Ischemic and hypoxic secondary brain insults are common and detrimental in traumatic brain injury (TBI). Treatment aims to maintain an adequate cerebral blood flow with sufficient arterial oxygen content. It has been suggested that arterial hyperoxia may be beneficial to the injured brain to compensate for cerebral ischemia, overcome diffusion barriers, and improve mitochondrial function. In this study, we investigated the relation between arterial oxygen levels and cerebral energy metabolism, pressure autoregulation, and clinical outcome.This retrospective study was based on 115 patients with severe TBI treated in the neurointensive care unit, Uppsala university hospital, Sweden, 2008 to 2018. Data from cerebral microdialysis (MD), arterial blood gases, hemodynamics, and intracranial pressure were analyzed the first 10 days post-injury. The first day post-injury was studied in particular.2 was significantly associated with better pressure autoregulation/lower pressure reactivity index (P = .02) and lower cerebral MD-lactate (P = .04) on day 1. Patients with limited cerebral energy metabolic substrate supply (MD-pyruvate below 120 µM) and metabolic disturbances with MD-lactate-/pyruvate ratio (LPR) above 25 had significantly lower arterial oxygen levels than those with limited MD-pyruvate supply and normal MD-LPR (P = .001) this day. Arterial oxygenation was not associated with clinical outcome.Arterial oxygen levels were higher and with greater variability on the first day post-injury, whereas it was more stable the following 9 days. Normal-to-high mean pO2 above 12 kPa and higher may improve oxidative cerebral energy metabolism and pressure autoregulation, particularly in cases of limited energy substrate supply in the early phase of TBI. Evaluating the cerebral energy metabolic profile could yield a better patient selection for hyperoxic treatment in future trials.Maintaining a pO Maintaining an adequate cerebral blood flow (CBF) and delivery of oxygen is essential in TBI management. Brain tissue oxygenation (pBtO2) below 20 to 29 mm Hg is associated with poor clinical outcome. The pBtO2 correlates with regional CBF and arterial oxygen content. High intracranial pressure (ICP) and low cerebral perfusion pressure (CPP) are associated with low pBtO2, but most hypoxic insults occur in the absence of these predictors and are probably caused by microvascular thrombosis or diffusion barriers such as cerebral edema.Ischemic and hypoxic secondary injury events are common in traumatic brain injury (TBI).2 (Fio2), for example, by normobaric hyperoxia (NBO), in order to increase arterial and brain oxygenation, has been suggested as treatment for cerebral hypoxia in TBI. The treatment may compensate for ischemic hypoxia, overcome cerebral diffusion barriers, and improve mitochondrial function, thereby improving oxidative cerebral energy metabolism and reducing secondary brain injuries. Normobaric hyperoxia may increase pBtO2, but the effect on cerebral energy metabolism is more controversial. Early cerebral microdialysis (MD) studies demonstrated decreased cerebral lactate following NBO treatment, but pyruvate also decreased and the lactate-/pyruvate-ratio (LPR) remained unchanged. However, other studies found that the hyperoxic effect depends on the current energy metabolic state, as hyperoxia was associated with improved cerebral metabolic rate of oxygen (CMRO2) in tissue at risk of ischemia and improved LPR in tissue with high cerebral lactate before treatment initiation. Outcome studies using NBO protocols have shown equivocal results. Spiotta et al found better clinical outcome for TBI patients treated with combined ICP-/pBtO2- versus ICP-oriented treatment alone, whereas Martini et al found no difference in outcome in a similar study. Thus, it is clear that hypoxia should be strictly avoided in TBI; however, the optimal (higher) pO2 level in certain situations needs to be studied further.Increasing the fraction of the inspired O2, pO2, and cerebral energy metabolism. Arterial hypoxia leads to increases in CBF by vasodilation, to maintain normal pBtO2. This specific capacity can be estimated as the tissue oxygenation response (TOR), that is, the difference in increased pBtO2 compared to the arterial blood flow after an increase in Fio2. Tissue oxygenation response is low if the cerebral oxygen autoregulation is intact, that is, an increase in arterial oxygenation generates only a modest increase in pBtO2 due to cerebral autoregulation. The cerebral oxygen autoregulatory status, as assessed using TOR, correlates with cerebral pressure autoregulation (PRx) and clinical outcome.The link between CBF autoregulation and oxygenation also needs to be further explored in TBI patients. Cerebral blood flow is controlled by changes in arterial blood pressure, pCOIn this study, we aimed to further elucidate the role of arterial oxygenation, incidence of hypoxia, and hyperoxia and the relation to cerebral energy metabolism, cerebrovascular reactivity, and clinical outcome in severe TBI. We hypothesized that arterial hypoxia would be disadvantageous and hyperoxia possibly beneficial in relation to these outcome measures.Patients with severe TBI admitted to our neurointensive care (NIC) unit at the Department of Neurosurgery at the University Hospital in Uppsala, Sweden, 2008 to 2018 were eligible for this retrospective study. Of 1001 patients, those 115 patients with mechanical ventilation and monitoring of arterial blood pressure, ICP, arterial blood gas (ABG), and cerebral energy metabolism  that did not develop total brain infarction were included. Treatment goals were ICP ≤ 20 mm Hg, CPP ≥ 60 mm Hg, systolic blood pressure > 100 mm Hg, central venous pressure 0 to 5 mm Hg, pO2 > 12 kPa, arterial glucose 5 to 10 mmol/L (mM), hemoglobin (Hb) > 100 g/L, electrolytes within normal ranges, normovolemia and body temperature <38 °C. Patients were initially mildly hyperventilated (4.0-4.5 kPa) and normoventilated as soon as ICP allowed.Patients were treated in accordance with our standardized ICP-oriented treatment protocol to avoid secondary insults. Pressure reactivity index, traditionally calculated as the 5-minute correlation of 10-second averages of ICP and MAP, was used in combination with a bandpass filter, limiting the analysis to oscillations with periods of 15 to 55 seconds (PRx55-15).Intracranial pressure was monitored with either an intraparenchymal sensor device  or an intraventricular catheter  with the tip in the frontal horn. Arterial blood pressure was measured invasively in the radial artery at heart level. Arterial blood gas data were generally analyzed in samples taken through the radial arterial line every fourth hour, more often if needed. Arterial blood gas samples were analyzed on an ABL800 FLEX instrument (Radiometer), running automatic calibrations every fourth hour and internal quality control samples twice daily. In addition, an external quality control program with monthly control samples administered by the accredited clinical chemistry laboratory at Uppsala university hospital was used. The physiological calculations mentioned below were done in the Odin software.2 1.2 mM, MgCl2 0.85 mM and 1.5% human albumin. Cerebral interstitial glucose, lactate, pyruvate, and urea were measured hourly, with the CMA 600 analyzer or the ISCUSflex Microdialysis Analyzer . The cerebral MD-urea was monitored to validate catheter performance. The analyzers were automatically calibrated when started, as well as every sixth hour using standard calibration solutions from the manufacturer . Quality controls were performed every weekday at 2 different concentrations for each substance (CMA 600 and ISCUSflex). Total imprecision coefficient of variation was <10% for all analytes. The correlation between CMA600 and ISCUSflex data was found to allow for direct comparisons of patient data.For MD, we used the 71 High Cut-Off Brain Microdialysis Catheter with a membrane length of 10 mm and a membrane cutoff of 100 kDa . The MD catheter was placed in normal-appearing brain tissue in the right frontal lobe, adjacent to the ICP monitor. The catheters were perfused with a microinjection pump  at a rate of 0.3 µL/min using custom made sterile artificial cerebrospinal fluid containing—NaCl 147 mmol/L (mM), KCl 2.7 mM, CaClClinical outcome was assessed at 6 months post-injury, by specially trained personnel with structured telephone interviews, using the Extended Glasgow Outcome Scale (GOS-E), containing 8 categories of global outcome, from death to upper good recovery.2, Fio2, and Hb was calculated for each patient the first 10 days post-injury. Similarly, the percentage (%) of ABGs below our oxygenation target (pO2 < 12 kPa), hyperoxia (pO2 > 20 kPa), and anemia (Hb < 100 g/L) was calculated. The calculation was based on the number of blood gases above/below those thresholds versus the total number of blood gases on the same day. Analysis of the first 10 days after injury (N = 115) showed that day 1 had the highest pO2, the greatest pO2-variability and the highest prevalence of anemia, and therefore we chose to focus on this dynamic day for further data analysis. The statistical analyses below were performed both with and without patients treated with decompressive craniectomy (DC) the first day post-injury.The temporal course of pO2 (kPa), pO2 < 12 kPa (%),pO2 > 20 kPa (%),pCO2 (kPa), Fio2 (%), Hb (g/L), ICP (mm Hg), CPP (mm Hg), PRx55-15, cerebral MD-glucose (mM), MD-pyruvate (µM), MD-lactate (mM), and MD-LPR in the software Odin. The mean values for ICP, CPP, and PRx55-15 were calculated using minute-by-minute data. The PRx55-15 was calculated minute-by-minute over a 5-minute moving window centered on the minute. The ABG parameters were analyzed approximately every fourth hour. The mean values of cerebral MD-glucose, pyruvate, lactate, and LPR were based on hourly analyses. All data were transferred to SPSS version 25 (IBM Corp) for further statistical analysis. We chiefly focused on pO2 as a measure of arterial oxygenation as this mean value carries more information than the percentage of hyperoxia/hypoxia. The Spearman correlation test was used to investigate the association between pO2 the first day post-injury with ICP, CPP, PRx55-15, cerebral MD-glucose, MD-lactate, MD-pyruvate, MD-LPR, and GOS-E. Similar correlation analyses were done using the (Δ(Day 2 − Day 1) values of the same variables. Those with missing values were excluded from the analyses. Multiple linear regression analyses were performed with PRx55-15 as the dependent variable for the first day post-injury and included the explanatory variables age, ICP, CPP, pCO2, and pO2. Differences in pO2 were evaluated in 4 patient groups that had complete data day 1 on pO2, cerebral pyruvate, and LPR (51 patients) in relation to their cerebral energy metabolic pattern (A) “Energy metabolic disturbances, limited substrate supply” , (B) “Normal energy metabolism, limited substrate supply” , (C) “Energy metabolic disturbances, normal substrate supply” , and (D) “Normal energy metabolism, normal substrate supply” . Group A versus B and C versus D were compared, respectively, with Student t tests. The cerebral MD-LPR threshold at 25 for metabolic disturbances was chosen in accordance with the consensus statement 2014. The cerebral pyruvate threshold for limited energy substrate supply at 120 µM was chosen based on previous studies suggesting that this is the highest pyruvate value for ischemic and the lowest value for nonischemic cerebral conditions. A