normally distributed data. Categorical data were compared using chi-square test or Fisher’s exact test, and continuous data were compared using Student’s Our hospital’s database revealed that 1,072 kidney transplants were performed at our hospital during January 2001 to June 2019. Among those cases, 67 TRAS patients were identified  in the PTRA group received bailout stenting. Patient data up to the last follow-up recorded in the medical record were included in our analysis. The longest follow-up was 146 months, with a median follow-up period of 54 months . All patients were treated by ad hoc procedure after angiogram confirmation of TRAS diagnosis, and the procedural success rate was 100%. Minor complications occurred in 2 patients, including non-flow limited dissection in 1 patient, and hematoma at the puncture site in the other patient.p = 0.166). The mean systolic BP and MAP decreased immediately after successful PTRA/PTRAS, while DBP decreased at a slower pace. MAP had clinical reduction for up to 6 months after revascularization. Mean blood pressure was not significantly different between the PTRA and PTRAS groups during the follow-up period. PTRAS was shown to have superior event-free survival for composite outcomes of kidney transplant graft failure or transplant renal artery restenosis at 1 year compared to PTRA . However, event-free survival for composite outcomes of kidney transplant graft failure or transplant renal artery restenosis at 10 years was similar between PTRA and PTRAS.Clinical outcomes are summarized in Table There were 13 cases with restenosis at the target lesion, and all cases were detected due to worsening renal function or uncontrolled hypertension. Median time from revascularization to restenosis was 18.0 months . Three cases in the PTRA group had transplant renal artery restenosis at 4.6 months, 5 months, and 11 months, respectively. None of those 3 patients required renal replacement therapy within 1 year. Event-free survival for transplant renal artery restenosis at 1-year was 95.4%, which was not significantly different between the PTRA and PTRAS groups. Event-free survival for transplant renal artery restenosis at 10 years was 80.0%, which was also not significantly different between groups . Three cases in the PTRA group had kidney transplant graft failure at 1 month, 3 months, and 4 months, respectively. Event-free survival for kidney transplant graft failure at 1-year was 95.4%, with no statistically significant difference between PTRA and PTRAS. Event-free survival for kidney transplant graft failure at 10 years was 89.2%, which was also not significantly difference between PTRA and PTRAS . Event-free survival for composite outcomes of kidney transplant graft failure or transplant renal artery restenosis at 10 years was 72.3%, which was not significantly different between groups , followed by post-anastomosis (35.4%). One-year clinical success according to renal outcome was 78.5%, and according to blood pressure reduction was 49.2%, Neither of those two outcomes were significantly different PTRA and PTRAS groups. Event-free survival for composite outcomes of kidney transplant graft failure or transplant renal artery restenosis was significantly higher in the PTRAS group at 1-year, but no significant difference between groups at 10 years.vs. 5 PTRAS patients. [Our study is unique in that it compared long-term 10 years outcomes between PTRA and PTRAS. Prior retrospective studies addressed the technical success, patency, and reintervention rates –8, 13; hatients.  Marini eatients.  demonstrPost-transplant graft loss can be caused by several reasons, including host immune response, graft rejection, primary allograft disease, infection, de novo glomerular disease, and vascular complication , 20. IncTo date, no randomized controlled studies have been conducted that establish the best context-appropriate treatments for TRAS. However, endovascular treatment has become the most frequently used method for revascularization in TRAS. PTRA/PTRAS is less invasive, has a shorter procedure duration time, allows faster recovery, and has fewer complications than surgery. PTRA was reported to be associated with a restenosis rate of 16–62%, while PTRAS was reported to have a restenosis rate of < 10%. , 27–29 WThe majority of TRAS in our study were stenosis at the anastomosis site, which suggests pathophysiology due to surgery-related fibrosis and scarring at the anastomosis site. This explains why only PTRA had a favorable long-term outcome in our study. This study addressed the advantages and disadvantages over the long-term between PTRA and PTRAS. Since TRAS supply the only kidney, the first strategy of treatment is PTRAS to reassure the patency of the remaining vessels. The second strategy is PTRA with bailout stenting if no major dissection is required, there is only < 20% residual stenosis, and there is no acute vessel closure. Stenting could be avoided. The second strategy may increase the risk of vessel closure, future restenosis, and renal transplant graft failure. In the present study, 6 of 34 patients in the PTRA group had either kidney transplant graft failure or transplant renal artery restenosis at 1 year. PTRAS had a higher event-free survival for composite of kidney transplant graft failure or transplant renal artery restenosis at 1 year, but event-free survival for composite of kidney transplant graft failure or transplant renal artery restenosis at 10-year was similar between the PTRAS and PTRA groups.This was a retrospective study. We did not directly compare between PTRA and PTRAS using a prospective randomized trial design, but we used the procedural entity to separate the group. Bias of referral pattern to specialist and specialist procedural preferences cannot be excluded. There existed the potential for more procedural complexity, more challenging lesion, and more unsatisfactory angiographic outcome after PTRA in the PTRAS group. Even though initial degree of renal artery stenosis between PTRA and PTRAS was not significantly different, we cannot exclude selection bias between two groups. We used only bare metal stent in all cases included in this study. Few studies reported a better outcome with drug-eluting stent, especially in arteries less than 5 mm in diameter . HoweverThis study did not show a significant difference in long-term outcome between PTRA and PTRAS in TRAS. However, our small sample size may have limited the statistical power of our study to identify all significant differences and associations between groups. Sample size required 213 patients per group for sufficient statistical power, and we were only able to identify a total of 65 patients.Endovascular treatment is a preferred treatment for TRAS. Due to the limited number of patients undergoing this procedure, there is no long-term outcome for PTRA versus PTRAS. We demonstrated similar 1-year clinical success between PTRA and PTRAS in TRAS patients; however, PTRAS was shown to confer superior event-free survival for composite outcome of kidney transplant failure or transplant renal artery restenosis at 1-year, but the results between groups were similar at 10 years. A larger-scale prospective multicenter study is needed to more accurately determine the outcome differences between PTRAS and PTRA in TRAS.


