Recent studies have demonstrated an association between high blood eosinophil counts and greater risk of asthma exacerbations. We sought to determine whether patients hospitalized for an asthma exacerbation were at greater risk of readmission if they had a high blood eosinophil count documented before the first hospitalization.9 cells/L) and readmission risk during 1 year of follow-up after hospital discharge, with adjustment for predefined, relevant confounders using forward selection.This historical cohort study drew on 2 years of medical record data  of patients (aged ≥5 years) admitted to hospital in England for asthma, with recorded blood eosinophil count within 1 baseline year before admission. We analyzed the association between high blood eosinophil count  and 76% women . Overall, 835/2,613 (32.0%) had a preadmission high blood eosinophil count. During the follow-up year, 130/2,613 patients (5.0%) were readmitted for asthma, including 55/835 (6.6%) with vs. 75/1,778 (4.2%) without high blood eosinophil count at baseline . The association was strongest in never-smokers  and absent in current smokers .A high blood eosinophil count in the year before an asthma-related hospitalization is associated with increased risk of readmission within the following year. These findings suggest that patients with asthma and preadmission high blood eosinophil count require careful follow-up, with treatment optimization, after discharge. Severe asthma exacerbations may result in hospital admissions, relatively rare but important events with adverse implications for patients’ quality of life, health care resource use, and related costs. Approximately 83,000 hospital episodes  were recorded as related to asthma in England in 2011–2012, representing approximately 3.3 million patients with clinician-reported, diagnosed-and-treated asthma in England during that time [9 cells/L than for those with counts of <0.4x109 cells/L [9 cells/L) experienced over 7 times the number of hospitalizations per year compared with the general asthma population [9 cells/L was associated with 13% greater rate of hospital admissions (vs. ≤0.3x109 cells/L) among patients with asthma [Recent studies have demonstrated an association between high blood eosinophil counts and greater risk of asthma exacerbations, especially in patients with asthma that is not well-controlled ,3. Moreopulation , and in h asthma . Targeteh asthma .9 cells/L) in the first blood sample upon hospitalization was associated with a lower incidence of hospital readmissions as compared with an eosinophil count <0.3x109 cells/L [9 cells/L at first hospitalization [Patients who are admitted to hospital for asthma-related reasons, such as a severe exacerbation, may be at risk of short-term readmission to hospital. For example, some patients with persistent airways inflammation are at risk of readmission after discharge despite treatment with corticosteroids ,10. Pred cells/L . Converslization . The varThe aim of this study was to determine if patients hospitalized for an asthma exacerbation were more likely to be readmitted if their preadmission blood eosinophil count was elevated. Our hypothesis was that standard management of asthma exacerbations is insufficient to prevent readmissions for patients who have high blood eosinophil counts in the year preceding a hospitalization.We used primary and secondary care data from the Clinical Practice Research Datalink (CPRD) and linked Hospital Episode Statistics (HES) for this historical cohort study of patients with asthma who had been admitted to hospital in England. The CPRD is a large well-validated database, frequently used for medical and health research, that contains de-identified, longitudinal medical records of 5 million patients from >600 UK practices . The linThe study dataset spanned the period from April 1997 through February 2016.Eligible patients were 5 years or older at the time of their most recent asthma diagnosis and had active asthma, which we defined as (1) a diagnostic Read code for asthma qualifying for inclusion in the asthma registry, which general practices in the UK maintain for the Quality Outcomes Framework (QOF) , (2) no Eligible patients had to have available, continuous data throughout the study period , which ia priori analysis plan, and study registration with commitment to publish [The study was performed in compliance with all applicable local and international laws and regulations and to standards suggested for observational studies, including an independent advisory group, use of an  publish . The stu publish . No pati9 cells/L . This value was chosen based on our findings in a prior study in which patients with blood eosinophil counts >0.3x109 cells/L experienced more severe exacerbations and poorer asthma control [The exposure of interest was the most recent blood eosinophil count measured within 1 year before hospital admission. For patients who had multiple tests in the baseline year, we used the blood eosinophil count  that was closest to the admission. A high blood eosinophil count was defined as ≥0.35x10The primary outcome was readmission to hospital with asthma as primary diagnosis (ICD-10 code J45/J46) over a 4-week outcome period and over a 1-year outcome period after discharge from the hospital . The sec2 test of independent categories for categorical variables, and the Mann-Whitney test for continuous variables.Patients’ baseline characteristics and hospital readmissions were compared between patients with high and normal blood eosinophil counts using Pearson's χKaplan-Meier curves were constructed for patients with and without high blood eosinophil count for the maximum follow-up period of 1 year after hospital discharge. Comparisons were made with log-rank analyses, and patients were censored if they died.Cox proportional hazard regression, with the time from hospital discharge date to the first readmission date as the “survival” time, was performed to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between high blood eosinophil count and time to readmission, adjusted for potential confounders. The following variables were evaluated for their potential confounding effect on the effect estimate: sex, age, body mass index (BMI), smoking habits, timing of blood eosinophil count relative to the first hospitalization, Charlson comorbidity index , comorbidities, and Global Initiative for Asthma  (GINA) t9 cells/L or ≥0.3x109 cells/L if rounded, and ≥0.45x109 cells/L or ≥0.5x109 cells/L if rounded) and examining outcomes in two subsets of patients: (1) after exclusion of those who initiated inhaled corticosteroids (ICS) after their first asthma-related hospital admission and (2) after exclusion of patients with a concomitant diagnosis of COPD.Potential effect modification of smoking status was tested for significance by including an interaction term into the full model. We conducted several sensitivity analyses, repeating the outcome analyses using alternative definitions of high blood eosinophil counts (≥0.25x10https://www.r-project.org/). A statistically significant result was defined as p≤0.05.Statistical analyses were conducted using IBM SPSS Statistics version 23  and R version 3.0.2  patients had at least one hospital admission for asthma and ≥2 years of medical record data, and 3,611 patients (16%) of those hospitalized had an eosinophil count recorded within 1 year before the hospitalization . Of these 3,611 patients, 2,613 patients (72%) were ≥5 years old, had active asthma, and were eligible for the study .In the study population, 482 of 2,613 patients (18%) were discharged from hospital on the same day. Six patients died  during 1 year of follow up.2), and receiving a higher median ICS dose  during the baseline year  and 13,016 patients with asthma who met all eligibility criteria except availability of blood eosinophil count during baseline are presented in ine year .9 cells/L) was recorded during the year before the hospital admission for 835 of 2,613 patients (32%). The high blood eosinophil cohort had a median age of 45 (vs. 54 years in the cohort with eosinophil count of <0.35x109 cells/L) and included proportionately fewer women and fewer overweight and obese patients  was the same in patients with and without a high blood eosinophil count; however, there were fewer patients with a high blood eosinophil count who had a long hospital stay .9 cells/L had a 49% higher adjusted risk of readmission to hospital for asthma in the first year of follow-up than patients without a high count  when tested by including an interaction term for current smoking (yes/no) and high blood eosinophil count (yes/no) into the model. The increased readmission rate with a high blood eosinophil count was found only in non-smokers  and not in current smokers . In this analysis of all 2,613 patients, 16 patients without recent, recorded smoking status were included as non-smokers (never-smokers plus ex-smokers).Results were similar for patients with known smoking status, with a significant 216% higher adjusted risk of readmission for never-smokers with high blood eosinophil count, and no additional risk for current smokers with high blood eosinophil count . Althoug9 cells/L, and for 588 patients (23%) when defined as ≥0.45x109 cells/L. The association between a high blood eosinophil count and readmission to hospital for asthma was less pronounced and not significant for patients with blood eosinophil count of either ≥0.25x109 cells/L  or ≥0.45x109 cells/L  when defined as ≥0.25x109 cells/L slightly increased as compared with those for the full population  had no prescription for ICS in the baseline year before being hospitalized for asthma; of the 169, 115 (68%) had ICS prescribed in the outcome year. After exclusion of these 115 patients, HRs for the association with blood eosinophil count of ≥0.35x10pulation . The HR Results of an additional subanalysis excluding patients with a concomitant diagnosis of COPD showed no relevant difference in association for the remaining 2,329 patients  were readmitted to hospital for asthma within 4 weeks after discharge, while by 1 year after discharge, 5%  patients were readmitted for asthma. The greater risk of readmission during 1 year follow-up was present only for patients with high blood eosinophil count who were never- or ex-smokers (not for current smokers).In this large, historical cohort study, we found that patients who had a blood eosinophil count of ≥0.35x10Our study is one of few studies examining hospital readmissions for asthma in a general asthma population and in the real-life setting. Readmissions in the present study were comparatively infrequent relative to results in other studies: for example, in one US study, approximately 4% of patients were readmitted for an asthma exacerbation within 30 days , and in Other recent studies of hospital readmissions have been limited to patients on systemic corticosteroids , have exAn interesting finding in the present study that requires further investigation is the effect of smoking status on association of readmissions with eosinophil count. Cigarette smoking increases levels of oxidative stress, alters airway immune responses, and increases risk of hospitalization in patients with asthma . WesterhThe median duration of hospitalization (2 nights) was the same in both normal and high blood eosinophil cohorts; however, patients with a high blood eosinophil count were less likely to have a hospital stay longer than 5 nights (17% vs. 24% of those without high eosinophil count). This finding illustrates the conundrum of eosinophilic asthma: while it tends to be more severe in terms of exacerbations and asthma control, eosinophilic asthma is also potentially more responsive to therapies targeting type 2 inflammation, including ICS and biologics.We speculated that the association between eosinophil count and readmission could be diluted for patients with eosinophil count performed several months before the first admission; therefore, we re-examined outcomes including only patients with eosinophil counts measured close to the initial hospitalization to see if the association were stronger. However, when selecting those with eosinophil count recorded within 4 months before hospitalization, the numbers became small and associations non-significant, although the direction of the effect was the same: for never- and ex-smokers pooled (n = 915), the risk of readmission was 51% greater but non-significant .A strength of this study is that we included a broad patient population with asthma, not limited to those with severe asthma. We selected inclusion criteria to ensure that patients’ asthma was actively managed in advance of the hospital admission, thereby excluding patients experiencing a first episode of asthma diagnosed at the time of admission. Moreover, we required that patients had not received an oral corticosteroid prescription within 2 weeks before the eosinophil count to obviate the eosinopenic effects of systemic corticosteroids ,33. The Nevertheless, a limitation is that the study dataset comprised information collected for clinical and routine use rather than specifically for research purposes. Moreover, prescriptions for drugs prescribed by specialists are not reliably recorded in the CPRD. Therefore, we could not evaluate treatment prescribed immediately after hospital discharge. However, the daily dose of ICS prescribed by GPs in the year after admission was not significantly different between patients with and without high eosinophil counts . Finally, as for all observational studies, there is the possibility of residual confounding from unrecognized and/or unmeasured factors.9 cells/L for high blood eosinophil count captured a clear association of high blood eosinophil count with risk of readmission, while there were fewer patients, hence limited statistical power, to evaluate the higher cut-point of ≥0.45x109 cells/L, although the direction of the effect was the same. Alternatively, new ICS use or better ICS adherence after the index hospitalization might have reduced the effect of elevated eosinophil count; however, it would not be easy to quantify this possibility in the framework of a historical cohort study, and in spite of this possibility we found a strong association at the ≥0.35x109 cells/L definition.A “count-response” association of blood eosinophil levels with risk of asthma exacerbations has been reported in both an observational study  and for We did not exclude patients with a concomitant diagnosis of COPD; therefore, approximately one-tenth of the study population appeared to have some form of physician-diagnosed asthma-COPD overlap , althougBy necessity we were able to include only patients who had a recorded blood eosinophil count, which is not routinely measured in clinical practice, a factor serving as a possible source of selection bias and thereby limiting the generalizability of our findings. There were large differences in baseline characteristics between the patients with available eosinophil count and those without, who tended to be younger; more likely female, a current smoker, and of normal weight; and less likely having comorbidities such as rhinitis, chronic sinusitis, gastroesophageal reflux disease, and cardiovascular disease. The age differences were expected because older people more frequently have full blood counts available. Further work is needed to examine the use of blood eosinophil count in the clinical assessment of the full spectrum of patients with asthma.Tailoring asthma therapy using sputum eosinophil counts appears to be effective in reducing exacerbations, particularly for adults with frequent exacerbations . Thus, bA high blood eosinophil count in the year before an asthma-related hospitalization is associated with increased risk of readmission within the following year. This risk was slightly greater in the subset of patients who were not new initiators of ICS treatment after their index hospital admission, suggesting that this trait is only partially treatable with anti-inflammatory therapy. This association was present only in non-smoking patients with high blood eosinophil count. Our findings support the benefit of including a full blood count with differential as a routine assessment in clinical practice for patients with not well-controlled asthma. Moreover, our findings support the need for careful follow-up, with treatment optimization, after hospital discharge for patients with asthma and preadmission high blood eosinophil count.S1 Fig(TIF)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.