P value <.05 was considered statistically significant.Mean values were calculated for each patient the first day and the difference in mean values between day 2 and 1 (Δ(Day 2 − Day 1)) post-injury for pOAll procedures performed in the studies involving humans were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments. Written informed consent was obtained from all individual patients included in the study or their next of kin.Of the 115 TBI patients included in the study, the mean age was 43 (±20) years and 76% were male. Median Glasgow Coma Scale Motor (GCS M) score was 5 (interquartile range [IQR]: 4-5). Twenty-one percent had a pupillary abnormality (anisocoria and/or fixed reaction) at admission. Seventy-five percent had diffuse injury  and 25% focal brain injury (evacuated mass lesion V or nonevacuated mass lesion VI) on the first computed tomography scan. One percent of the patients had an impression fracture, 6% epidural hemorrhage (EDH), 20% acute subdural hemorrhage (ASDH), 6% traumatic subarachnoid hemorrhage (SAH), 35% cerebral contusions, 16% diffuse axonal injuries (DAIs), and 16% mixed intracranial injuries. Thirty-three percent had a thoracic injury and 41% had other extracranial injuries . Only one patient had extensive bleeding. Eleven percent was treated with thiopental and 15% with DC. Mean days in respirator was 12 (±8) days and mean stay at the NIC unit was 13 (±12) days. Outcome data 6 months after injury showed a mortality rate of 8% and median GOS-E was 5 (IQR: 3-7). The physiological data are presented in 2 peaked the first day post-injury and gradually decreased (2 > 20 kPa) decreased gradually, whereas the percentage of ABGs below our oxygen target (pO2 < 12 kPa) increased over the first 10 days. Fio2 gradually increased over the 10 days. The mean Hb was higher the first day and then slightly lower, but stable and above 100 g/L . Mean pO2 events (% of ABGs) below 12 kPa or above 20 kPa on the first day post-injury did not correlate with clinical outcome .Mean arterial pOecreased . The per 100 g/L . The per outcome . Similar2 was significantly associated with lower cerebral MD-lactate  at 20 ± 6 kPa (P = .001). Both of these groups had similar P/F (pO2/Fio2)-ratios , GCS M at admission , and Marshall score . Furthermore, there was no significant difference in arterial oxygen levels between those with energy metabolic disturbances with limited substrate supply (LPR > 25 and pyruvate < 120) versus those with energy metabolic disturbances with normal substrate supply . Exclusion of those patients treated with DC on the first day post-injury did not have any impact on the results.Patients (N = 51) were divided into 4 groups based on their metabolic pattern of mean MD and pOor day 1 . The pat2 between those with low cerebral MD-pyruvate and normal versus elevated MD-LPR (data not shown).Of those with a mean cerebral pyruvate below 120 µM and LPR above 25, all but one patient had a mean cerebral MD-glucose above 1 mM. None of these patients had an ICP > 20 mm Hg or CPP < 60 mm Hg. All patients had a mean Hb above 100 g/L. There was no significant difference in mean ICP, CPP, and pCO2 or ABG events below our oxygen target did not correlate with ICP or CPP, higher percentage of hyperoxia day 1 was significantly associated with lower ICP  and a significantly lower CPP  from day 1 to day 2 post-injury.Although the mean pO2 was significantly associated with lower PRx55-15  day 1 post-injury  from day 1 to day 2 post-injury. However, the association between arterial oxygenation and PRx55-15 was not significant in the later course . Exclusion of those patients treated with DC on the first day post-injury did not have any impact on the results.In addition, higher mean pOt-injury . Similar2 and pO2, higher pO2 was marginally associated with lower PRx55-15 (P = .054).In the multiple linear regression analysis for PRx55-15 , includi2 was associated with better PRx55-15 and improved oxidative cerebral energy metabolism on the first day post-injury. In TBI patients with a cerebral metabolic pattern indicative of limited pyruvate supply, those with preserved oxidative energy metabolism  had significantly higher arterial oxygen (20 vs 15 kPa) than those with energy disturbances (elevated MD-LPR). This suggests that TBI patients with disturbed energy metabolism with limited cerebral MD-pyruvate may benefit from a higher pO2-threshold than 12 kPa in early TBI management, although prospective studies are needed to validate this.In this retrospective study including 115 patients with severe TBI, we found that high mean arterial pO Optimizing cerebral oxygen delivery by maintaining adequate CBF and arterial oxygen pressure has been discussed extensively the last decades. This has traditionally been achieved by CPP-oriented treatment protocols to increase CBF and maintaining arterial oxygen content sufficient by keeping Hb above 70 to 100 g/L together with normal saturation. More recently, NBO treatment has been suggested to compensate for cerebral ischemic hypoxia, overcome diffusion barriers from cerebral edema, and to improve mitochondrial function in TBI.Cerebral ischemia and hypoxia are common secondary insults following severe TBI. Diringer et al found no global cerebral improvement in CMRO2 following NBO, whereas Nortje et al found increased CMRO2 in ischemic regions. Furthermore, many energy metabolic studies have found reductions in cerebral lactate following NBO, but no improvement in MD-LPR. However, another study found that the beneficial effect of hyperoxia depends on the concurrent cerebral energy metabolic state, as improvements in oxidative energy metabolism were only seen in cases of high cerebral MD-lactate before treatment initiation. Similar to these previous studies, our patients who had higher mean arterial oxygen levels had lower cerebral lactate  with concurrently low cerebral pyruvate, indicative of limited substrate supply, had significantly higher arterial oxygen levels compared with those with limited substrate supply and deranged oxidative energy metabolism . However, it is difficult to evaluate the energy metabolic effects of different oxygen levels from this analysis, since the extent of mitochondrial injury in each group is unknown and probably differ. It would be better to evaluate the effect of arterial oxygenation prospectively in future trials with a hyperoxic challenge in patients with a metabolic pattern indicative of mitochondrial failure.The benefits of NBO are debated. lactate  and those levels , possibltabolism . However The cerebral vasoresponse to various regulators such as arterial blood pressure, pCO2, and cerebral energy metabolism represent the general health of the vessels and intact vessel response to one of these regulators usually corresponds to intact vessel response to the other regulators. It is well known that arterial hyperoxia generates an autoregulatory reduction in CBF to maintain a normal pBtO2 and this has been further elaborated in the NIC setting by, for example, evaluating the cerebral TOR to an increase in Fio2. Tissue oxygenation response is highly correlated with PRx, indicating that these indexes evaluate different but still common aspects of general cerebral autoregulation. In this study, we found that higher arterial oxygen levels were associated with better pressure reactivity  day 1 post-injury was associated with favorable clinical outcome in a study including 417 patients, indicating that our study may be underpowered to detect a small, but significant, effect of arterial hyperoxia on outcome.Too low and too high arterial oxygen levels have been shown to be associated with worse outcome following TBI.2 and pBtO2 are correlated, we lacked sufficient data regarding cerebral oxygenation to evaluate the relation between pO2, pBtO2, and cerebral energy metabolism. Second, the number of patients with energy metabolic disturbances (MD-LPR > 25) was low, limiting the reliability of the analysis in 2) and could in the future help determine the correlation between these physiological variables with higher resolution. There is also a need for prospective trials to better study the intraindividual neurophysiological response to hyperoxia. Fifth, the association between arterial oxygen levels and cerebral energy metabolism may be confounded by other important variables such as injury severity. However, we found no association between thoracic/extracranial injuries and arterial oxygen content indices.First, although pOlimited energy substrate supply could benefit from higher arterial oxygen levels in the early phase of TBI. Furthermore, arterial oxygen may be used to optimize cerebral vasoreactivity and hence used in an integrated autoregulatory-oriented treatment regime. Future prospective studies are needed to determine whether there is a causal relationship of arterial hyperoxia in relation to autoregulation, cerebral energy metabolism, and clinical outcome.Higher mean arterial oxygen levels the first day post-injury in severe TBI patients was associated with better PRx55-15 and improved oxidative cerebral energy metabolism. Particularly, patients with a cerebral metabolic profile indicative of


We hypothesized that severe α1-antitrypsin deficiency is associated with reduced blood pressure and susceptibility to cardiovascular disease.Increased elastase activity in α1-Antitrypsin Deficiency Registry and recorded baseline blood pressure, baseline plasma lipids and cardiovascular events during follow-up. 185 participants carried the ZZ genotype, 207 carried the SZ genotype and 91,148 carried the MM genotype.We genotyped 91,353 adults randomly selected from the Danish general population and 187 patients from the Danish α1-Antitrypsin deficiency was associated with decreases in blood pressure of up to 5 mmHg for systolic blood pressure and up to 2 mmHg for diastolic blood pressure, in ZZ vs SZ vs MM individuals . Plasma triglycerides and remnant cholesterol were reduced in ZZ individuals compared with MM individuals . α1-Antitrypsin deficiency was associated with lower risk of myocardial infarction (trend test P = 0.03), but not with ischemic heart disease, ischemic cerebrovascular disease or hypertension . However, when results for ischemic heart disease were summarized in meta-analysis with results from four previous studies, individuals with versus without α1-antitrypsin deficiency had an odds ratio for ischemic heart disease of 0.66 (95% CI:0.53–0.84).