Previous studies indicate that the prevalence of hypothyroidism is much higher in patients with lupus nephritis (LN) than in the general population, and is associated with LN’s activity. Principal component analysis (PCA) and logistic regression can help determine relevant risk factors and identify LN patients at high risk of hypothyroidism; as such, these tools may prove useful in managing this disease.We carried out a cross-sectional study of 143 LN patients diagnosed by renal biopsy, all of whom had been admitted to Xiangya Hospital of Central South University in Changsha, China, between June 2012 and December 2016. The PCA–logistic regression model was used to determine the influential principal components for LN patients who have hypothyroidism.Our PCA–logistic regression analysis results demonstrated that serum creatinine, blood urea nitrogen, blood uric acid, total protein, albumin, and anti-ribonucleoprotein antibody were important clinical variables for LN patients with hypothyroidism. The area under the curve of this model was 0.855.The PCA–logistic regression model performed well in identifying important risk factors for certain clinical outcomes, and promoting clinical research on other diseases will be beneficial. Using this model, clinicians can identify at-risk subjects and either implement preventative strategies or manage current treatments. Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, and lupus nephritis (LN) is a frequently occurring and serious complication of SLE , 2. StudHowever, the pathological and physiological mechanisms underlying SLE with hypothyroidism are sophisticated. Furthermore, the availability of multiple indicators and of large relevant datasets makes it difficult to analyse clinical data directly; therefore, the precise nature of these mechanisms remains unknown –8.Logistic regression is widely used to analyse the relationship between individual risk/protective factors and outcomes . HoweverThe current study examines the laboratory test results of selected patient populations, and leverages PCA–logistic regression analysis to pinpoint key PCs. Such information may greatly assist in the prevention or management of this disease.In our cross-sectional study, we investigated 143 LN patients diagnosed through renal biopsy who had been admitted to Xiangya Hospital of Central South University in Changsha, China during the June 2012–December 2016 period. The exclusion criteria included the coexistence of another autoimmune disease or having been diagnosed with thyroid disease prior to LN. All patients were informed of the objectives of this study, and each provided signed written consent prior to enrolment. As this research did not affect patient treatment, as per Central South University policies, ethics board approval was not required.Data on patient characteristics, clinical symptoms, and laboratory results were retrospectively collected from each patient’s medical records. These included: (1) general information, including age and sex; (2) clinical symptoms, including course of disease, hypertension, fever, cutaneous manifestations, alopecia, oral ulcer, malar rash, renal dysfunction (proteinuria), and haematological disease; and (3) laboratory results, including white blood cell count, haemoglobin (Hb) concentration, concentration of total protein (TP), serum lipid, erythrocyte sedimentation rate, C-reactive protein, C3, C4, and antibodies to dsDNA, simth, SSA, SSB, anti-U1 ribonucleoprotein, and ribosomal P protein. Patients’ SLE disease activity  scores were collected from medical records and calculated by an experienced clinician.χ2 test, and between continuous variables in two independent groups by using the t-test. In cases where we were unable to establish a normal distribution for a variable, we performed the Mann–Whitney U-test.Values herein are expressed as mean (standard deviation), median, and interquartile range, or as a number and percentage. We undertook comparisons between categorical variables by using the 1 represents the group of variables that induced the greatest amount of variation in the data. We used logistic regression to further screen clinically significant eigenvalues and scrutinize critical factors that affect outcomes among LN patients.We performed PCA by using SPSS software , to determine the interplay of clinical variables among LN patients with and without hypothyroidism. We achieved convergence during an Oblimin rotation with Kaiser normalization. In the final PCA iteration, we covered nine clinical variables in the patient group analysed. To be considered a PC, a variable’s eigenvalue had to exceed 1, and PCp-values less than 0.05 were considered statistically significant.We performed the analysis in three stages. First, we performed a monofactor analysis to examine differences between LN patients with and without hypothyroidism. Second, we performed PCA with regard to all the serology, immunology, and biochemistry variables of LN patients. We truncated those data by rotational reorientation to maximize variance along the new axis  while concurrently preserving the relationship and order among the data points; the PCs could then be used in further classification, as they retain information from the original data. Third, the absolute majority of cumulative contribution (> 2/3) was used to extract PCs as independent variables, and the clinical outcome was used as a dependent variable for logistic regression modelling. In this way, we were able to obtain the PCs that significantly correlated with certain clinical outcomes. We generated an ROC of multivariate observations to assess the PCA—logistic regression model’s performance. Statistical analysis was performed using SPSS (version 19), and all p > 0.05), sex , and disease duration . LN patients with hypothyroidism had a significantly higher frequency of rash, and higher levels of serum creatinine (SCr), blood urea nitrogen (BUN), blood uric acid (UA), triglyceride (TG), and low-density lipoprotein (LDL) concentrations. Additionally, Table We compared the clinical characteristics of 48 LN patients with hypothyroidism and 94 LN patients with euthyroidism Table . The twop < 0.05 were included as input variables for PCA. The Kaiser–Meyer–Olkin value was 0.7 when all the clinical variables were included; meanwhile, the p-value of the Bartlett test of primary data was 0.000, indicating that the data were suitable for use in PCA. We removed symptomatic variables and those of which the extract value were too small in the common factor variance table. The model generated nine PCs that explained 74% of the variation within the dataset; two of these, taken together, explained 30% of the variation. From the viewpoint of variance contribution rate, when eigenvalue λ1 = 3.515, the PC1 contribution rate was 15.3%—the highest value—and it contained the most information . For the nine main PCs  > TP > C3; likewise, the first three degrees of importance of PC2 in the sequence were SCr > BUN > UA. In focusing on the indices whose loading was obviously higher than those of others, we could clearly see that PC1 was mainly about renal functions ; PC2 was about serum protein factor (including TP and ALB); PC3 was a leukocyte factor; and PC4 was a globulin factor. We additionally found that PC5–PC8 could not be accurately classified as any certain factor bearing a specific meaning, and PC9 was an autoantibody factor.To cover as many indices that affect the outcomes of LN with hypothyroidism as possible, factors with 1, PC2, and PC9 were the PCs that have a significant influence on whether LN was combined with hypothyroidism .We used the nine PCs as input variables and the clinical outcome (LN with or without hypothyroidism) as a dependent variable in logistic regression modelling. Our analytical results showed that PCsm Table —that is 1, PC2 and PC9, which included SCr, BUN, UA, TP, ALB, and anti-RNP antibody—were found to be important clinical variables with respect to LN patients with hypothyroidism. The Exp(B) of PC2 and PC9 was 2.361 and 4.724, respectively, indicating that the correlation between these two PCs and the outcome was much stronger than that among others.We applied PCA–logistic regression analysis to demonstrate that three PCs—namely, PCPrevious studies conclude that the most common kidney derangements associated with hypothyroidism are elevated SCr levels, reduced estimated glomerular filtration rate, and water–electrolyte imbalance , 15. MorSevere hypoalbuminemia was observed in SLE patient with subclinical hypothyroidism , correspAdditionally, in this study, higher anti-RNP antibody level had massive effect among LN patients with hypothyroidism, which has not been reported before. Anti-RNP antibody reacts with proteins that are associated with U1 RNA and form U1snRNP, autoimmunity to RNP autoantigens is frequently seen in systemic autoimmune diseases including lupus and it may induce the occurrence of renal disease –25, thyr9—which mainly involved the anti-RNP antibody—was the strongest among these patients: its Exp(B) was 4.724, the highest among nine principal components. SCr, BUN, UA, TP, ALB, and autoantibody levels are modifiable factors that can be improved through early treatment to improve renal function and strengthen nutrition support, in order to reduce risk among LN patients with hypothyroidism. Ultimately, PCA offers great insights in exploring the influence of clinical variables or measuring the important factors that affect patient outcomes.The principal component analysis (PCA)–logistic regression model approach used herein is a useful statistical method by which to analyse the effects of multiple clinical index interactions in lupus nephritis (LN) patients who also have hypothyroidism. Using this model, we found serum creatinine (SCr), blood urea nitrogen (BUN), blood uric acid (UA), total protein (TP), albumin (ALB), and anti-ribonucleoprotein (RNP) antibody to be particularly vital factors with respect to these patients. What is more, the impact of PC