The real‐world relationships between the demographic and clinical characteristics of asthma patients, their prehospitalization management and the frequency of hospitalization due to asthma exacerbation is poorly established.To determine the risk factors of recurrent asthma exacerbations requiring hospitalizations and evaluate the standard of baseline asthma care.A territory‐wide, multicentre retrospective study in Hong Kong was performed. Medical records of patients aged ≥18 years admitted to 11 acute general hospitals from January 1 to December 31, 2016 for asthma exacerbations were reviewed.There were 2280 patients with 3154 admissions . Among them, 1830 (80.3%) had at least one asthma‐associated comorbidity, 1060 (46.5%) and 885 (38.9%) of patients had Accident and Emergency Department (AED) attendance and hospitalization in the preceding year, respectively. Patients with advancing age (incidence rate ratio [IRR]: 1.003 for every year increment), a history of AED visits or hospitalization  for asthma exacerbation in the preceding year, the presence of neuropsychiatric (IRR: 1.142) and gastrointestinal (IRR: 1.154) comorbidities were risk factors for an increasing number of admissions for asthma exacerbation. For patients with ≥2 admissions, 17.1% were not prescribed inhaled corticosteroid and only 44.6% had spirometry checked before the index admission. Asthma phenotyping was often incomplete, as assessment of atopy  was only performed in 30 (5.8%) patients with ≥2 admissions.Improving asthma care, especially in elderly patients with a prior history of urgent healthcare utilization and comorbidities, may help reduce healthcare burden. Suboptimal management before the index admission was common in patients hospitalized for asthma exacerbations. Early identification of patients at risk and enhancement of baseline asthma management may help to prevent recurrent asthma exacerbation and subsequent hospitalization. AEDAccident and Emergency DepartmentBDbronchodilatorCOPDchronic obstructive pulmonary diseaseFEV1forced expiratory volume in 1 sFVCforced vital capacityGINAGlobal Initiative for AsthmaGOPCgeneral outpatient clinicICSinhaled corticosteroidsICUintensive care unitIgEimmunoglobulin EIMVinvasive mechanical ventilationIQRinterquartile rangeIRRincidence rate ratioMAmultiple admissionsPEFRpeak expiratory flow rateRASTradioallergosorbent testSAsingle admissionSABAshort‐acting beta‐agonistSAMAshort‐acting muscarinic antagonist1Asthma is the most prevalent chronic respiratory disease worldwide.2This was a territory‐wide, multicentre retrospective study in Hong Kong. Eleven acute general public hospitals participated in this study.2.1By using the International Classification of Diseases, Ninth Revision, Clinical Modification code 493.xx, each participating hospital identified all admissions to the medical department with a primary hospital discharge diagnosis of asthma exacerbation over 12 months . Asthma exacerbation was defined as an event characterized by a worsening of asthma control status requiring the use of systemic corticosteroids (OCS), or an increase from a stable maintenance dose, for at least 3 days.All relevant electronic and paper medical records of the included admissions were reviewed manually by respiratory specialists of the corresponding hospital. Patients who were ≥18 years old on the day of admission were included in the analysis. Patients with an inappropriate diagnosis of asthma exacerbation or incomplete drug records were excluded. Patients admitted to different hospitals were cross‐referenced to verify the exact number of admissions in the Year 2016.2.2Clinical information of the patients including baseline demographics, asthma‐related comorbidities, asthma history and related care including a history of prior severe asthma exacerbation requiring intensive care unit (ICU) admission and invasive mechanical ventilation (IMV), use of urgent healthcare utilization due to asthma exacerbation in the preceding year, assessment of symptom control ,Comparisons were performed between patients with single admission  and multiple admissions  for asthma exacerbation in the Year 2016, to identify the patient‐based risk factors for recurrent exacerbations requiring hospitalizations. Comparisons were also performed between patients with and without long‐term follow‐up, to evaluate any difference in the baseline characteristics.2.3SD, median with interquartile range (IQR) and absolute number with percentage as appropriate. Comparison between patient groups was performed by chi‐square or Fisher's exact test for categorical variables, and independent t test or Mann–Whitney U test for continuous variables. Significance of potential risk factors for asthma exacerbations leading to hospitalization was identified by Poisson regression analysis. All tests were two‐tailed, and a value of p < .05 was considered significant.Data were analyzed by the Statistical Package of the Social Science Statistical Software (SPSS) for Window, Version 26 (IBM SPSS In.c). The demographic and clinical characteristics were presented with descriptive statistics, as mean with 2.4Ethics application was approved by the corresponding clinical research ethics committee for each participating hospital, with the name of committees and approval reference numbers listed as follow: Joint Chinese University of Hong Kong‐New Territories East Cluster Clinical Research Ethics Committee (CREC 2017.503), Research Ethics Committee  , Kowloon West Cluster Research Ethics Committee (KW/EX‐17‐148(117‐15)), Hong Kong East Cluster Research Ethics Committee (HKECREC‐2017‐082) and Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster (UW 17‐507) (Table S1). Patient consent was exempted by the committees as it was a retrospective study and no patient identifiers were obtained. The study was conformed to the standards of the Declaration of Helsinki.3A total of 3515 admissions were identified. After manual review of records, 361 admissions were excluded due to inappropriate discharge coding (343), incomplete drug records (15) and duplication of patients (3). Data of 3154 hospitalization episodes from 2280 patients remained for analysis.3.1The baseline demographics, clinical characteristics, healthcare utilization related to asthma exacerbation and drug prescription are listed in Table 3.2Most  patients had the onset of asthma ≥18 years old. A total of 162 (7.1%) and 137 (6.0%) patients required ICU admission and IMV for asthma exacerbations respectively, while 885 (38.9%) patients were hospitalized, and 1060 (46.5%) attended the AED at least once for asthma exacerbation in the preceding year.9/L. About one‐third of patients  had spirometry done before. Total serum IgE was checked in 138 (6.1%) patients. Adequate atopic phenotyping, with total serum IgE plus either allergy skin prick tests or RAST, were performed in 60 (2.6%) patients of the whole cohort and 30 (5.8%) MA patients  and 127 (5.6%) patients had that in public and private sectors respectively, with 368 (16.1%) patients either had no regular follow‐up for asthma. Before the index admission, blood eosinophil count was available for most patients , with a median count of 0.2 (IQR: 0.1–0.4) × 103.3A total of 1470 (64.5%) patients received ICS‐containing regimen for asthma, while 782 (34.3%) patients were receiving Step 1 treatment of GINA in the Year 2016 with no controller medication. Use of long‐term OCS and biologics were both uncommon  had either partly controlled or uncontrolled asthma, defined by the GINA 2016 recommendation,3.5Significant differences in various aspects existed between patients with and without long‐term follow‐up Table . Patient3.6For asthma exacerbations, 1761 and 519 patients had SA and MA in the Year 2016, respectively. Figure 3.79/L was not significantly associated with hospitalizations.Clinical factors significantly associated with MA were included in the Poisson regression analysis Table . Factors4This large, multicentre, territory‐wide retrospective study evaluated the relationships between patients' demographic, clinical characteristics, baseline disease management, level of asthma control, and severe exacerbation requiring hospitalization. Similar to other large asthma studies, our cohort had a predominance of elderly, female, nonsmokers and a high prevalence of asthma‐associated comorbidities.Ageing and asthma‐related comorbidities increase the risk of severe asthma exacerbation and healthcare costs.9/L and more severe exacerbations, however, could not be confirmed by our study.The difference between SA and MA patients in our study also shared some other similarities with previously reported cohorts, while retaining its unique features. MA patients had significantly lower pre‐ and postbronchodilator spirometric parameters than SA patients.The level of asthma control captured in our cohort fell far short of the goals for long‐term management in international guidelines. Although it has long been recognized in community‐based studies worldwide,Asthma care should be optimized by overcoming management gaps for several groups of asthma patients. Patients on GINA Steps 4 and 5 treatment and had multiple hospitalizations for asthma exacerbations , and those with either partly controlled or uncontrolled asthma before the index admission , should have early and regular review as an important part of their usual care. Optimal care should include a proper assessment of asthma control, identify and prevent the triggers of asthma exacerbations, review diagnosis and medications adherence, and suitable pharmacological treatment. Treatment with biologics in appropriately selected patients should be considered as they have been shown to reduce exacerbations, including those required AED visit and hospitalization, and maintain disease control.The biggest strength of this multi‐center territory‐wide study is that it comprised a large patient population from 11 participating general hospitals which covered 70% of all emergency admissions to the public healthcare sector in Hong KongThere are several limitations related to the study design. The retrospective study has its intrinsic disadvantage in understanding the complex interaction between asthma exacerbation and different clinical factors, including drug adherenceIn conclusion, we examined the baseline clinical characteristics of asthma patients and identified risk factors associated with multiple hospitalizations for asthma exacerbation in this territory‐wide retrospective review. Patients with increasing age, an increasing number of hospitalizations or AED visits for asthma exacerbation in the preceding year, the presence of neuropsychiatric or GI comorbidities, and the use of ICS at the baseline were associated with an increasing number of hospitalizations due to asthma exacerbation. We have also found significant management deficiencies before their index admission for severe asthma exacerbations. Targeting these at‐risk patients with appropriate management strategy including pharmacologic (ICS‐containing medications and biologics) and nonpharmacologic (proper assessments and education) measures may reduce the risk of severe exacerbations and in turn the economic burden of asthma.The authors declare that there are no conflict of interests.Ka Pang Chan had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis, including and especially any adverse effects.Fanny Wai San Ko, Kwun Cheung Ling, Pik Shan Cheung, Lee Veronica Chan, Yu Hong Chan, Yi Tat Lo, Chun Kong Ng, Macy Mei‐sze Lui, Kwok Sang Wilson Yee, Cee Zhung Steven Tseng, Pak Yiu Tse, Mo Lin Maureen Wong, Kah Lin Choo, Wai Kei Lam, Chun Man Wong, Sheng Sheng Ho, Chung Tat Lun, and Christopher Kei Wai Lai contributed substantially to the study design, data analysis and interpretation, and the writing of the manuscript.5


