High-sensitivity C-reactive protein (hs-CRP) is an inflammatory marker. This study aimed to identify the correlation between hs-CRP levels and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM).This cross-sectional and observational study included 927 patients with T2DM. We collected the data of patients based on their medical data, including sociodemographic characteristics, concomitant diseases, laboratory results, and medical therapy. Multivariate logistic regression analysis was conducted to assess the relationship between hs-CRP levels and DKD. A restricted cubic spline (RCS) was used to assess the correlation of hs-CRP levels on a continuous scale with the DKD.In total, 927 patients were recruited in our study. The median age of the recruited patients was 55 years, and there were 346 female patients and 581 male patients. The hs-CRP levels were evidently higher in patients with DKD than those without DKD. After adjusting for age, sex, diastolic blood pressure, systolic blood pressure, body mass index, neck circumference, waist circumference, hypertension, duration of diabetes, common carotid artery plaque, fasting plasma glucose, glycated hemoglobin, hemoglobin, erythrocyte, leukocyte, γ-glutamyl transferase, albumin, urea nitrogen, uric acid and triglyceride, a significant increase in the odds ratios (ORs) for DKD in the fourth hs-CRP quartile compared with the first quartile was observed , and the ORs  in the fourth quartile of hs-CRP were 1.968 (1.244–3.114) for DKD compared to the first quartile.. Moreover, the RCS curves presented a positive association between hs-CRP and DKD in total subjects, male subjects and female subjects, respectively.The results of our study indicated that hs-CRP levels were significantly and positively correlated with the presence of DKD, which may provide predictive and diagnostic values in clinical practice. Diabetes mellitus (DM) has become a major and serious threat to global human health. In the population aged 20 to 79 years, approximately 536.6 million people were diagnosed with DM worldwide in 2021, and this number will rapidly grow to 783.2 million in 2045 worldwide . The study was approved by the Ethics Committee of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine.All the data analyzed in this study were extracted from the National Metabolic Management Center. In total, 927 patients with a prior diagnosis of T2DM were included in this study. The inclusion criteria of this study were as follows: with a prior diagnosis of T2DM, the diagnostic criteria for T2DM that were in accordance with the guidelines of the 1999 World Health Organization criteria , age ≥18We collected data on patients from the National Metabolic Management Center based on their medical data, including sociodemographic characteristics, concomitant diseases, laboratory results, and medical therapy. The study variables were as follows: age; sex ; educational level (under high school/high school or above); body mass index (BMI); diastolic blood pressure (DBP); systolic blood pressure (SBP); heart rate; head, neck, waist, and hip circumferences, duration of diabetes; hemoglobin, erythrocyte, leukocyte, albumin, urea nitrogen, creatinine, uric acid, triglyceride, total cholesterol, fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), alanine transaminase, aspartate aminotransferase, γ-glutamyl transferase (γ-GT), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) levels, urinary albumin-to-creatinine ratio (UACR), hs-CRP levels and estimated glomerular infiltration rate (eGFR), hypertension (no/yes), hyperlipidemia (no/yes), and common carotid artery (CCA) plaque (no/yes).2 . Continuous variables with skewed distribution were analyzed using Mann–Whitney U test, and categorical variables were evaluated using the χMoreover, multivariate logistic regression analysis was conducted to assess the relationship between hs-CRP levels and DKD, and the odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Model 1 was adjusted for age and sex. Model 2 was further adjusted for DBP, SBP, BMI, neck circumference, and waist circumference. Model 3 was further adjusted for hypertension, duration of diabetes, and CCA plaque. Model 4 was further adjusted for FPG, HbA1c, hemoglobin, erythrocyte, leukocyte, γ-GT, albumin, urea nitrogen, uric acid, and triglyceride.The restricted cubic spline (RCS) with four knots at the 5th, 35th, 65th, and 95th percentiles was executed on a continuous scale with the presence of DKD. Furthermore, the associations between hs-CRP and DKD in different subgroups by grouping age, sex, BMI, hypertension, CCA plaque and HbA1c were identified by multivariate logistic regression models, and the ORs and 95% CI were calculated. In addition, the interaction between these subgroup variables and hs-CRP were calculated. All statistical analyses in our study were executed by IBM SPSS (version 25.0) and R statistical software (version 4.0.5).A total of 927 patients were enrolled in our study. The median age of the recruited patients including 346 female patients and 581 male patients was 55 years, and there were 322 patients with DKD and 605 patients without DKD in our study. The characteristics of the patients with and without DKD were summarized in In our study, we further executed the RCS to flexibly model the correlation of hs-CRP on a continuous scale with DKD in total subjects, male subjects and female subjects, respectively. The RCS curves showed a positive association in total subjects (P for non-linearity <0.001), male subjects (P for non-linearity =0.004) and female subjects (P for non-linearity =0.249), respectively Figure 12), hypertension (no or yes), CCA plaque (no or yes) and HbA1c (< 7 or ≥ 7%), respectively. The results of subgroup analyses showed that hs-CRP was positively correlated with DKD in most categories. No significant interaction was found between hs-CRP level and age, sex, BMI, hypertension, CCA plaque, or HbA1c, respectively , sex , BMI  and the Natural Science Foundation of Shanghai (21ZR1451200).