To investigate the metabolic profiles of newly diagnosed type 2 diabetes (NEW2D) in Chinese older adults (≥65 years) and assess the proportion of patients who achieved the targeted goals of blood glucose, blood pressure, and blood lipid.  NEW2D study was an observational, longitudinal, prospective cohort study involving patients who were diagnosed with type 2 diabetes (T2D) within the past 6 months and had a follow-up of 12 months. Participants were divided into younger NEW2D group (aged 20-65 years old) and older NEW2D group (aged ≥65 years old) according to age of diabetes onset. The baseline metabolic profiles were compared and the proportion of patients achieving adequate control of blood glucose, blood pressure, and blood lipids in reference to target goals were assessed during treatment. n = 1362) had a lower BMI, HbA1c%, diastolic blood pressure, triglyceride, low-density lipoprotein cholesterol (LDL-C), and total cholesterol, higher systolic blood pressure, and high-density lipoprotein cholesterol levels at baseline. 47.8%, 66.7%, and 39.4% reached the target of HbA1c < 7.0%, BP < 140/90 mmHg, and LDL − C < 2.6 mmol/L, respectively. After 12 months, the proportion achieving above three targets increased to 70.2%, 76.1%, and 47.5%, respectively. The proportions of patients achieving three combined therapeutic targets doubled from 13.5% to 26.7%.  The older NEW2D ( The older NEW2D patients have special metabolic profiles compared with younger patients. The control of cardiovascular disease risk factors was suboptimal in older adults with type 2 diabetes. Diabetes, particularly type 2 diabetes (T2D), is becoming more prevalent in the general population, especially in older people . In 2010Diabetes mellitus, hypertension, and dyslipidemia, which often coexist in older people, have been shown to increase the risk of cardiovascular disease (CVD) and mortality , 5. HoweThe older and younger people with newly diagnosed diabetes have unique metabolic characteristics. A cross-sectional survey of China National HbA1c Surveillance System (CNHSS) reported diabetes participants aged >40 years old had higher systolic blood pressure (SBP), higher low-density lipoprotein cholesterol (LDL-C), lower glycated hemoglobin (HbA1c), and similar BMI and triglyceride (TG) levels compared with early-onset diabetes participants (aged ≤40 years) . HoweverTherefore, the aim of our study was to evaluate the metabolic characteristics and control of glycemia, blood pressure, and lipid in the older NEW2D in a study of the China Cardiometabolic Registry for newly diagnosed type 2 diabetic patients (CCMR-NEW2D).http://www.clinicaltrials.gov (NCT01525693) on February 3rd, 2012.This study was a prospective, observational cohort study with 12-month follow-up , 14. FroEthical approval was first obtained from the Ethic committees of Peking University People's Hospital and then was approved by all the participating hospitals. All patients provided written informed consent to participate in the study prior to being screened. The research methods of the study adhered to the Declaration on Helsinki and all research was reported in accordance with strengthening the reporting of observational studies in epidemiology (STROBE) Statement.The primary objectives of NEW2D study was to assess the evolution of treatment patterns for newly diagnosed T2D patients and the clinical outcomes during 12-month follow-up in real-world condition. The patients all received routine lifestyle suggestions as diet and exercise by the investigators and also medications prescribed by the investigators. These patients were required to return to the same physician for the follow-up visits at 3, 6, 9, and 12 months after the first visit. If the patient was lost at follow-up, a structured telephone interview would be performed by the investigator to realize the patient's condition.2 means thin, 18.5 ≤ BMI < 24 kg/m2 means normal, 24 ≤ BMI < 28 kg/m2 means overweight, and BMI ≥ 28 kg/m2 means obese. Target goals of blood glucose, blood pressure, and blood lipids (3Bs) were as follows: HbA1c < 7%, BP < 140/90 mmHg, and LDL − C < 2.6 mmol/L. Another more strict treatment targets of HbA1c and BP were also set for this analysis: HbA1c < 6.5% and BP < 140/80 mmHg. Another less strict treatment target of HbA1c < 7.5% was also set for this analysis. The overall proportion of patients reaching the target at baseline and follow-up were reported. For data collection and quality control, all the data were recorded in the approved case report form and entered into a web-based electronic data capture system designed by VitalStrategic Research Institute (VSRI) .Physical examinations and lab tests were performed at the baseline and follow-up visits, which were described previously , 14. Thep value <0.05 for the two-tailed test was considered statistically significant. Statistical analyses were conducted using statistical analysis system (SAS) version 9.3 .Newly diagnosed diabetes participants were divided into two groups according to age: the younger NEW2D group (aged <65 years old) and the older NEW2D group (aged ≥65 years old). Descriptive statistics were used to characterize the data in the study, including calculations of means and standard deviations. The frequency and percentages (based on the nonmissing sample size) of observed levels were reported for all categorical measures. Comparisons were statistically analyzed using one-way ANOVA and chi-squared tests. Totally, 5770 patients from 79 hospitals, across six geographic regions of China, were included in this study. The average age of the patients was 55.7 ± 12.6 years. Among all the newly diagnosed diabetes participants, 1362 (23.6%) participants were classified as older NEW2D.p < 0.0001). Older NEW2D participants had higher proportion of females and less current smokers and drinking. The older participants were more likely to take regular exercises than their younger counterparts. The older participants had lower BMI, HbA1c%, FPG, CHO, TG, LDL-C, and DBP and higher SBP and HDL-C levels compared with that of younger diabetes participants. In older NEW2D, 54.8% patients had hypertension and 41.0% had dyslipidemia at baseline. 29.0%, 15.2%, and 25.8% had comorbid hypertension, dyslipidemia, or both. Baseline characteristics of younger and older newly diagnosed type 2 diabetes participants in China were shown in 38.6%, 25.8%, and 35.5% of the older NEW2D patients were from tier 1, tier 2, and tier 3 hospitals, respectively, of which the pattern distribution was different from that in younger diabetes group . Similarly, the mean DBP was 78 ± 9 mmHg at the baseline and decreased to 77 ± 7 mmHg at 12 months (p < 0.001) (BP < 140/90 mmHg) at baseline and 44.9% of them reached the stricter target goal of BP < 140/80 mmHg (The mean SBP in the older NEW2D was 133 ± 15 mmHg at the baseline and slightly decreased to 131 ± 12 mmHg at 12 months (< 0.001) . Overall/80 mmHg . At 12 mp < 0.0001). Overall, the proportion of the older NEW2D who achieved LDL − C < 2.6 mmol/L increased from 39.4% at baseline to 47.5% after 12 months (p < 0.0001) (p < 0.0001), and the mean level of HDL-C increased significantly after 12 months (p < 0.0001) (p < 0.0001) (p < 0.0001) was used.The mean LDL-C was 2.8 ± 0.9 mmol/L at the baseline and reduced to 2.7 ± 0.9 mmol/L at 12 months ( 0.0001) . The mea 0.0001) . The pro 0.0001) . And theAt baseline, 42.7% of the older NEW2D were on diet and exercise alone and 1.0% of them had herbal medicine only. 41.9% of the patients took OHD only . 5.9% participating patients were treated with OHA in combination with insulin; 8.5% were treated with insulin alone. Only 16.7% of the older patients received statin therapy.This large, multicentre, cross-sectional, hospital-based study in China revealed that 23.6% of patients were elderly among newly diagnosed patients with diabetes. The older NEW2D in China was characterized by lower BMI, HbA1c%, FPG, CHO, TG, LDL-C, and DBP and higher SBP and HDL-C levels compared with younger patients aged less than 65 years old. The proportion of patients achieving adequate control of blood glucose, blood pressure, and blood lipids in reference to target goals improved during the 12-month follow-up, but still far from satisfactory.It is well established that hyperglycemia, hypertension, and dyslipidemia are risk factors for microvascular diseases in T2D. Patients with T2D who had risk factor variables  within the target ranges appeared to have little or no excess risk of death, myocardial infarction, or stroke, as compared with the general population . HoweverEvidence suggests that the benefit of intensive glucose-lowering therapy is not uniform across all patients with T2D. There were few data specifically addressing optimal target HbA1c goals in older patients . The widThe older NEW2D patients had better glycemic control at the baseline compared to patients < 65 years of age no matter if we use the glycemic target of HbA1c < 7.0% or a more or less strict target, which was consistent with previous studies , 22. PreLDL-C reduction was associated with the greatest CVD risk reduction, followed by blood pressure and glycemic control . HoweverThere are some limitations of this study. First, given the limitations of observational research and our short follow-up time, the clinical implication of the observed characteristics in the older NEW2D participants was not known. Prospective cohort studies with longer follow-up are necessary to observe the natural history of newly diagnosed diabetes in Chinese older patients. Secondly, the HbA1c target for older patients was still controversial. However, as this study was an observational cohort study, with the aim to evaluate clinical outcomes and glycemic control in the real world in China, we did not stratify the target of glucose control for different ages in this study. Randomized, prospective trials that have examined glycemic control and complications focusing on the older patient (>65 years) are needed to obtain the optimal glycemic target.The older NEW2D patients have special metabolic profiles and higher proportion of comorbid hypertension and hyperlipidemia. The proportion achieving adequate control of risk factors for cardiovascular disease in older NEW2D patients were improved during treatment. However, control of glycemia, BP, and LDL were far from optimal despite the widespread use of guidelines for the management of diabetes and CVD. Awareness and application of published recommendations need to be reinforced.