For the analysis of eNose signals, principal component (PC) and linear discriminant analysis (LDA) were performed. LDA, based on PC1-4, reliably discriminated between patients who had a recent exacerbation from those who had not (training receiver operating characteristic (ROC)–area under the curve (AUC) = 0.76,95% CI 0.69–0.82), . Our study showed that, exhaled breath analysis using eNose could accurately identify asthma patients who recently had an exacerbation, and could indicate that asthma exacerbations have a specific exhaled breath pattern detectable by eNose.Asthma is a chronic respiratory disease that can lead to exacerbations, defined as acute episodes of worsening respiratory symptoms and lung function. Predicting the occurrence of these exacerbations is an important goal in asthma management. The measurement of exhaled breath by electronic nose (eNose) may allow for the monitoring of clinically unstable asthma and exacerbations. However, data on its ability to perform this is lacking. We aimed to evaluate whether eNose could identify patients that recently had asthma exacerbations. We performed a cross-sectional study, measuring exhaled breath using the SpiroNose in adults with a physician-reported diagnosis of asthma. Patients were randomly divided into a training ( Asthma is a common chronic disease that affects approximately 5% to 10% of the global population with an increasing prevalence . It is cConsidered now to be key in defining the severity of the disease, exacerbations and their prevention is an important metric to measure the success of asthma treatments. Currently, biomarkers such as sputum eosinophils have shown some utility in monitoring and assessing disease severity, but are not predictive, and are often complex and invasive . InsteadThe analysis of metabolites in exhaled breath using an electronic nose (eNose) is a non-invasive technique that shows promise. It detects patterns of volatile organic compounds (VOCs) that may reflect (patho)physiological changes related to chronic airway inflammation . PreviouThe analysis of breath profiles using a quick and non-invasive technique such as eNose, may allow for the identification of asthma instability. However, to date, the supporting data is limited. Consequently, assessing whether it is possible to detect a recent asthma exacerbation using eNose would be an important first step in exploring its potential. We hypothesized that asthma patients with a recent exacerbation display a different exhaled breath profile compared to those without a recent exacerbation.In total 361 asthma patients were included in the analysis; 252 were randomly allocated to the training dataset and 109 to the validation dataset. The number of patients with exacerbations was 41 in the training set (16.3%) and 11 (10.1%) in the validation set. Baseline patient characteristics of both the training and the validation dataset are shown in Linear discriminant analysis (LDA) based on these relevant principal components (PC) showed an ability for eNose sensor signals to discriminate between patients who had had an exacerbation from those who had not (ROC-AUC = 0.78 (95%-CI: 0.72–0.84)). After cross-validation, this resulted in a ROC-AUC = 0.76 (95%-CI: 0.69–0.82). A similar accuracy was observed in the validation dataset (ROC-AUC = 0.76 (95%-CI: 0.64–0.87)), See The ROC analysis was repeated while omitting patients with: (1) a recent history of antibiotic use for acute worsening of respiratory symptoms; (2) current smokers at the time of measuring or (3) those who did not use inhaled corticosteroids as maintenance treatment. Similar results were seen for the discrimination in both the training and validation datasets . All AUC results can be found in This study showed that the measurement of exhaled breath patterns by eNose could accurately discriminate between asthma patients with a recent exacerbation and those without. These results were validated and confirmed in a validation set. A sensitivity analysis showed that despite recent use of antibiotics, smoking history or ICS use, the discriminative accuracy was preserved. Our results suggest that there is a difference in exhaled metabolites between asthma patients who have had a recent exacerbation in the previous 3 months and those who have not. This might be of interest for the monitoring of disease stability. To our knowledge, this is the first study that proved the ability of exhaled breath patterns measured with eNose to detect recent asthma exacerbations in adult patients.In several studies, the predictive properties of exhaled VOCs associated with asthma exacerbations have been explored in children by analyzing gas chromatography coupled with mass spectrometry (GC-MS) data ,17,18. AA recent study, looking into the differences in exhaled breath patterns after a viral challenge in asthma patients, found a detectable change in fluctuations in eNose signals after viral infection. These changes appeared to commence before the expression of viral symptoms . Since vThe, hereby, presented results are in line with a similar study conducted by our group in COPD patients. They demonstrated that eNose analysis was able to discriminate between COPD patients who had experienced an exacerbation and those who had not. However, the overall accuracy was better for COPD patients compared to asthma patients presented in the current study  .These differences maybe attributable to several reasons; firstly, VOCs and consequently exhaled breath patterns measured by eNose, could be different in asthma exacerbations compared to COPD exacerbations due different pathologic triggers. It has been demonstrated that allergen and viral exposure can trigger asthma exacerbations, while, bacterial infections play less of a role . For insAnother reason for the differences in accuracy maybe be related to the influence of smoking exposure on exhaled breath patterns. Oxidative stress induced by exposure to smoking is an important risk-factor for disease pathogenesis in COPD patients . Asthma In our study we found a differences in recent exposure to antibiotics for the treatment of acute respiratory symptoms between the exacerbation and no-exacerbation groups. Respiratory infections impact metabolism and exhaled breath VOCs that can result from systemic effects , thus reThe strengths of the current study are the relatively large sample size and the heterogeneous population of the asthma cohort, which has been recruited from centers of primary, secondary and tertiary care, reflecting a real-life asthma population. The use of  cross-validation and splitting our dataset to allow validation of the training discriminant model in a separate dataset, support the validity of the obtained results. Furthermore, current results are in line with our previous similar study in a COPD population, however with lower accuracy.This study has several limitations; defining exacerbations is challenging. It is possible that the definition used for exacerbations in our study (current or previous treatment with OCS for acute worsening of respiratory symptoms) is not really representative of all patients with exacerbations even though, in most clinical trials, exacerbations are defined as a significant deterioration of asthma signaled by the need for a systemic corticosteroid course (≥3 days) and/or hospitalization for asthma and/or emergency room attendance for asthma ,32,33. IAnother limitation of our study is related to the lack of information regarding the timing of the exacerbations. In the current study patients only reported whether they used OCS for worsening of respiratory symptoms within 3 months prior measurement (yes/no) and information on specific timing was not available. We know from previous studies , that paA further limitation is that eNose identifies breath patterns, therefore a mixture of VOCs, rather than specific volatile compounds. Nonetheless, this makes eNose breath profiles identifiable as a pattern of biomarkers mostly focused on giving a particular probability of the presence/absence of a clinical condition . SpecifiOur findings support future studies with more emphasis on the timing of the exacerbations and the relation of fluctuations of exhaled VOCs to (in)stability of asthma patients. Differences in, for example, diet and comorbidities could influence exhaled breath composition, and due to these (probably still unknown) confounding signals it will be difficult to achieve a high enough accuracy in diagnosing. Patterns that diverge from baseline measurements could indicate instability and with this study we show that eNose measurements are indeed able to detect possible changes related to exacerbations. eNose is a non-invasive and easy to use technique, that could be beneficial for future patient monitoring. It could be used for assessing treatment efficacy or as an early-warning for the onset of exacerbations, enabling timely treatment. Furthermore, as past exacerbations are a risk factor for future exacerbations in patients with asthma, our results suggest a role in identifying patients at risk of future exacerbations and optimizing treatment. This was an exploratory cross-sectional study and data was retrieved between December 2015 and January 2017 from the multicenter BreathCloud database, which contains exhaled breath and clinical data of patients with respiratory diseases  and healthy controls ,28,40,41Recent exacerbations were defined as an acute worsening of respiratory symptoms, which required the use of oral corticosteroids anytime during 3 months prior to or during the eNose measurement .2), is printed on electrodes using an alumina substrate and those sensors  have been selected for their good stability and performance [2S, butane, propane, methane, hydrogen, ethanol, trimethylamine, methylmercaptan and solvent vapors in the 1–10.000 ppm range. The sensors are heated and acquire semiconducting characteristics as a result. Signals are derived from changes in resistance (and therefore conductance) in the sensors due to interactions with oxidizing/reducing gases.Volatile organic compounds in exhaled breath were measured with the SpiroNose . This eNose uses different cross-reactive metal oxide semiconducting sensors (MOS), grouped in eight arrays of three or four sensors; four arrays are used for measuring exhaled breath and four arrays are used to measure ambient air VOCs. The sensor material, mostly composed of Tin dioxide  maneuver existed of five tidal breaths followed by a single full inspiration, a 5 s breath hold and a slow maximal expiration to residual volume. Sensor data was captured in real-time and directly stored on the BreathCloud server . Pre-prop < 0.05. Multiple group comparisons (>2 groups) used one-way ANOVA, Kruskall–Wallis or Chi-squared tests as appropriate. Statistical analyses was performed in R studio  using R version 4.0.5 . Between groups comparison used independent t-tests, Wilcoxon rank-sum tests, and Pearson’s chi-squared tests as appropriate with a significance level The included asthma patients were divided into a training (70%) and validation (30%) dataset, similar to a previous similar study . To copeVariables that differ between the exacerbation and no exacerbation groups and are expected to have a potential influence on eNose sensor signals were used in extra sensitivity analysis. To assess the effect of these variables on the outcome, the ROC analyses were repeated while omitting study participants with these characteristics from the analysis.Exhaled breath analysis by eNose can accurately discriminate between asthma patients who have experienced an exacerbation and were treated with OCS during the previous 3 months and those who did not. The current study suggests that asthma patients during or after a recent exacerbation have a specific exhaled molecular ‘breathprint’ that can be detected, thus suggesting a role in monitoring disease control and (in)stability for these patients.