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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Caffeinated beverages are popular throughout the world, especially due to their stimulating effects on body physiology. However, short- and long-term outcome studies have shown variable results on general health. In this pilot study, we exposed a cohort of 23 healthy individuals to 240 mg of caffeine either in the form of coffee or energy drinks and performed repetitive pulse wave analyses. This experimental approach was chosen to investigate the acute effects of caffeine consumption on vascular tone depending on the form of caffeine intake. Our data indicate that energy drinks, in contrast to coffee, might negatively impact systolic blood pressure and pulse wave velocity. This issue needs special attention in the light of cardiovascular health as the observed effects have been associated with an increased risk of cardiovascular events upon persistent exposure. Caffeinated beverages are among the most consumed drinks worldwide, and their stimulating effect is socially accepted . CaffeinTo detect physiological changes in vascular properties, a pulse wave analysis (PWA) is a commonly used non-invasive diagnostic tool, which records multiple parameters of arterial stiffness that are not assessed during routine blood pressure measurements. The European Society of Hypertension and the European Society of Cardiology included pulse wave velocity (PWV) in their guidelines to assess arterial stiffness as it is associated with increased cardiovascular morbidity and mortality and correlates with end organ damage .Various studies so far have explored the effect of caffeinated beverages on cardiac function, arterial stiffness and pulse pressure, but their effects are still under debate due to conflicting findings. The discrepancies regarding blood pressure elevation and enhanced arterial stiffness range from a linear or inverse association to no observed effects, and study results vary depending on the length of exposure ,11,12. MIn the present study, we aimed to further elucidate the acute impact of caffeine intake from either coffee or energy drinks on blood pressure behavior and the parameters of vascular tone.2  with an age of 31.1  years ) and a median body mass index of 23.7 kg/m2 . SubjectThe cohort of this cross-over interventional pilot study was exposed to 240 mg of caffeine in two independent experiments, either by consumption of coffee or an energy drink. Therefore, each study participant took part in two independent sessions in a randomized order: In one session, volunteers consumed 750 mL of a commercial energy drink (containing 32 mg caffeine/100 mL (0.03%), 0.4% taurine, 11 g/100 mL sugar according to the manufacturer’s information). In the other session, study participants consumed three cups (40 mL/cup) of coffee (containing 80 mg caffeine/cup according to the manufacturer’s information). Coffee was brewed using three sealed espresso capsules with a constant extraction time providing altogether 120 mL. Beverages were then consumed within 15 min. There was an interval of at least 48 h between the two sessions. We urged study participants to avoid any other caffeinated beverages or alcohol for 48 h before each session.During the sessions, pulse wave parameters were collected with a BR-102 plus pulse wave analyzer (PWA)  in a seated resting position, and volunteers were encouraged not to talk or move. After baseline PWA recordings, the respective beverage was then consumed within approximately 15 min. In humans, 99 percent of caffeine is absorbed within 45 min of ingestion and peak blood concentrations can be detected between 15 and 120 min after oral ingestion [All data were collected and analyzed by the study investigators at the Department of Cardiology at the University Hospital Munich (LMU). The study protocol was approved by the local ethics committee . Informed consent was obtained from each patient, and the study protocol conformed to the ethical guidelines of the Declaration of Helsinki.p < 0.05 (*), p < 0.01 (**), p < 0.001 (***).Statistics were calculated with GraphPad software Prism 9 . Results are presented as median and IQR. Due to limited sample sizes, we did not assume normality. P values were calculated by paired sample Wilcoxon tests and corrected for multiple comparisons using the Holm–Sidak method; Baseline heart rate was between 75–80 bpm in all experimental groups, and we did not observe any significant changes after caffeine exposure. While blood pressure remained unaffected by coffee consumption , we detePulse wave velocity did not change after coffee intake but increased by 0.17 m/s after energy drink consumption . Again, In this pilot study, we found strong indications that energy drink consumption leads to an increase in systolic blood pressure, as well as pulse wave velocity. However, the observed effects did not reach statistical significance after correction for multiple testing due to our small sample size. Consistent with preceding studies, diastolic blood pressure was not affected . The obsIndependent of the underlying biophysiological mechanism, systolic blood pressure and pulse wave velocity have clearly been associated with cardiovascular health. Our study supports previous investigations that suggest a negative impact of energy drinks on cardiovascular health due to elevated blood pressure and potential proarrhythmic effects . Higher Our study might be limited by the fact that subject volunteers could not be blinded to treatment. In addition, we did not measure caffeine blood concentration so we might have missed the window of peak blood concentration during our recordings.Changes in systolic blood pressure and PWV require special attention and larger studies will be needed to identify the causative component beyond caffeine itself. Our pilot study indicates a negative impact of energy drinks on vascular stiffness; however, validity is limited by the small sample size. Nevertheless, our data clearly underline the usefulness of further investigation and pave the way for larger studies. In addition, even though short-term effects were only mild, they might become more relevant in the context of habitual long-term exposure. Future long-term head-to-head comparisons between coffee and energy drinks should address the question as to whether a stimulating effect can be achieved without negative side effects, as assumed for energy drink consumption.