α1-antitrypsin deficiency have lower systolic and diastolic blood pressure, lower plasma triglycerides and remnant cholesterol, reduced risk of myocardial infarction, and a 34% reduced risk of ischemic heart disease.Individuals with severe αThe online version contains supplementary material available at 10.1186/s12931-022-01973-3. The S- and Z variants cause different degrees of α1-antitrypsin deficiency, the ZZ genotype being the most severe with a reduction in circulating α1-antitrypsin of up to 85% [1-Antitrypsin deficiency is mostly known to result in an early onset of chronic obstructive pulmonary disease (COPD), due to the lack of inhibition of neutrophil elastase, and liver cirrhosis due to polymerization of mutant α1-antitrypsin in the endoplasmic reticulum, resulting in hepatocyte damage [αhe lungs . The codhe lungs , 3. The 1-antitrypsin deficiency changes the elasticity of the vessel wall, resulting in decreased resistance and thereby a lower blood pressure [1-antitrypsin deficiency could contribute to a reduced risk of cardiovascular disease, for example ischemic heart disease and stroke [Studies have suggested that the increased elastase activity over time also affects the elastic properties of the arterial walls , 5. The pressure . Reduced1-antitrypsin deficiency is associated with reduced blood pressure and susceptibility to cardiovascular disease in individuals in the general population. To test this hypothesis, we genotyped 91,353 adults from the Copenhagen General Population Study and 187 patients from the Danish α1-Antitrypsin Deficiency Registry and recorded baseline blood pressure, baseline plasma lipids and cardiovascular disease during follow-up as outcomes. As a secondary aim, we also performed a meta-analysis of previous studies examining the risk of ischemic heart disease in individuals with α1-antitrypsin deficiency.We hypothesized that α1-Antitrypsin Deficiency Registry. Cases from the two studies did not differ significantly for any of the outcomes studied (P’s for interaction ≥ 0.1), and were therefore combined yielding a total population of 91,540, within which 185 were ZZ individuals, 207 were SZ individuals, and 91,148 were MM individuals. Individuals with MZ, SS, and MS α1-antitrypsin deficiencies were excluded from the analysis . However, if these individuals were included in the analysis the results were similar to those presented.We included participants from The Copenhagen General Population Study and the Danish αThe Copenhagen General Population Study was initiated in 2003 with ongoing enrollment . Individ1-Antitrypsin Deficiency Registry was initiated in 1978 and includes patients diagnosed with severe α1-antitrypsin deficiency. Patients from the registry were examined from August 31st 2009 to October 6th 2009 as part of the Copenhagen General Population Study undergoing the exact same investigations as all other participants in this survey. We included 187 participants from the registry, within which 137 carried the ZZ genotype and 50 carried the SZ genotype.The Danish α1-antitrypsin, lipids, and liver markers were measured by standard hospital assays; remnant cholesterol was calculated as total cholesterol minus low-density lipoprotein (LDL) cholesterol minus high-density lipoprotein (HDL) cholesterol. Ischemic heart disease , ischemic cerebrovascular disease , myocardial infarction , and COPD  were defined as hospital admissions with the diagnosis as the primary discharge diagnosis, obtained from the national Danish Patient Registry. Hypertension was systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg, and/or current use of antihypertensive medication [Blood pressure was measured by trained technicians on the left upper arm after 5 min rest with the individual in the sitting position. An automatic Digital Blood Pressure Monitor  with a cuff measuring 22 × 32 cm was used; if the circumference of the upper arm was > 46 cm, we used a cuff measuring 32 × 45 cm. All participants had their blood pressure measured within the 3-7 pm time interval. From March 2009 and onward, blood pressure was measured on both arms and legs with the participants resting in supine position. Systolic blood pressure of the posterior tibial artery or the dorsalis pedis artery was obtained by a handheld Doppler. Ankle-brachial index (ABI) was calculated as the lowest ankle systolic blood pressure level divided by the right arm brachial systolic blood pressure level. Plasma αWe genotyped for the S  and Z (Glu342Lys) variants by using TaqMan-based PCR assays and an ABI PRISM 7900HT Sequence Detection system . The following primers and probes were used: Exon 3 , forward primer CTGATGAAATACCTGGGCAATGC, reverse primer TGGTGATGATATCGTGGGTGAGT, VIC probe CACCTGGAAAATGA, and 6-FAM probe CACCTGGTAAATGA; exon 5 , forward primer CTTACAACGTGTCTCTGCTTCTCT, reverse primerCAAAGGGTTTGTTGAACTTGACCTC, VIC probe CTTCAGTCCCTTTCTCGTCGA, and 6-FAM probe TTCAGTCCCTTTCTTGTCGA.2 test for categorical data. Plasma triglycerides, HDL cholesterol, lipoprotein (a), remnant cholesterol, and bilirubin were logarithmically transformed due to positively skewed distributions. Cox-regression adjusting for age, sex, smoking status and COPD was used to assess risk of cardiovascular disease prospectively in individuals with versus without α1-antitrypsin deficiency, and logistic regression adjusting for age, sex, smoking status and COPD was used to asses risk of hypertension cross-sectionally in individuals with versus without α1-antitrypsin deficiency. Interactions between genotype and sex, age, smoking, and COPD on cardiovascular outcomes were tested in logistic regression models. Because outcomes did not differ significantly according to sex (P’s > 0.05), combined results were presented. In sensitivity analyses, multiple logistic regression was performed using stepwise forward inclusion, where continuous variables were dichotomized by the median value, and genotype was added to the final model irrespective of significance. The forward inclusion method adds variables one by one to the regression model, based on the overall significance of the test statistic, i.e. minimizing the p-value of the likelihood ratio chi-squared (LR χ2) test statistic. In sensitivity analyses, the associations between plasma α1-antitrypsin and systolic blood pressure, and cardiovascular outcomes were analyzed using binned scatter plots with R2 as a measure of the correlation.All statistical analyses were performed using STATA version 12.1 . Student’s t-test was used for continuous variables, and Pearson’s χst 2021 querying for  AND  using MESH terms and free text. Reference lists were searched for additional relevant publications. 5 studies (the present study and [1-antitrypsin deficiency in relation to ischemic heart disease as the primary endpoint were included. Severe α1-antitrypsin deficiency was either physician diagnosed α1-antitrypsin deficiency with an ICD10 code (E88.0), self-reported physician diagnosed α1-antitrypsin deficiency, or a diagnosis of α1-antitrypsin deficiency based on PCR or isoeletric focusing. Because previous studies were based on SZ and ZZ combined we also pooled data on SZ and ZZ in our own dataset. Myocardial infarction was used as the primary endpoint in studies where both ischemic heart disease and myocardial infarction results were reported. Meta-analysis was conducted using the MIX 2.0  using a random effects model. The meta-analysis was conducted according to the PRISMA guidelines [We searched PubMed up until October 1tudy and –12) examidelines .1-antitrypsin deficiency versus MM individuals in the population are shown in Table 1-antitrypsin deficiency were younger, had reduced values of plasma α1-antitrypsin and FEV1/FVC, were less likely current smokers, and had more often COPD compared with MM individuals. Individuals with SZ α1-antitrypsin deficiency vs MM individuals had reduced plasma α1-antitrypsin and had more often COPD, but did not differ in any other clinical characteristics. Use of antihypertensive medication did not differ between individuals with ZZ or SZ α1-antitrypsin deficiency versus MM individuals.Clinical characteristics of individuals with ZZ and SZ α1-antitrypsin genotype  and 136 mmHg (P = 0.17), respectively, compared with 138 mmHg in MM individuals. Diastolic blood pressure was also reduced as a function of α1-antitrypsin genotype  and 78.9 mmHg (P = 0.20), respectively, compared with 80.0 mmHg in MM individuals . When measuring blood pressure and ankle-brachial index in the supine position in a subgroup of individuals, similar results were seen for systolic blood pressure , but not for diastolic blood pressure or ankle-brachial index  and 138 mmHg (P = 0.006), respectively, compared with 142 mmHg in MM individuals.Systolic blood pressure was lower as a function of α1-antitrypsin deficiency vs MM individuals had 0.3 mmol/L lower plasma triglycerides (t-test: P < 0.001) and 0.1 mmol/L lower remnant cholesterol (P < 0.001), and higher values of plasma ALAT , bilirubin  and alkaline phosphatase   and alkaline phosphatase (P < 0.001), but did not differ in any other plasma lipid or liver parameters. If these results were adjusted for age, sex, and smoking status similar results to those presented were seen .Individuals with ZZ α1-Antitrypsin deficiency was associated with lower risk of myocardial infarction , but there were no significant associations of α1-antitrypsin deficiency with risks of ischemic heart disease, ischemic cerebrovascular disease or hypertension  , while there were no associations with ischemic heart disease, ischemic cerebrovascular disease, or hypertension  Fig. . In sens1-antitrypsin deficiency had an odds ratio for ischemic heart disease of 0.66   and provided robust summary odds ratios in sensitivity analyses (Additional file When the results for ischemic heart disease were summarized in meta-analysis with results from four previous studies, individuals with versus without α1-antitrypsin deficiency vs MM individuals. The results revealed that individuals with severe α1-antitrypsin deficiency had 2 and 5 mmHg lower diastolic and systolic blood pressure, 0.3 mmol/L lower plasma triglycerides, 0.1 mmol/L lower remnant cholesterol, reduced risk of myocardial infarction, and a 34% reduced risk of ischemic heart disease in meta-analysis.In this large Danish cohort study, we evaluated blood pressure, plasma lipids, and risk of cardiovascular disease in individuals with α1-antitrypsin deficiency [1-antitrypsin deficiency [1-antitrypsin level and systolic blood pressure [1-antitrypsin deficiency or humans receiving pancreatic elastase therapy have also been performed but with differing results [1-antitrypsin deficiency, the reduction of 5 mmHg in systolic blood pressure may not be trivial as it is comparable to the minimal clinically important difference of 2 mmHg proposed for systolic blood pressure in previous studies [In the current analysis and in the subgroup analysis, we confirm our previous findings in the Copenhagen City Heart Study of reduced systolic blood pressure in individuals with αficiency . Compareficiency , reducedficiency , 14, 15,pressure , as was  results –20. If o studies .1-antitrypsin deficiency also had reduced risk of myocardial infarction and a 0.66 fold reduced risk of ischemic heart disease in meta-analysis. Greulich et al. showed that patients with α1-antitrypsin deficiency had a lower prevalence of ischemic heart disease when compared to age and gender matched controls with known chronic obstructive pulmonary disease [1-antitrypsin deficiency and a reduced frequency of ischemic heart disease when looking at patients with α1-antitrypsin deficiency with and without augmentation therapy [1-antitrypsin deficiency, but were not included in the meta-analysis due to lack of data [1-antitrypsin deficiency in the meta-analysis is also in line with research by Tanash et al. showing a reduced mortality from ischemic heart disease as well as no other increased mortality with regard to stroke, aorta dissection, or cardiovascular disease in individuals with α1-antitrypsin deficiency [In line with reductions of 5 and 2 mmHg in systolic and diastolic blood pressures in the present study, individuals with α disease , and Fäh therapy . Two oth of data , 23. Theficiency .1-antitrypsin deficiency in the current study had lower levels of plasma triglycerides and remnant cholesterol compared to MM controls, confirming previous results by Hamesch et al. [1-antitrypsin deficiency could perhaps also contribute to the reduced risk of ischemic heart disease observed in individuals with