Background and objectiveThe aim of this study was to investigate whether the maximum inspiratory and expiratory pressure are correlated with the apnea-hypopnea index (AHI) in patients with obstructive sleep apnea syndrome (OSAS).Methods2), carbon dioxide output (VCO2), heart rate (HR), minute ventilation (VE), tidal volume at inspiratory (TVin) and expiratory (TVex), breath frequency (fβ), end-tidal carbon dioxide pressure (PETCO2), end-tidal oxygen pressure (PETO2), and mean arterial pressure (MAP)) in sitting position for three minutes were recorded. The independent t-test was used to measure the differences between groups (events/hours <30 versus ≥30) and Pearson correlation analysis was used for statistical comparison between parameters.Fifty-two patients with OSAS were divided into two groups . For each patient, anthropometric characteristics, spirometry parameters, maximum inspiratory (MIP) and expiratory pressure (MEP), and cardiopulmonary function (CPF) parameters , and MAP . Pearson correlation analysis between respiratory muscle strength (MIP and MEP) and polysomnography (PSG) parameters, MIP is related to AHI  and desaturation index , as well as MEP to percent of REM sleep stage .Results showed differences between groups  in MIP  and CPF parameters TVin , PConclusionThe data from the present study support that maximal inspiratory pressure relates to the severity of AHI and intermittent breath-holding during sleep increases the inspiratory muscle strength. Obstructive sleep apnea syndrome (OSAS) is a common condition affecting 9% to 38% of the general population  and is cOn the other hand, breath-holding (BH) is a widespread tactic of athletes to improve endurance by weakening the chemical signals of hypercapnia that trigger breathing . The difThe purpose of this study was to investigate whether the maximum inspiratory and expiratory pressure are associated with the apnea-hypopnea index in patients with OSAS. Moreover, we examined possible differences among patients in cardiopulmonary function in resting relate to the severity of the syndrome. We hypothesized that the OSAS syndrome could affect the respiratory muscle strength independent of the severity of the syndrome.Participants2, neurological and psychiatric disorders, musculoskeletal disorders [Fifty-two newly diagnosed male volunteers patients with OSAS were consecutively enrolled in our study and divided into two groups . All subjects completed the PSG study in the Sleep Apnea Laboratory of Respiratory Medicine Department, University of Thessaly [isorders , daily pisorders , manual isorders .Data collectedFor each patient, anthropometric and morphological characteristics /height (m)2), neck, waist and hip circumference, and body composition ) were recorded. Moreover, calculating the body surface area (BSA = (height (cm) x weight (kg))/3600½) and estimated the lean body mass (LBM (kg) = 0.407 x weight (kg) + 0.267 x height (cm)-19.2).All participants underwent standard spirometry and lung volume measurements, in line with American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines . For eacIn addition, we recorded the maximum inspiratory (MIP) and expiratory pressure (MEP) by a MicroRPM portable device  and calculated the percent of predicted values according to the equation :MIP (cmH2O) = 142 - (1.03 x Age(yrs)), MEP (cmH2O) = 180 - (0.91 x Age (yrs))ETCO2, mmHg), end-tidal oxygen pressure ) in sitting position for three minutes by a MasterScreen-CPX  [Moreover, we recorded parameters for cardiopulmonary function at rest , carbon dioxide output , heart rate , minute ventilation , tidal volume in inspiratory  and expiratory , breath frequency , end-tidal carbon dioxide pressure . Pearson correlation analysis was used for statistical comparison between parameters. For each test, the level of significance was set to p<0.05. Continuous variables of interest were characterized by mean values with standard deviation (Mean±Sd). The IBM Statistical Package for the Social Sciences (SPSS) 21 statistical package  was used for statistical analyses.Polysomnography studyResults showed a difference between groups in polysomnography study parameters. Patients with AHI ≥30 events/hours observed higher values compare to the group with AHI <30 events/hours in apnea, desaturation index, and minimum oxygen saturation during sleep Table . The perSpirometry and respiratory strengthAdditionally, MIP showed differences between groups. Patients with AHI ≥30 events/hours observed higher values as compared to the group with AHI <30 events/hours =2.590, p=0.013, Figure Cardiopulmonary functionETCO2: 34.6±4.2 versus 31.4±3.7, mmHg, t(50)=2.838, p=0.007), and mean arterial pressure =3.175, p=0.003) =2.041, p=0.047), end-tidal carbon dioxide pressure  and PSG parameters, MIP is related to AHI  and desaturation index  and MEP is related to percent of REM sleep stage  and sleep duration .The aim of this study was to investigate whether the maximum inspiratory and expiratory pressure are correlated with the apnea-hypopnea index in patients with OSAS. Our main finding was that MIP is related to the severity of AHI and affected by the desaturation index.ETCO2 is indicative of the instability of central respiratory motor output to airway and pump muscles during sleep while the association between OSAS and hypertension has been well-established in the context of chronic sympathetic excitation [ETCO2, tidal volume in inspiratory, mean arterial pressure, and heart rate in resting in patients with AHI ≥30 compared to the group with <30 events/hours. In agreement with our findings, Stavrou et al. reported increased PETCO2 (approximately 4 mmHg) in patients with OSAS as compared to the control group [Previous studies have reported that AHI severity was correlated with some respiratory parameters, as well as mean arterial pressure . The inccitation . In the 2 and CO2 gases in order to remove the excess of CO2 from the system. CO2 is a regulator of blood pH and its fluctuations may disturb the homeostasis if levels are not maintained in the normal range [ETCO2 at 3.1 mmHg than patients with AHI <30 events/hours group. The increased PETCO2, like the ones measured in our patients, is an end product of a complex conglomerate influenced by factors such as the severity of sleep apnea, daytime PaO2, blunted respiratory drive, respiratory mechanics, and respiratory muscle fatigue [2 retention. Central and peripheral chemoreflexes are activated due to hypoxia, the sympathetic nervous system (SNS) tone is increased due to the stimulation of VMC and CC, leading to hypertension and bradycardia due to the stimulation of the vagus nerve, and lung volume is reduced due to chest compression and dilation of thoracic vasculature [Our data present that patients with AHI ≥30 events/hours had higher values in TV in inspiratory compared to patients with AHI <30 events/hours group Table . Breathial range . Voluntaal range . In our culature . HoweverAccording to our results, observed higher values in MIP in patients with AHI ≥30 events/hours as compared to the <30 events/hours group. The intermittent breath-holding during hypoxia re-oxygenation in patients with OSAS probably increases the intrathoracic pressure with successive alteration in the transmural pressure of the cardiac cavities, similar to the ones produced during exercise . During ETCO2: 31.4±3.7 versus 34.6±4.2 mmHg). The chemoreflex is stimulated entirely, increasing the SNS tone during both sleep and wakefulness, leading to the clinical manifestation of hypertension and tachycardia [Regulation of breathing during sleep is principally under the control of chemoreceptors while many of the inputs witnessed in wakefulness and, therefore, BH, are diminished . Consequhycardia  in contrhycardia . Therefohycardia . Besideshycardia .The suboptimal length of a muscle such as the diaphragm leads to the suboptimal release of force according to the basic properties of muscles . MIP is Nevertheless, in our study, there were some limitations. The participants were only men and the low number of participants might be a statistical bias in our conclusions.To conclude, data from the present study support that the maximal inspiratory pressure associated with the severity of AHI and intermittent BH during sleep increases the inspiratory muscle strength. However, its effects differ, since OSAS is detrimental due to the sympathoexcitation that persists, contributing to comorbidities, whereas BH is not only reversible but also beneficial for athletic performance. As oxygen desaturation and arterial re-oxygenation seem to affect only chemoreflex upregulation in part, further research on respiratory muscle strength as a potential candidate for elucidating the relationship of apneas in OSAS and BH is required.