Early identification of intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) is important for making a suitable therapeutic strategy for children with KD.This study included a training set and an external validation set. The training set included 635 children (588 IVIG-sensitive and 47 IVIG-resistant KD) hospitalized in Wuhan Children’s Hospital, Hubei, China. Univariate analyses and binary logistic regression equation was incorporated to find the associated variables of the IVIG-resistant KD. A scoring model for predicting IVIG-resistant KD was established according to odds ratio (OR) values and receiver operating characteristic curves. The external validation set consisted of 391 children (358 IVIG-sensitive and 33 IVIG-resistant KD) hospitalized in Peking University First Hospital, Beijing, China. The predictive ability of the model of IVIG-resistant KD were externally validated by the real clinically diagnosed KD cases.Fifteen variables in the training set were statistically different between IVIG-sensitive and IVIG-resistant KD children, including rash, duration of fever, peripheral blood neutrophil-to-lymphocyte ratio (NLR), prognostic nutritional index (PNI), percentage of monocytes and percentage of eosinophils, and serum alanine aminotransferase, aspartate aminotransferase, total bilirubin (TB), direct bilirubin, glutamyl transpeptidase, prealbumin, sodium ion, potassium ion and high-sensitivity C-reactive protein. According to logistic equation analysis, the final three independent correlates to IVIG-resistant KD were serum TB ≥ 12.8 μmol/L, peripheral blood NLR ≥ 5.0 and peripheral blood PNI ≤ 52.4. According to the OR values, three variables were assigned the points of 2, 2 and 1, respectively. When the score was ≥ 3 points, the sensitivity to predict IVIG-resistant KD was 80.9% and the specificity was 77.6%. In the validation set, the sensitivity, specificity and accuracy of the predictive model of IVIG-resistant KD were 72.7%, 84.9%, and 83.9%, respectively.A scoring model was constructed to predict IVIG-resistant KD, which would greatly assist pediatricians in the early prediction of IVIG-resistant KD. Kawasaki disease (KD) is an acute vasculitic disease, the pathogenesis of which has not yet been clear . In partSeveral studies have shown that the initial IVIG combined with corticosteroids could decrease the occurrence of IVIG resistance and CAL , 10. HowCurrently, a Japanese team used the IVIG-resistance prediction model in clinical and some prospective multicenter clinical control studies , 19. HowTherefore, this study was undertaken to explore a useful predictive scoring model of IVIG-resistant KD to help pediatricians in implementing proper assessment and treatment strategy for children with KD.We screened 1056 patients with KD, of whom 1026 (97.2%) were eligible . The stuCriteria for the diagnosis of classic KD (CKD): CKD was classified as containing 5 or more of the 6 clinical characteristics; or the existence of 4 clinical characteristics, excluding fever caused by other diseases or rash diseases, presence of coronary artery dilatation. Six of these clinical characteristics were as below: (1) fever; (2) conjunctival congestion; (3) orofacial lesions: red lips, strawberry tongue; (4) rash; (5) peripheral limb changes: redness and swelling of palms and feet in the initial phase, and peeling of skin at the ends of limbs in the recovery phase; and (6) non-suppurative cervical lymphadenitis , 28.Criteria for the diagnosis of incomplete KD (IKD): IKD was characterized by the existence of 3 of the 6 clinical characteristics and combined with CAL; or only 3 or 4 major clinical characteristics without CAL, but with one of the “other important clinical features”. Other important clinical features were referred to the diagnostic guidelines in the United States and Japan , 27, 28.Criteria for diagnosis of IVIG-resistant KD: IVIG-resistant KD was defined according to the KD diagnostic criteria and having fever or re-fever after 36 h of initial IVIG treatment , 27, 29.Inclusion criteria: children hospitalized with CKD or IKD had their blood routine examination and biochemistry indicator tests completed within 2 days prior to treatment with IVIG; IVIG and aspirin were routinely administered in accordance with guideline criteria .Exclusion criteria: children received non-standard IVIG treatment; use of corticosteroids or other immunosuppressive drugs before the initial IVIG treatment; use of corticosteroids or other immunosuppressive drugs at the same time as the initial IVIG treatment; presence of other serious complications such as macrophage activation syndrome, shock, severe infection, septic lesions, multi-organ dysfunction, hemophagocytic syndrome, etc.; and some clinical data missing during hospitalization.Z-value) at the acute stage of KD . The above medical records were recorded by a dedicated staff and carefully proofread by another professional.The medical records of the study subjects were obtained from the electronic case system . The information included the demographic data, clinical characteristics and the laboratory results. The demographic data included hospitalization date, hospitalization number, sex, age and body mass index (BMI). Clinical features included CKD symptoms , frequency and dose of IVIG, presence of complications  and other underlying diseases . Laboratory test results included routine blood test results, biochemical indicators , infection indicators , and cardiac ultrasound  and Peking University First Hospital (2020–108), and a waiver of the informed consent was