α1-antitrypsin deficiency in the present study.Individuals with ZZ αh et al. , and Fähh et al. . The undh et al.  and the 1-antitrypsin deficiency and severe disease may not have attended the physical examination and participated in the study. Hardy–Weinberg equilibrium calculation suggested that 31 ZZ individuals were not included in the sample from the Copenhagen General Population Study; however, we do not think that this substantially influenced the results as sensitivity analysis showed almost similar results in the two study samples separately (P’s for interaction ≥ 0.1, Additional file 1-antitrypsin deficiency was replicated in ethnically homogenous and independent studies of the Danish population ([1-antitrypsin deficiency was due to the use of augmentation therapy or the α1-antitrypsin deficiency genotype itself. Augmentation therapy was not available in Denmark at the time of data collection. Our investigation thus supports that the α1-antitrypsin deficiency genotype is protective against ischemic heart disease, perhaps through the reduction in risk factors like systolic and diastolic blood pressure, plasma triglycerides and remnant cholesterol, rather than through augmentation therapy. Further studies are needed with regards to the possible molecular mechanisms underlying the observed reductions in blood pressure, plasma lipids, and ischemic heart disease risk in individuals with α1-antitrypsin deficiency.Strengths of our study include a randomly chosen sample of an ethnically homogenous population, and blinding of investigators to risk factor status and the clinical outcomes investigated. A potential limitation of our study is that some of the individuals suffering from αulation (, the preulation ( question1-antitrypsin deficiency had reductions of 2 and 5 mmHg in diastolic and systolic blood pressure, reduced risk of myocardial infarction, and a 34% lower risk of ischemic heart disease. The study also revealed reductions of plasma triglycerides and remnant cholesterol levels in ZZ vs MM individuals, and a dose–response relation between severe α1-antitrypsin deficiency and reduced blood pressure in the population.In conclusion, individuals with αAdditional file 1.Figure S1. Supine blood pressure according to α1-antitrypsin deficiency genotype. Figure S2. Ankle-brachial index according to α1-antitrypsin deficiency genotype. Figure S3. Risk of cardiovascular disease according to α1-antitrypsin deficiency genotype by step-up logistic regression. Figure S4. Risk of cardiovascular disease according to α1-antitrypsin deficiency genotype, stratified by sex, age, smoking status and COPD. Figure S5. Binscatter plots of systolic blood pressure, ischemic heart disease, ischemic cerebrovascular disease, or hypertension versus plasma α1-antitrypsin partitioned into 20 bins. Figure S6. Exclusion sensitivity plot. Figure S7. Systolic blood pressure according to α1-antitrypsin deficiency genotype, stratified by study population.


P > 0.05). After the exercise intelligence management, the SBP levels of the control group and the observation group were (132.76 ± 4.48) mmHg and (130.06 ± 2.48) mmHg, respectively. The DBP levels of the control group and the observation group were (85.48 ± 5.38) mmHg and (83.47 ± 3.35) mmHg, respectively. The difference was statistically significant (P < 0.05). The scores of each index of quality of life in the observation group were higher than those in the control group, and the differences of physical function and psychological/mental scores were significant. The scores of physical function in the two groups before administration were (48.36 ± 1.69) and (48.74 ± 1.62), and the differences were not statistically significant (P > 0.05). After management, the physiological function scores of the two groups were (40.32 ± 1.33) and (32.15 ± 1.54) and the difference was statistically significant (P < 0.05). There were no significant differences in the psychological (30.75 ± 1.26)/mental scores (30.26 ± 1.48) between the two groups before management (P > 0.05), but there were significant differences in the psychological (25.30 ± 1.02)/mental scores (18.76 ± 1.36) between the two groups after management (P < 0.05). The combination of natural convalescent factors and intelligent exercise management can effectively control the blood pressure level and improve the quality of life of patients with hypertension, and the clinical application effect is good.To explore the application of natural convalescent factors combined with exercise intelligence management in blood pressure control of patients with hypertension, 102 patients with hypertension who were admitted from January 2017 to August 2019 were selected as the research subjects. According to the odd-even number method, they were divided into two groups with 51 cases in each group. The control group was treated with natural convalescent factor therapy alone, and the observation group was treated with natural convalescent factor combined with motor intelligence management. The application effects of the two groups were compared. Before sports intelligence management, the levels of systolic blood pressure (SBP) in control group and observation group were (145.45 ± 8.44) mmHg (1 mmHg = 0.133 kPa) and (146.55 ± 8.37) mmHg, respectively; the diastolic blood pressure (DBP) levels of the control group and the observation group were (98.47 ± 3.48) mmHg and (98.94 ± 3.48) mmHg, respectively, with no statistical significance ( In recent years, with the rapid development of social economy, the problem of population aging has become increasingly prominent. The aging of the population is accompanied by cardiovascular and cerebrovascular diseases, chronic respiratory diseases, and other chronic diseases. Hypertension is a typical representative of chronic diseases, and its causes include heredity, living habits, mental stress, and so on. The large number of patients has caused a huge economic and social burden. According to statistics, by 2010, the prevalence rate of hypertension among Chinese adults was as high as 33.5%, with a total population of more than 330 million [The aim of hypertension treatment is to effectively control blood pressure, prevent and slow down the occurrence of complications, and improve the quality of life of patients. Therefore, scientific and effective self-health management is an effective means to control hypertension. The advent of the mobile Internet era has brought a lot of new development opportunities for the field of self-health management, and the rapid development of mobile phone applications has also brought more possibilities for the effective realization of self-health management.P > 0.05). After sports smart management, the SBP levels of the control and observation groups were (132.76 ± 4.48) mmHg and (130.06 ± 2.48) mmHg, respectively. The DBP levels in the control and observation groups were (85.48 ± 5.38) mmHg and (83.47 ± 3.35) mmHg, respectively. Differences are significant (P < 0.05). The quality-of-life scores were higher than the control group. Among them, the physiological function and psychological/mental scores are significantly different. Managing the previous two group physiological functional scores (48.36 ± 1.69) and (48.74 ± 1.62), the differences are not statistically significant (P > 0.05), with management of (40.32 ± 1.33) and (32.15 ± 1.54), differences are significant (P < 0.05); managing the previous two group psychological/mental scores (30.75 ± 1.26) and (30.26 ± 1.48), the differences are not statistically significant (P > 0.05); managing the two group psychological/mental scores (25.30 ± 1.02) and (18.76 ± 1.36), the differences is statistically significant (P < 0.05). The use of natural recuperation factors combined with exercise intelligent management in patients with hypertension can effectively control the blood pressure level of patients, improve their quality of life, and have a good clinical application effect.With the advent of the era of mobile Internet, the penetration rate of smart phones has been increasing unprecedentedly, followed by all kinds of mobile application software, namely, APP. With the improvement of living standards, the public has become more concerned about health issues, and more and more self-health management APP products have come into people's sight. According to statistics, by 2012, the capital scale of the national mobile medical market was as high as 1.86 billion yuan, which makes an increase of 17.7% over the previous year. According to iMedia Research, the figure will reach 12.53 billion yuan by 2017, which is a promising prospect. The development of intelligent wearable devices also provides more possibilities for the medical and health field. Wearable device products in this area are mainly focused on intelligent health and medical fields. The intelligent health direction is represented by the bracelet, which focuses on health, sports, fashion, and so on. Products related to the medical field pay more attention to heart rate, blood oxygen, and other monitoring. Michael et al. held that hypertension is caused by complex environment and gene influence and effective treatment can avoid nephropathy and myocardial infarction caused by hypertension, etc. . With thP > 0.05).102 patients with hypertension admitted to our center from January 2017 to August 2019 were selected for this study. All the patients are divided into two groups according to the odd-even method: in the control group, there were 51 patients, including 31 males and 20 females, aged 55 ∼ 70 years, with an average age of (60.36 ± 3.45) years, course of disease 1∼16 years, and an average course of (8.46 ± 2.32) years; in observation group, there were 51 patients, including 30 males and 21 females, aged 56∼70 years, average age (60.81 ± 3.89) years, course of disease (1∼15 years), average course of disease (7.56 ± 2.07) years, as shown in After admission, the two groups received routine nursing. The responsible nurse measured blood pressure regularly and guided the patients to master the correct medication and dietary intake methods. The control group received natural recuperation factor therapy alone: after the patients were admitted to hospital, the responsible nurse introduced the recuperation environment and relevant regulations to the patients and provided the patients with warm and comfortable recuperation room. The room temperature was set at 24–27°C and the humidity was set at 45%–55% to ensure the patients' body surface comfort. Before breakfast, patients can be guided to carry out outdoor activities, such as 30 ∼ 40 min of walking exercise. While forming good exercise behavior, it can promote new excitement transmission in the cerebral cortex by appreciating the natural scenery, so as to alleviate the bad psychology after the disease. According to the patient's physical condition, air bath, forest bath, mountain climbing, sea bath, and other natural recuperation methods are arranged, 3 ∼ 4 times a week; the duration of a single time should be controlled within 90 minutes, to avoid excessive fatigue; after lunch, patients are encouraged to take a nap then, combined with personal will, carry out aerobics, chess, and cards, Taijiquan, watching TV, and other entertainment projects. After dinner, the patient can start activities on his own but avoid overstimulating projects and maintain a good schedule. The observation group received natural convalescent factors combined with motor intelligence management: the natural convalescent factor was the same as