The recommended position for measuring Intra-Abdominal Pressure (IAP) is the supine position. However, patients put in this position are prone to Ventilator-associated pneumonia. This study was done to evaluate the relationship between bed head angle and IAP measurements of intubated patients in the intensive care unit.In this clinical trial, seventy-six critically ill patients under mechanical ventilation were enrolled. IAP measurement was performed every 8 hours for 24 hours using the KORN method in three different degrees of the head of bed (HOB) elevation (0o (p = 0.0001). The IAP measurement bias between HOB angle 0°and HOB angle 15° was 1.13 mmHg. This bias was 2.66 mmHg between HOB angle 0° and HOB angle 30°. The prevalence of intra-abdominal hypertension was 18.42%. Mean ± standard deviation (SD) of IAP were 8.44 ± 4.02 mmHg for HOB angle 0°, 9.58 ± 4.52 for HOB angle 15Elevation of HOB angle from 0 to 30 degree significantly increases IAP. It seems that the measurement of IAP at HOB angle 15° was more reliable than 30°. Intra-abdominal pressure (IAP) is increasingly considered an important pathological factor among the patients admitted to intensive care unit (ICU) . ElevateThe prevalence of IAH in intensive care patients has been reported as 18% to 58.8% . This wiPutting the patient in supine position is contrary to the policies recommended by Centers for Disease Control (CDC). These policies prevent aspiration pneumonia and ventilator-associated pneumonia. On the other hand, measurement of IAP at 0° of HOB, in case of patients' intolerance and the existence of both abdominal and bladder muscle retraction, leads to the false increase of IAP , 14, 15 There is some evidence that body position can affect measured IAP values, but the effect of HOB elevation degree, which is applied for changing the position of ICU patients, is not clearly defined . This stStudy Design and settings The current study is a clinical trial aimed to compare the changes of IAP with HOB angle at 0°, 15ParticipantsPatients admitted to ICU during the study period with age over 18 years, Richmond Agitation Sedation scale (RASS) score equal to -4 or -5, mechanically ventilated for at least 24 hours, lacking spinal cord damage, with normal Intracranial Pressure, without recent bladder surgery, and without both nasogastric tube and Foley catheter, were included. Exclusion criterion was intolerance to HOB elevation, which didn’t occur during our study. Data gathering The research instrument was obtained from WSACS and consisted of three sections: The first section was dedicated to the personal characteristics of the patients, including age, gender, body mass index, disease diagnosis and the length of stay. The second section included Sequential Organ Failure Assessment (SOFA) score, and the third section was related to IAP measurement and recording, ventilator mode variables, mean arterial pressure (MAP), mean IAP, mean airway pressure, maximum airway pressure, plateau pressure, abdominal perfusion pressure (APP), and positive end-expiratory pressure measurement at 0°, 15Interventiono every 8 hours during 24 hours . The patients were followed during this period. All patients were flexed at the waist without readjustment of the manometer's zero reference. IAPs were measured at end-expiration with a minimum of 1 minute delay after patient positioning, for equilibration. IAPs were measured in cmH2O and then converted into mmHg through multiplying by 0.74. The measurement of the bed angle was carried out by the index in the rail beside the bed based on the horizon level in each condition. To avoid technical errors, the same person carried out all of the measurements. After each measurement, the clamp was opened to discharge the normal saline from the patient’s bladder completely. Also, the patient's nurse was noted to subtracts the volume of the normal saline infused into the bladder from the total volume of urine drainage of the patient in that hour. By monitoring the patient’s ventilator, other pressure variables  were recorded. Importantly, the duration of each measurement was about 7 to 8 minutes. The triplicate IAP measurements for each body position were done. The IAP was measured 228 times in each HOB angle and 684 times in total. During the measurement, in the case of IAH, the nurse or physician was called for treatment.IAP measurement was performed through KORN method using Foley catheter , 13. AftIn the present study, IAP was an independent variable. IAH IAP≥12 mmHg) was categorized as indicated below: grade I (12-15 mmHg), grade II (16-20 mmHg), grade III (21-25 mmHg), grade IV (>25 mmHg) . Mean ± standard deviation (SD) was calculated for quantitative variables and frequency (%) for qualitative variables. Kolmogorov Smirnov test was utilized to check the normal distribution of data. All data were distributed normally. Repeated measure analysis of variance (ANOVA) and Bonferroni post hoc tests were used to compare the mean abdominal pressure at different measurement angles. Considering the insignificance of the Mauchly test, Sphericity and repeated measures ANOVA tests were used to compare the trend and amount of IAP changes with qualitative variables. To investigate the correlation of quantitative variables with mean IAP, Pearson test and Fisher’s exact test were used. Bland-Altman analysis was performed to identify the bias and limits of agreement among the three positions. The WSACS states that a bias of <1 mm Hg and limits of agreement between -4 and +4 are required for considering the two IAP techniques equivalent (9. Mean ±° (57.9%), and grade III IAH prevalence was increased from 0° to 30° (3.9%). In other words, with the increase in HOB angle, IAP was changed from a normal state to IAH (p = 0.04). 289 patients were evaluated, out of which 76 cases with the mean age of 50.31 ± 20.47 years met the predefined inclusion criteria and were enrolled in the study . The baseline characteristics of patients are presented in o. In other words, by increasing HOB angle, the normal IAP turned in to IAH. The results showed that increase in HOB angle from 0 to 30 degrees led to significant increase in IAP and the prevalence of IAH also increased from 0° to 30°  . Vasquez 30°)  . Ejike eIt can be said that the prevalence of comorbidities is higher in older age and the comorbidities themselves can increase IAP. Therefore, the difference in the results of different studies, mentioned previously, may be due the differences in participants and measurement techniques. BMI was considered an effective factor in our study, and it was significantly associated with IAP (P=0.007). Vasquez et al., in their study, showed that there was a significant correlation between BMI and mean IAP. They found that BMI was in charge of 25-36% of the changes in IAP . Blaser There was a significant correlation between the changes of IAP and disease diagnosis (P=0.04) as the change increased among non-trauma patients compared to trauma patients. In a study by McBeth et al., it was shown that IAP and the diagnosis of Neurologic disease had a significant correlation P=0.001). In contrast, in surgical and trauma patients, no significant correlation was observed . In cont. Moreoveo with various respiratory pressures, mean airway pressure, plateau pressure and positive end-expiratory pressure (P=0.05). The mean arterial pressure and IAP also significantly correlated with each other at the three angles (P=0.0001). The rib cage and abdominal cavity are connected via diaphragm as averagely, 50% (25 to 80%) of the pressure of these two sections (abdomen and ribcage) are transferred to each other. With increase in IAP, the diaphragm is elevated and leads to the compression of lungs and increase in the pressure of ribcage. Following the rise in the pressure of the ribcage, increase in mean airway pressure, maximum airway pressure, plateau pressure, and positive end-expiratory pressure are expected. With an increase in ribcage pressure, the heart function and mean arterial pressure are also reduced. Eventually, these events lead to the increase of IAP  were approximately equal. However, the upper limits of agreement in both angles were higher than the WSACS upper limit, and the limit was much more near to the WSACS limit at 15°. It was found that 87.6% of the agreement limit obtained between 0°and 15° in this study was in the range proposed by the WSACS, and only about 13% was out of this limit and about the limits obtained between 0° and 30°, 66.19% of the agreement limit obtained was in the range and 33.81% was out. In the study by Cheatham et al., it was shown that the bias between 0 and 15 degrees was 1.5 mmHg, and the agreement limit was -2.8 to 5.8 and the bias between 0 and 30 degrees was 3.7 mmHg ,and the agreement limit was -2.2 to 9.6 , and between 0° and 30°  with bias and agreement limit (-4 to +4) suggested by the WSACS, it was shown that the bias at 15 degrees compared to 0° (standard position) was closer to the required bias. The lower limit of the agreement in both 15°and 30According to the results of previous studies, as also found in our study, an increase in HOB will lead to a clinically important increase in