granted.Immediately after the initial diagnosis of CKD or IKD was established, all patients were given standard treatment for KD, including IVIG (2 g/kg) and oral aspirin (30–50 mg/kg/day) in 3 divided doses , 30. A dg for 5 min. The non-hemolyzed serum was obtained, generally using a Cobas–8000 automatic biochemical analyzer  for biochemical parameters and a BNII auto-analyzer system  for hsCRP. All specimens were tested on the machine within 2 h in the laboratory department, and the results were verified by a dedicated staff in the laboratory. Then, the blood routine, liver function, electrolytes, cardiac enzymes and hsCRP were uploaded to the electronic medical record system. Our fully automated testers were regularly calibrated and accuracy tested with coefficients of variation within normal limits. In particular, prognostic nutritional index (PNI) = albumin  + 5 × absolute value of lymphocytes (×109/L) (9/L)/lymphocytes (×109/L).Blood routine examination, biochemical indicators and hsCRP were performed as follows. At the child’s first admission to the hospital prior to the initial use of IVIG, 2.0 mL of venous blood was obtained with an EDTA–K2 anticoagulated vacuum collection tube and mixed upside down and sent to the laboratory for testing. A fully automated hematology analyzer XN–3000  and BC–6800 plus  was used to measure blood routine examination. At the same time, 2.0 mL of venous blood was collected and centrifuged using a BY–600A centrifuge  at 3300 (×109/L)  and neutt-test, otherwise by the Mann–Whitney U test. The chi-square test was performed to compare the difference in dichotomous variables. Variables with statistical differences between groups were added to the multifactorial analysis (P < 0.05). Covariance diagnosis was performed and covariates were excluded before entering the multifactorial analysis. And continuous variables were transformed into dichotomous variables for an easy use. Finally, the above statistically different dichotomous variables were included into a binary logistic regression equation, and independent associated factors were obtained by stepwise regression using the backward conditional method. P > 0.05 for the Hosmer-Lemeshow test suggested a good fit of the equation. And finally, a predictive scoring model was established by assigning the scores by the odds ratio (OR) values of each independent risk factor, and the total points of the assignment were summarized for each child. The receiver operating characteristic (ROC) curve was performed to calculate the maximum Youden index corresponding to the cutoff value, sensitivity and specificity of the total score. Finally, in external validation set, scores were computed separately for each child, and a four-grid table was constructed based on the true clinical diagnosis and the cutoff value of the predictive scoring model to validate the sensitivity, specificity and accuracy of the model. Statistical differences were set at P < 0.05.We used SPSS 23.0  for the data analysis. If the data of continuous variables in both the IVIG-sensitive and IVIG-resistant groups obeyed a normal distribution (Shapiro–Wilk test), the difference was compared by P > 0.05). The clinical manifestations of KD in training set mainly included the duration of fever before initial IVIG, conjunctival congestion, red lips/strawberry tongue, enlarged lymph nodes, rash, and stiffness of hands and feet. The median days of fever before the initial IVIG were shorter in the IVIG-resistant group than the IVIG-sensitive group , and the incidence of generalized rash was higher  in the IVIG-resistant group than the IVIG-sensitive group. The conjunctival congestion, redness of lips and tongue, enlarged lymph nodes, and stiffness of hands and feet in children between the two groups did not differ statistically , eosinophil (EO)%  and PNI  than the IVIG-sensitive KD group. In contrast, the IVIG-resistant KD group showed significantly larger peripheral blood NLR  and higher hsCRP  than the IVIG-sensitive KD group. No significant differences were found in total peripheral blood white blood cell, hematocrit, mean corpuscular hemoglobin and hemoglobin (P > 0.05). In terms of biochemical parameters, the IVIG-resistant children showed much higher serum alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , total bilirubin (TB) , direct bilirubin (DB)  and glutamyl transpeptidase (GGT)  than the IVIG-sensitive KD children did. In contrast, the IVIG-resistant KD children showed lower serum prealbumin (PAB) , sodium ion (Na)  and potassium ion (K)  than the IVIG-sensitive children. And there was no statistical difference in serum cardiac enzymes (lactate dehydrogenase and creatine kinase-MB) and ALB between the two groups %  which significantly differed between the IVIG-resistant and IVIG-sensitive KD groups as demonstrated by univariate analysis, serum TB and DB had significant covariance and thus the serum DB was deleted based on the frequency of clinical use. Of the remaining 14 variables, all 13 were continuous numerical variables, except for rash which was a categorical variable. For the convenience of the clinical use, the continuous variables were transformed into dichotomous variables based on the cutoff values obtained from the ROC curves. The results were illustrated in The aforementioned 14 variables were incorporated into the binary logistic regression equation, and the backward conditional stepwise regression finally yielded three variables  as associated indicators to IVIG sensitivity. The OR (95% CI) values for diagnosing IVIG-resistant KD at serum TB ≥ 12.8 μmol/L were 4.273 , peripheral blood NLR ≥ 5.0 for diagnosing IVIG-resistant KD were 4.761 , and peripheral blood PNI ≤ 52.4 for diagnosing IVIG-resistant KD were 2.478 .P < 0.001). When the score was ≥3 points, the sensitivity of this scoring model was 80.9% and the specificity was 77.6% in predicting IVIG-resistant KD  of 0.850  and northern (Beijing) areas of China, we developed a predictive scoring model for the early IVIG-resistant KD prediction. The