Purpose of the present study was to investigate the incidence of renal function impairment after adjuvant treatment for gastric cancer and the impact of radiotherapy on estimated glomerular filtration rate (eGFR) five years after gastric surgery. Of the 663 patients who were followed up for ≥5 years without disease recurrence and whose baseline kidney function was normal, only 2.0% of patients developed renal function impairment after adjuvant treatment for gastric cancer. While radiotherapy was negatively associated with the five-year eGFR in linear regression analysis, its impact was minimal if the kidneys were properly shielded. This study could serve as a partial basis for further research on radiation-related renal function impairment in patients who received radiotherapy for abdominal malignancy.2. Logistic and linear regression analyses were performed to determine independent factors associated with the five-year eGFR. A total of 13 (2.0%) patients developed renal function impairment (five-year eGFR <60 mL/min/1.73 m2). In logistic regression analysis, the baseline eGFR was identified as a prognostic factor for renal function impairment (odds ratio (OR), 0.878; 95% confidence interval (CI), 0.831–0.927; p < 0.001), but radiotherapy was not . In linear regression analysis, age , baseline eGFR , cisplatin , and radiotherapy  were predictive variables for the five-year eGFR. Among patients who received adjuvant radiotherapy, age , hypertension , baseline eGFR , and volume of the kidneys receiving ≥20 Gy  were predictive variables for the five-year eGFR. Development of renal function impairment after adjuvant treatment for gastric cancer was rare among patients with normal baseline kidney function. While radiotherapy was negatively associated with the five-year eGFR, its impact would have been minimal if the kidneys were properly shielded. Further studies are needed to confirm the impact of radiotherapy in patients with poor kidney function.We investigated the incidence of renal function impairment after adjuvant treatment for gastric cancer and analyzed the impact of radiotherapy on estimated glomerular filtration rate (eGFR) five years after gastric surgery. We reviewed the medical records of 1490 patients with stomach cancer who underwent curative surgery and adjuvant treatment for gastric cancer. Finally, we included 663 patients who were followed up for ≥5 years without disease recurrence and whose baseline eGFR was ≥60 mL/min/1.73 m Stomach cancer is the most common cancer and the fourth leading cause of cancer-related deaths in South Korea . Age-staIn the Adjuvant Chemoradiation Therapy in Stomach Cancer (ARTIST) trial, a randomized controlled trial comparing adjuvant chemotherapy and chemoradiation therapy after complete resection with D2 LN dissection, the most common non-hematological grade-three and -four toxicities in the chemoradiation therapy arm were nausea 12.3%), vomiting (3.1%), hand–foot syndrome (3.1%), stomatitis (1.8%), diarrhea (0.9%), and constipation (0.9%) [%, vomitiSince the radiation field encompasses para-aortic LNs between the upper margin of the origin of the celiac artery and the lower border of the left renal artery, the upper portion of the bilateral kidneys is also included in radiation field . SeveralIn the present study, we included patients who received adjuvant treatment for gastric cancer and were followed up for five years or longer, without disease recurrence. First, we investigated the incidence of renal function impairment five years after gastric surgery and its potential risk factors, including usage of radiotherapy. Then, the relationship between the kidney-function change over five years and the dose-volume histogram (DVH) of the kidney was analyzed with other risk factors in the subgroup receiving adjuvant radiotherapy.n = 90) and 10.3% (n = 68), respectively. In total, 183, 184, and 296 patients were treated according to the ARTIST, Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer (ACTS-GC), and Intergroup-0116 (INT-0116) trial protocols, respectively. The numbers of patients with stage IB, II, and III cancer were 72 (10.9%), 293 (44.2%), and 298 (44.9%), respectively. Most patients had LN metastasis . A total of 389 (58.7%) patients received radiotherapy. Patients who received radiotherapy were younger  and had a lower prevalence of hypertension  and diabetes , as compared to those who did not receive radiotherapy . The prevalence of hypertension and diabetes was higher in these 13 patients than in the other 650 patients . The mean eGFR decreased from 74.5 ± 11.8 mL/min/1.73 m2 to 49.6 ± 10.5 mL/min/1.73 m2 (p < 0.001) among patients who developed renal function impairment, while it decreased from 93.6 ± 12.2 mL/min/1.73 m2 to 89.3 ± 12.1 mL/min/1.73 m2 (p < 0.001) among patients whose eGFR remained normal .A total of 13 (2.0%) patients developed renal function impairment, which was defined as an eGFR <60 mL/min/1.73 md normal . There wp = 0.002) and baseline eGFR , were associated with the development of renal function impairment. Categorical variables, including hypertension  and diabetes , were also relevant. However, sex , cisplatin , and radiotherapy  were not relevant. In the multivariate analysis analyzing all variables that attained statistical significance in the univariate analysis, only baseline eGFR remained a significant prognostic factor of renal function impairment .In the univariate analysis, continuous variables, including age (odds ratio (OR), 1.109; 95% confidence interval (CI), 1.038–1.184; 2 = 0.528, p < 0.001). The younger the age or the higher the baseline eGFR, the higher the five-year eGFR . Radiotherapy and cisplatin were negative predictive variables for the five-year eGFR .The results of the multiple linear regression analysis are presented in n = 172). In multivariate analysis, age , radiotherapy , and baseline eGFR  were associated with the decrease in five-year eGFR , mean radiation dose (Gy) to the kidney (Dmean), and five-year eGFR was performed in these patients. The median kidney V5Gy, V20Gy, and Dmean were 35.9% , 14.9% , and 8.2 Gy , respectively  receiving ≥5 Gy and ≥20 Gy  . Although kidney V5Gy and Dmean were not associated with the five-year eGFR, kidney V20Gy  and hypertension  were negative predictive variables for the five-year eGFR.In the multivariate analysis, age, hypertension, baseline eGFR, and kidney V< 0.001) . Similarp = 0.038) and kidney V20Gy  were associated with the decrease in five-year eGFR . In multivariate analysis, diabetes . Baseline eGFR was the sole prognostic factor for renal function impairment in the multivariate logistic regression analysis . Radiotherapy was not a prognostic factor in logistic regression analysis, but it was a predictive variable for the five-year eGFR in linear regression analysis . Furthermore, kidney V20Gy was a negative predictive variable among patients who received adjuvant radiotherapy. However, its coefficient was quite small ; when the kidney V20Gy was increased by 1%, the five-year eGFR decreased by 0.209 mL/min/1.73 m2. We assumed that, although the impact of radiotherapy on the five-year eGFR was significant, it was too small to lead to renal function impairment.In the present study evaluating the incidence and risk factors of renal function impairment at five years after surgery and adjuvant treatment for gastric cancer, the incidence of new-onset renal function impairment was very low, at 2.0%  remains the best index of kidney function. It can be determined by measuring the urinary clearance of exogenous filtration markers or be estimated from serum creatinine levels. Although the former method is considered the gold standard, the latter method is preferred because of its convenience. There are three estimation equations, namely the Cockcroft–Gault equation, Modification of Diet in Renal Disease (MDRD) study equation, and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation ,11,12. Tmean < 18 Gy and V20Gy < 32% when the partial kidney is irradiated [mean and V20Gy were 8.2 Gy and 14.9%, respectively, which were much lower than the constraints.Kidneys are dose-limiting organs in radiotherapy, and the estimated radiation dose with 5% risk of nephrosclerosis at five years (TD 5/5) is 23 Gy for the whole kidney . The tolradiated . In the p = 0.010). Cisplatin is excreted by the kidneys, but it can also be transported into renal epithelial cells, leading to kidney injury [2) in 69% of patients, even though radiotherapy was delivered to the head and neck [2 cisplatin was administered before and after radiotherapy in the present study. Although the dosage of cisplatin was much lower than that in the former study, the development of kidney injury from sequential administration of cisplatin and radiotherapy might have been more severe than injury from individual treatment modalities. However, cisplatin was not included as a variable in the subgroup analysis, since patients receiving cisplatin were treated with two-dimensional radiotherapy; hence, we could not obtain DVH data. If we were able to obtain DVH data of patients receiving cisplatin, we could have compared the impact of cisplatin and radiation dose on kidney function in more detail.Along with radiotherapy, cisplatin was a negative predictive variable for the five-year eGFR  [p = 0.004); however, this result requires careful interpretation because hypertension and diabetes were determined based only on the history of the patient’s medication. To investigate the impact of comorbid diseases, it would have been more appropriate to investigate the duration and control status of comorbid diseases.In addition to treatment-related factors, several patient factors affect kidney function. In general, kidney function gradually decreases with age. The Baltimore Longitudinal Study of Aging showed a mean decrease in creatinine clearance of 0.75 mL/min/year among 254 healthy subjects . The ann< 0.001) . Other s< 0.001) ,23. The This study had several limitations. First, this was a retrospective study among patients with locally advanced stomach cancer. Second, although the radiotherapy scheme was identical throughout the study period, there were three different adjuvant treatment strategies, and the choice depended on the time of surgery. Patients were randomly assigned to receive chemotherapy with radiotherapy or chemotherapy alone in the ARTIST trial, while it was determined according to patient preference in those who were treated after the closure of the ARTIST trial. Hence, there were significant differences in patient characteristics between those who received radiotherapy and those who did not . Patient2 were excluded. Patients whose serum creatinine levels were not available 5 years after surgery were also excluded.We reviewed the medical records of 1490 patients with stomach cancer who underwent curative surgery and adjuvant treatment at Samsung Medical Center between October 2004 and February 2013. Among them, patients who were followed up for ≥5 years without disease recurrence were included, because recurrent disease itself and/or treatment for recurrent disease can affect kidney function. Patients whose baseline serum creatinine levels were not available or whose baseline eGFR was <60 mL/min/1.73 mAdjuvant treatment varied according to the time of surgery . Patient2 capecitabine per day on days 1–14 and 60 mg/m2 cisplatin on day 1) every 3 weeks. The XP/XRT/XP arm administered 2 cycles of XP chemotherapy, followed by 45 Gy of radiotherapy with 1650 mg/m2 capecitabine per day for 5 weeks, followed by 2 additional cycles of XP chemotherapy. Radiotherapy was administered by using the anterior–posterior/posterior–anterior technique. The target of radiotherapy was the tumor bed, anastomosis site, duodenal stump, regional LNs, and 2 cm beyond the proximal and distal resection margins. The remnant stomach was not routinely included within the radiation field. The radiation dose was 45 Gy, with daily fractions of 1.8 Gy delivered over 5 weeks. The DVH data were not available, since two-dimensional radiotherapy was used in this period.The ARTIST trial was a phase III trial comparing adjuvant XP (capecitabine and cisplatin) chemotherapy alone and XP with radiotherapy (XP/XRT/XP). The XP arm administered 6 cycles of XP chemotherapy . A p-value < 0.05 indicated statistical significance. All statistical analyses were performed by using SPSS version 24 . Nomogram was drawn by using R version 3.6.1 (http://www.r-project.org).The baseline and five-year eGFRs were compared by using the paired 2) after adjuvant treatment for gastric cancer was rare. Radiotherapy, low baseline eGFR, old age, cisplatin, and hypertension were negatively associated with the five-year eGFR. However, if the kidneys would have been properly shielded and kidney V20Gy kept low, the impact of radiotherapy on the five-year eGFR could be minimal. Thus, every effort should be made to minimize the radiation dose received by the kidneys without compromising the quality of radiotherapy. Since the present study was limited to patients with normal kidney function, further studies are needed to confirm the impact of radiotherapy in patients with poor kidney function.In the present study evaluating the incidence and risk factors of renal function impairment at five years after surgery and adjuvant treatment for gastric cancer, renal function impairment (eGFR < 60 mL/min/1.73 m