IAP. Moreover, it can be concluded that IAP at 15°, in comparison to 30°, can be considered more equal to IAP at standard position. So considering HOB seems to be important in interpretation of IAP.The elevation of HOB significantly increased IAP. Although IAP needs to be measured for the patients admitted to ICU, putting the patient at zero degree is not possible in some conditions because it led to signs of intolerance to the position and unavoidable complications among the patients. The results of our study showed that 87.6% of IAPs measured at 15° were in the agreement limit in accordance with the WSACS. The HOB angle in ICUs is often recommended to be adjusted to 30 degrees. It seems that measuring IAP at 15° HOB angle is more reliable than 30° in ICU patients who cannot tolerate supine position. To determine the appropriate HOB angle to measure IAP in ICU patients, further studies are needed to reveal any other factors that may affects IAP, besides HOB. There is also the need to evaluate whether the increase in HOB leads to an equal increase in the IAPs of four quadrants of the abdomen cavity or not. As long as more extensive studies evaluating the effects of position on IAP aren’t available, it's better to measure IAP at 0° or standard position. One of the limitations of our study was lack of a special kit for measuring the IAP. Also, the patients who would not endure an elevation in HOB were excluded in our study. Unfortunately, many of these patients were at high risk for IAH/ACS. One of the positive aspects in our study is the evaluation of a larger sample size. According to the WSACS website, the minimum sample size for research on the IAP measurement methods is 20 cases.Elevation of HOB angle from 0 to 30 degree significantly increases IAP. It seems that the measurement of IAP at HOB angle 15° was more reliable than 30°.


The rapid growth in the e-cigarette market after the launch of JUUL e-cigarettes led to much discussion on the potential benefits and risks of pods, JUUL devices, and conventional e-cigarettes compared with combustible cigarettes. Independent data are required to assess the effects of these products on cardiovascular surrogate parameters and cardiovascular risk.We conducted a single-center three-arm study comparing combustible cigarettes with JUUL e-cigarettes with the old and new technology. We recruited 32 participants who were active smokers (n=15) or vapers (n=17) and performed a total of 39 measurements before and 5, 15, and 30 minutes, after participants smoked a combustible cigarette or vaped a JUUL e-cigarette with the new or old technology. Measurements included peripheral and central blood pressures and parameters of arterial stiffness, including pulse wave velocity and augmentation index.Peripheral systolic blood pressure, central blood pressure, and peripheral pulse rate increased significantly in all three groups (each p<0.05). Heart rate (HR) changes lasted significantly longer than blood pressure changes. The augmentation index and pulse wave velocity increased in all three groups, and a multivariate analysis of variance showed that the increases were independent of systolic blood pressure, sex, age, device, and HR.Changes in blood pressure and arterial stiffness are similar after cigarette smoking and JUUL use. These changes may be associated with an increased cardiovascular risk compared with no product use. However, a long-term follow-up evaluation of JUUL use and a head-to-head comparison with conventional e-cigarettes are still needed. As a result of marketing and advertising strategies, JUUL became the e-cigarette brand used by over half of middle and high school students2, and its widespread use among young people led to much discussion in the entire field of healthcare providers, not just among pediatricians. Besides advertising, this discussion referred to the lack of information about the health risks that may be associated with e-cigarettes and other nicotine delivery devices3. As a result of the popularity of e-cigarettes among young people and the outbreak of e-cigarette or vaping product use-associated lung injury (EVALI) in October 20194, the FDA passed a legislative decision in January 2020 that tobacco products may be sold only to people aged ≥21 years5.After the launch of the JUUL device on the US market in 2015, retail sales increased over the following three years, and the device became the best selling e-cigarette with 40% of the retail market share6. Studies have shown that vaping may increase the risk of initiation of cigarettes, especially among teenagers8. Smoking is still one of the leading causes of mortality in Germany and is responsible for 110000–140000 premature deaths9. The levels of many hazardous and potentially hazardous substances are significantly lower in e-cigarette emissions than in cigarette smoke, leading to a reduced exposure to these compounds while vaping11. Thus, e-cigarette use is expected to reduce the risks for some diseases, especially cancer, and therefore JUUL and other kinds of e-cigarettes have started to be used as tools for smoking cessation12. However, e-cigarettes still deliver nicotine, so their use is less likely to reduce the rate of cardiovascular diseases, although this aspect requires further research.The large market share of e-cigarettes and their popularity among young people in the US increased interest not only in the question of long-term harm but also the gateway hypothesis14, but it is also one of the most modifiable risk factors15. Several studies evaluated the chronic effects of smoking on cardiovascular events. To assess subclinical end-organ damage, the European Society of Hypertensiology and European Society of Cardiology recommend measuring arterial stiffness and endothelial dysfunction, parameters that also provide some initial indications of the onset of systemic cardiovascular disease16. A clear association between smoking and the increase in arterial stiffness is known17 and several studies have shown the rise in arterial stiffness of both e-cigarettes and heated tobacco products20. Some evidence shows that e-cigarettes, which are often marketed as a healthier smoking alternative21, can indeed increase cardiovascular risks. For example, Alzahrani et al.22 found that non-daily and in particular daily e-cigarette use increased the risk of myocardial infarction. However, a recent epidemiological analysis did not confirm increased cardiovascular risks for vapers who never smoked cigarettes23. Because conclusive evidence is still limited24, more data and analyses are required, especially for devices that deliver high levels of nicotine, such as the JUUL25. Although JUUL pods sold in the US contain up to 58 mg/mL of nicotine, the maximum concentration of nicotine in e-liquids allowed in the European Union is 20 mg/mL26. Therefore, in the European Union conventional JUUL pods were replaced by what JUUL lab employees supposedly refer to as ‘Turbo JUUL’ which uses different wick material27. A study on the Turbo JUUL found that the new wick material increased the amount of vapor generated and subsequently increased the amount of nicotine released per puff25.In general, smoking has been described as one of the most important risk factors for cardiovascular eventsTo date, information is lacking on the effects of JUUL use on the pathogenesis of cardiovascular diseases, specifically on arterial stiffness and endothelial dysfunction. Therefore, we aimed to compare the acute effects on peripheral and central blood pressure and arterial stiffness of the new and old JUUL devices and conventional cigarettes, assuming that the use of the European JUUL versions as well as cigarette consumption increases the respective parameters.28. Participants were recruited from the population of the city of Munich by advertising and were assigned to the tobacco cigarette group or one of the two JUUL groups (old and new JUUL technology) according to the product that they normally used. At screening, inclusion criteria were checked as follows: 1) smoker or vaper, 2) no mental disorder, 3) no cardiovascular disease, 4) no thyroid disease, 5) no diabetes, 6) no abnormalities in physical examination, 7) no hypertension, and 8) no hypercholesterolemia. In addition, a pregnancy test was performed to exclude possible pregnancies in women who were not taking oral contraception. The measurements were made during the same phase of the menstrual cycle or pill period. All participants were asked to follow the guidelines for measuring arterial stiffness30. Therefore, cigarette smoking and nicotine intake in general were prohibited for the 12 hours before the study visit. The smoke-free time was tested by a Micro+Smokerlyzer™  with a cut-off of 5 ppm carbon monoxide. In e-cigarette users, concentrations in the baseline blood sample were checked for possible elevated nicotine concentration. Participants were excluded if they declared that they were strict non-smokers. All participants provided written informed consent. The study was approved by the ethics committee of the LMU Munich (Amendment to project number 72-15) and performed in accordance with the principles of the Declaration of