predictive scoring model consisted of three variables, serum TB and peripheral blood NLR and PNI. Among them, serum TB ≥ 12.8 μmol/L was scored by 2 points, peripheral blood NLR ≥ 5.0 scored 2 points and peripheral blood PNI ≤ 52.4 scored 1 point, with the total score being 5 points. The sensitivity of the prediction of IVIG-resistant KD was 80.9% and the specificity was 77.6% when a child had a total score of ≥3 points, which was externally validated at different area of China.P < 0.001), suggesting that IVIG-resistant KD children had severer liver function injury than those with IVIG-sensitive KD.Serum TB was scored 2 points in the predictive scoring model and was shown to be an independent predictor. The higher level of TB in the IVIG-resistant KD group was also consistent with previous studies . HoweverP < 0.001). Peripheral blood routine indicators such as leukocytes, neutrophils and lymphocytes fluctuate in response to various factors such as inflammation and single indicators are highly variable and non-specific. However, the ratios of the above indicators could better reflect to some extent the inflammatory response (The peripheral blood NLR score was 2 points in the predictive scoring model. In clinical practice, some children with KD presented with a markedly elevated neutrophils and a decreased lymphocytes in number, and thereby a markedly elevated peripheral blood NLR. In the study, we revealed that children with IVIG-resistant KD had significantly higher peripheral blood NLR than those with IVIG-sensitive KD (6.4 vs. 4.4, response . IVIG-reresponse . In the PNI was an index for nutritional assessment and risk prediction established by Japanese scholars Onodera et al. and was initially applied to the assessment after gastric and intestinal surgery . PNI alsOur study successfully constructed a useful scoring model to predict IVIG-resistant KD patients consisting of three indicators: serum TB, peripheral blood NLR and PNI. This predictive scoring model is simple and easy to use and inexpensive. Whether a predictive scoring model can be externally validated in other medical institution is an important factor for the evaluation. The Japanese Egami or Kobayashi scoring model was the currently accepted scoring model with high sensitivity and applicability in Japanese children , 17. HowHowever, the present study also had some limitations. As a retrospective study, it would have a selective bias of the subjects. Therefore, a prospective randomized and controlled study is needed in the future to assist in predicting early optimization in children with IVIG-resistant KD.Early identification and prediction of IVIG-resistant KD patients are extremely necessary in clinical pediatrics. In this study, we successfully constructed a helpful easy-to-perform and inexpensive predictive scoring model in different centers with a satisfactory predictive ability for IVIG-resistant KD cases. This model would be useful in assisting pediatricians in predicting the IVIG-resistant KD patients so as to provide reasonable therapeutic strategy for KD in children.The 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 Ethics Committee of Wuhan Children’s Hospital and Peking University First Hospital. Written informed consent from the participants’ legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.JD, HJ, and YZ conceived and designed the project and directed the revision of the manuscript. CL, SW, YL, YS, JF, and DZ acquired the data. YYS, HY, and QZ directed the statistical methods, analyzed and interpreted the data. All authors wrote the manuscript, critically reviewed the manuscript, and approved the final version, access to the primary data and were responsible for the accuracy and completeness of the results.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Acromegaly is associated with symptoms in many organs, including the heart, colon, skin, bones, and many joints. Patients with long-term treatment or biochemical control still suffer from acromegaly arthropathy (AA). Primarily, the weight-bearing joints of the lower extremity are affected and at last deformation emerges. The aim of this study is to detect the changes in the feet with pedabarography in patients with acromegaly. p=0.31). There was no difference between acromegaly patients and controls in terms of gender, age, and BMI; median age and BMI were (54 (20–67) vs. 52 (30–58), p=0.85) and (32.5 (20.3–42.7) vs. 29.5 (22.4–38.6), p=0.93), respectively. Static plantar pressures of bilateral foot of all participants in the standing position were measured by pedabarography.  Nineteen patients with acromegaly  and 13 healthy controls  were included in the study (p=0.04 and p=0.01), respectively. The mean of the right rearfoot surface (43.5 cm2 vs. 36.6 cm2) and the mean of the left rear foot surface were higher than the controls (47.4 cm2 vs. 40.2 cm2). Forefoot surface, forefoot load, forefoot weight ratio, rearfoot load, total foot surface, total load, total peak pressure, and total average pressure were higher in left foot in both groups, but there was no difference between the two groups.  In pedabarographic analysis, there were only significant difference in rearfoot surface right and rearfoot surface left ( In our study, there was a significant difference between acromegaly patients and healthy controls, only on the right rarefoot surface and the left rarefoot surface, and was higher on the left in both groups. These patients often experience changes in the hindfoot and heel, and foot surface area and pressure distribution may vary. Early diagnosis and proper treatment of the disease can prevent the development of complications and improve the quality of life. Foot scanning using pedabarography in the management of AA is a useful tool that can be used to manufacture customized orthopedic insoles and ergonomic shoe designs to prevent irreversible damage and reduce overload and lower extremity pain. Acromegaly is a chronic disease characterized by excessive secretion of growth hormone (GH), usually