Respiratory tract infections are common, and when affecting the lower airways and lungs, can result in significant morbidity and mortality. There is an unfilled need for simple, non-invasive tools that can be used to screen for such infections at the clinical point of care. The electronic nose (eNose) is a novel technology that detects volatile organic compounds (VOCs). Early studies have shown that certain diseases and infections can result in characteristic changes in VOC profiles in the exhaled breath. This review summarizes current knowledge on breath analysis by the electronic nose and its potential for the detection of respiratory diseases with and without infection. Human-exhaled breath contains over 3000 volatile organic compounds (VOCs) in gas phase, which are detectable by different laboratory methods such as gas chromatography and mass spectrometry. Exhaled VOCs include molecules such as alkanes, benzene derivatives, acetone, dimethyl sulfide, phenol, and aromatic compounds . The comDetection of VOCs in exhaled air is showing immense promise for improving diagnostic and screening standards of certain lung and airway diseases. Lung cancer is among the most commonly diagnosed malignancies and also among the leading causes of death worldwide . In lungSalmonella contaminating packaged meat [Mycobacterium tuberculosis (TB) in human sputum [M. tuberculosis, M. avium, M. scrofulaceum, P. aeruginosa cultures, and non-infected control samples in vitro. Using principal component analysis (PCA), 100% of TB cultures were identified and discriminated from other bacterial cultures [Staphylococcus aureus (SA) or Pseudomonas aeruginosa (PA), could be distinguished by eNose from patients without infection, allowing for correct diagnosis in 72% of cases [Electronic noses were developed for olfactory analysis in commercial settings such as food quality control, environmental monitoring, military purposes and, more relevant for this review, also in areas of research with focus on diagnosis of disease . With reged meat . As earlged meat  and in 2n sputum . A 14-secultures . In a stcultures . Furtherof cases .ENO) and pulmonary function testing for asthmatics [With advances in technology, there is now accumulating evidence that eNoses have the potential to address significant unmet clinical needs in both discrimination of one disease from another, as well as in the timely detection of airway infections in patients with underlying respiratory diseases at the point of care (POC) ,34,35. Ithmatics . As thisLate diagnosis of lung cancer contributes to its high lethality; only about 15% of patients are diagnosed with early stage disease, five-year survival rate is low, and over half of all lung cancer patients die within one year of diagnosis ,38. Thern = 16), asymptomatic asbestos-exposed subjects , patients with benign asbestos-related disease , and MPM patients (n = 14). Data were analyzed using AUROC graphs, and the final eNose breathprints were established by merging the sensor data of all four eNoses [Frequent screening tests are of great importance for individuals exposed to asbestos because of the lifetime increased risk for malignant pleural mesothelioma (MPM). In a study on detection of MPM, Lamote et al. utilized a combination of four different eNoses—Cyranose 320, Tor Vergata eNose, Owlstone Lonestar eNose, and Common Invent eNose—and GC-MS . The aimr eNoses . GC-MS ar eNoses . Thus, ip-value = 0.008, AUROC 0.92), and paucigranulocytic asthma , and neutrophilic was different from the paucigranulocytic phenotype , supporting the concept of using an eNose as an alternative to sputum cytology. Plaza et al.’s observations were consistent with similar studies. Ibrahim et al., reported an 83% accuracy discriminating eosinophilic from non-eosinophilic asthma, and 72% for distinguishing neutrophilic from non-neutrophilic phenotypes, using GC-MS to detect exhaled VOCs [p-value = 0.008 vs. AUROC 0.610, p-value = 0.441 respectively) or FENO  [n = 26/33/19). A four-eNose panel was used, including the Tor Vergata, Cyranose 320, Owlstone Lonestar, and Common Invent eNose. At baseline and at 12–18 month follow-up visits, FENO, spirometry, and induced sputum marker values were obtained. Asthma patients falling into each of these clusters showed differing clinical characteristics, such as systemic inflammatory markers, circulating eosinophil and neutrophil counts, and oral corticosteroid use. These data supported the notion that exhaled VOCs in asthma may be associated with systemic and local eosinophilic inflammation and may help to close the gap between clinical and laboratory tests in phenotyping severe asthma [n = 9), partially controlled (n = 7), or uncontrolled (n = 12) groups [n = 10) plus controlled asthma (non-symptomatic) and partially-controlled plus uncontrolled asthma (symptomatic) with an AUROC of 0.85, and a sensitivity and specificity of 0.79 and 0.84, respectively [Diagnosing asthma, as well as differentiating between eosinophilic, neutrophilic or other asthma endotypes, can be challenging. Dragonieri et al. investigated whether people with an established diagnosis of asthma could be discriminated from controls by eNose, and whether different degrees of asthma severity could also be identified. Subjects inspired VOC-filtered air by tidal breathing for 5 min, and a single expiratory vital capacity was collected into a Tedlar bag, which was subsequently sampled by a Cyranose 320 . Based oled VOCs . Wagenerled VOCs . Interes= 0.751) . Here, se asthma . There i) groups . A Cyranectively .ENO, and pulmonary function testing. Twenty-seven patients with intermittent or mild persistent asthma and 24 healthy subjects were studied. Exhaled breath was collected in Tedlar bags following a 2 h period of fasting. GC-MS was performed to confirm differences in VOC patterns between groups, and to confirm that exhaled breath samples remained stable within 48 h from collection [ENO (79.2%), spirometry (70.8%), and the combination of FENO and spirometry (83.3%). The combination of eNose analysis of exhaled alveolar air with FENO had the highest diagnostic accuracy for asthma (95.8%) [ENO, and lung function in asthma or healthy controls [eNose technology for asthma diagnosis and phenotyping also showed promising results when compared to conventional testing methods. Montuschi et al., compared the diagnostic accuracy of a Tor Vergata eNose, Fllection . eNose a (95.8%) . No corrcontrols .Bannier et al. investigated the potential of an eNose for accurate diagnosis of lung disease by comparing patients with asthma, CF, and healthy controls . This crFinally, Brinkman et al., utilized eNose in combination with GC-MS to differentiate between stable and unstable episodes of asthma . A panelChronic obstructive pulmonary disease (COPD) and asthma are both common and despite the fact that they are different disease entities, there can be significant clinical overlap between the two. The potential for accurate diagnosis of COPD and discrimination from asthma by exhaled breath profiles was first studied by Fens et al. . This cr2 corresponds to GOLD class A, 112–145 m/m2 to B, 146–165 m/m2 to C, and 166–215 m/m2 to D (quartiles 1–4) [There are several indexes of COPD severity and disease progression, including the six-minute walk test distance (6MWD), body mass index (BMI), airflow obstruction, dyspnea, and exercise (BODE), that can be used to assess the functional status of COPD patients. Since many of these tests are limited by patient compliance, space and time , Finamore et al. investigated whether VOC analysis by eNose could predict the functional status and its variation over time in COPD patients . In thisles 1–4) . A changles 1–4) .Finally, van Velzen et al. performed a randomized controlled trial measuring exhaled breath profiles in COPD patients with and without exacerbations over a period of three years, comparing eNose and GC-MS . This stLung disease in cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) share similarities as both are genetic diseases associated with neutrophil-dominated airway inflammation, recurrent and chronic bacterial infections, retention of suppurative airway secretion, development of bronchiectasis, and chronic loss of lung function ,61,62. IAspergillus fumigatus were identified by way of an eNose in studies by de Heer et al. [A. fumigatus airway colonization in patients with CF also led to a distinct breathprint [A. fumigatus, were correctly classified by eNose with a cross-validated accuracy of 89%. eNose data were analyzed using PCA, the factors of which were then used for linear canonical discriminant analysis (LCDA). Overall, eNose-generated breathprints of CF patients with and without A. fumigatus colonization were significantly different [A. fumigatus-induced invasive disease and colonization, 2-pentylfuran by GC-MS analysis [A few studies have explored the potential role of eNose in detecting airway colonization with pathogens. Fungal infections with r et al. . In the r et al. . In a moathprint . 