Helsinki in the currently valid version and was registered at the German Clinical Trials Register . It was conducted according to the World Medical Association Declaration of Helsinki.This single-center, three-arm study included 15 active smokers and 17 active e-cigarette users. A total of 39 measurements were performed, whereby the e-cigarette users were mostly tested in both the old and the new JUUL groups in order not to offer an entry into ‘dual use’ which seems to be a possible potentiation of health risks25. All participants had to consume the respective product depending on the group affiliation at a frequency of 1 puff every 30 s for 10 puffs, with a puff duration of 3 s, as described in other publications31.The three different study arms used the following products: 1) a commercial, combustible tobacco cigarette ; 2) a JUUL e-cigarette with the new technology (new JUUL group); and 3) a JUUL e-cigarette with the old technology (old JUUL group). The use of the JUUL device was explained to participants in groups 2) and 3) on the basis of the producer’s manual and vapers who were inexperienced in the use of JUUL e-cigarettes were trained in their use before the study. JUUL Pods with the flavor ‘Rich Tobacco’ were used and vegetable glycerol (VG), propylene glycol (PG), nicotine, benzoic acid and ‘aromas’ are specified as ingredients by the manufactor. Both the old and the new JUUL pods do not seem to differ much in the composition of ingredients. The VG/PG ratio is approximately 2:1 (w/w)During the consumption sessions in the tobacco cigarette and new/modified JUUL arms, electroencephalography (EEG) measurements and blood samples for nicotine concentration during and after consumption were taken. Results on EEG and nicotine concentration in venous blood will be analyzed and published separately.34 before and at three times after using the specific device: at 5 minutes, 15 minutes, and at 30 minutes.Generally, measurements were started at least 15 minutes before smoking or JUUL use. Peripheral and central hemodynamics were measured by the Mobil-O-Graph™ 35. Like many other devices, the Mobil-O-Graph™ uses the oscillometric technique in which a standard blood pressure cuff is placed at the arteria brachialis32. Besides the peripheral blood pressure, heart rate is also measured using the oscillometric technique. Central systolic blood pressure is determined from brachial waveforms which are recorded with the cuff at the level of diastolic blood pressure and processed with the ARCSolver transfer function. In addition, stroke volume and total peripheral resistance are calculated via a transfer function similar to the ARCSolver transfer function32. The derived central waveforms are used for pulse waveform analysis and the augmentation index and augmentation pressure are derived from them34. The augmentation index is adjusted for a heart rate of 75 beats per minute (bpm). After participants had rested for a short period, measurements were made at least 15 minutes before participants smoked or vaped in a sitting position. These data were used as a baseline and as references for statistical analyses.Blood pressure and additional variables were measured with the validated Mobil-O-Graph™ , which allows peripheral and central blood pressures, heart rate and arterial stiffness to be recordedStatistical analyses and graph editing were performed with SPSS statistical software  and GraphPad Prism 4 , respectively. Baseline mean values of blood pressure and arterial stiffness were used as statistical references.post hoc tests (Bonferroni) with G*Power. Also, we analyzed the data with a paired Student’s t-test or Wilcoxon rank sum test, as appropriate, to compare measurements at the four times. Where applicable, we performed a multivariate analysis of variance (MANOVA) correcting for age, mean arterial pressure (MAP), heart rate (HR), and sex. If not otherwise stated, all data are expressed as mean ± SD. A p<0.05 was considered statistically significant.Before further analysis, peripheral and central blood pressures were analyzed for normal distribution by Kolmogorov-Smirnov tests. Because of the longitudinal design, we used a two-way repeated-measures analysis of variance (ANOVA) to evaluate the effect of time. Accordingly, if we found no interaction we performed 36.Baseline characteristics for all 32 participants are presented in At the initial measurement after 5 minutes, peripheral systolic blood pressure (pSBP) increased significantly by more than 3% in all three groups p<0.05; , Table 2pDBP did not change significantly in either cigarette (Cig) or the old JUUL group p>0.05; , Table 2Peripheral mean arterial pressure (pMAP) increased significantly in the Cig (+4%) and new JUUL (+2%) groups after 5 minutes, and in the new JUUL (+ 1%) and old JUUL (+5%) groups after 15 minutes  increased significantly, by more than 20%, in all three study groups after 5 minutes p<0.05; , Table 2After 5 minutes, HR increased significantly, by more than 8%, in all three study groups  increased significantly, by more than 6%, in the Cig group p<0.05; , Table 2Central diastolic blood pressure (cDBP) was significantly increased after 5 minutes in the Cig (+6%), new JUUL (+1%), and old JUUL (+7%) groups  increased significantly, by more than 20%, in the Cig group after 5 minutes and by more than 20% in the new JUUL group after 15 minutes  increased significantly in the Cig (+97%), new JUUL (+17%), and old JUUL groups (+102%) after 5 minutes and in the old JUUL group (+86%) after 15 minutes  showed a significant change after 5 minutes in the Cig (+5%), new JUUL (+1%), and old JUUL (+2%) groups and after 15 minutes in the new JUUL (+1%) and old JUUL (+1%) groups  increased significantly, by more than 15%, in the Cig group, by more than 15% in the new JUUL group, and by more than 9% in the old JUUL group after 5 minutes, and by more than 15% in the Cig and by more than 20% in the new JUUL groups after 15 minutes  increased after 5 minutes in the Cig (+11%) and new JUUL (+4%) groups and after 15 minutes in the old JUUL group (+16%) (each p<0.05; 41. In particular, the effects on arterial stiffness of JUUL use were as yet unknown, although recent studies have shown that heart rate as well as mean arterial pressure are influenced by vaping the American JUUL version42. This is in accordance with our data which showed acute increases in peripheral and central blood pressure for a short period after both JUUL use and smoking.To the best of our knowledge, this study is one of the first to compare the impact of vaping the European JUUL version and cigarette smoking on peripheral and central hemodynamics and arterial stiffness43. In line with our previously published study on e-cigarettes, Franzen et al.18 and Vlachopoulos et al.39 showed an impact of vaping on central hemodynamic and peripheral blood pressure. As expected and already published43, heated tobacco products, cigarettes, and e-cigarettes with nicotine-containing liquids lead to an increase of peripheral and central hemodynamic parameters and arterial stiffness. For the JUUL device, we were also able to show an increase in peripheral and central hemodynamics that was comparable to the changes found with combustible cigarettes. With regard to these parameters, only minor differences were found between the new and old JUUL technology.Recently published studies provided a contradictory picture with regard to arterial stiffness after vaping and smoking46. However, our results showed that a small part of the increase in arterial stiffness remained unexplained by the device, blood pressure, heart rate, or sex. This unexplained change might be due to the effects of the cigarette and JUUL on the endothelium. Therefore, a combination of nicotine and harmful or potentially harmful compounds in smoke and vapor is one of the most likely explanations for this observation. Similar results were shown in an animal model by Nabavizadeh et al.47 who compared combustible cigarettes with heated tobacco products. In addition, population-based studies on cardiovascular diseases found an association between e-cigarette use and increased risk of myocardial infarction22. However, the influence of former or current smoking is unclear. The pathogenesis of coronary heart disease and other cardiovascular events includes stiffening of the arteries48, an effect that could be shown here to occur with JUUL use. Besides central hemodynamics, arterial stiffness seems to be even more important than peripheral blood pressures as a surrogate parameter for cardiovascular events50. It should be noted that cigarette smoke not only affects the cardiovascular system but also has other negative effects on health, and e-cigarette aerosols contain much lower amounts of harmful and potentially harmful substances than cigarette smoke51. Thus, a complete switch from tobacco cigarettes to e-cigarettes is widely acknowledged to reduce the exposure to many carcinogens and other toxicologically relevant compounds52.In line with the previously published trials, AIx@75 increased significantly after JUUL use. As another parameter of arterial stiffness, we showed significant raises in PWV in the