caused by a pituitary adenoma . It has Patients with acromegaly usually present with acral bone growth resulting in frontal protrusion, increased hand and foot size, prognathism, and widening between lower incisors. It is also associated with manifestations of cardiovascular, gastrointestinal, skeletal system, and skin . AcromegBecause acromegaly joint disease has common features with primary osteoarthritis (OA), it is often considered a degenerative joint disease. However, despite the narrowing of the joint space due to cartilage loss in osteoarthrosis, the enlargement of the joint space due to cartilage hypertrophy accompanied by severe osteophytosis in AA is the most important difference between them . EnlargeAA is mostly evaluated by clinical and radiographic abnormalities. Although several clinical methods have been used to assess stiffness, pain, joint function, and quality of life, these have only been validated in primary OA patients. Early diagnosis of acromegaly can improve quality of life by reducing the risk of bone and joint disease. With the treatment of acromegaly, structural changes such as cartilage hypertrophy and joint thickening are partially reversed .The foot has a structure that can easily adapt to both weight changes and changes in the printed surface. Chronic enlargement of soft tissue and bone can cause both somatic and gait disturbances. In addition, gait may be impaired due to biomechanical changes in acromegaly altering posture and balance, deformities may develop especially in the feet, and this may be irreversible. Foot deformities also change plantar pressure, and it has been proven that pressure characteristics differ according to foot deformities . KnowingPedobarography examines interactions between foot and support surface and also performs biomechanical analysis of gait and posture. Static pedobarography analyzes plantar pressure while standing, and dynamic pedobarography provides data during activities. Plantar foot pressure measurements can provide information about posture control . Its tecIn the long run, irreversible changes in posture, balance, gait, and plantar pressure occur in the joints, especially in the foot joints, and reduce the quality of life in patients with acromegaly. Hitherto is the bony feature of acromegaly has only been observed from radiographic images, mostly in a few studies using ultrasonography or magnetic resonance imaging (MRI) for joints of the hands and a few studies using x-rays and ultrasound for foot changes –15. NoneNineteen acromegalic adult patients  and thirteen healthy subjects  admitted to the endocrinology clinic of Ankara Training and Research Hospital were enrolled in this cross-sectional study. The diagnosis of acromegaly was confirmed by clinical, hormonal, and radiological data. The control group included volunteers who had no previous foot or ankle problems and whose gender, age, and body mass index were matched with acromegaly patients.Those with foot deformities such as pes cavus, pes planus, hallux valgus, and a history of foot surgery or major trauma and those with rheumatic diseases or nerve entrapment lesions such as mortone neuroma were excluded from the study.Demographic and clinical features of acromegaly patients and control group were recorded into a predefined protocol. All the patients underwent analysis with a static pedobarogram to evaluate plantar pressure changes and compared with the healthy control group.Ethics approval was obtained from the Ankara Numune Training and Research Hospital Ethics Committee. The research protocol is in line with the 2000 Helsinki Declaration and written informed consent was obtained from all participants.μg/L. The interassay CV was %1.9, while the intra-assay CV was % 3.0. Serum IGF-1 levels were analyzed by RIA (Berthold gama gaunter). The intra-assay CV was 3.3%, while the interassay CV was 7.2%.All serum samples were taken in the early morning hours with a 12-hour fast. Serum GH concentrations were analyzed by electrochemiluminescence  with a detection limit of 0.01 μg/L were classified as acromegaly in remission.Patients with normal IGF-1 values according to age- and gender-specific levels and a spot or suppressible GH values < 1 Plantar pressure during static standing position was measured using the Footscan® 3D System . The system includes pressure-sensing platform, power unit, camera, monitor, and printer connections and connected to the computer system. The pressure platform contained 16384 resistive sensors arranged in 200 cm × 40 cm active sensor area with dimensions of 1800 cm × 40 cm and with a data acquisition frequency 100 Hz. The Footscan® 3D system was calibrated before each test session, according to the manufacturer's manual. By software analysis, the pressure distribution of low and high pressure in the form of specific “hot” and “cold” zones is determined topographically. Using software support, the device we used in this study evaluated the foot by dividing it into the forefoot and rearfoot regions. Plantar pressure was determined using the peak pressure (kPa), force (Ns), and area (cm) parameters.Prior to data collection, at least 3 statistical posture rehearsals were completed on the pressure platform to ensure conditioning. They were asked to place their feet in the designated area on the platform. After maintaining a static posture on the platform, they were asked to look at the object placed at eye level and placed on the wall in front of them and measurements provided. In the static pedobarographic evaluation of the foot, maximal pressure values in the forefoot and hindfoot, total pressure in the foot, percentages of total pressure on the front/rear part of the foot, and total contact area and percentage share values of the total contact area to the fore and hind foot are obtained.t-test or Mann–Whitney U test. The Chi-square test was used to compare groups for categorical variables. p value <0.05 was considered significant in all statistical analyzes.Statistical analysis was performed