the control group. On this basis, intelligent management of movement was carried out reasonably. According to the patient's body tolerance, a professional exercise intelligent management program is developed to guide the patient to carry out walking exercise training. If the patient exercises ≥7 d a week, any one of the activities of walking, jogging, cycling, and swimming can be selected according to the patient's preference. The weekly amount of exercise should include 150 minutes of moderate aerobic exercise and 75 minutes of intensive exercise. Specific amount of exercise can be adjusted according to the patient's body tolerance, and before and after exercise, patients will be guided to do warm-up exercises, relax muscles, and avoid unexpected situations during exercise. During exercise, the patients shall be subject to hand rubbing, ear rubbing, face rubbing, and other health exercises to improve blood circulation and blood circulation. During exercise, if dizziness, palpitation, and other abnormal conditions occur, it is necessary to stop immediately and take a rest. The nurses conducted 3-day training to correctly use the app. The app displayed the blood pressure index records before and after exercise, recorded the daily exercise diary and the corresponding blood pressure index, and insisted on recycling the diary every week. During the exercise intelligence management, full-time nurses will make remote follow-up calls every week and supervise and guide the compliance of blood pressure indexes recorded by smart phone APP from time to time by QQ group or WeChat group. Patients can also call the department for consultation at any time when they meet with difficulties. Full-time nurses will conduct blood pressure monitoring training for all patients, explain blood pressure monitoring methods, precautions, APP data acquisition, etc., and conduct assessment.The effect of blood pressure control was compared between the two groups. The blood pressure was controlled according to the regulations of the World Health Organization. The diastolic blood pressure was <90 mmHg (12 kPa) (1 mmHg = 0.133 kPa) and the systolic blood pressure was ≤130 mmHg (18.6 kPa). The changes of systolic and diastolic pressure before and after the two groups were observed. The psychological status changes were observed after the two groups of intervention, which are mainly evaluated by anxiety self-evaluation scale (SAS) and depression self-evaluation scale (SDS). The higher the score is, the worse the situation is indicated. The changes of fasting blood glucose, 2 h blood glucose, glycosylated hemoglobin, and heart rate before and after the two groups were observed.α = 0.05.SPSS20.0 statistical software was used, and t or t'test was used for comparison of measurement data. The test level P > 0.05). After sports intelligence management, the levels of SBP and DBP in the observation group were lower than those in the control group, and the difference was statistically significant (P < 0.05).Comparison of blood pressure levels between the two groups before and after exercise intelligence management is shown in P > 0.05). After management, the scores of treatment, physiological function, and psychological/spiritual and social relations in the observation group were lower than those in the control group, with statistical significance (P < 0.05).Comparison of quality of life between the two groups before and after management is shown in The natural recuperation factors used in this institute mainly include natural landscape, environmental climate, sea bathing, sunbathing, air negative ions, etc., which can encourage patients to relax and effectively relieve their anxiety, depression, and other bad psychology. Moreover, the air negative ions used in this study can regulate the patient's central nervous system function, improve the internal hormone secretion status, and promote the rapid recovery of hypertension combined with diabetic diseases. In addition, air negative ions can also promote the excitability of the upper respiratory tract, enhance the ventilation function, and treat chronic obstructive pulmonary diseases to a certain extent. A large number of clinical studies have found that moderate exercise can adjust the nervous system function of the body, enhance the effect of drug control blood pressure, reduce the damage caused by drugs to target organs, improve the quality of life of patients, and play an important role in the treatment of hypertension with diabetes. This study performed exercise management for the study group and found that aerobic activity promotes upregulation of glucose transporters and promotes insulin signaling, thus improving glycopeptide metabolism in diabetic patients and enhancing insulin sensitivity.At present, mobile medical services and products emerge in an endless stream in the market. In the market segment of hypertension, the combination of hardware and software is the mainstream trend, and the data transmitted by hardware can be stored and analyzed through cloud technology. The main functions of this product are self-testing, intelligent monitoring, and data analysis. In addition to the function of blood pressure data recording and analysis, some simple software products also focus on the acquisition of disease knowledge, diet management, and exercise management. In general, hypertension self-health management products mainly fall into the following categories.One of the most traditional products in self-health management of hypertension is a blood pressure monitor. According to the measurement method, the blood pressure apparatus can be divided into two types: arm type and wrist type. According to the working principle, it can be divided into three kinds: traditional mercury sphygmomanometer, barometer sphygmomanometer, and electronic sphygmomanometer. Currently, the most common type in the home is an electronic blood pressure monitor. In addition to traditional blood pressure gauges, there are also many intelligent blood pressure gauges combined with intelligent devices on the market. For example, the iHealth sphygmomanometer, a smart series of blood pressure monitors owned by Jiu'an Medical, can measure blood pressure intelligently by connecting with the Bluetooth client in the smart phone. It also has real-time monitoring data and summary analysis, family monitoring data sharing, and other functions. In addition, there are also Lexin WIFI intelligent blood pressure monitor and Kangkang portable intelligent blood pressure monitor in China, which are intelligent blood pressure monitors used with mobile terminals and can realize remote data sharing and data analysis and other functions.In addition to blood pressure monitors, other products are being positioned more like wearable devices, which are more smart and portable and highlight 24/7 blood pressure monitoring. The Visi Mobile Vital Sign Monitor, as shown in In addition to the APP products used with hardware, there are also some APP products used separately from hardware. Its functions mainly focus on health data recording analysis, diet and exercise management, health guidance, and online consultation of doctors and medicines. The prevention and control of hypertension management depend on patients themselves to a great extent. Through these APP products, patients have created certain conditions for self-management: It can learn more health knowledge from doctors and hospitals, record and manage blood pressure to understand the changes of blood pressure, communicate directly with your doctor, and socially interact with family, friends, etc.At present, there are still some problems in self-health management of hypertension in China: ① Lack of knowledge of hypertension. Because hypertension is a chronic disease, clinical treatment is supplementary and self-management is the main task. After taking drugs for a period of time, some patients' blood pressure began to stabilize, so they would arbitrarily reduce or even stop taking drugs and stop blood pressure monitoring and reexamination, without realizing that hypertension requires long-term and effective self-management. There are some knowledge misunderstandings in disease cognition of such patients. ② Patients with hypertension who are too dependent on doctors and hospitals are mostly middle-aged and elderly people, and there are few ways to acquire knowledge of related diseases, which are mainly orally transmitted by doctors. In the implementation of self-health management, mainly follow the doctor's advice. In the face of disease emergencies, it is easy to lack the ability to cope with the problem. ③ The attitude of self-health management of hypertension patient needs to be improved. In terms of basic management such as medication, most patients can follow the doctor's advice well. However, in terms of blood pressure measurement and exercise, most patients do not conduct self-management. In particular, many middle-aged male patients follow the attitude of “drinking wine, smoking, medicine” for hypertension health management, and the attitude of health management is not correct.Monitoring blood pressure by smartphone APP can effectively control blood pressure. The management mode based on monitoring by smartphone APP can greatly improve the exercise compliance of blood pressure patients, promote patients to exercise regularly for a long time, and establish good treatment habits. Long-term and regular exercise can effectively reduce the patient's blood pressure and BMI, so it plays a positive role in the control of blood pressure and the prevention of complications.P > 0.05). After sports smart management, the SBP levels of the control and observation groups were (132.76 ± 4.48) mmHg and (130.06 ± 2.48) mmHg, respectively. The DBP levels in the control and observation groups were (85.48 ± 5.38) mmHg and (83.47 ± 3.35) mmHg, respectively. Differences are significant (P < 0.05). The quality-of-life scores were higher than the control group. Among them, the physiological function and psychological/mental scores are significantly different. Managing the previous two group physiological functional scores (48.36 ± 1.69) and (48.74 ± 1.62), the differences are not statistically significant (P > 0.05); managing (40.32 ± 1.33) and (32.15 ± 1.54), differences are significant (P < 0.05); to manage the previous two group psychological/mental scores (30.75 ± 1.26) and (30.26 ± 1.48), the differences are not statistically significant (P > 0.05); managing the two group psychological/mental scores (25.30 ± 1.02) and (18.76 ± 1.36), the differences are statistically significant (P < 0.05). The use of natural recuperation factors combined with exercise intelligent management in patients with hypertension can effectively control the blood pressure level of patients, improve their quality of life, and have a good clinical application effect.The blood pressure level of hypertensive patients is greatly affected by bad living habits, social environment, and emotions. In different environmental conditions, the human body can automatically adjust nerve secretion in order to adapt to the environment. For example, when the environment is too cold and dry, the sympathetic nerve will be in a relatively excited state, and when stimulated by catecholamines, a large amount of secretion will be produced, which will affect the contractile activity of the body's blood vessels, increase the original circulation resistance, and increase blood pressure . In the