27 CF pifferent . They hianalysis ,71.Pseudomonas aeruginosa (PA). Persistent PA infection is known to be associated with increased morbidity and mortality in patients with CF [Achromobacter xylosoxidans or Stenotrophomonas maltophilia, were not different (AUROC of 0.59). Significant differences were also not found between breath profiles of PCD patients with or without chronic PA infection [n = 7) were distinguished from PA-negative (n = 53) BAL samples with an AUROC of 0.86. Similar results were seen for Staph. aureus (SA)-positive and -negative samples [One of the most common opportunistic pathogens leading to chronic bacterial lung infections in CF is  with CF . Distinc with CF . In this with CF . Breathpnfection . Findingnfection . Based onfection . This wonfection . Utilizi samples . Finally samples ,76, is c samples , and sim samples . In a st samples . FurtherA. fumigatus and P. aeruginosa (PA) [To summarize, the currently published data suggest that eNoses may be able to distinguish between exhaled breath profiles of patients with CF, PCD, and bronchiectasis, and to detect certain infections with pathogens such as osa (PA) ,69,70,73osa (PA) . Utiliziosa (PA) .Current results of detecting both respiratory and non-respiratory diseases by eNose, as well as specific infections in some conditions, are promising. Rapid improvements in eNose technologies may overcome their current limitations, as newer generations of eNoses are being upgraded with more advanced sensor technologies and data analysis systems . With thA. fumigatus colonization of patients with CF by de Heer et al., GC-MS analysis was suggested to complement eNose testing [A. fumigatus infection, including 2-pentylfuran as well as monoterpenes and sesquiterpenes have been identified [A. fumigatus metabolites such as host inflammatory responses to A. fumigatus, exposure to antimicrobial therapy or corticosteroids, or more-severe CF lung disease, also contribute to the VOC patterns detectable by eNose in these patients [Further, studies investigating VOC metabolomics have also yielded promising results in respiratory and non-respiratory conditions. By combining the eNose with GC-MS, detecting individual VOCs may not only improve sensitivity and specificity, but also allow for the detection of novel, previously unrecognized biomarkers and biological pathways . Several testing . Definitentified . It is ppatients . Howeverpatients ,50,64,73Taking advantage of detecting VOCs exhaled in human breath, eNose technology has enormous potential to improve or offer alternative solutions to current diagnostic tests for respiratory diseases. eNoses provide increasingly accurate and sensitive discriminative power to help differentiate between health and disease, sub-types of diseases and also disease activity and control . In addi


To describe the behavior of inspiratory resistance components when positive end-expiratory pressure (PEEP) increases in patients with acute respiratory distress syndrome under a protective ventilation strategy.2O PEEP. Peak, initial and plateau pressure values were assessed, calculating the maximum, minimum and differential resistances. The results were compared by repeated measures analysis of variance (ANOVA) with post hoc Bonferroni correction, considering p < 0.05 significant.In volume-controlled mode, at 6mL/kg and constant flow, end-inspiratory occlusions were performed at 0, 5 10, 15 and 20cmH2O PEEP significantly differed from those for 5 and 0cmH2O PEEP, whereas that for 20cmH2O PEEP only significantly differed from that for 0cmH2O PEEP (p < 0.05). The minimum resistance behaved similarly to the maximum resistance; the values for PEEP levels from 10cmH2O to 20cmH2O significantly differed from those for 0 and 5cmH2O PEEP (p < 0.05). Differential resistance showed the opposite variation to the maximum and minimum resistances. The only PEEP level that showed significant differences from 0 and 5cmH2O PEEP was 20cmH2O PEEP. Significant differences were also found between 15 and 5cmH2O PEEP (p < 0.05).The highest maximum resistance was observed at the lowest PEEP levels. The values for 10 and 15cmHDuring protective ventilation in patients with acute respiratory distress syndrome, the maximum resistance of the respiratory system decreases with PEEP, reflecting the minimum resistance response, whereas differential resistance increases with PEEP. Basic monitoring of patients under mechanical ventilation (MV) in volume-controlled continuous mandatory ventilation (VC-CMV) mode with constant flow is an invaluable diagnosis, treatment and follow-up tool. Knowledge and experience in interpreting respirator graphics allow a personalized approach to the patient. This monitoring makes it possible to classify the state of the respiratory system according to its modifications in elastance and resistance (Rrs). The elastance of the respiratory system has been the focus of considerable research, whereas Rrs has been mostly overlooked. Several methods for assessing Rrs have been described, including the "rapid airway occlusion technique", which consists of performing a 2-second end-inspiratory pause and observing pressure changes under constant flow. This abrupt flow interruption will generate a drop in system pressure. This pressure has biphasic morphology: a sharp decrease in pressure, whose variation occurs between the peak (Ppeak) and initial (P1) pressures in the first phase, is followed by a00 more gradual decrease in pressure in the second phase. In this case, the change in pressure occurs between P1 and the pressure after a 2-second end-inspiratory pause (Pplat). The first is termed "minimum resistance" (Rinit): because the inertia of the gas is negligible, the initial decrease in pressure after interrupting the flow is exclusively attributed to its friction with the airway. The second is termed "differential resistance" (DRrs), which is linked to stress relaxation and the pendelluft phenomenon typical of lung heterogeneity. The first is a condition of the materials, related to the temporal dependence of mechanical measures: over time, the energy required to maintain a deformed system decreases, which applies to the respiratory system. In turn, pendelluft explains the gas redistribution inside the lung in the absence of flow, which increases under heterogeneous conditions. However, these 2 phenomena are apparently indistinguishable from each other  is an acute-onset respiratory condition that presents with hypoxemia, bilateral opacities on chest X-ray and changes in the mechanics of the respiratory system.ch other . The rat-6Several studies have assessed positive end-expiratory pressure (PEEP) effects on Rrs in ARDS. They showed that Rrs increased with PEEP, as a result of the increase in DRrs due to a possible overdistension of ventilated units, to an increase in lung heterogeneity, or to both.The objective of the present study was to describe the behavior of different inspiratory resistance components when PEEP increases in patients with moderate/severe ARDS under ventilation with a low tidal volume (TV) strategy.Sanatorio de La Trinidad Mitre, Autonomous City of Buenos Aires, from October 2015 to September 2017.The measurements were conducted at the intensive care unit (ICU) of the A cross-sectional, descriptive, retrospective study was conducted. at the beginning of MV or as a complication were included in the study. Pregnant patients and those with limited therapeutic effort, history of neuromuscular disease or bronchopleural fistula or unable to use an esophageal balloon were excluded from the study.Patients under MV older than 18 years old who met ARDS diagnostic criteria according to the Berlin definitionDemographic data of the participants were collected, in addition to severity scores, oxygenation rates, ventilatory monitoring variables, reasons for MV, and outcome variables.2O), were used. Before connecting the patient to MV, the ventilator was checked for compressible volume compensation and circuit resistance, in addition to testing the proportional valves, inspiratory and expiratory modules, flow and pressure sensors. Data were acquired using a respiratory mechanics monitor  to measure airway flow and pressure (Paw) with a fixed-orifice differential pressure sensor connected to the endotracheal tube or tracheostomy tube of the patient. The volume was calculated by integrating flow over time. Flow and Paw signals were acquired simultaneously using specialized software . Before starting the measurements, the patient was aligned and semiseated at 45º. Subsequently, the endotracheal tube cuff was controlled, followed by aspiration of secretions if necessary. After the inclusion, the ventilator was set to VC-CMV mode, adjusting the TV to 4 to 6mL/kg predicted body weight, with a constant flow of 60L/min, 10cmH2O PEEP and previous FiO2. In all patients included in the study, esophageal pressure (Pes) was used as a guide to set the MV. Its correct positioning was confirmed using the dynamic occlusion method, confirming the absence of respiratory effort by inspecting the curve. Subsequently, the PEEP was set to 20cmH2O, gradually decreasing from 20 to 0cmH2O, in 4 5cmH2O steps. The duration of each step was 10 minutes . At the end of each step, end-inspiratory pause maneuvers were performed using the function provided in the ventilators used. An offline observational analysis of Paw, flow and esophageal pressure signals from the respiratory mechanics monitor was performed. At each PEEP level, Ppeak, P1, and plateau (Pplat) pressures, total PEEP (PEEPtot) and end-inspiratory (Pesi) and end-expiratory (Pese) esophageal pressure values were recorded, calculating the end-inspiratory (Ptpi) and end-expiratory (Ptpe) transpulmonary pressures, which were defined as follows:Evita XL  and Maquet Servo I and S  ventilators, with low ventilator circuit compliance , Rinit was calculated as the difference between Ppeak and P1 divided by inspiratory flow (Rinit = PPeak - P1/F), and DRrs was calculated as the difference between P1 and PPlat divided by flow (DRrs = P1 - Pplat/F) .To observe the behavior of the elastic component of the respiratory system when changing the PEEP, the elastance of the respiratory system was calculated as the difference between Pplat and total PEEP divided by TV, lung elastance was calculated as the difference between inspiratory and expiratory transpulmonary pressures divided by TV, and chest wall elastance was calculated as the difference between Pesi and Pese divided by TV.The study was approved by the Research and Education Committee of the Hospital, under record number F004-01-A(01)2018. Considering its retrospective nature, informed consent was not required. Data confidentiality was preserved by creating a coded registration form for each participant. Names or any data that could identify the participants will be kept under extreme confidentiality, and in no case will the participants' identities be made public.2O) and low (0 and 5cmH2O). A value of p < 0.05 was considered significant.Descriptive analysis of the variables was performed. The values expressed as the mean and standard deviation or median and interquartile range depending on the distribution of the numerical variables or as numbers and