Thyroid dysfunction may alter kidney function via direct renal effects and systemic haemodynamic effects, but information on the effect of thyroid function on postoperative acute kidney injury (AKI) following thyroidectomy remains scarce. We reviewed the medical records of 486 patients who underwent thyroidectomy between January 2010 and December 2014. Thyroid function was evaluated based on the free thyroxine or thyroid stimulating hormone levels. The presence of postoperative AKI was determined using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. AKI developed in 24 (4.9%) patients after thyroidectomy. There was no association between preoperative thyroid function and postoperative AKI. Patients with postoperative hypothyroidism showed a higher incidence of AKI than patients with normal thyroid function or hyperthyroidism . Multivariable logistic regression analysis showed that male sex , preoperative use of beta-blockers , low preoperative serum albumin levels , and colloid administration  were associated with postoperative AKI. Our results showed that postoperative hypothyroidism might increase the incidence of AKI after thyroidectomy. They also affect physiological functions, including sodium and water homeostasis, renal blood flow, and glomerular filtration rate (GFR)4. These influences may be mediated via direct renal effects, including the function of many transport systems along the nephron7, as well as via cardiovascular and systemic haemodynamic effects10. Thus, both hypothyroidism and hyperthyroidism are associated with marked alterations in kidney function.Thyroid gland hormones affect almost all organ systems in the body, and their interactions with the kidneys have been well characterized. Thyroid hormones influence renal development and histological changes in kidney structure12. Hypothyroidism is associated with elevated serum creatinine levels, as well as reduced GFR and renal blood flow14. Thus, hypothyroidism may induce AKI or contribute to the occurrence of AKI in the presence of other renal insults. Nevertheless, scarce information is available on the relationship between thyroidectomy and postoperative AKI. Hence, we aimed to determine the effect of thyroid function on the prevalence of AKI after thyroidectomy. Moreover, we evaluated factors related to postoperative AKI and the impact of AKI on outcomes following thyroidectomy.Acute kidney injury (AKI) is related to increased health costs and adverse outcomes, including the progression to chronic kidney disease and deathA total of 486 patients were included in the analysis. Of these patients, AKI was diagnosed in 24 (4.9%) based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria.The preoperative and intraoperative characteristics of these patients are shown in Tables There was no association between preoperative thyroid function and the occurrence of postoperative AKI (P = 0.661). For 72 patients, thyroid function was evaluated within 7 postoperative days. There was a higher incidence of AKI among patients with postoperative hypothyroidism than among patients with normal thyroid function or hyperthyroidism .Multivariable logistic regression analysis indicated that male sex , preoperative use of beta-blockers , low preoperative serum albumin levels , and colloid administration  were associated with the occurrence of postoperative AKI Table .Table 3UBased on outcome analyses, patients with AKI were more likely to stay longer in hospital  than patients without AKI  criteria, and in 5.5% of patients based on the Risk, Injury, Failure, Loss, and End-stage Renal Failure (RIFLE) criteria19. The prevalence of AKI in the present study is consistent with previous reports, although it should be noted that thyroidectomy is a relatively low-risk surgery in terms of bleeding or haemodynamic instability.The occurrence of postoperative AKI raises major concerns regarding patient safety, but few studies to date have assessed AKI incidence after thyroidectomy. Previous studies have reported that AKI develops in 0.8–10% of patients after non-cardiac surgeries6. They also affect water and electrolyte metabolism, as well as cardiovascular function9. All these effects lead to important alterations in renal function in both hyperthyroidism and hypothyroidism. Serum creatinine levels are lower in cases of hyperthyroidism, whereas contrast findings are noted in cases of hypothyroidism. The renal impairment associated with hypothyroidism is primarily believed to be a result of reduced cardiac output and the subsequent decrease in the renal blood flow and GFR21. Thus, hypothyroidism may contribute to the exacerbation of pre-existing chronic kidney disease or the occurrence of AKI in the presence of other renal insults. Before radioiodine scanning for thyroid cancer follow-up, patients must stop taking levothyroxine and placed in a hypothyroid state. Kreisman et al. reported that such patients show a consistent elevation of serum creatinine levels in the hypothyroid state, and that this elevation is reversible after replacement of levothyroxine7. Our study showed comparable results in that patients with postoperative hypothyroidism exhibited a higher incidence of AKI than patients with normal thyroid function or hyperthyroidism .The impact of thyroid dysfunction on renal function has been emphasized in recent studies. Thyroid hormones play important roles in renal development and the function of many transport systems along the nephron7. We defined AKI using the KDIGO criteria based on the serum creatinine level within 7 days, and this may be an insufficient period to detect the effect of postoperative hypothyroidism on postoperative AKI. Nevertheless, the association between postoperative thyroid function and serum creatinine level should be carefully considered by clinicians, because hypothyroidism can lead to AKI in patients with normal preoperative creatinine levels. Although the elevation of serum creatinine levels typically normalizes following thyroid hormone replacement after a short period of hypothyroidism, slower and incomplete recovery has been noted in cases with more prolonged periods of severe hypothyroidism20. Furthermore, the changes in renal function in the hypothyroid state may also lead to potential alterations in therapeutic drug doses7.The time over which AKI develops in patients with hypothyroidism remains unknown. In a previous study, the serum creatinine levels were found to be elevated within 2 weeks of the onset hypothyroidism23. Moreover, it functions as a reservoir for signalling molecules and donors of nitric oxide (NO) that enhance the renal blood flow and GFR by dilating vessels and improving renal function24. Furthermore, albumin tends to improve the microcirculatory performance that supports the maintenance of major organ functions25. Thus, both preoperative and postoperative hypoalbuminaemia are major risk factors for AKI in many previous studies28. Although controversial, beta-blockers have similar effects to albumin on renal function. Despite the concerns about haemodynamic effects including a decrease in renal blood flow, several beta-blockers are known to mitigate renal injury by antioxidant properties or activating NO synthase. Several animal studies have reported that beta-blockers reduce the severity of AKI or have renal protective effects31. However, Le Manach et al. reported that the use of preoperative beta-blockers was associated with an increased frequency of renal failure because beta-blockers limit the increase of compensated cardiac output when major blood loss occurs32. In a number of studies of the effects of beta-blockers on advanced liver diseases, patients receiving beta-blockers had a high probability of developing AKI, and this was related to the inhibited cardiac compensatory reserve34. These harmful effects of beta-blockers could be related to renal hypoperfusion35. Furthermore, beta-blockers are recommended as third-line antihypertensive agents in patients with proteinuria according to the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines36. Thus, the effectiveness of beta-blockers against postoperative AKI among patients in normal haemodynamic states after minor surgery remains unclear. Further studies are required to clarify the effects of beta-blockers on renal function.Our multivariable analysis agreed with previous studies in terms of factors associated with AKI, including male sex, preoperative use of beta-blockers, low serum albumin level, and colloid administration. Albumin is known to have a renoprotective effect, mediated by antioxidant and anti-inflammatory properties37. Another potential pathologic mechanism involves renal interstitial proliferation, macrophage infiltration, and tubular damage contributing to hydroxyethyl starch-induced nephrotoxicity38. Previous studies have shown the adverse renal effects of colloid administration in critically ill and septic patients40, although sufficient evidence on this topic is not available for healthy patients under perioperative care. A retrospective study of 174 patients who underwent orthotropic liver transplantation showed a higher incidence of AKI after colloid administration as compared to albumin administration41. In contrast, another study showed no association between intraoperative colloid administration and increased AKI risk after living donor hepatectomy42. Despite the relatively healthy patient characteristics in the present study, colloid administration was associated with AKI after thyroidectomy. However, additional studies with a randomized, controlled design are needed to clarify the findings regarding the nephrotoxicity of colloid administration in surgical patients.The detrimental effect of colloid administration on renal function remains a major concern. The oncotic force of these solutions may decrease renal filtration pressure, and this may inhibit renal function43. This may affect our results because we excluded patients with CKD. Additionally, the development of postoperative AKI is related to the type of operation. Previous reports about the relationship between diabetes and postoperative CKD showed inconsistent results varying by procedure44. Lastly, the low incidence of postoperative AKI in our study may have affected the multivariable analysis findings.The prevalence of underlying diabetes mellitus was higher in the AKI group, but it showed no statistical relationship with AKI following multivariable analysis. Diabetes is also known as one of the risk factors of for postoperative AKI; and this association is thought to result from the possibility of pre-existing CKD45. A lack of urine analysis, including sodium concentration and proteinuria, can be another concern. The analysis of urine sodium concentration can identify the cause of AKI after thyroidectomy. Although the renal impairment associated with hypothyroidism is primarily believed to be a result of reduced cardiac output and the subsequent decrease in renal blood flow and GFR, thyroid hormone is also known to affect kidney function by direct effects on the renal tubular system. Additionally, the presence of proteinuria in diabetes can result in the loss of thyroid hormone, and diabetes itself can contribute to AKI incidence. Although we considered as many variables as possible and performed multivariable analysis to obtain reliable results, we could not eliminate the possibility of residual confounding variables. Additionally, the low incidence of postoperative AKI among patients involved in this retrospective study limited the power to detect the relationship between thyroid function and AKI, as well as the effects of the investigated variables on AKI. Nevertheless, this was a suitable strategy for evaluating the effect of thyroid function on postoperative AKI in the absence of prospective studies. Further prospective studies with well-constructed designs for clarifying the effect of thyroid function on postoperative AKI are needed.The retrospective observational study design resulted in some important limitations. As serum creatinine was not measured on every single day of postoperative admission and