using the 21.0 version of the Statistical Package for Social Sciences (SPSS) program . The Kolmogorov–Smirnov test helped us to check whether continuous variables showed a normal distribution. Normally distributed continuous variables are defined as mean ± SD, while nonnormally distributed parameters are reported as medians (minimum-maximum). Comparison between groups of continuous variables was carried out using Student's p=0.31), ages, and body mass indexes were matched between acromegaly patients and control group; median age and BMI were (54 (20–67) vs. 52 (30–58), p=0.85) and (32.5 (20.3–42.7) vs. 29.5 (22.4–38.6), p=0.93), respectively. The main characteristics of patients with acromegaly are presented in p=0.04 and p=0.01, respectively (2 vs. 36.6 cm2) and the mean of the left hind foot surface was higher than the controls (47.4 cm2 vs. 40.2 cm2). Forefoot surface , forefoot load , forefoot weight ratio  (p=0.18), total foot surface , total load , total peak pressure , and total average pressure  were higher in left foot in both groups, but there was no difference between the two groups (The gender (ectively . In acro p=0.32) , rearfooo groups .In this study, we inspected the static barefoot plantar pressure changes in acromegaly patients. The present study is one of the first research studies to address plantar statics using pedobarography in this patient group. In this study, we found that there was a difference in the surface of the right rear foot and the surface of the left rear foot in patients with acromegaly compared to healthy controls. Also, the mean of rearfoot surface right and left in acromegaly patients was higher than controls. Although there was no difference between the two groups, the total surface area was higher in the acromegaly group in the left foot, while it was similar in the right foot. Although weight matched between groups, the total load on the right foot was higher in the control group, while the total load on the left foot was higher in the acromegaly group. Peak pressure and average pressure in both forefoot and rearfoot were higher in the acromegaly group.Because of the insidious nature of the disease, the diagnosis of acromegaly is significantly delayed. The musculoskeletal manifestations of the syndrome are common, and almost all patients develop symptoms or signs of arthropathy, but these symptoms have been poorly studied . On joinCurrently, only IGF-1 and GH blood values are recommended for acromegaly to detect possible disease activity and to evaluate treatment outcomes or possible complications during the follow-up period. However, these values may not adequately reflect disease activity in peripheral tissues, especially during medical treatment. Since the effectiveness of treatment modalities such as humidity and infection control, hyperbaric oxygen therapy, negative pressure wound therapy, and debridement, which are frequently used in diabetic foot ulcers, are not always successful, as a new treatment modality adding Lactiplantibacillus plantarum ATCC 10241 cultures on venous ulcers has been tried, and encouraging positive results have been obtained . It is aIn acromegaly patients, the shoe size showing the increase in the plantar surface grows over time. Sponginess and puffiness hands and feet (predominantly due to soft tissue swelling) are present in the vast majority of acromegalic patients; this is particularly noticeable in heel pads. The vast majority of acromegalic patients have spongy and swollen hands and feet (mostly due to soft tissue swelling); this is particularly evident in heel pads. This finding can be made by clinical examination or imaging studies and is quite evident.Radiogram abnormalities of the hip, knee, and hand are also found in more than 50% of patients . ParticuColao et al. demonstrated the usefulness of joint ultrasound in measuring cartilage thickness and monitoring the effect of octreotide therapy . They alThere is only one study in the literature by Sendur et al. in which pedabarography was used in acromegaly patients . In theiWhether AA can be reversed by controlling GH and IGF-I levels is still being questioned. Significant structural changes in the joints and limited restorative ability of chondrocytes seem to prevent healing in AA. However, surgery or treatment with somatostatin analogues has been shown to improve the signs and symptoms of AA .However, in the study of Colao A et al. it was observed that neither cure nor octreotide treatment was sufficient for cartilage thickness to return to similar values with healthy subjects . HoweverFirst of all, although the prevalence of inflammatory rheumatic diseases is low in these patients, its exclusion and accurate diagnosis of AA is necessary. Since there are no sensitive biomarkers to manage AA other than monitoring disease activity with IGF-1 and GH testing, it is usually followed according to the clinical course of joint problems. In general, when joint problems become serious, consultation with a rheumatologist or orthopedic surgeon is considered to evaluate possible treatment options. However, the role of the physiotherapist in this regard has not been investigated yet. The findings of present study underline that AA is a distinct clinical entity with its own characteristics. Future studies are needed to determine whether acromegaly-specific interventions such as physiotherapy could be useful in the management of AA.The type of material to be used in the manufacture of orthopedic insoles is selected according to the clinical picture, pedobarography findings, and the need to reduce the load on certain parts of the foot. Therefore, in the diagnosis and follow-up of AA, footscan is a useful tool that can be used to prevent irreversible damage to the foot. So, the pedabarographic examination results enable the selection of suitable insoles that help reduce overload and lower extremity pain and back pain.This study has a few limitations. Firstly, the number of patients in this pilot study is relatively small. Studies involving