percentages for qualitative variables. The results were compared by repeated measures analysis of variance (ANOVA) with post hoc Bonferroni correction. Different PEEP levels were analyzed as previously reported in the literature: medium-to-high  according to the Berlin Definition were included in the study .The highest Rrs was observed at the lowest PEEP levels. Values at 10 and 15cmH2O PEEP and 20cmH2O PEEP, all variables showed significant differences from 0 and 5cmH2O PEEP (p < 0.05).Rinit showed the same behavior as has Rrs. Higher values were observed at lower PEEP levels. For 10cmH2O PEEP were significantly different from those at 0 and 5cmH2O PEEP. Significant differences also occurred between 15cmH2O PEEP and 5cmH2O PEEP (p < 0.05).Differential resistances showed the opposite behavior to Rrs and Rinit, with lower DRrs at lower PEEP levels. In this case, only values at 20cmH2O), similarly to lung elastance, albeit with nonsignificant differences /acute respiratory distress syndrome (ARDS) (ARMA) trial,, whereas patients with ARDS were subjected to 5 PEEP levels . In addition to differences from healthy subjects, the study showed that Rrs increased as the PEEP level increased, reflecting the behavior of DRrs, with significant differences when comparing 10cmH2O PEEP with 15 and 20cmH2O PEEP. The authors explained that high PEEP levels, in highly heterogeneous lungs, could increase stress relaxation and that PEEP could cause overdistention, thus increasing the "pendelluft" effect. However, they were unable to find a diagnostic method through which the viscoelastic effect could be differentiated from the increase in heterogeneity. A ventilatory strategy with high TVs was used in this study.In 1991, Pesenti et al.. The authors found significant differences in Rrs, DRrs and Rinit both among groups and among PEEP levels. In line with previous studies, DRrs increased as PEEP levels increased, which was reflected in Rrs, whereas Rinit decreased as PEEP levels increased. In this case, volumetric capnography prevented extending the conclusions of previous studies because this technique reflects changes in both ventilation and perfusion, without differentiating the incidence of the increase in stress relaxation or the pendelluft effect. The ventilatory strategy did not differ from that used in the evidence described above: TVs were high. Both in the study by Pelosi et al.(5 and in the study by Blanch et al.,(6 Rmin decreased with the increase in PEEP levels. This would be explained by the increase in anatomic dead space,(12 thereby decreasing frictional resistance to flow.Last, Blanch et al.,The main differences from our study were in terms of the ventilatory strategy used. The TV implemented was 382 mL, which represented 5.8mL/kg predicted weight. Setting a lower TV weakened the effects on stress relaxation and lung heterogeneity, and thus, the values were lower than those in the aforementioned studies. Accordingly, the patients in our study experienced a decrease in Rrs with the increase in PEEP levels, that is, when using high TVs, the magnitude of the effect on DRrs ultimately prevailed over changes in Rrs. This phenomenon could be explained by the changes PEEP causes in lung elastance: at higher PEEP levels, lung elastance, overdistension, lung heterogeneity and stress relaxation are higher. In turn, when the TV is low, the DRrs effect is weaker than the effect generated by the increase in PEEP on airway overdistension, thereby decreasing Rrs.This study had limitations. First, we did not assess the effect of PEEP on different Rrs components, although this was a retrospective analysis of a database collected prospectively. Second, the PEEP levels were gradually but not randomly decreased.In conclusion, unlike the reported evidence, when using a low tidal volume strategy, the maximum resistance of the respiratory system decreases as PEEP levels increase, reflecting the minimum resistance response, whereas differential resistance increases as PEEP levels increase.


Blood pressure (BP) shows short-term variability within the 24 h, which can only be assessed with 24-h ambulatory blood pressure monitoring (ABPM). It is of utmost importance to control BP throughout the night to reduce incidence of hypertension complications. The purpose of this study is to evaluate the effect of timing and frequency of antihypertensive medications on the average nighttime and 24-h blood pressure control.p = 0.421). ABPM readings for both groups were as follows: mean daytime SBP was 125.4 ± 11.6 mmHg vs 130.1 ± 12.9, p = 0.011; mean nighttime SBP was 117.0 ± 12.4 mmHg vs 123.1 ± 13.9 mmHg, p = 0.002, and mean 24-h SBP was 122.7 ± 10.6 mmHg vs 127.5 ± 12.0, p = 0.005. The prevalence of non-dipping was 68.9% in group 1 vs 70.3% in group 2 patients, p = 0.8 . The prevalence of masked hypertension was higher in group 2 .The study enrolled 199 hypertensive patients with controlled office blood pressure; 135 (67.8%) patients were on once daily antihypertensive medication (group 1) while 64 (32.2%) patients were on twice daily doses (group 2). The mean office SBP was 128.7 ± 7.8 mmHg in group 1 vs 129.6 ± 6.6 mmHg in group 2, (Taking an extra antihypertensive pill at night did not show a decrease in the nighttime or the average 24H blood pressure in hypertensive patients with controlled office BP. On the contrary, patients who used twice daily antihypertensive medications seem to have higher nighttime and 24-h SBP, although the dipping ratio was comparable in both groups. Hypertension (HTN) contributes adversely to cardiovascular morbidity and mortality, and treating its complications constitutes an economic burden on both developing and developed countries. Achieving guidelines-recommended blood pressure (BP) targets is of an extreme importance to reduce the cardiovascular burden worldwide , 2.Despite its many drawbacks, office BP measurement is still considered the golden standard for diagnosing HTN and for determining the threshold of initiation and follow-up of anti-hypertensive medications. Many studies showed that data provided by ambulatory blood pressure (ABPM) as nighttime blood pressure and dipping status are stronger predictors of cardiovascular outcome than office BP . BecauseThe frequency of daily administration of anti-hypertensive medications may influence the adequacy of the 24-h (24H) BP control which is the ultimate goal when approaching hypertensive patients. The exact mechanism of such phenomenon is not fully understood but may be related to several factors as adherence and compliance to prescribed drugs and change in efficacy of therapeutic coverage when various drugs are combined [The aim of this study is to determine the effect of the frequency of daily doses of antihypertensive drugs on ABPM nocturnal BP readings in patients with controlled office BP.This is a prospective, non-randomized, observational, cross sectional study in which 199 hypertensive patients were enrolled from the Specialized HTN clinics (SHCs) at two university hospitals. Inclusion criteria included hypertensive patients with controlled office blood pressure readings  and on regular antihypertensive medications regime [> 30 Kg/m2) and supine heart rate.The study protocol was approved by the local institutional ethics committee. A detailed, written, informed consent was taken from all the patients. Patients had full clinical evaluation including cardiovascular risk factors assessment, e.g., history of diabetes mellitus, smoking history and duration, dyslipidemia, family history of cardiovascular (CV) risk factors, and current antihypertensive drugs . Compliance to antihypertensive drugs was assessed by patient self-reporting, and a cutoff point of ≥ 80% adherence to prescribed medications was used for definition of patient’s compliance and non-compliance . ExaminaWe recorded office blood pressure using a digital fully automated device (Omron-6 automated device) . Patient2, albuminuria or both on at least two occasions ≥ 3months apart [Routine laboratory workup included urinalysis, serum creatinine, hemoglobin level, serum potassium, total cholesterol, low density lipoprotein, high density lipoprotein, triglycerides, fasting blood glucose, and serum uric acid. Patients underwent fundus examination to determine clinically significant hypertensive retinopathy (≥ grade II). Patients had performed albumin creatinine (A/C) ratio if there was an evidence of proteinuria in urinalysis. Abnormal A/C ratio  was used as a marker of target organ damage . Diabetehs apart .Patients underwent a standard 12-lead ECG to identify left ventricular hypertrophy (LVH) using Sokolow’s established criteria for LVH diagnosis  and to dTarget organ damage (TOD) was defined when LVH, carotid bruit, more than grade II hypertensive retinopathy, peripheral arterial disease, and clinical CVD  were diagnosed, using the appropriate investigations.Patients underwent 24H ABPM, recorded from their non-dominant arm using Holter system Model DMS300-4A8 with the device set to measure BP every 30 min in daytime and every hour during the night, according to the preset patient’s sleep cycle. Patients sustained their normal daily routines and were instructed to remain still during BP measurement. Average day, night, and 24H BP and pulse rates were recorded. Dipping  is calculated as the ratio between mean nighttime to mean daytime systolic BP. According to the ratios obtained, dipping has been categorized into four categories: (a) normal dipping (ratio = 0.8–0.9), (b) no dipping (ratio = 0.9–1), (c) reverse dipping (ratio = ˃ 1), and (d) extreme dipping (ratio < 0.8). Non-dippers were defined as patients with no or reverse dipping [Masked uncontrolled hypertension (MUCH) was defined when the average daytime, nighttime, or 24H BP readings were elevated in the presence of well-controlled office BP measurements. Hypertension is defined as been controlled when the mean daytime reading is < 135/85 mmHg, mean nighttime reading is < 120/70 mmHg, and mean 24H reading is < 130/80 mmHg.Valid ABPM recordings had to fulfill a series of pre-established criteria, including successful recording of more than 80% of systolic BP (SBP) and diastolic BP (DBP) during both the day- and nighttime periods, with at least one BP measurement per hour.t test for quantitative data. All statistical tests were 2-sided, and a p value of < 0.05 was considered significant. All analyses were carried out using SPSS 20.Quantitative variables were expressed as mean and standard deviation (SD), while qualitative variables were presented as numbers and percentages. We divided the study patients into two groups; group 1 included patients using once daily antihypertensive medications, while group 2 included patients using twice daily drugs. We compared the two groups regarding demographics, risk factors, TOD, and other clinical parameters by means of chi-square/Fisher’s exact test for qualitative data, and