follow-up, there might be some undetected cases of postoperative AKI. Nevertheless, the incidence of postoperative AKI in this study was 4.9%, which is consistent with previous reports. Additionally, in accordance with KDIGO guidelines, the frequency of serum creatinine and urine output measurements to detect AKI should be individualized based on patient riskIn conclusion, AKI developed in 4.9% of patients who underwent thyroidectomy. We found that there was a higher incidence of AKI among patients with postoperative hypothyroidism than among patients with normal thyroid function or hyperthyroidism after thyroidectomy. As the knowledge of the association between postoperative thyroid function and postoperative AKI may have important clinical implications, further prospective studies should be conducted to clarify the effect of thyroid function on postoperative AKI incidence in thyroidectomy patients.After approval was obtained from the Institutional Review Board of Asan Medical Center, we reviewed the records of all patients who underwent thyroidectomy for thyroid cancer at Asan Medical Center, Seoul, Republic of Korea, between January 2010 and December 2014. Informed consent was waived due to the retrospective nature of our study. Of the 516 identified patients, we excluded those aged <18 years (n = 7) and those with chronic kidney disease (n = 23). Thus, a total of 486 patients were finally included in the present study . Baseline characteristics included sex, age, body mass index, comorbidities , and the use of prescribed medications (beta-blockers and levothyroxine). Pathological diagnosis, tumour stage, and tumour size were also included as cancer characteristics. Laboratory data included sodium, potassium, chloride, calcium, haemoglobin, albumin, uric acid, and serum creatinine levels. To evaluate thyroid function, free thyroxine (FT4), and thyroid stimulating hormone (TSH) levels were recorded. Levels of serum TSH and FT4 were measured using the TSH-CTK-3 immunoradiometric assay (IRMA) kit  and fT4 radioimmunoassay (RIA) kit , respectively. Hyperthyroidism was defined as having a TSH level < 0.45 mIU/L with normal FT4 levels or FT4 levels >2.0 ng/dL. Hypothyroidism was defined as having a TSH level >4.5 mIU/L with normal FT4 levels or FT4 levels <0.8 ng/dL45. Serum creatinine was measured on days 1, 2, 3, 5, and 7 after surgery and at least one time during that period in all patients. We did not use the urinary output criterion due to the unreliability of urine output measurements. The other outcome variables included the occurrence of postoperative intensive care unit (ICU) admission and the duration of hospital stay.The primary outcome of this study was the prevalence of AKI based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. According to the KDIGO criteria, AKI was defined as an increase in the serum creatinine level by ≥0.3 mg/dL within 48 hours or an increase in serum creatinine by ≥1.5 times within 7 days2-test or Fisher’s exact test was used to compare categorical variables in postoperative AKI groups. Continuous variables in these two groups were compared using the t-test, or the Mann-Whitney U test if the distribution was not normal. To identify the risk factors for postoperative AKI, logistic regression analysis was used to calculate ORs with 95% CIs. All variables in Tables Data are presented as mean ± standard deviation, median (interquartile range), or number (percentage), as appropriate. The χ


Incidence of Acute Kidney Injury (AKI) among Type 2 diabetic patients is significantly increasing. But, earlier studies has focused on the admitted patients which may hide the true nature of the Acute Kidney Injury among Type 2 Diabetic (T2D) patients. So, this study was conducted to determine the time to Acute Kidney Injury and its predictors among Type 2 Diabetic patients in Harari Region, East Ethiopia.We conducted a retrospective cohort study among type 2 diabetic patients who had been receiving treatment at government hospitals of Harari region, Ethiopia from 2013 to 2017. We extracted data from patients’ medical records. We estimated incidence rate and compared survival curves between different exposure groups using Kaplan-Meier and log-rank test. Weibull regression model was fitted to the data to identify the predictor variables. Variables with p-value <0.05 were considered statistically significant.Overall, 14.5% (95%CI: 11.7–17.9) of the study population developed acute kidney injury, with median survival time of 57 months. The significant predictors were physical activity , congestive heart failure , chronic kidney disease , hypertension , obesity , diabetic nephropathy , diuretics & beta blockers , and delay of follow-up .Incidence of acute kidney injury was high in our study area. Hence, identification and controlling of comorbidities along with regular monitoring of kidney function are needed to prevent or delay the risk of acute kidney injury in type 2 diabetic patients. Diabetes mellitus (DM) is a chronic metabolic disorder that occurs when the body’s response to insulin is impaired because of the incapacity of pancreas to produce enough insulin or the body cannot effectively use the insulin produced ,2. Type The Burden of Diabetes is rising in alarming rate, becoming among the three priority non-communicable chronic disease in the World . GloballAcute kidney injury is the sudden and rapid increase in serum Cr (a rapid decrease in eGFR(Glomerular Filtration Rate)) . It replEvidence indicated that despite intensive glucose control provided by medication, patients with T2D remain at increased risk for kidney-related complications . This coStudies conducted at different setups and times indicated that morbidity of Acute Kidney injury has been increasing over the past few decades ,10,11. SData on the rate of impaired kidney function and its contributing factors on patients with T2D is scarce in Ethiopia. There is little evidence on the development of AKI and its association with change in biomarkers of kidney function, specifically, in the country. Even, most of the prior studies has focused on hospitalized patients or patients in intensive care units. So, this study was conducted to determine the time to Acute Kidney Injury and its predictors among type 2 Diabetes Mellitus patients in government hospitals of Harari Region, Ethiopia. The findings will be helpful for the timely identification and treatment of AKI thereby decreasing the risks of progressive CKD (chronic kidney disease) and other complications.We conducted an institution based retrospective cohort study from March 28 to April 30, 2018 among patients diagnosed with Type 2 Diabetes Mellitus from January 1, 2013 to December 31, 2017.The study was conducted at three urban government hospitals in Harari Regional State, Ethiopia that have Diabetes follow-up services. The Harari Regional State is one of the nine ethnically-based regional states of Ethiopia. Its capital is Harar, 500 km far from the capital of Ethiopia, Addis Ababa. The total population of the region by 2017 was 246,000 . In the The study included all patients who were newly diagnosed with Type 2 diabetes during the follow-up visits from January 1, 2013, to December 31, 2017. Patients with end-stage renal disease, renal transplant and history of dialysis at the diagnosis of Type 2 Diabetes, pregnant women, initially present with AKI or no baseline records were excluded.Newly Diagnosed Type 2 Diabetic (T2D) Patients–Patients who were diagnosed for Type 2 Diabetes after December 31, 2012.Acute Kidney Injury–Is an abrupt decrease in kidney function characterized by increase in Serum Creatinine (SCr) by = 0.3 mg/dl (= 26.5 μmol/l) versus the baseline or increase in SCr to 1.5 to 2 times baseline value , congestive heart failure , Chronic kidney disease , Hypertension , Obesity , Diabetic nephropathy , Diuretics & Beta Blockers , and Delay of follow up  were statistically significantly associated with AKI among T2D patients .This study has examined the time to develop acute kidney injury and its determinant factors in Type 2 Diabetic patients. A total of eight factors were identified to determine the time to develop AKI in T2D patients. These factors included, physically activity, hypertension, chronic kidney disease, congestive heart failure, diabetic nephropathy, diuretic anti-hypertension medication, delay to start DM follow-up and obesity.Our study revealed that the incidence of AKI was 14.5%  in T2D patients. This is in line with a study conducted in Kenya, Ghana and Nigeria that around 13.4% of T2D patients have experienced Kidney injury during the follow up in these countries . HoweverIn our study, diabetic nephropathy was independently associated with AKI. The time to develop AKI was significantly faster among the T2D patients with diabetic nephropathy compared to T2D patients without diabetic nephropathy. This is consistent with the result of a review study in Africa and a study conducted in New Zealand ,23.In this study, the risk of developing AKI among hypertensive patients was higher by three-fold than non-hypertensives. Several studies from different settings supported this result. For example, a study conducted from 28 countries indicated T2D patients with hypertension were at increased risk of developing AKI . AnotherObesity was found to accelerate the time to AKI irrespective of its severity in this study. After controlling for the other factors, the time to develop the AKI among obese patients was significantly decreased compared to non-obese patients. This result was in line with the study conducted in the UK in 2016, which reported that obesity was the risk factor in the presence or absence of HTN, Congestive heart failure (CHF) or other cardiac comorbidities . A similCongestive heart failure and chronic kidney disease were significant predictors of AKI. Congestive heart failure patients, irrespective of underline cause, were at higher risk of developing AKI than those who did not experienced CHF. A study conducted in the UK, which analyzed the effects of specific co‐morbidities with T2D found that CHF has increased the risk of AKI . There aThis study has also identified that nephrotoxic drugs were important predictors of AKI. This is similar a study conducted in the UK and from other 28 countries ,24.Delay for follow up after the patients were diagnosed with Type 2 Diabetes was independent predictor of AKI development. The time to AKI development has decreased significantly among patients delayed at least for a month to start treatment. Previous studies also suggested that the early initiation of follow up treatment after the diagnosis is a crucial step to prevent or delay the development of complications from Type 2 diabetes. Even though the recommended visit is varied, it is advised that patients should have a comprehensive assessment with intensive follow-up. Early initiation of follow up is helpful in the control of hyperglycemia, which is the initial cause of varies long-term complication in T2D patients ,32.This study is not without limitations. The exact time of onset of T2D and AKI was not known. As a result, it was difficult to determine how long an individual delayed to start medication. This result might have affected by residual confounding since some data were missed from the record. Important investigation for kidney trajectories and HbA1c were not available for all patients. Despite, of these limitations, this study assessed the factors that determine the time to develop acute kidney injury using the best possible model available.The incidence of acute kidney injury was relatively high among the Type 2 Diabetic patients. It was confirmed that acute kidney injury among Type 2 Diabetic patients was determined by physical activity, congestive heart failure, chronic kidney disease, hypertension, Obesity, Diabetic nephropathy, Diuretics & Beta Blockers and Delay of follow up.We suggest that starting the follow up immediately after diagnoses, a regular checkup for comorbidities, and promoting physical activity are advisable to reduce or delay the risk of AKI.S1 Data(XLSX)Click here for additional data file.