We investigated effects of submacular fluid volume (SMFV) on visual outcomes following surgery for macula‐off primary rhegmatogenous retinal detachment (RRD) using automated fluid volumetric quantification with optical coherence tomography (OCT).We analysed 127 eyes that were surgically treated for macula‐off RRDs. We obtained preoperative images following the spectral domain (SD)‐OCT dense volume protocol, applied automated retinal segmentation and used an automated algorithm to quantify each eye's SMFV. We used multivariate models to identify various risk factors for impaired visual outcome.P = .005) was significantly associated with a reduced visual outcome 12 months after the treatment of macula‐off RRDs. SMFV was negatively correlated with 12‐month postoperative  visual acuity (VA). The group with low preoperative SMFV (≤9.0 mm3) showed an increasing VA up to 12 months postoperatively (P < .001), while the VA did not increase in the group with high SMFV (>9.0 mm3) beyond 3 months of follow‐up. Patients with a high SMFV were 8.0 times more likely to have worse visual outcomes after 12 months of follow‐up (P = .018).Linear regression showed that preoperative SMFV (ß = 0.013; 3 12 months after surgery had an 8.0 times greater chance for better visual recovery than patients with high preoperative SMFV. Our findings highlight the efficacy of automated SMFV quantification in predicting surgical outcomes in patients with RRDs, which could be useful in future clinical practice and the development of research models.SMFV was negatively correlated with visual outcomes after the surgical treatment of macula‐off RRDs. Patients with SMFV <9.0 mm Even after surgical reattachment, in cases of central detachment vision improvement and neuroretinal recovery remain compromised because of permanent functional damage to the macula.Previous studies investigating the importance of oxygen and nutrition supply in experimental RRD have supported the association between detachment height and photoreceptor damage.To address this research gap, we employed an automated method to quantify SMFV using the segmentation software designed for spectral‐domain (SD)‐OCT. The main objective of our study was to determine the effect of SMFV on the visual outcome in patients undergoing surgical treatment for macula‐off primary RRD by comprehensively analysing clinical, surgical and SD‐OCT findings.2The data of all patients with primary RRD were collected from the Department of Ophthalmology of the Medical University of Innsbruck, Austria from a standardised structured electronic database. The implementation and application of the RRD register were validated by the Department for Strategic Quality Management of the University Clinic Innsbruck, Innsbruck, Austria. According to the dataset protocol, all patients underwent SD‐OCT  and ultra‐widefield retinal imaging.Our retrospective register study was approved by the Local Committee for Medical Research Ethics. Due to the retrospective nature of the study, the requirement of consent was waived by the institutional review board of the Medical University of Innsbruck, Innsbruck, Austria. All procedures involving human participants were performed in accordance with the ethical standards of the institutional and/or national research committee and the 1964 Declaration of Helsinki, and its later amendments, or comparable ethical standards.2.1This institutional retrospective study was conducted from January 2014 to June 2019 at the University Clinic Innsbruck, Innsbruck, Austria.2.2We enrolled 127 consecutive patients with macula‐off RRD, all of whom received small‐gauge (G) vitrectomy  for surgical reattachment. The data were collected using a structured electronic database for patients with macula‐off primary RRD. Included patients presented directly to the emergency department of the clinic or were referred from other hospitals or private ophthalmologists.The inclusion criteria were: (a) patients with primary RRD without macular involvement, (b) patients with a follow‐up of at least 6 months after surgical reattachment and (c) patients with no complications. The exclusion criteria included patients with any of the following: (a) previous vitreoretinal surgery; (b) vitreous haemorrhage at first presentation; (c) re‐detachment during the follow up; or (d) a history of posterior uveitis, penetrating or non‐penetrating trauma, potential sight‐threatening diseases  developed during the study or in the fellow eye.The following data were collected for analysis: sex; eye affected; lens status; best‐corrected visual acuity (BCVA) displayed as the logarithm of the minimum angle of resolution (logMAR) before surgery as well as 3, 6 and 12 months after surgery; onset of central vision loss; the presence of pathological myopia ; a history of trauma and complicated surgeries ; the presence of vitreous bleeding; characteristics and location of retinal tears; the extent of retinal detachment and affected quadrants; the presence of PVR and the PVR grade; surgical technique ; foveal detachment; and various OCT characteristics . After the diagnosis, all patients were admitted to the ward for posturing while awaiting surgery.2.3We used electronic medical records to analyse the patients' surgical outcomes. Experienced retinal specialists performed ophthalmological examinations while the patients were hospitalised. We assessed the foveal status on SD‐OCT images using a standardised protocol for RRD. To acquire the images, we used a dense volume scan protocol with 25 B‐scans, wherein each scan comprised 512 A‐scans and a field of view of 20° × 20° (6 × 6 mm). An eye‐tracking software  ensured automated eye alignment. The SD‐OCT software automatically executed retinal layer segmentation. For each case, we confirmed that foveal fixation and correct segmentation were adequate in the 25 B‐scans; a retinal specialist then manually corrected smaller segmentation failures.3) between the basal membrane and outer border of the retinal pigment epithelium (RPE)  and a centre point with a 6‐mm diameter through the fovea. The built‐in segmentation algorithm measured the average thickness and average volume of each zone and the centre. We measured SMFV (mm) Figure  of the c3. Thus, we imputed a conservative value of 1.635 mm and 20.6 mm3 for each value exceeding the threshold to perform calculations in cases with increased detachment or SMFV.The software calibrated a height up to 1.635 mm and calculate cases with an SMFV up to 20.6 mm2.43F8) as an endo‐tamponade. Heavy liquids (perfluorocarbon) and retinotomies for internal drainage were optional elements of PPV procedures.Vitreoretinal surgery was conducted at a tertiary medical centre based in the federal state of Tyrol. The surgeries were performed under peribulbar or general anaesthesia. All cases were treated with standard small gauge  pars plana vitrectomy (PPV) with the use of fluid‐air exchange with gas .We also calculated Pearson's correlation or Spearman's rank correlation coefficient to analyse correlations among parameters. Furthermore, we conducted univariate and multivariate regression analyses to determine the potential confounders of BCVA at 12 months after macula‐off RRD surgery. All factors with a 33.1A total of 127 eyes met our inclusion criteria for retrospective analysis. The mean patient age at the time of presentation at our clinic was 63 ± 14 years. Fifty‐six (44%) patients were phakic at the time of RRD diagnosis. Three (2%) patients underwent a lens‐sparing vitrectomy, none of whom showed significant lens opacities at the follow‐up examinations. Further characteristics are listed in detail in Table R = 0.238; P = .015), preoperative BCVA , CMT . There was no correlation between SMFV and macula‐off duration .Preoperative SMFV was significantly correlated with retinal detachment extent (3.2P = .005), foveal detachment height (P < .001), CMT (P = .011), lower BCVA (P = .002) at baseline and central SMFV (P < .001) were significantly associated with lower visual outcomes 12 months after foveal reattachment. After creating a linear regression model, central SMFV  and a macula‐off duration  were determined to be the factors that principally influenced FVA 12‐months post‐RRD surgery.Table P‐value <.2 in the univariate analysis were included in the multivariate analysis to scrutinise their effect on visual outcomes at 3‐ and 6‐month follow‐up. Multivariate analysis of the 3‐month follow‐up revealed that detachment for over 8 hours was the only factor associated with reduced BCVA . SMFV  and macula‐off duration  were significantly associated with a reduced BCVA 6‐month post‐surgery   and 0.196 ± 0.075 (P = .001) worse than patients with low SMFVs 6‐ and 12‐month post‐surgery, respectively. When the binary logistic regression was adjusted based on the extent of retinal detachment, detached quadrants, PVR and macula‐off duration, we found that patients with a low SMFV  had significantly better visual outcomes than patients with a high SMFV (9.0‐20.6 mm3) at 6‐months [ = 1.057‐24.894] and 12‐month post‐surgery  and from baseline (1.54 ± 0.40) to 12‐month  follow‐up in the high SMFV group   to 12‐month  and transforming growth factor beta‐3 (TGFβ‐3) in the vitreous humour, which indicates an inflammatory reaction due to an underlying apoptotic process in the detached outer retinal layer.Animal studies also support the correlation between detachment height in RRD cases and outer retinal damage. Disruption and loss of photoreceptors and 20% thinning of the outer nuclear layer have been observed within 72 hours of detachment.3 were recorded as 20.6 mm3 due to technical limitations of SD‐OCT. In these cases, the long wavelength used by swept source (SS)‐OCT devices could provide the potential of deeper axial imaging ranges.There are several limitations to our study. First, this study is retrospective and used data collected in a structured electronic register to monitor quality and efficacy indicators for vitreoretinal surgery in patients with primary RRD at one tertiary referral centre. Second, the effect of SMFV and central height of detachment on the visual outcomes may have been underestimated because heights over 1.635 mm were recorded as 1.635 mm and SMFVs >20.6 mmA strength of the study was that SD‐OCT was performed in all cases to assess and confirm the foveal involvement of the RRD. We used a segmentation algorithm that facilitated the exact volumetric quantification of submacular fluid in patients undergoing surgical intervention for primary RRD. To the best of our knowledge, the present study is the first that measured SMFV using OCT volumetric quantification in patients with macula‐off primary RRD. The findings of our study could help clinicians understand the extent to which SMFV affects visual recovery after surgical management of macula‐involved primary RRD. Future studies should investigate submacular volume rather than retinal detachment height as a more accurate parameter.3 experienced a steady improvement of VA up to 12 months post‐surgery, patients with high preoperative SMFV of 9.0 mm3 had no VA improvement more than 3 months after surgery. Patients presenting with low SMFV had an 8.0 times greater chance of visual recovery after surgical reattachment.In conclusion, this study identified a negative correlation of preoperative SMFV and final visual outcome. Macula‐off duration and SMFV were key independent risk factors for an impaired visual outcome following surgical intervention for macula‐off RRD. While patients with preoperative SMFV <9.0 mmNone declared.