Student’s The study included 199 patients of whom 135 (67.8%) used to take their antihypertensive drug(s) once daily (group 1), and the remaining 64 patients (32.2%) used to take the antihypertensive drug(s) twice daily (group 2) , sudden cardiac death (SCD), and stroke.Office BP measurements (supine and standing) were comparable between both groups, so were the basic laboratory findings. Group 2 patients had a lower BMI, but the prevalence of obesity was the same between the two groups.n = 70, 61.4%).ABPM data is presented in Table Analysis of the different antihypertensive drugs taken by group 1 patients revealed absence of a significant association between the type of anti-HTN medication and the development of MUCH Fig. .Fig. 2CThe ultimate goal of treating hypertension is to achieve a 24H adequate blood pressure control. This cannot be detected using only office BP measurements. ABPM is the only method that can detect BP during sleep, and accordingly, the only method that can reliably define the adequacy of the 24H BP control in HTN patients .p = 0.0026) [ABPM measurement is an independent predictor of subsequent CV events and mortality. For every 12-mmHg increase in 24H SBP, there is a 49% increased risk of CV events, and the relative hazard per 1 mmHg for cardiovascular mortality is significantly related to the 24H SBP . Patient 0.0026) . Additio 0.0026) , 15.BP regulation is characterized by physiological circadian rhythm: early morning increase in BP is known as  drastic decrease in BP during sleep in most individuals (dipping status) and a period of plateau throughout the afternoon . Such ciAchieving 24H BP control may be considerably affected by the frequency of antihypertensive medications dosing. Once daily administration is currently the preferred method of antihypertensive drug prescription given its higher edge over twice daily administration specifically related to increased patient’s adherence to simpler regimens . Anti-hyThis study aims at demonstrating the status of nighttime BP control in HTN patients with fairly controlled office BP readings and relating nighttime control rates to the daily dosing of the antihypertensive medications.In this study, most of the patients were taking their antihypertensive medications once/daily. Yet patients who were prescribed a twice/daily dosing of anti-hypertensive medications had a significantly higher nighttime SBP as compared to patients who used to take the drugs only once. Dipping ratio and dipping frequency were the same in the two groups; this is probably because the daytime BP of group 2 patients was also higher than the controlled values. The prevalence of MUCH  was higher among group 2 patients. On the other hand, more than half of the patients (57%) had elevated nighttime BP readings, and most of them were from group 1. This high prevalence of nocturnal HTN may be due to the high risk profile of the patients or the unanticipated stress accompanying the cuff inflation which awakens most patients from sleep .In contrast to our study, the MAPEC study showed that patients who received their anti-hypertensive medications in two doses had lower mean 24H systolic and diastolic pressures compared to a single morning dose . This diThe high cardiovascular risk profile of group 2 patients may explain why these patients needed many drugs and accordingly why were they prescribed these many drugs twice a day. Most of the antihypertensive medications were prescribed, not only for HTN, but also for the associated comorbid conditions. This, in addition to improving compliance, explains why most of our patients were using combination pills.p < 0.001), and it was associated with a lower BP control (27% vs. 41%) [The different classes of anti-hypertensive medications which is recommended to reach the BP goals may lead to uneven 24H BP control as the use of different drugs with uneven therapeutic coverage may lead to therapeutic coverage gaps . The stuvs. 41%) .This study does not reflect the general HTN population as patients were recruited from the specialized HTN clinics (SHC), and a multicenter population-based study may be required. A single ABPM recording was done, and it would have been better to repeat the ABPM to test the reproducibility of our results. Patients’ adherence to medications were assessed by self-reporting which is not the most reliable tool to confirm drug compliance.Giving two daily doses of antihypertensive medications failed to control the nighttime HTN in patients with controlled office BP. ABPM is needed in patients with high cardiovascular risk profile to detect the nighttime control of HTN and to guide the drug therapy.


P = 0.037), whereas tympanic temperature did not change (P = 0.879) during WWI. After 5-min WWI, heart rate (HR) and brachial diastolic blood pressure (BP) were significantly decreased. Aortic and leg PWV were decreased by 7.5 and 3.1%, respectively (P = 0.006 and P = 0.040). Femoral arterial blood flow was increased by 45.9% (P = 0.002), and leg vascular resistance was decreased by 29.1% (P < 0.001). Regarding central hemodynamic variables , aortic BP and augmentation index (AIx) did not change significantly, but the subendocardial viability ratio (SEVR), an index of coronary perfusion, was increased (P = 0.049). Our results indicate that a short-term WWI acutely improves aortic and peripheral arterial stiffness and coronary perfusion. Further studies to determine the interaction between the residual effect of a single bout of short-term WWI and chronic change  in arterial stiffness and central hemodynamics are needed.Warm water immersion (WWI) has a potentially favorable effect on vascular health. However, the effects of short-term WWI on vascular function and central hemodynamics remain unclear. The present study aimed to determine the acute effects of short-term WWI on arterial stiffness and central hemodynamics in healthy men. Ten healthy men  underwent 5-min WWI (40–41°C) at the heart level. Systemic hemodynamics and tympanic temperature were monitored during WWI. Furthermore, pulse wave velocity (PWV) and aortic hemodynamics were measured before and 10 min after WWI. Cardiac output (CO) (via the Modelflow method) increased ( Cardiovascular disease (CVD) is a leading cause of death in the world . Currentper se evokes cardiovascular reflexes , an index of arterial stiffness, are inconsistent in previous studies. For example, A recent prospective survey of the emergency events related to bathing reveals that consciousness disturbance and exhaustion are the most frequent symptoms and which are presumably attributed to hyperthermia and dehydration . From th2, body fat of 15.4 ± 6.8%, mean ± standard deviation [SD]) were studied. Exclusion criteria were medicated individuals, having overt CVDs as assessed by medical history, and current smokers. The sample size was based on that of similar previous studies . Upon arrival, subjects underwent height and weight assessments, which were followed by supine rest for more than 10 min and the main experimental protocol which consisted of 5-min WWI and two (pre- and post-WWI) vascular measurements as listed in the Arterial pressure waveform was continuously recorded at the left middle finger by Finometer system  during WWI and stored on a computer using a data acquisition system  at the 1000 Hz of sampling rate. Throughout the WWI, subject was asked to keep the left hand at the heart level: on the side-table out of the bathtub. SV, CO, and total peripheral resistance (TPR) were estimated with a non-invasive blood pressure (BP) measurement device incorporated Modelflow-based hemodynamics measurement software . The validity of the Modelflow method to derive hemodynamic measurements has been established in a variety of conditions . HR, bra∗100) was calculated as the ratio of the myocardial oxygen demand and the blood supply to the heart . Measurements of aortic pulse wave analysis are presented in he heart .4 (with the constant 6 × 104 being the conversion factor from m/s to L/min). Data reported are the time averages of ≥10 measurements for all variables. Femoral arterial shear stress (SS) was calculated using the following equation: 8 × blood viscosity (assumed to be 0.035 dyn × s/cm2) × mean blood velocity/baseline diameter (at end-diastole)  , as we previously reported . Brieflyiastole) .t-test was applied for comparison between pre- and post-WWI. A simple correlation analysis was performed to determine the relations of interests. All data are reported as mean ± SD. Statistical significance was set a priori at P-values less than 0.05.A paired P = 0.879). P = 0.034) and brachial DBP (P = 0.043) slightly but significantly decreased, whereas there were no significant differences in SV (P = 0.694), CO (P = 0.431), TPR (P = 0.319), brachial SBP (P = 0.202), brachial PP (P = 0.900), aortic SBP (P = 0.565), aortic DBP (P = 0.300), aortic PP (P = 0.927), AP (P = 0.067), AIx (P = 0.167), and AIx@HR75bpm (P = 0.398) between pre- and post-WWI. DPTI did not change significantly (P = 0.832), whereas TTI tended to be decreased (P = 0.061). Consecutively, SEVR significantly increased   .P = 0.006, Power[1−β] = 0.88) and 3.1% , respectively  and by 49.9%   and SS   . Change = 0.154) .The main results of this study are as follows. First, following 5-min WWI which did not elicit significant change in tympanic temperature, aortic and leg PWV were decreased; second, aortic BP and Alx did not change significantly but SEVR was increased. These results suggest that a short-term WWI acutely improves central and peripheral arterial stiffness and hemodynamics.Large elastic arteries have important roles  to buffer the cyclic mechanical forces of cardiac pulsations, maintain coronary perfusion, and protect vulnerable microvasculature such as that in the brain . A reducWe can speculate underlying mechanisms of decreased PWV. Arterial stiffness is determined by anatomical  and physiological  components . Since aSeveral studies reported that heat stimulation which induced the elevation of core temperature did not reduce central arterial stiffness. It is well known that passive heat stress increases sympathetic activation , and symExperimental considerations should be mentioned. First, the present study confirmed a temporary change of arterial stiffness immediately after WWI (within 10–15 min). However, we did not observe its recovery . Besides, whether such change directly links to chronic adaptation is still unknown. Second, since PWV is influenced by BP, it might not reflect arterial stiffness appropriately when the concomitant BP change occurs . HoweverThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the institutional review board in National Institute of Advanced Industrial Science and Technology. The patients/participants provided their written informed consent to participate in this study.JS decided on the conception and design of the research. JS and TT performed the experiments, analyzed the data, and interpreted the results of the experiments. JS prepared figures. JS drafted the manuscript. All authors edited and revised the manuscript, and read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