Tp–e and Tp–e/QT ratio were measured, together with standard markers: QT, QTc. It was found that NT-pro BNP was significantly increased after HSCT in comparison to results before it, and no significant changes were present in Troponin levels. Simultaneously, Tp–e interval and Tp–e/QT ratio were significantly higher after HSCT. The use of cyclophosphamide, advanced age, and higher level of blood cholesterol concentration were risk factors for the increase in NT-proBNP and treatment with cyclophosphamide as well as fludarabine and higher creatinine levels were risk factors for the increase in Tp–e/QT ratio. In conclusion, in the early term evaluation after HSCT in patients with no previously diagnosed heart disease, the mild changes in markers of heart overload and repolarization were noted. The observations suggest that in all patients undergoing HSCT, even the ones without pre-existing cardiovascular disease, the evaluation, and monitoring of heart function should be considered.High-dose chemotherapy (HDC) followed by stem cell transplantation (HSCT) is a well-established method in patients with hematological malignancies, and for last few years, many efforts have been made to estimate short- and long-term efficacy of this method, as well as early and late complications. The present study concentrates on cardiotoxic effects, mainly early changes using biochemical markers such as N-terminal natriuretic peptide type B (NT-proBNP) and cardiac troponins (cTn). Simultaneously, the analysis of 12-lead ECG was done before and after the procedure in which the novel repolarization markers:  The problem of cardiotoxicity of chemotherapy has been known for last decades. However, the influence of the peripheral blood stem cell transplantation with prior high dose chemotherapy is still under study.A procedure of high-dose chemotherapy (HDC) followed by autologous hematopoietic stem cell transplantation (HSCT) is used to treat numerous diseases. Nowadays, HSCT is a cure for many patients with hematologic malignancies; however, this treatment can also cause early and late complications and still long-term mortality rates remain higher than in the general population . That isOne of the proposed markers to evaluate early cardiotoxic effects are troponin and natriuretic peptides, that is mainly B-type natriuretic peptide (BNP). N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin are known biochemical markers, in diagnosis of the heart failure and myocardial infarction, respectively. NT-pro-BNP is secreted by myocardial cells in response to increased pressure and volume and is used to identify left ventricular dysfunction; however, there are more data on supporting the role in predicting future cardiac events especially in coronary artery disease, and new data are being gathered as for the screening tool for left ventricular dysfunction in different populations –5.Roziakova et al. showed that the increase in biomarkers, that is NT-proBNP and hs-cTnT (high-sensitive cardiac troponin T), especially at day 14 after HSCT predicts the future risk of developing cardiac events during next 6 months .Tp–e interval, Tp–e/QT, and Tp–e/QTc ratio can be suitable for prediction of ventricular arrhythmias and mortality [Tp–e interval as independent of heart rate may be a valuable tool in several diseases including Bruggada syndrome, hypertrophic cardiomyopathy, and in patients with myocardial infarction [It was found that novel electrocardiographic markers connected with dispersion of repolarization such as ortality –10. Espefarction .Up till now, there were rather few reports on the influence of high-dose chemotherapy and HSCT carried out in patients with hematological malignancies on electrocardiographic repolarization markers, that is mainly QTc was under study, indicating that long QT may be a risk factor of non-relapse mortality or heart failure incidence , 14.The aim of the study was to evaluate the analysis of blood concentrations of N-terminal natriuretic peptide type B and cardiac troponin as well as novel electrocardiographic markers of repolarization in patients with hematological malignancies undergoing HSCT with high-dose chemotherapy in early period after the procedure.A study group of patients was selected from the candidates to high-dose chemotheraphy with consecutive HSCT, included to the project entitled: “The evaluation of the early cardiotoxicity of high-dose chemotherapy and hematopoietic stem cells transplantation in patients with blood neoplasms”. Inclusion and exclusion criteria and the characteristics of the population participating in the project were presented in a the former publication of the authors .The final study group consisted of 48 patients with blood neoplasms undergoing HSCT with prior HDC procedure in accordance with current guidelines. We excluded from the study group all patients with the previously diagnosed cardiovascular diseases and in exclusion criteria were arterial hypertension, heart failure, diabetes, coronary artery disease, and stroke in medical history. In 28 patients, autologous HSCT was done and in the rest 20 patients—allogeneic HSCT. Type of HDC was appropriate to the diagnosed malignancy, and chemotherapy doses were calculated based on patient’s body weight or body surface area. Clinical characteristics of the study group and results of laboratory tests are presented in Tables In all patients enrolled in the study, cardiac biomarkers were measured in blood, that is NT-proBNP and TnT (Troponin) as well as 12-lead electrocardiography (ECG) was performed; all tests we done twice. First test was carried out prior to the HSCT procedure (test A), and the second—after the whole procedure of HSCT (test B). The precise time of test B was dependent on the patient’s condition, mainly risk of severe infection, and the level of granulocytes, and ranged between 13 and 41 days and mean time between test A and test B was 25.86 ± 8.75 days.From each patient, a sample of heparinized venous whole blood was taken twice for troponin T and NT-proBNP and analyzed with the use of the Cardiac Reader . For troponin T measurement range was 0, 1–2 ng ng/mL. Values above or below this range are displayed as “HI” for high or “LO” for low, and for NT-proBNP, measurement range was: 6–3000 pg/mL and values above or below this range are displayed as “HI” for high or “LO” for low, respectively.Tp–e interval were measured manually in the precordial leads and checked with the caliper and Tp–e/QT ratio was calculated from these measurements. Tp–e interval was defined as the time from the peak to the end of T wave and it is considered to represent transmural dispersion index of the ventricular repolarization [In each patient, standard 12-lead surface ECG was performed at rest in supine position with a paper speed of 50 mm/s and a voltage of 10 mm/mV . Duration of QRS, QT interval, and rization , 10, 16.The research has been conducted in compliance with the principles of Good Clinical Practice and Declaration of Helsinki, on the basis of the consent from the Wroclaw Medical University Bioethical Committee. The written consent has been obtained from all the patients taking part in the research. All data collected from the patients were anonymized.W-Shapiro–Wilk tests. For the dependent quantitative variables of the normal distribution, the t test for linked variables was used. In case of quantitative dependent variables showing the distribution distinct from normal, the pair sequence test of Wilcoxon was applied. Results for qualitative variables were expressed in a form of percentages. For dependent qualitative variables, statistical analysis involved the test of McNemar or the Cochran test. In order to define the relationships between variables, analysis of multivariable regression was performed. Parameters of the model obtained in regression analysis were estimated using the technique of least squares. Results at the level of p < 0.05 were assumed to be of statistical significance.Statistic analysis was conducted using the STATISTICA 12 software (StatSoft Polska). For the quantitative variables, arithmetic means and standard deviations of estimated parameters were calculated. Distribution of variables was examined using Lilliefors and Tp–e interval and Tp–e/QT ratio were significantly higher after HSCT than before the procedure. The results of biochemical of as well as electrocardiographic parameters are presented in Table On analysis of biochemical markers of heart function, no increase in Troponin T levels was found before and after HSCT. However, NT-proBNP concentration was statistically significantly higher after transplantation in comparison with the results before the procedure. In electrocardiographic parameters of repolarization, no differences were found in QTc before and after the transplantation, but Multivariate backward regression analysis enabled to assess the following models:Tp–e/QT ratio (expressed as higher difference between test B and test A). The results of estimations for the models obtained in regression analysis are presented in Table The obtained models show that in the group of patients with hematologic malignancies undergoing HDC in the course of HSCT the use of cyclophosphamide, advanced age, and higher initial blood level of total cholesterol represent the independent risk factors for the increase in NT-proBNP concentration (displayed as the increased difference between test A and test B). Moreover, it was shown that in the study group, treatment with cyclophosphamide and fludarabine as well as the higher creatinine blood concentration were the independent risk factors for the increased It is known that HSCT recipients are at 2–4-fold higher risk of death due to heart complications when compared with general population –19. ThusNT-proBNP a known marker of heart failure released in the ventricles in response to pressure overload or stretching of myocytes are also used together with troponin concentration, a marker of myocardial injury, in diagnosis of cardiotoxity after anti-cancer treatment , 24. TheIn our results, we observed no elevations of troponin level in patients undergoing HSCT, and we suggest that it was a result of the selection of the study group as we excluded all patients with the previously diagnosed heart disease and other cardiovascular status that may increase the potential risk of developing cardiac complications. As to NT-pro BNP concentration, we have shown the elevation after transplantation in comparison with initial level, noted before the procedure, that is, the second test was done on average on the 25 day after first evaluation. Moreover, in our study, it was disclosed that the use of cyclophosphamide, older age, and higher blood cholesterol concentration were risk factors for the increase in NT-proBNP in the second test after HSCT. In our opinion, it is the next evidence that alkylating agent, namely, cyclophosphamide may have the influence on cardiotoxicity measured by biochemical markers in the setting of stem cell transplantation. In the interesting study of Sandri, authors underlined the usefulness on NT-proBNP after