combustible cigarette and JUUL groups. These temporary alterations of hemodynamic and arterial stiffness are likely triggered by nicotine as an acute vasoconstrictor and also by local and circulating catecholamines which are released during nicotine consumption. These catecholamines also indicate the activity and stimulation of sympathetic ganglia, among other things. As a consequence of the stimulation due to nicotine, sympathetic neuronal discharge-impaired nitric oxide production increases in the central nervous system, which in turn leads to an increase in arterial stiffness39 on blood pressure and arterial stiffness which included four study arms, the present study included only three arms. Also, the sample size was limited, and a cross-over design was not used. In addition, participants were not randomized to the study arms, and only acute effects were assessed. Last, the intensity of JUUL use, i.e. the intensity of the puff, could not be standardized, although the frequency, number, and duration of puffs were defined to avoid large differences in vaping behavior. In this study, other measurements like EEG and blood samples were carried out in parallel to increase the information output. However, possible influences on the individual stress level of the participants could not be excluded.Unlike the study by Vlachopoulos et al.Future studies should focus on the chronic effects of the JUUL device and compare them with the long-term effects of conventional e-cigarettes with nicotine-containing or nicotine-free liquids or combustible cigarettes. The literature describes neither endothelial dysfunction nor cardiac inflammation for JUUL use, so future studies should address these issues. Also, a head-to-head comparison of e-cigarettes, JUUL, heated tobacco products, and combustible cigarettes should be conducted and should focus on peripheral blood pressure, arterial stiffness, and endothelial dysfunction.Comparable adverse changes for blood pressure, heart rate, and arterial stiffness parameters were shown between both smoking a filter cigarette and JUUL use. In our interpretation, these and especially the changes in arterial stiffness may be associated with increased cardiovascular risk. However, a long-term follow-up evaluation of JUUL use and a head-to-head comparison with conventional e-cigarettes are still needed.


The association between blood pressure measured at home and handgrip strength in patients with diabetes has not been investigated. Therefore, in this study, we aimed to assess this association among patients with type 2 diabetes. In this cross-sectional study, 157 patients with type 2 diabetes underwent muscle tests and morning and evening blood-pressure measurements at home in triplicate for 14 consecutive days throughout the study period. Univariate and multivariate regression analyses were conducted to analyze the relationship between home blood-pressure parameters and handgrip strength. The average age and hemoglobin A1c of the patients were 70.5 years and 7.1%, respectively. Morning diastolic blood pressure of [β : 0.20 ] was associated with handgrip strength in men, while morning systolic blood pressure of [−0.09 ], morning pulse pressure of [−0.14 ], and evening pulse pressure of [−0.12 ] were associated with handgrip strength in women. Home-measured blood pressure was associated with handgrip strength. Sex differences were found in the relationship between home blood-pressure parameters and handgrip strength. Hypertension is the most common risk factor for cardiovascular diseases (CVDs), and it remains highly prevalent worldwide . ObservaThis study was a cross-sectional study, and baseline data from patients participating in both the type 2 diabetes HBP cohort study (KAMOGAWA-HBP study ) and theIn this cross-sectional study, 903 and 274 patients with type 2 diabetes underwent blood-pressure measurement at home and a muscle test, respectively, between 2008 and 2017. We included 164 patients who underwent both HBP measurement and handgrip strength measurement. Among them, 2 and 5 patients were excluded because of insufficient data on HBP and unavailability of handgrip strength data, respectively. The study population finally comprised 157 patients . Morning and evening BP measurements were performed in triplicate for 14 consecutive days. Morning BP was measured within 1 h of waking, before eating breakfast or taking any drugs, while the patient was seated, and had rested for at least 5 min. Evening BP measurement was performed immediately before going to bed. The cuff was placed over the bare upper arm and was positioned at the heart level . We calcHandgrip strength was measured twice in the outpatient examination room using a dynamometer  with each hand in a standing position with elbows fully extended. The values were checked by the attending physician, and the maximum value among them was used in this study.Venous blood was collected after an overnight fast, for biochemical measurements. Hemoglobin A1c (HbA1c) was measured using high-performance liquid chromatography, and results were expressed as a national glycohemoglobin standardization program unit. Body mass index was defined as body weight (kg) divided by the square of the height (m). Patient information, such as age, smoking status (no smoking/current or past smoking), exercise (without exercise habits/with exercise habits), and antihypertensive medication use (without antihypertensive medication/with antihypertensive medication), was collected using a standardized questionnaire at the time of study entry.p value of <0.05 was considered statistically significant. Continuous variables are presented as mean ± standard deviation. Pearson’s correlation analysis was used to investigate the relationship between values of handgrip strength measurement and SBP, DBP, and PP. Univariate and multivariate regression analyses were performed to analyze the relationship between HBP and PP, and handgrip strength. β coefficients were calculated to compare the relationship between HBP and PP, and handgrip strength. To adjust the effects of various factors on handgrip strength, the following known risk factors for handgrip strength were considered as covariates: age, smoking status, exercise, BMI, HbA1c, and antihypertensive medication use  and evening DBP of [0.19 ] were associated with handgrip strength in men, while morning SBP of [−0.08 ], morning PP of [−0.13 ], evening SBP of [−0.07 ], and evening PP of [−0.13 ] were associated with handgrip strength in women . In the We assessed, for the first time, the association between HBP parameters and handgrip strength among patients with type 2 diabetes. The main findings of this study were the association of HBP parameters with handgrip strength and the sex differences in the relationship between HBP parameters and handgrip strength. Morning DBP was associated with handgrip strength in men, while morning SBP, morning PP, and evening PP were associated with handgrip strength in women.In addition to an age-related decrease in activity level and changes in nutrient intake, molecular mechanisms, such as insulin resistance, oxidative stress, chronic inflammation, and changes in sex hormones, have been postulated to contribute to muscle weakness . Type 2 In this study, the association between HBP and grip strength was stronger in women than in men. This result is consistent with previous reports in which arterial stiffness, measured using cardio-ankle vascular index, was significantly associated with handgrip strength in Japanese non-hypertensive women but not in men . The simIn the present study, SBP and PP were negatively associated with handgrip strength in women. On the contrary, Taekema et al.  found thIn this study, DBP was positively associated with handgrip strength in men. Lower levels of DBP were reported to be associated with an increased risk of CVD and death . This maThis study has several limitations. First, a cross-sectional design was adopted, which did not show the precise determination of the cause–effect relationship between HBP parameters and handgrip strength. Prospective studies are required to evaluate their association. Second, the small sample size could have influenced the results obtained. Therefore, further studies on bigger groups are needed to fully understand the relationship between HBP and handgrip strength in patients with type 2 diabetes. Third, detailed data on the intake of protein and total energy, which might affect muscle strength, were not available. Fourth, there is no quality control of HBP measurements to ensure that the recommendations given to patients are systematically followed. Fifth, this study included patients with a relatively high capacity for self-care, who were able to self-monitor their HBP. Because of this selection bias, the results of this study may not be applicable to all patients with diabetes. Finally, the mechanism underlying the association between HBP parameters and handgrip strength could not be elucidated because of missing data on inflammatory or oxidative stress markers.Our study showed the association between HBP and handgrip strength, particularly in female patients with type 2 diabetes.