P = 0.010); baseline CVP; age; pre-operative creatinine level; and left ventricular (LV) dysfunction (ejection fraction (EF) < 45%). On alternative modelling, the cumulative number of MPP values during CPB that were 10% below baseline was also independently associated with AKICS (P = 0.003). Modelling without taking into account CVP also supported this association. The duration of differences in perfusion pressure to the kidneys during CPB compared to baseline is an independent predictor of AKICS.Acute kidney injury after cardiac surgery (AKICS) is common. Previous studies examining the role that mean arterial pressure (MAP) during cardiopulmonary bypass (CPB) may have on AKICS have not taken into account how baseline central venous pressure (CVP) and mean perfusion pressure (MPP) (i.e. MAP − CVP) can influence its evolution. To assess whether the change in MPP to the kidneys (i.e. delta MPP or DMPP) during CPB compared to baseline is an independent predictor of AKICS. After ethical approval, a retrospective observational study was performed on all patients undergoing CPB between October 2013 and June 2015 at a university-affiliated hospital. Known risk factors for the development of AKICS were recorded, as were the MPP values at baseline and during CPB. From this, statistical modelling was performed to identify predictors of postoperative AKICS. 664 patients were identified. Analysis was performed on 513 patients after exclusion. On logistic regression, significant and independent predictors of AKICS included: d20DMPP  ( Acute kidney injury (AKI) can be defined by a rise in creatinine of greater than 50% from baseline, according to the RIFLE criteria . In patiPatients who develop AKICS are known to have a higher EuroScore, and be more likely to have valve surgery, emergency surgery or previous cardiac surgery , 9. NeveA high central venous pressure (CVP) has also been associated with AKI in the critical care setting and in cardiac surgical patients, which has been attributed to renal congestion –25, whicDespite the above considerations, previous studies examining the effect of MAP during CPB on AKI in the cardiac surgical population have not accounted for CVP nor for perfusion pressure (MAP − CVP) to the kidneys. Accordingly, we aimed to explore the association between the difference in perfusion pressure to the kidneys during bypass compared to perfusion pressure to the kidneys at baseline on the development of AKICS. This difference has been termed the “Delta Mean Perfusion Pressure” (DMPP). We performed this modelling using DMPP and other factors with the view of ascertaining the particular components of pathophysiology that might be associated with AKICS genesis.In a retrospective, observational cohort study, the medical records of patients who underwent cardiopulmonary bypass between October 2013 and June 2015 at our tertiary referral centre were identified. Study approval was granted (LNR/17/Austin/561) and written informed consent was waived.Intra-arterial MAP values were recorded on a CPB data storage software , immediately after aortic cannulation and recorded every 20 s until the end of CPB. Baseline hemoglobin values and creatinine values were taken from electronic medical records from the immediate pre-operative visit of each patient (approximately 0–7 days preoperatively). Post-operative serum creatinine was measured at least daily for all patients during their hospital stay. Patient data on comorbidities and vasopressor support were obtained from local Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZCTS) database.. any period of circulatory arrest or anterograde cerebral perfusion or missing data during bypass); if the cardiac surgery was not the first operation during their admission; or if cross clamp was not applied (viz. pump assist or off-pump cases).We excluded patients if baseline hemodynamic data was unavailable; if AKICS could not be determined ; continuous systemic arterial pressure during cardiopulmonary bypass was not available . The use of crystalloids or colloids, and vasopressors was allowed to achieve these targets. Postoperative renal replacement therapy was considered if there was at least one of: urine output < 100 mL for > 6 h unresponsive to fluid resuscitation, potassium > 6.5 mmol/L, pH < 7.2 or clinically significant organ oedema in the setting of renal failure.Patients were managed as described by Haase et al. . In brieBaseline MAP measurements were performed by sphygmomanometry in the holding bay area after routine premedication with opioids  and benzodiazepines  to remove anxiety as a possible contributor to hypertension, which is our routine practice. Baseline MAP was estimated as diastolic blood pressure + 1/3 times pulse pressure difference. Baseline CVP was taken from the first reading post induction.baseline) was derived from baseline MAP − baseline CVP. Mean perfusion pressure during bypass (MPPCPB) was assumed to equal MAP during bypass, as CVP falls to 0 with venous drainage. Three-minutely median MAP values were obtained during CPB to provide a more robust definition of central tendency, and to mitigate against the effect of transient outliers of MAP values.Baseline mean perfusion pressure baseline. = cumulative number of median 3-minutely MPP values that are > 20% below MPPd20DMPPCPB values are > 20% below MPPbaseline . = number of times that MPPt20DMPPDMPP was a priori defined in three separate ways:AKI after cardiac surgery was defined by the RIFLE criteria, i.e. increase in serum creatinine of greater than 50% from baseline to a peak value within the first seven days, postoperatively .Statistical plan consisted of logistic regression modelling using the three definitions of DMPP as the key independent variable and AKICS within 7 days as the outcome, in the presence of other variables.Model was as outlined by Hosmer et al. , while tCPB, baseline CVP, age, pre-operative creatinine, diabetes, moderate or severe left ventricular (LV) dysfunction (i.e. estimated LVEF < 45%), stroke, New York Heart Association (NYHA) Class III or IV, bypass time, cross clamp time, lowest hemoglobin on bypass, use of intraoperative inotropes, use of ventricular assist device (VAD)/extra corporeal membrane oxygenation (ECMO) and use of intra arterial balloon pump (IABP). These data were obtained from the ANZCTS database according to their data definitions manual  or from the medical records. These variables were reduced following univariate analysis of each potential independent variable and then using best subset selection with models being tested for the strongest fit using the Hosmer–Lemeshow goodness-of-fit test and a likelihood ratio test [The following variables were considered for the prediction of AKICS: coefficient of variation of MPPtio test .CBP values that are > 10% below MPPbaseline.d10DMPP = cumulative number of median 3-minutely MPPCBP values are > 10% below MPPbaseline .t10DMPP = number of times that MPPAlternate modelling examining the following variables as covariates in the model instead of the original definitions of DMPP:baseline − time weighted MAPCBP values.uDMAP = MAPCPB values that are > 20% below MAPbaseline.d20DMAP = cumulative number of median 3-minutely MAPCBP values are > 20% below MAPbaseline .t20DMAP = number of times that MAPCPB values that are > 10% below MAPbaseline.d10DMAP = cumulative number of median 3-minutely MAPCBP values are > 10% below MAPbaseline .t10DMAP = number of times that MAPAlternate modelling without accounting for CVP. Note that DMPP is mathematically the same as the difference in MAP on bypass compared to baseline + CVP. That is, delta mean arterial pressure (DMAP) + CVP = DMPP. Therefore, removing CVP from modelling would mean that the following corresponding variables would be tested for significance:Planned testing for robustness of the model included:All statistical calculations were performed using STATA/SE Version 15.1 software, StatCorp LLC, College Station, TX, USA. The STROBE statement guidelines were followed for reporting of observational studies .Of the 664 records identified, 513 records were used in this model , baseline CVP, age, pre-operative creatinine, and LV dysfunction (EF < 45%) were found to be significant, and independently associated with AKICS .  incorporated all variables with Alternative analysis using a 10% deviation of mean perfusion pressure from baseline also showed that this variable (d10DMPP) was independently associated with AKICS. Similar associations were found for CVP, age, preoperative creatinine and LV dysfunction Table .Table 4Abaseline and MAPCPB (delta MAP or DMAP) also revealed that d20DMAP  and d10MAP  were independently associated with AKICS together with age, preoperative creatinine and LV dysfunction  was also associated with the development of AKICS; furthermore, these relationships remained when CVP was excluded in the modelling. Our study is the first to explore the relationship of DMPP relationship on AKICS. It also confirms the association of baseline CVP as an independent predictor of the development of AKICS.We performed a retrospective observational study involving 664 cardiac surgery patients receiving cardiopulmonary bypass to assess the independent association between changes in mean perfusion pressure during CPB compared to baseline values and the development of AKICS. On a dataset involving 513 patients, our modelling found that the cumulative number of median 3-minutely values of MPP during bypass that were > 20% from baseline (d20DMPP) was independently associated with the development of AKICS. In particular, every additional minute of d20DMPP was associated with an adjusted odds ratio of 1.006, meaning that if d20MPP was 30, the odds for developing AKICS would be 1.20. Of note, CPB time and cross clamp time did not emerge as independent risk factors after accounting for d20DMPP, which takes into account duration of MPPPost-operative AKI occurred in 65 patients (12.6% of patients). This is similar to the incidence of post-operative AKI 3.7–9%) in two previous observational studies investigating AKICS –9% in tw. In our As expected, there were differences between those who did and those who did not develop AKICS with regard to their global scores for survival  as well as the proportion of patients who had valve surgery, emergency surgery, previous cardiac surgery, and infective endocarditis Table . These a. explored the synergistic effect of severe hypotension (MAP < 60 mmHg) and anaemia during CPB. Patients with severe hypotension and anaemia developed AKI more frequently than those patients with severe hypotension [., who did not find differences in the rates of AKI between patients who had anaemia