high-dose therapy with cyclophosphamide . AdditioGenerally, to the proposed diagnostic tools for the detection of cardiotoxicity belong, basically echocardiography, cardiac magnetic resonance, and MUGA (nuclear cardiac imaging) by which the ejection fraction of the left ventricle (LVEF) may be assessed 24). However, there is a discussion in this matter that such proceeding may underestimate minor and early changes which could be seen in other tests , 24, 33.. HoweverTpeak–Tend parameter measured from 12-lead ECG, best from precordial leads, represents transmural dispersion of repolarization reflecting changes in spatial dispersion of repolarization, particularly transmural dispersion of repolarization, and it may be connected with arrhythmias [Tpeak–Tend parameter is better in predicting TdP, the serious ventricular arrhythmia, in patients with long QT syndrome [The another problem discussed in our study was the search for the connection between cardiotoxicity and repolarization markers. Some authors revealed that QTc may be prolonged in patients undergoing HSCT and Akahori discovered that not only the QTc had the tendency to be longer after HSCT, but also it was associated with the higher incidence of heart failure with a predictive value , 14. Addhythmias –10, 40. syndrome , 42. Alssyndrome , 44. Altsyndrome , 14, 43.Tp–e interval and Tp–e/QT ratio were significantly prolonged after the transplantation in comparison with the test before it, which suggests the impaired dispersion of repolarization. The novel markers of repolarization may be very promising tools for future helping to predict the incidence of heart failure and arrhythmias. It is known that arrhythmias, when they happen, may precede the forthcoming cardiac pathology as cardiomyopathy or heart failure also as a complication due to cardiotoxicity. From this point of view, 24-h Holter monitoring should be recommended routinely at peri-transplant period as we suggested in our previous paper [In our study, no connection was found between QTc before and after HSCT; however, us paper . Generalus paper , 45–47. us paper .Limitation of the study may be as usual in this kind of study not numerous number of patients and heterogeneity of the study group. It is, however, due to the specificity of the type of the population undergoing HSCT and organization of the Transplantation Department, and additionally for the fact we specially excluded patients with prior diagnosed cardiovascular disease or status to obtain the initial low-risk population.Tp–e interval and Tp–e/QT ratio in electrocardiographic recording after the procedure in comparison with results obtained before this treatmentIn patients with hematologic malignancies undergoing high-dose chemotherapy and HSCT, higher blood concentrations of NT-pro BNP were noted and additionally, higher values of Tp–e/QT ratio in electrocardiographic evaluation after HSCT.In a group of patients with blood neoplasms undergoing HSCT the use of cyclophosphamide, advanced age and higher cholesterol level are the independent risk factors for the increase in NT-proBNP level after the procedure and the administration of cyclophosphamide and fludarabine are independent risk factors for the increase in


Heterogeneity of microvascular blood flow leading to tissue hypoxia is a common finding in patients with septic shock. It may be related to suboptimal systemic perfusion pressure and lead to organ failure. Mapping of skin microcirculatory oxygen saturation and relative hemoglobin concentration using hyperspectral imaging allows to identify heterogeneity of perfusion and perform targeted measurement of oxygenation. We hypothesized that increasing mean arterial pressure would result in improved oxygenation in areas of the skin with most microvascular blood pooling.We included adult patients admitted to the intensive care unit within the previous 24 h with sepsis and receiving a noradrenaline infusion. Skin oxygen saturation was measured using hyperspectral imaging-based method at baseline and after the increase in mean arterial pressure by 20 mm Hg by titration of noradrenaline doses. The primary outcome was an increase in skin oxygen saturation depending upon disease severity.p = 0.04). After adjustment for baseline saturation, patients with higher SOFA scores achieved higher oxygen saturation after the intervention . Skin oxygen saturation measured at higher pressure was found to be marginally predictive of mortality .We studied 30 patients with septic shock. Median skin oxygen saturation changed from 26.0 (24.5–27.0) % at baseline to 30.0 (29.0–31.0) % after increase in mean arterial pressure (Improvement of microcirculatory oxygenation can be achieved with an increase in mean arterial pressure in most patients. Response to study intervention is proportional to disease severity. Tissues depend upon microcirculation, a network of vessels of less than 100 μm in diameter, for delivery of oxygenated blood . The goaNoninvasive techniques based on either measurement of microcirculatory flow or tissue oxygenation have been used to characterize microcirculation in the sublingual mucosa, muscle and skin of septic patients. A known feature of microcirculation in sepsis is its heterogeneity, with areas of preserved blood flow coexisting with non-perfused areas –7. UnderIn the skin, heterogeneity of perfusion can be seen as mottling. The characteristic discoloration in mottling is created by the pattern of light reflected from the skin surface. It reflects the relative concentration and distribution of chromophores, including oxy- and deoxyhemoglobin contained in the microcirculation. The light absorption properties of these chromophores are known, and measurements of diffuse reflectance spectra can be used to determine their relative concentrations. The hyperspectral camera combines digital photography with measurement of reflected light intensity at multiple spectral bands for each pixel. Hyperspectral imaging (HSI) enables precise mapping of oxy- and deoxyhemoglobin distribution in the dermal layer of the skin. When microcirculation is heterogeneous, hyperspectral images allow to identify poorly oxygenated areas and perform targeted tissue oxygen saturation measurements there .Thooft et al. have shown that increasing MAP by noradrenaline during septic shock improved the perfused vessel density and the microvascular flow index but not tissue oxygenation measured by near-infrared spectroscopy . In contWe aimed to assess the effects of increased mean arterial pressure on microcirculatory saturation in hypoxic skin areas in patients with septic shock using hyperspectral imaging. We hypothesized that increasing MAP by 20 mm Hg by an escalation of noradrenaline doses will result in increase in skin oxygen saturation in these areas.After approval by the Scientific Research Ethics Committee of the Institute of Cardiology and Regenerative Medicine (26/23.02.2017), consecutive vasopressor-requiring adult patients with sepsis admitted within the previous 24 h were recruited from a single 16-bed intensive care unit. We defined vasopressor-requiring septic patients as patients with sepsis or septic shock defined according to The Third International Consensus Definitions for Sepsis and Septic Shock  who had A radial artery and a central venous catheter were in situ in all patients, and noradrenaline was infused through a dedicated lumen. The hemodynamic management of patients was performed by intensive care physicians according to local protocols. All patients received initial fluid resuscitation of 20 ml/kg of crystalloid solution. Additional fluid boluses were given if judged to improve available hemodynamic variables . The decision to start noradrenaline was taken by intensive care physicians if the patient had signs of shock evidenced by fluid unresponsive arterial hypotension (MAP ≤ 65 mm Hg) associated with clinical signs of inadequate peripheral perfusion and rate of infusion individualized to obtain clinical improvement .The study was performed in the intensive care unit at the bedside with windows shaded and ambient light dimmed to limit light interference. The acquisition of images was performed using the hyperspectral camera Nuance EX  which allows acquisition of high-resolution (1392 × 1024 pixel) image sets in the range of 470–820 nm by the step 5 nm. The camera was equipped with a 60-mm f2.8D lens , and a coaxial platform with 5x185 lm halogen tungsten lamps Aluline  and 10 × 140 lm 567.5 nm (lime color) LUXEON light emitting diodes  was used to illuminate the skin surface. To reduce skin specular surface reflectance, linear polarizers were placed in front of the light source oriented orthogonally to the filter’s polarizer.Images of the knee area were captured with the camera positioned at a distance of 25–35 cm from the patient’s patella and at a straight angle to the patient’s longitudinal axis. The captured skin area was 50 × 35 mm. 4 × 4 pixel binning was used resulting in 0.05 × 0.05 mm spatial resolution. The skin area imaged was marked by permanent marker as a reference for repeated imaging. All HSI data were saved as a set of lossless monochrome.tiff files.2) value was calculated from the fourth cluster with the highest blood content by using the diffusion light transport model based on a three-layer skin structure containing melanin, oxyhemoglobin and deoxyhemoglobin chromophores [The processing of the HSI data was performed offline in semiautomatic mode using custom-developed MATLAB  code comprising several stages as shown in Fig. mophores . This momophores .Fig. 1MeThe setting of MAP targets in this study was clinician driven. Published data show that clinicians target higher MAP values than recommended by the guidelines , 19. It Baseline noradrenaline infusion was adjusted to achieve a mean arterial pressure (MAP) of 65 ± 5 mm Hg. In thirteen patients, the lowest achieved baseline value of MAP was > 70 mm Hg when noradrenaline infusion was discontinued during adjustment. Patients with noradrenaline infusion at baseline were included in the septic shock group, patients who had their noradrenaline infusion discontinued into the sepsis group. The resulting set of hemodynamic variables  was recorded after a 30-min stabilization period and HSI performed. The dose of noradrenaline was then increased by 0.05 mcg/kg/min every 10 min to increase MAP by 20 ± 5 mm Hg. After 30-min stabilization period, a repeated set of hemodynamic variables, dose of noradrenaline and HSI of the same area were obtained.During adjustment of noradrenaline, patients were monitored for the development of arrhythmias and excessive peripheral vasoconstriction. All other infusions and ventilator settings were maintained unchanged.All subjects were followed up to 28 days or until death.2.The primary outcome was skin oxygen saturation at baseline MAP and after adjustment of noradrenaline dose to increase MAP by 20 ± 5 mm Hg in relation to disease severity measured by SOFA score. Secondary outcomes were intensive care unit mortality in relation to the effect of increased MAP on μHbO2 at baseline and after study