This study investigated the different blood pressure patterns that were evaluated by ambulatory blood pressure monitoring (ABPM) among elderly patients and explored the effect of pressure patterns on cognitive impairment and mortality.n = 130) and the non-cognitive impairment group  according to the MMSE score. All participants underwent ABPM to evaluate possible hypertensive disorder and cerebral MRI for the evaluation of cerebral small vessel disease. Follow-up was performed by telephone or medical records. The primary outcome was all-cause mortality. Secondary endpoints were major adverse cardiac and cerebrovascular events (MACCE).A total of 305 elderly participants aged ≥65 years were divided into the cognitive impairment group , and more participants had nocturnal BP rise . Nocturnal BP rise was associated with greater white matter hyperintensities (WMH) (p = 0.013). After 2.03 years of follow-up, there were 35 all-cause deaths and 33 cases of major adverse cardiac and cerebrovascular events (MACCE). CI was independently associated with all-cause mortality during long-term observation (p < 0.01). Nocturnal BP rise had no significant predictive ability for all-cause mortality in elderly patients (p = 0.178).Among 305 participants, 130 (42.6%) were identified with cognitive impairment (CI), with average systolic blood pressure (BP) of 127 mmHg and diastolic BP of 66 mmHg. According to ABPM, only 13.1% had a dipper pattern, 45.6% had a nocturnal BP rise, while 41.3% had a non-dipper pattern. Compared with NCI patients, the CI group had significantly higher night-time systolic BP (130.0 ± 18.2 vs. 123.9 ± 15.1, Nocturnal BP rise contributed to greater cognitive impairment in elderly patients. Not nocturnal BP rise, but CI could significantly increase all-cause mortality. Controlling BP based on ABPM is critical for preventing the progression of cognitive dysfunction. Dementia affects approximately 50 million people worldwide and is expected to increase by nearly 9.9 million new cases each year. While Alzheimer’s disease is the leading cause of cognitive impairment (CI), vascular dementia is the second leading cause, with no effective therapies . CerebraTwenty-four-hour ambulatory BP monitoring (ABPM) offers much more information on variability and circadian BP pattern compared to office BP measurements and is superior in predicting future cardiovascular events . AlthougPrevious studies have reported on a cognitive impairment-mortality relationship and indicated that baseline cognitive impairment increases the risk of all-cause mortality , 10. HowThe present study assessed the relationship between BPV and CI in elderly patients with different levels of cognitive function assessed by MMSE and investigated the association of cognitive impairment on mortality.This study included 583 inpatients, ≥65 years of age, who received cognitive assessment and cerebral MRI at the Geriatric Medicine department of the Beijing Friendship Hospital between January 2014 and September 2019. The participants were followed up until March 2020. Among these subjects, 3 were excluded for chronic kidney disease, 57 were excluded for incomplete clinical information, 165 were excluded for the incomplete ambulatory blood pressure monitoring (ABPM), 37 were excluded for the incomplete MRI, and 16 were excluded for missed follow-up. Finally, 305 participants were included in this analysis to assess the effect of BPV and its risk factors on cognitive function in elderly subjects  and was conducted in accordance with the Declaration of Helsinki.Demographic characteristics, including years of education, medical history, clinical information, and concurrent medications, were collected.Hypertension was defined as systolic blood pressure (SBP) ≥140 mmHg, diastolic blood pressure (DBP) ≥90 mmHg, or ongoing therapy for hypertension. Type-2 diabetes was defined as glycosylated hemoglobin (HbA1c) ≥6.5%, a non-fasting plasma glucose concentration ≥ 200 mg/dL, fasting plasma glucose concentration ≥ 126 mg/dl, or if the patient was treated with oral hypoglycemic medications or insulin.Lipids, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), were measured using standard methods of the central laboratory of the Beijing Friendship Hospital. Fasting glucose, glycosylated hemoglobin (HbA1c), liver and renal function, and albumin (ALB) were also measured. The CKD-EPI (the Chronic Kidney Disease Epidemiology Collaboration equation) calculated the estimated glomerular filtration rate (EGFR).A validated ambulatory recorder  and cuff were used on the non-dominant arm to perform ABPM. BP was measured at 30-min intervals for daytime (06.00–21.59 h) and 1-h intervals for night-time (22.00–05.59 h). BP, including 24-h mean value, mean daytime value, and mean night-time value, were calculated from recorded measurements and used in data analyses.n = 6). Nocturnal hypertension was defined as a night-time SBP ≥120 mmHg and/or night-time DBP ≥70 mmHg, based on the 2014 guidelines for the management of hypertension published by The Japanese Society of Hypertension.The nocturnal BP fall (%) was calculated using the following formula: (daytime SBP  − night-time SBP)/daytime SBP. We classified the nocturnal BP fall into the following three patterns: the dipper pattern if the nocturnal BP fall was > 10%; the non-dipper pattern, if the nocturnal BP fall was between 0 and 10%; and the rising pattern, if the nocturnal BP fall was < 0%. Patients with an extreme dipper pattern  were combined with those with the dipper pattern due to the limited number of cases  in the Radiology Department of our hospital. Sequences included T2-weighted imaging (T2WI), T1-weighted imaging (T1WI), diffusion-weighted imaging (DWI), fluid-attenuated inversion recovery imaging (FLAIR), and susceptibility-weighted imaging (SWI). The main parameters were as follows: repetition time (TR) = 4500 ms, echo time (TE) = 84 ms, flip angle (FA) = 120°, matrix = 256 *256, field of view (FOV) = 220 * 220 mmWhite matter hyperintensities (WMHs) were identified as hyperintense areas in the periventricular and deep white matter on both T2WI and FLAIR. WMH was rated using the Fazekas scale on FLAIR images. Lacunar infarcts (LACs) were defined as small (diameter of 3–15 mm), sharply demarcated hyperintense lesions on T2WI with corresponding foci of FLAIR low signal intensity and assessed in the basal ganglia, internal capsule, thalamus, brainstem, radiating crown, and semioval center. The number of WMHs and LCIs were calculated to assess the severity of cerebral small vessel disease. MRI assessments were performed by two experienced neuroradiologists who were blinded to the clinical information.Cognitive function was assessed by the Mini-Mental Status Examination (MMSE) with a total score 0–30. It included 11 items, categorized as: orientation (10 points), memory registration (3 points), attention and calculation (5 points), recall (3 points), language (10 points). A 27-point was proved to be an appropriate cutoff for cognitive impairment in a population with relatively high educational attainment .Follow-up was performed by reviewing data from medical records or by telephone interviews. The primary outcome was all-cause mortality. Secondary endpoints were major adverse cardiac and cerebrovascular events (MACCE), including acute coronary syndrome , heart failure of NYHA III-IV, stroke/transient ischemic attacks (TIA), and cerebral hemorrhage.p-value < 0.05 was considered statistically significant.All continuous variables were reported as mean ± standard deviation (M ± SD), and categorical variables were presented as counts and percentages. The Kolmogorov–Smirnov test was used for the normality assumption. Pearson’s chi-squared test was used to investigate the categorical variables. For the analyses of continuous variables with normal distribution, a t-test was used to examine the differences between the normal cognition and impaired cognition patients. Kruskal–Wallis with post hoc Mann–Whitney U-test was used to analyze the continuous variables with non-normal distribution. Correlations between nocturnal BP fall and MMSE were evaluated using linear regression. Cox regression and Kaplan–Meier curves were used for survival analysis. All statistical analyses were performed using SPSS statistical software version 24.0 for Windows (SPSS Inc.), and a A total of 305 participants with a mean age of 81 years were included in the study. The average years of education received was 14; 69% of participants were men; the average BMI was 24; 10.2% were smokers; 79% had hypertension, and 39.3% had diabetes. As shown in Table n = 130) and without CI  were compared according to demographic and clinical characteristics and risk factors. As shown in Table p < 0.001), less educated , had higher fasting glucose , lower HgB , significantly lower ALB , significantly lower eGFR , and more severe WMH  and LCI .Among 305 participants, 42.6% were identified as having CI with MMSE scores < 27. Subjects with , and more patients had nocturnal BP rise . In contrast, there was no significant inter-group difference in DBP. The incidence of daytime SBP and nocturnal hypertension was higher in the patients with CI compared to those with normal cognition; the difference was not statistically significant  , with 500% increase during follow-up , .62–13.78Cognitive impairment (CI) is rampant among the elderly worldwide. This study enrolled 305 cases, with a mean SBP of 127.4 mmHg and DBP of 66 mmHg. Among them, 130 (42.6%) participants were identified with CI. These patients had worse nutrition and kidney function than individuals with normal cognition, which negatively affected their life quality and long-term prognosis. Hypertension is a major risk factor for cognitive dysfunction , 12, andThis study demonstrated that in elderly patients (mean age of 81 years), night-time SBP and nocturnal BP rise were positively correlated with CI, even if the patients had normal BP. Mean BP and daytime BP showed no correlation. Nocturnal hypertension was not significantly higher in the CI group. These results are consistent with the findings of Manabu Kokubo and his colleagues , who repDespite enormous evidence supporting the role of atherosclerosis in the pathogenesis and progression of CI, the mechanistic relationship between nocturnal BP and CI remains unknown. Following are some of the possible mechanisms: first, nocturnal BP rise decreased cerebral blood flow and was related to higher levels of insulin resistance markers in normotensive and untreated mildly hypertensive adults . Second,We observed that nocturnal BP rise was associated with lower cognition, which could decrease MMSE by 2.9%. Although several studies have suggested that the impact of hypertension on cognition is global, not all studies broadly investigated the distinct cognitive domains. Some studies reported attention and executive functioning domains as cognitive domains that are most vulnerable to hypertension  since cop = 0.027). Still, nocturnal BP rise was not significantly associated with all-cause mortality. Perhaps nocturnal BP rise was more closely associated with cardiovascular events than mortality. The patients in this study were much older, and most of them died of infection or another disease, while only 11.4% died of cardiovascular events. So it is important to emphasize the importance of controlling BP using ABPM as an indicator to control cardiovascular events [The present study showed that baseline CI measured by MMSE score was associated with an elevated risk of all-cause mortality, which was consistent with previous studies , 18. Yetr events .The present study has some limitations. First, as the present study was a cross-sectional study, the cause-effect relationship was unclear. Second, in addition to LCI and WMH, cerebral microbleeds are also a form of cerebral small vessel disease, which has been reported to be highly prevalent in memory clinic patients and those with Alzheimer’s disease –24. ThirThe present study showed that nocturnal BP rise contributed to cognitive impairment in elderly patients. CI increased the mortality in the elderly, but the nocturnal BP rise did not. Further studies are required to determine whether lowering nocturnal BP should be targeted to prevent the progression of CI.