with hypotension compared to those patients who only had anaemia [Several previous studies have investigated the relationship between MAP during CPB and the incidence of AKI, yielding conflicting results. A study by Haase et alotension . This fi anaemia . In both. performed a prospective observational cohort study examining the hemodynamic management of patients undergoing CPB for cardiac surgery, investigating the impact of the difference between baseline MAP and the average MAP on CPB on the development of AKI postoperatively [Kanji et alratively . Using m. involving the use of an ‘Acute Kidney Injury in Cardiac Surgery’ (AKICS) score to predict AKI in cardiac surgery patients, it was found that low cardiac output and CVP were the only independent hemodynamic risk factors for the development of postoperative AKI [The influence of CVP on AKI in cardiac patients has been investigated in both medical and surgical settings. In a study by Palomba et altive AKI . Using utive AKI . It has tive AKI . Severaltive AKI –25.Mean perfusion pressure (MPP), defined as the difference between MAP and CVP has been explored in the management of septic shock, as an important factor in the development of AKI. Two previous studies involving septic ICU patients, have found that new onset or progressive AKI has been associated with greater MPP deficits compared to those without AKI progression , 21.Our results add support to the notion that the management of mean arterial pressure during bypass is important to mitigate the risk of acute kidney injury after cardiac surgery and needs to consider baseline mean arterial pressure. Additionally, our results suggest that the deleterious effects of a change in mean arterial pressure during bypass from baseline although modest are cumulative. Whilst other risk factors are associated with a higher adjusted odds ratio of developing AKICS (particularly LVEF < 45%), the management of arterial pressure on bypass remains the only modifiable risk factor in the development of acute kidney injury after cardiac surgery. This needs to be investigated in a prospective manner in a wider population. The role of CVP management on renal outcomes also deserves further inquiry and should be investigated in future trials.Our study utilised multiple known variables that have been associated with AKICS and has examined the role that hemodynamic management at baseline and during bypass may have on AKICS and is the first study to do so. Our study confirmed associations found in other studies in our univariate analysis, which supports the choice of variables investigated. The verification of our findings with pre-planned alternative assumption analyses also supports the role that hemodynamic management may have on AKICS.Our study has some notable limitations. First, our planned statistical analysis was based on anticipated high rates of AKI. Additionally, the RIFLE criteria is known to underestimate AKI when compared with the Kidney Disease Improving Global Outcomes (KDIGO) classification . NeverthThe measurement of pre-induction blood pressure by sphygmomanometry may not reflect blood pressure at other points of the day or night  and may Our study was an observational, single centred study, which needs to be replicated in a larger setting. As with all observational studies, confounders may not be accounted for and the potential for bias is possible. An important aspect that was not modelled was the hemodynamics of patients in the pre-bypass period and immediate postoperative period. On the other hand, the potential for collinearity when examining similar variables across different timeframes would have been a limitation with this strategy.The cumulative duration of a difference of more than 20% between mean perfusion pressure to the kidneys during cardiopulmonary bypass compared to mean perfusion pressure to the kidneys at baseline is an independent and modifiable predictor of postoperative AKI. This effect was also seen at more modest deviations in perfusion pressure and when CVP values were not known. These observations suggest the need to conduct randomized trials comparing different blood pressure targets during cardiopulmonary bypass relative to baseline values to determine whether limiting the duration of differences can safely prevent or attenuate post-operative AKI.


Patients’ clinical data, blood and urine bacterial culture, and drug sensitivity were collected and analyzed. The incidence of AP associated with ureteral stent after PCNL was 13.01% and diabetes mellitus (P = 0.001), postoperative stone residue (P = 0.002), urinary leucocytes ≥ 100/HP (P = 0.018), positive urine culture results (P = 0.001), ureteral stent retention time ≥ 8 weeks (P = 0.004), and high S.T.O.N.E. score (P = 0.014) are independent risk factors for it. Escherichia coli , Klebsiella pneumoniae , Pseudomonas aeruginosa , Enterococcus faecalis , and epidermis Staphylococci  are the main pathogens in blood and urine. The main sensitive drugs of pathogenic bacteria are imipenem, meropenem, tigecycline, piperacillin/tazobactam, ceftazidime, linezolid, teicoplanin, levofloxacin, vancomycin, tigecycline, etc., while levofloxacin, norfloxacin, penicillin G, first, and second-generation cephalosporins showed a strong drug resistance rate (> 70%). This study found that diabetes, postoperative stone residuals, urinary leukocytes ≧ 100 cells/HP, positive urine culture results, ureteral stent indwelling time ≧ 8 weeks, and high S.T.O.N.E. score were independent of AP associated with ureteral stent after PCNL risk factors and Escherichia coli is the main pathogenic bacteria and shows drug resistance.The purpose of this study is to explore the risk factors, bacterial species, and drug resistance of acute pyelonephritis (AP) associated with ureteral stent after percutaneous nephrolithotomy (PCNL) and to provide reference for clinical intervention. The clinical data of 415 patients with indwelling ureteral stent after PCNL from December 2016 to May 2019 were analyzed retrospectively. The patients were divided into infection group ( Kidney stones are a common and frequently occurring disease of the urinary system. The incidence is 10.34% in men and 6.62% in women . But aftn = 54) and non-infection group (n = 361). Inclusion criteria: (1) first diagnosis of kidney stones by abdominal ultrasound, CT, or intravenous pyelography; (2) first kidney stones undergoing PCNL and indwelling ureteral stent; (3) patients and family members agreed with the study and signed informed consent. Exclusion criteria: (1) patients with contraindications for renal calculi operation; (2) patients with severe cardiopulmonary dysfunction; (3) patients with immune system disease; (4) patients with blood system disease; (5) patients with severe liver and kidney dysfunction; (6) patients with previous history of renal calculi operation; (7) patients with pyonephrosis; (8) patients with other organ infection and febrile diseases. Diagnostic criteria of AP: (1) the patient has acute pain in one or both sides of the back ; (2) percussion pain or tenderness of costal ridge angle; (3) body temperature ≥ 38.0 °C; (4) blood routine examination showed that leukocyte was more than 10.0 × 109/L; (5) urine routine white blood cell count > 5/HP and/or middle urine culture positive, and colony count ≥ 105 CFU/mL. It can be diagnosed as AP if it is greater than or equal to the three of the above 5 [From December 2016 to May 2019, 415 cases of PCNL patients with ureteral stent (retention time ≥ 4 weeks) were collected. According to whether the patients had AP, they were divided into infection group  and analyzed by χ2 test. The factors with statistical significance were analyzed by logistic regression analysis, and the regression coefficient (β), relative risk ratio (or), and 95% confidence interval (95% CI) were calculated. The difference was statistically significant (P < 0.05).SPSS 19.0 statistical analysis software is used for data analysis. The data of measurement data are expressed in mean ± standard deviation, analyzed by According to the exclusion and inclusion criteria, a total of 415 patients were included in the study, 54 cases in the infected group and 361 cases in the non-infected group. There were 192 women (46.26%) and 223 men (53.73%). The incidence of AP associated with ureteral stent after PCNL is 13.01%. As shown in Table P = 0.001), postoperative stone residue (P = 0.002), urinary leucocytes ≥ 100/HP (P = 0.018), positive urine culture results (P = 0.001), ureteral stent retention time ≥ 8 weeks (P = 0.004), and high S.T.O.N.E. score  are independent risk factors for AP associated with ureteral stent after PCNL. Among them, diabetes history, postoperative stone residue, positive urine culture results, and ureteral stent retention time ≥ 8 weeks had the highest impact.As shown in Table Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa, and Gram-positive bacteria are mainly Enterococcus faecalis and Staphylococcus epidermidis. As shown in Table As shown in Table Ureteral stent is the most commonly used medical implant for urological surgery. It is widely used in clinical practice because it can relieve urinary tract obstruction, drain urine, and protect renal function , 15. AftStudies suggest that infections are a more common complication after PCNL. Long operation time, intraoperative bleeding, excessive intrapelvic pressure, and urinary tract obstruction are all risk factors for postoperative infection of PCNL –21. In tEscherichia coli, Enterococcus, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa are the common pathogens of urinary tract infection induced by urinary stones [Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa, and Gram-positive bacteria are mainly Enterococcus faecalis and Staphylococcus epidermidis. In recent years, the unreasonable use or abuse of antibiotics in China, the drug resistance of pathogenic bacteria is becoming more and more serious, especially in patients with kidney stones and urinary tract infection. In China, the resistance rate of E. coli to quinolones (levofloxacin) and gentamycin was close to 50%, and the resistance rate to cephalosporins increased gradually, among which 79.2% and 66.5% to the first and second-generation cephalosporins respectively [It is suggested that y stones , 25. In ectively –28. In tEscherichia coli, Enterococcus faecalis, Staphylococcus epidermidis, Klebsiella pneumoniae, and Pseudomonas aeruginosa are the main pathogens of AP associated with double J-tube after PCNL. The pathogenic bacteria were sensitive to amikacin, β-lactam combined with enzyme inhibitor compound, carbapenems, and other drugs.In conclusion, diabetes mellitus, postoperative stone residue, leukocyte count ≥ 100/HP, positive urine culture result, ureteral stent retention time ≥ 8 weeks, and high S.T.O.N.E. score  were independent risk factors of AP associated with ureteral stent retention after PCNL.