intervention. Kruskal–Wallis and Mann–Whitney U tests were used for comparisons between groups. Multiple linear regression modeling was used to test association between severity of disease measured by SOFA score, intensive care survival and μHbO2 at baseline and after adjustment of MAP. p < 0.05 was considered statistically significant. Statistical analysis was performed using R version 3.2 .Continuous variables are reported as median values and interquartile range (IQR), binary and categorical variables—as counts and proportions. Wilcoxon signed-rank test was used to compare hemodynamic variables and μHbOr = 0.5; α = 0.05; 1 − β = 0.8).We assumed that skin oxygen saturation and disease severity will be moderately correlated and estimated that a total sample size of ≥ 30 patients would be necessary  mm Hg. After adjustment of noradrenaline dose according to protocol, mean arterial pressure increased to 85 (83 to 90) mm Hg.Dynamics of systolic arterial pressure, mean arterial pressure and dose of noradrenaline over the course of the study are shown in Fig. 2 in the patient cohort ranged from 12 to 44%. It was significantly lower in sepsis and septic shock groups, compared to healthy volunteers (35.0 (31.0–39.0) %, 18.0 (13.0–26.0) % and 85.0 (81.0–89.0) %; p < 0.001). Improvement of skin μHbO2 after study intervention was seen in 21 of 28 patients, 10 in the sepsis group and 11 in the septic shock group. Overall, skin μHbO2 changed from 26.0 (24.5–27.0) % at baseline to 30.0 (29.0–31.0) % after noradrenaline dose adjustment (p = 0.04). Change in skin μHbO2 did not differ between the sepsis and septic shock groups (p = 0.69). Changes of μHbO2 in individual patients depending on changes in mean arterial, systolic pressure and dose of noradrenaline are shown in Fig. Baseline skin μHbO2 at lower and higher MAP and disease severity measured by SOFA score modeled by multiple linear regression. Lower baseline skin μHbO2 was significantly associated with higher severity of illness as measured by SOFA score. When MAP was increased by 20 mm Hg and adjustment made for baseline μHbO2, patients with higher SOFA scores had higher skin μHbO2 .Figure 2 measured at higher MAP was found to be marginally predictive of mortality .Skin μHbOThe objective of this study was to evaluate the effects of increasing mean arterial pressure by titration of noradrenaline dose on microcirculatory oxygenation of the skin in vasopressor-requiring patients with sepsis using hyperspectral imaging.2 compared to healthy controls. As microcirculatory oxygenation is the reflection of tissue oxygen supply and demand, we hypothesize that lower values reflect suboptimal oxygen supply at least in some patients and increase their risk of organ failure. Indeed, in this study higher severity of organ failure measured by SOFA score was associated with lower skin oxygen saturation values. Similar to our study, low thenar muscle oxygen saturation measured by near-infrared spectroscopy (NIRS) was found to be present in 60% of patients with sepsis [In our study septic patients, all of whom had achieved macro hemodynamic resuscitation targets, had significantly lower skin μHbOh sepsis , but onlh sepsis . In our 2 in response to change in perfusion pressure.Several techniques can be used to assess skin microcirculation in critically ill patients. Comprehensive assessment of microcirculation should include the magnitude of microcirculatory flow and oxygenation, functional capillary density and extent of heterogeneity . Laser D2 in our study, more improvement in oxygen saturation values was achieved by patients with higher SOFA scores. The study was not powered to detect differences in mortality; yet, lower skin oxygenation at MAP of 85 mm Hg was associated with higher mortality. These findings suggest that the most severely ill patients might benefit more from manipulation of blood pressure to increase their tissue oxygen supply. This effect seems to be variable, and low μHbO2 values even at high MAP convey a poor prognosis.In sepsis achievement of adequate systemic perfusion pressure is considered crucial during the early phase of hemodynamic resuscitation. The newest update of Surviving Sepsis Campaign guidelines recommends early introduction of vasopressors to meet the mean arterial pressure target of at least 65 mm Hg . NonetheA small proportion of patients had a reduction in skin oxygenation with doses of noradrenaline required to increase MAP to 85 mm Hg. Such variability of response has been shown in previous research  and most2 should be interpreted with caution as they are significantly lower than those reported by other technologies, such as NIRS. A meta-analysis of near-infrared spectroscopy in septic patients by Neto et al. reported baseline value of thenar oxygen saturation of 78% in patients with septic shock [2 values of 81 to 89% which are significantly higher than 40 to 50% in a previous report [2 measured by HSI in critical illness is available from porcine model of hemorrhagic shock. Cancio et al. showed a linear decrease of μHbO2 with progressive blood withdrawal; the minimum value observed was 19% [2 values observed in our study seem to fall within the range described in the animal model of shock.The values of skin μHbOic shock . Previous report . Informa was 19% . Skin μH2 after increase in MAP and these changes were not limited to patients with more severe cardiovascular failure. The study cohort was also small but comparable to other similar studies [2 were associated with longer-term changes in organ dysfunction. Whether short-term increase in skin microcirculatory oxygenation leads to improved outcomes has yet to be shown.There are several limitations to this study. A subgroup of patients who could maintain baseline MAP of 65 mm Hg without vasopressor support was included. That resulted in significant differences between patients in terms of initial hemodynamic status. In comparison with other studies investigating the effects of increasing MAP on microcirculation, our study did not use predefined MAP values but aimed to increase MAP by 20 mm Hg from baseline. Nevertheless, like studies which included only patients with septic shock and used predefined MAP values, we obtained a significant response in μHbO studies , 10. ThiThe potential of hyperspectral imaging to quantitatively evaluate skin perfusion and oxygenation in critically ill has not been fully explored. Yet, results from our study need to be replicated in a larger and more diverse patient population with determination of critical cutoff values and confirmation that targeting microcirculatory oxygenation in early sepsis results in better clinical outcomes in patients with septic shock.2 values at baseline, but patients with more severe sepsis-related organ damage showed greater improvement in μHbO2 when mean arterial pressure was increased by 20 mm Hg.We have shown improvement of skin microcirculatory oxygenation measured by hyperspectral imaging with increase in mean arterial pressure in a cohort of patients with sepsis. Non-survivors had lower skin μHbO


The pathophysiology of hemophilic arthropathy is complex and not completely understood. In this study, we aimed to identify biomarkers that can affect the hemophilic arthropathy severity.FV 1691G>A, FII 20210G>A, MTHFR 677C>T and 1298A>C, TNFα‐308G>A and ‐238G>A, ACAN VNTR, and IL1RN*2‐VNTR were identified.Fifty patients were analyzed for biomarker frequencies; in 37 patients, articular symptoms were evaluated based on the physical joint examination score, and in 18, it was based on magnetic resonance imaging. Eight polymorphisms, namely MTHFR 677TT genotype showed a higher number of affected joints , whereas those with the MTHFR 1298AC genotype exhibited higher effusion according to two radiologists . In addition, patients with the TNFα‐308GA genotype had more subchondral cysts .Patients with the MTHFR and TNFα‐308GA suggests their association with clinical parameters of hemophilic arthropathy. Cohort studies are essential to verify these associations.The distribution of risk genotypes for  A major symptom is recurrent hemarthrosis and subsequent progressive arthropathy  on F5 coding sequence (CDS) (Chr1); “FII 20210G>A”, NM_000506.4:c.*97G>A, NG_008953.1:g.25313G>A (dbSNP: rs1799963) on F2 (Chr11); “MTHFR 677C>T”, NM_005957.4(MTHFR):c.665C>T, NG_013351.1:g.14783C>T (dbSNP: rs1801133); “MTHFR 1298A>C”, NM_005957.4(MTHFR):c.1286A>C, NG_013351.1:g.16685A>C (dbSNP: rs1801131), the last two being in MTHFR CDS (Chr1). We also considered the genetic biomarkers linked to inflammation, two single nucleotide substitutions and one VNTR (IL1RN): “TNFα‐308G>A”, TNF (NG_007462.1):g.4752G>A; TNF (NM_000594.3): c.‐418G>A (dbSNP: rs1800629); “TNFα‐238G>A”, TNF (NG_007462.1):g.4682G>A; TNF (NM_000594.3): c.‐488G>A (dbSNP: rs361525), both on the TNF promoter (Chr6); “IL1RN*2 VNTR”, NM_173841.2:c. (dbSNP: rs2234663) consisted of 4 intronic repeats of an 86‐bp (Chr2) core sequence , in which the shortest allele  was associated with high gene expression and increased IL‐1RA plasma levels. We explored its association with genetic biomarkers linked to cartilage compression resistance. The “ACAN VNTR”, NG_012794.1 (variant of cartilage‐specific proteoglycan aggrecan) contained 13 alleles ranging from 17 to 31 repeats of a 57‐bp core sequence in the CDS (Chr15) of ACAN exon 12 (the reference sequence contains 26 repeats), and shorter alleles associated with a reduced resistance to compression in the cartilage, also possibly associated with higher risks of joint damage.Hemophilia A (HA) and B (HB) are an X‐linked recessive disease caused by mutations in 22.1Fifty patients were analyzed for biomarker frequencies. The clinical data were collected from 2007 to 2010 for hemophilic patients from western Mexico who underwent timely on‐demand treatment within 1–2 hr after the onset of major hemorrhage (FVIII 20–30 IU/kg or FIX 40–50 IU/kg every 12 hr)  system . Because the published data for ACAN VNTR are absent and for IL1RN*2 VNTR limited, we genotyped 62 healthy individuals  as a population reference, and tested the Hardy–Weinberg equilibrium (HWE).The following variants were analyzed: 2.3t‐test, and nonparametric data were expressed as the median (range) and evaluated using Fisher's exact test, Mann–Whitney's U test, and Kruskal–Wallis test; statistical significance was considered at p < .05 (two‐tailed test). The concordance between radiologists was assessed using Cohen's kappa coefficient (k) and Spearman's rank correlation. In addition, allele frequencies of ACAN VNTR (n = 62) and IL1RN*2 VNTR (n = 58) were directly obtained using the the gene counting method in the reference group. HWE was analyzed by comparing the observed and expected genotype frequencies (Fisher's exact test). Statistical analyses were performed using SPSS v.22 for Windows (IBM).Parametric data were expressed as the mean ± standard deviation and analyzed using one‐way ANOVA and 3p = .38).Clinicopathological parameters of the patients , such as disease severity (coagulant activity), patient's current age, age at first symptoms, and arthropathies number, are