The optimal cut-off values were 292 for EOS counts and 19 for the Fractional exhaled Nitric Oxide (FeNO) measure. Patients with an EOS count ≥ 300  or FeNO measure ≥ 20  had a significantly higher risk of exacerbation. Moreover, patients with both an EOS count ≥ 300 and FeNO measure ≥ 20 had a significantly higher risk of exacerbation than those with lower EOS count or lower FeNO measure . Conclusions: Higher EOS counts and FeNO measures were associated with increased risk of exacerbation. These biomarkers may help physicians identify patients at risk of exacerbations and personalize treatment for asthma patients.Purpose: To understand the association between biomarkers and exacerbations of severe asthma in adult patients in Taiwan. Materials and Methods: Demographic, clinical characteristics and biomarkers were retrospectively collected from the medical charts of severe asthma patients in six hospitals in Taiwan. Exacerbations were defined as those requiring asthma-specific emergency department visits/hospitalizations, or systemic steroids. Enrolled patients were divided into: (1) those with no exacerbations (non-exacerbators) and (2) those with one or more exacerbations (exacerbators). Receiver operating characteristic curves were used to determine the optimal cut-off value for biomarkers. Generalized linear models evaluated the association between exacerbation and biomarkers. Results: 132 patients were enrolled in the study with 80 non-exacerbators and 52 exacerbators. There was no significant difference in demographic and clinical characteristics between the two groups. Exacerbators had significantly higher eosinophils (EOS) counts (367.8 ± 357.18 vs. 210.05 ± 175.24,  Asthma is a heterogeneous disease with different phenotypes affecting children and adults worldwide ,2. The dThe Global Initiative for Asthma (GINA) reports that asthma prevalence varies across the world, impacting 1–18% of populations in different countries . A natioAsthma in adults is associated with various morbidities, creating higher utilization of healthcare systems. In countries such as Taiwan, governments must bear the financial burden of caring for adults with asthma-related disability through their healthcare systems . A studyThe goal of treatment, as outlined by the 2020 GINA guidelines, is to control the symptoms of asthma and prevent any exacerbations. Initial treatment includes the use of short-acting bronchodilators and systemic corticosteroids [Biomarkers are measurable and reproducible biological processes that often correlate with the “clinical state” of a patient . BiomarkRecent studies have shown that some traits can predict future exacerbation, which includes past exacerbation history, asthma control and type 2 inflammation. Type 2 inflammation is found in approximately 50–70% of severe asthma patients ,13 and ihttps://www.clinicaltrials. gov (NCT02871947) on 18 August 2016. Informed consent was obtained from all subjects involved in the study.This is a multicenter retrospective cohort study to compare patient characteristics, clinical outcomes and biomarkers for severe asthma patients in Taiwan. The severe asthma patients were enrolled in outpatient visits in six hospitals during 2016–2019, including Far Eastern Memorial Hospital, National Taiwan University Hospital, Taipei Veterans General Hospital, Kaohsiung Medical University Hospital, Changhua Christian Hospital and Poh-Ai Hospital.  and conducted in accordance with the Declaration of Helsinki. All patients provided written informed consent for participation, and the study was registered at All patients with more than 1 year follow up in outpatient visits were enrolled. Patients requiring medium to high dose ICS and LABA or leukotriene modifier/theophylline for the previous year, or those treated with systemic corticosteroids for more than half a year to prevent from becoming uncontrolled, or those remaining uncontrolled despite this therapy were further included in the study as severe asthma patients. Patients fulfilling at least one of the following criteria are defined as uncontrolled asthma: (1) having ACQ score > 1.5 or ACT score < 19, (2) treated with two or more bursts of systemic corticosteroids, (3) having at least one hospitalization, ICU stay or mechanical ventilation in the previous year, (4) having FEV1 < 80% predicted after appropriate bronchodilator withheld and with reduced FEV1/FVC.Patients with COPD or other pulmonary disease, with lung or other end-stage cancers, with oxygen therapy for more than 15 h a day, with long-term use of non-invasive positive pressure ventilation (NIPPV), with active tuberculosis disease or other infection or without agreement were excluded.We have collected the following information for 1 year from medical charts: age, gender, BMI, smoking history, pre-existing comorbidities, lung function, biomarker data, treatment and frequency of serious exacerbations. Pre-existing comorbidities contained allergic rhinitis, nasal polyps, hypertension, gastroesophageal reflux disease (GERD), heart failure (HF), diabetes mellitus (DM), and atopic history. At the time of enrollment, the participants were assessed for Asthma Control Test (ACT), lung function and biomarker data including IL-5, IL-13, IL-8, IL-17, IL-33, Tryptase, Periostin, TGF Beta, TNF Alpha, vascular endothelial growth factor (VEGF), placenta growth factor (PlGF), TSLP, eosinophil (EOS) count, and fractional exhaled nitric oxide (FeNO) and Immunoglobulin E (IgE) level.Serious exacerbations were evaluated in the current study and defined as requiring asthma-specific emergency department visits or hospitalization, or systemic steroids after entering the database.p values less than 0.05 were considered statistically significant. All analyses were performed using the SAS/Stat system for Windows, version 9.3 .The demographic and clinical characteristics of the study subjects were described. Continuous variables were presented as mean ± standard deviation, and the difference between groups was evaluated using the independent t test. Categorical variables were presented as numbers and percentages, and the chi-squared or Fisher’s exact test was used to evaluate the difference between groups. The receiver operating characteristic (ROC) curves were plotted to determine the optimal cut-off point value for EOS counts and FeNO measure. The optimal cut-point value was then obtained using the maximum value of Youden’s index in ROC analysis. The association between exacerbation and biomarkers was analyzed by the generalized linear model and presented using the forest plot. The The demographic and clinical characteristics of enrolled patients are described in p = 0.0043) and TSLP levels , but significantly lower tryptase levels .Patient biomarker data are presented in p = 0.0029) or with FeNO measure ≥ 20 ; however, there was no significant difference in IgE level between exacerbators and non-exacerbators   .p = < 0.0001).The generalized linear models demonstrated a significant association between the biomarker group and exacerbation . PatientWe conducted a retrospective review study in Taiwan to analyze the clinical and demographic characteristics of asthma patients and the association between biomarkers and number of asthma exacerbations, compared with our optimal cut-off point. We found that patients with higher EOS and FeNO levels corresponded with a higher number of exacerbations. Additionally, the combination of the two biomarkers EOS count ≥ 300 and FeNO measure ≥ 20 was significantly associated with more exacerbations compared to those with a lower level of EOS and FeNO. We concentrated on these biomarkers, considering that the GINA guidelines note that FeNO is a useful biomarker for type 2 asthma, identifies airway inflammation, and is related to levels of blood eosinophils [9 cells/L) were more likely to have an increased rate of exacerbations (RR: 3.67) compared their matched counterparts [A cross-sectional matched cohort study by Price et al. (2019), used real-world evidence to understand biomarkers in predicting asthma exacerbations for patients using inhaled corticosteroids, and validates the findings of our own study . The stuterparts . As theiterparts . A studyterparts . Studiesterparts . While tWhile we studied the utility of lung function in predicting exacerbation (FEV1), our study found no correlation between the two factors. In contrast, a Swedish study by Malinovschi et al. (2016), looked at the relationship between FeNO and EOS levels and lung function . This stAdditionally, while we examined the roll of the blood biomarker IgE, we found no association between exacerbations and IgE. IgE, like FEV is associated with “lower lung function” and higher levels of “allergen-specific IgE are associated with risk of asthma .” HoweveAccording to the 2020 GINA report, type 2 inflammation in asthma is common in approximately 50% of patients with asthma. It is “characterized by various cytokines ((IL)-4, IL-5, and IL-3))”, and that are produced in “adaptive immune system on recognition of allergens” [While we did not group patients into type 1 and type 2 inflammation categories, we did look at treatment behavior among sub-groups . We founHigher efficiency biologics are correlated with higher levels of FeNO and EOS two other seminal studies. A trial by Castro et al. (2018) compared an anti-IL4 inhibitor (dupilumab) at various dosages with a placebo. They found that asthma exacerbations were lower among patients who received the biologic drug, approximately 48% lower for those who received either 200 mg or 300 mg. Patients who took this drug also had higher FEV1. The higher efficacy in terms of reducing exacerbations and improving lung function are correlated with higher baseline levels of FeNO >25 ppm) and EOS counts (>300 cells per μL) . Another ppm and In our study, another marker is tryptase. Patients with severe asthma with high blood eosinophil counts and low serum tryptase levels were more likely to have greater risk of exacerbation. This result was reported in our previous study . The genThis study had several limitations. We did not control for baseline differences between the exacerbations and no exacerbations groups. Therefore, there is no matching of the cohort on underlying comorbidities, patient covaries, or baseline treatments. However, this reflects the real application of our study, considering that not all patients who have asthma will also have the same underlying conditions. Follow up for our study was only limited to one year. A longer follow up period would allow us to see long-term effects.Our study demonstrated that higher EOS counts and FeNO measure were associated with an increased risk of exacerbation. Identification of these biomarkers may help physicians identify patients at risk of exacerbations and personalize treatment for asthma patients. In the future, because of the heterogenous nature of asthma in adults, the identification of biomarkers that put adults at risk of increased exacerbations may help with treatment selection by clinicians. In the future, payers and HTAs will seek the most relevant populations to make decisions about coverage with various medications. Additional studies might examine outcomes (reduction in exacerbations) based on different treatments once the patients have been identified in terms of biomarkers.