shown in Table After assessment of arthropathy using PJEs and D/ES, the patients were divided into three categories according to joint damage. Concordance analysis between the two radiologists using the progressive/additive D/ES revealed a substantial interassessment agreement only in some progressive items, and good correlation in total score, but a weak‐to‐moderate agreement in the soft tissue additive items Table .ACAN and IL1RN*2 VNTR polymorphisms in the reference group revealed that their genotype frequencies corresponded to HWE (p > .9). This is the first report on the frequency of ACAN VNTR polymorphisms in Mexico. No differences were observed between hemophilia patients and the reference group in ACAN VNTR (p > .10) and IL1RN*2 VNTR (p > .5) allele frequencies, as well as in the most common IL1RN*2 VNTR genotypes 4,4 and 4,2 (p = .32) or total genotypes of ACAN VNTR (p > .6). Specific IL1RN*2 allele combinations representing the minority showed different frequencies (p = .016) depending on the geographical origin of individuals in the reference population.Genotype and allele frequencies of the biomarkers in hemophilic patients and the reference population are summarized in Table MTHFR 677TT genotype had a higher number of affected joints than those with the CC genotype, and patients with the MTHFR 1298AC genotype had a greater degree of effusion compared to those with the AA genotype  and a clear tendency to have more hemarthrosis episodes (according to radiologist 2) compared to the wild‐type group.Table pe Table . Regardi4MTHFR 677C>T, preferential distribution of the TT genotype in patients with a higher number of affected joints was an unexpected finding. Several studies indicated that the MTHFR 677C>T polymorphism, especially in the homozygous state, could be associated with a milder clinical phenotype of hemophilia  ; however, two patients had a coagulant activity of about 10%, which decreased the statistical significance of the results. The same tendency  was observed in a larger group of patients . The MTHFR 677TT genotype alone or in combination with the heterozygous 1298AC genotype, causes mild hyperhomocysteinemia in the presence of low folate status, while thrombotic disease seems to be primarily associated with homocystinuria , we did not statistically analyze the concordance between PJEs and D/ES. Other systems such as the Hemophilia Joint Health score, which had good correlation with the radiological Pettersson score and moderate correlation with MRI regarding the osteochondral component, could be used. Ultrasonography is also employed to evaluate hemophilic arthropathy; however, there is insufficient evidence that it can replace MRI  was followed‐up at 6‐month intervals for 7 years; the results indicated only the knees to show an inverse tendency, i.e. when the mean ROM score in the left knee was low, that in the right knee increased  in a group of patients  in accordance with the Declaration of Helsinki. Informed consent was obtained from all participants and/or their parents or guardians.The authors declare no conflicts of interest.JJLJ and ARJC designed the study, performed the research, statistically analyzed the data, and wrote the paper; ROC performed the assessment of the knee condition by physical joint examination, and analyzed the results; HLZ and RTS evaluated the results and performed statistical analyses; ALFR, CPBM and JATP analyzed the results; JMSP performed clinical assessment of the hemophilia patients. All authors have critically reviewed and approved the final version of the manuscript.


Asthma is a disease characterized by a chronic inflammation of the airways caused by the interaction of genetic susceptibility with environmental factors. Inflammation and remodeling are critical components of asthma. It is shown that many genes are involved in the pathogenesis of asthma.To identify/compare the association between HLA-DRB1 alleles and development of asthma in a sample of Iraqi Arab Muslims.A case-control study  was carried out in Medical city Teaching Hospital, Baghdad-Iraq. The study participants were patients with asthma consulted the hospital from September - 2013 to January - 2015. HLA –DRB1genotyping was done using a panel of sequence-specific oligonucleotide probes (SSOP) using HLA-DRB1amplification and hybridization kits (SSO HLA type DRB1 plus and Mastermix for HLA type DRB1 Amp plus kits -Innogenetics-Belgium) using automated method by AutoLipa – 48Innogenetics-Belgum.There was an increased frequency of HLADRB1*03:01:01 in control group compared with patients group . Other allele like HLA-DRB1* 070101was significantly increased in asthmatic patients in compares with control group .HLA alleles have an effect on development asthma in patients with HLA-DRB1*070101 while HLADRB1* 030101 may have a protective effect in Iraqi Arab Muslims individuals against development of asthma. •Asthma is a disease characterized by a chronic inflammation of the airways caused by the interaction of genetic susceptibility with environmental factors.•To identify/compare the association between HLA-DRB1 alleles and development of asthma in a sample of Iraqi Arab Muslims.•A case-control study  was carried out in Medical city Teaching Hospital, Baghdad-Iraq.•There was an increased frequency of HLADRB1*03:01:01 in control group compared with patients group . Other allele like HLA-DRB1* 070101 was significantly increased in asthmatic patients in compares with control group .•HLA alleles have an effect on development asthma in patients with HLA-DRB1*070101 while HLADRB1* 030101 may have a protective effect. It induces recurrent episodes of wheezing, cough, chest tightness and shortness of breath. The airways are chronically inflamed and obstructed by contraction smooth muscle around airways, making the air way smaller and thick mucus plug it . The inf+ cytotoxic T lymphocytes and HLA Class II molecules present foreign antigenic peptides to CD4+ T helper cells [Asthma is a complex obstructive respiratory disease that is caused by the interaction of genetic susceptibility with environmental influences. Genome-wide screening studies have identified many chromosomal regions containing susceptibility genes for asthma such as 2q, 3p, 5q, 6p21 and 12q23 . Human Ler cells . Howeverer cells . Researcer cells  reporteder cells  showed ter cells demonstra2Forty unrelated patients with asthma , referred to Medical city Teaching Hospital at Baghdad University were enrolled in this study. All of the patients were diagnosed based on the definition of American Thoracic Society including clinical symptoms of asthma like wheezing, cough, chest tightness, dyspnea relieved by an inhalation β-agonist drug and corticosteroids according to guidelines for the diagnosis and management of asthma and did not classified according to their severity of symptoms .Forty normal blood donors  ethnically and age matched with patients group with no history of atopy, asthma and allergic diseases were randomly selected as control group. The mean age of the control group was 36.4 ± 0.2 years with range 23–58 years.The Scientific and Ethical Committee of Al-kindy medical college and Medical City Hospital had approved the study. Written informed consents were obtained from the patients with asthma and control normal blood donors.2.1Five mL of venous blood were collected by venipuncture from study and control population in EDTA containers for DNA extraction by blood kit . DNA product was verified by electrophoresis in a 2% agarose gel containing ethidium bromide and was visualized under UV light. Locus- and allele-specific amplification of genomic DNA was performed for DRB1. Amplification and Hybridization was performed using a panel of sequence-specific oligonucleotide probes (SSOP) using HLA-DRB1amplification and hybridization kits (SSO HLA type DRB1 plus and Mastermix for HLA type DRB1 Amp plus kits -Innogenetics-Belgium) using automated method by AutoLipa – 48Innogenetics-Belgum. The results were interpreted using LiRas version-5.0 software- Innogenetics-Belgium.2.2HLA frequencies were determined by direct counting. The frequency of each allele was compared between asthmatics and normal control group using chi-square test fisher exact test using MiniTab version. 3.0 software. In each comparison, the Odds ratio (OR) along with the 95% confidence interval (95% CI) was used. P-value less than 0.05 were considered statistically significant.2.3The work has been reported in line with STROCSS criteria and site the paper as follows:Mahdi BM, Al-Hadithi ATR, Raouf H, Zalzala HH, Abid LA and Nehad Z, Effect of HLA on development of asthma.3A total of 40 patients with asthma were enrolled in this study. 20 (50%) of the patients were females, 20 (50%) were males, with ratio 1:1 males to females. Mean age was 36.5 ± 0.2 years with range 23–58 years. The other group was forty normal blood donors , their ages were 36.4 ± 0.2 years with range 23–58 years .Table-1DThe distribution of HLA polymorphism HLA*DRB1 was investigated in the control and patients groups of Iraqi Arab Muslims. The observed and expected phenotypes of all loci for the control group as demonstrated in Control and asthmatic patients were typed for identifying the DRB1* alleles using DNA based methodology (PCR-SSOP). There was an increased frequency of HLADRB1*03:01:01 in control group compared with patients group . Other allele like HLA-DRB1* 070101was significantly increased in asthmatic patients in compares with control group  as shown in 4There are numerous genome-wide studies showing the importance of genetic factors in development of asthma such as those located in 2q, 3p, 5q, 6p21 and 12q23 chromosomal regions . After dIn conclusion, it is suggested that HLADRB1*0701 and HLADRB1*0301 alleles might be the possible genetic factors for susceptibility and protection against asthma respectively. This is the first study showing HLA allele association with asthma in Iraqi population. Future studies are needed to investigate the association of HLA alleles in patients with allergic asthma to certain environmental allergens. Also, other identified HLA alleles associated with total IgE level should be confirmed through another study using allergen-specific IgE level. There is a limitation to this study like small number size of the patients' sample and studying other alleles of other locus. So the suggestion is include larger number of the asthmatic population and sorted them according to age like childhood asthma and adult asthma.5HLA alleles have an effect on development asthma in patients with HLA-DRB1*070101 while HLADRB1* 030101 is a protective allele in Iraqi Arab Muslims individuals against development of asthma.Yes.Iraqi Research and development department- Ministry of Higher Education and Scientific Research. University of Baghdad and Al-Kindy College of Medicine.Dr. Batool wrote paper.Dr Arwa collected samples.Dr Hyam did tests.Dr Haider did tests.Laheeb and Zena did tests.The authors have declared that no competing interest exists.UIN = 4079.Consultant Dr Ali Ghalib Mutar Mahdi.Not commissioned, externally peer reviewed.