more patients are needed to reach more accurate results. Secondly, the acromegaly group in the study was quite heterogeneous as it included both active and remitting patients. We did not consider foot types, which is another factor that will affect pressure distribution.Acromegaly is usually a slow progressing disorder. The foot changes that mostly skipped can cause imbalance and falls by time. Early diagnosis and proper treatment of the disease can prevent the development of complications and improve the quality of life. These patients often experience changes in the hindfoot and heel, and foot surface area and pressure distribution may vary. In our study, by pedabarographic analysis, there was a significant difference between acromegaly patients and healthy controls, only on the right rarefoot surface and the left rarefoot surface, and was higher on the left in both groups. However, rarefoot load, forefoot surface, and forefoot load were also higher on the left in both groups, but there was no difference between the groups. Foot scanning using pedabarography in the management of AA is a useful tool that can be used to produce customized orthopedic insoles and ergonomic shoe designs to prevent irreversible damage, reduce overload, and lower extremity pain and back pain.


Conclusion: Pulmonary vascular remodeling  was not associated with prognosis in a selected sample of adults evaluated for elective heart transplants. Pulmonary OCT is safe and feasible for the evaluation of these patients.Objective: In patients with advanced heart failure, the intravascular optical coherence tomography (OCT) of subsegmental pulmonary artery measurements is correlated with right heart catheterization parameters. Our aim was to study the prognostic value of pulmonary OCT, right heart catheterization data, and the echocardiographic estimation of pulmonary pressure in patients studied for elective heart transplants. Methods: This research is an observational, prospective, multicenter study involving 90 adults with a one-year follow-up. Results: A total of 10 patients (11.1%) died due to worsening heart failure before heart transplantation, 50 underwent a heart transplant (55.6%), and 9 died in the first year after the transplant. The patients with and without events  had similar data regarding echocardiography, right heart catheterization, and pulmonary OCT  of 30.3–50.0 vs. 47.0 mmHg, IQR 34.6–59.5 and  Pulmonary hypertension secondary to left-heart disease (PH-LHD) is highly prevalent and associated with an increased disease burden and poor outcomes ,2,3. TheOptical coherence tomography (OCT) was first used in the field of retinal pathology but is now widely used in the diagnosis and treatment of coronary artery disease. OCT is based on a near-infrared light source with a resolution of 10–20 mm, which is particularly useful for tissue characterization . RecentlOur aim was to assess the prognostic value of pulmonary vascular remodeling in HF patients evaluated for an elective HT.Our data come from the Optical Coherence Tomography Observation of Pulmonary Ultra-Structural Changes in Heart Failure (OCTOPUS-CHF) study. The design of this study has already been published . BrieflyThe normality of the continuous variables was studied via the Shapiro–Wilk test. Normally distributed variables are presented as mean ± standard deviation, and non-normal variables as median (interquartile range). Categorical variables are shown as absolute values and percentages. Student’s t test was used to compare normally distributed variables, Kruskal–Wallis test was employed for non-normal ones, and Chi-square test was used for categorical variables. All analyses were performed with R version 4.0.2  and SPSS 25.0 software .The study followed the Declaration of Helsinki. The protocol was approved by the Ethics Committee of each participating center. All patients provided written informed consent.There were no serious immediate or long-term complications secondary to the procedure. Echocardiographic evaluations were carried out in 78 patients.The one-year follow-up outcomes are depicted in p = 0.79, median pulmonary vascular resistance of 2.2 Wood units, IQR of 1.3–3.7 vs. 2.0 Wood units, IQR of 1.4–3.2 with p = 0.99, and median pulmonary artery wall thickness 0.2 ± 0.5 mm vs. 0.2 ± 0.6 mm with p = 0.87). The primary endpoint was associated with male sex, an INTEragency Registry for Mechanically Assisted Circulatory Support (INTERMACS) status of 3–4, atrial fibrillation, and significant mitral regurgitation  and those who did not  of 30.3–50.0 vs. 47.0 mmHg, IQR of 34.6–59.5 with gitation , but onlgitation . Pulmonagitation  or in thgitation . In the present multicenter, observational study, we sought to evaluate the prognostic role of the in vivo assessment of pulmonary vascular remodeling with different techniques—including pulmonary OCT—in advanced HF patients referred for an elective HT. The use of pulmonary OCT was feasible and safe for these patients, with no severe complications during the procedure and after a one-year follow-up. Our main finding is that there were no significant differences in the pulmonary vascular remodeling measurements  between the patients who met the primary endpoint  and those who did not. Across the spectrum of HF, more than 50% of the cases present with secondary PH; this value is virtually 100% in the case of end-stage disease . Once esRight heart catheterization is still the cornerstone for a PH assessment. However, a knowledge gap around its interpretation has been reported . This prThe morphological study of PH used to be achievable only through a pulmonary biopsy or necropsy; however, this changed with the recent rise of intravascular imaging techniques. Previous pulmonary OCT studies  reportedRetrospective studies on pulmonary hemodynamics of patients undergoing HT have generated concern about the risk of right ventricular failure and mortality among those patients with higher pulmonary vascular resistance and transpulmonary gradient ,37,38,39However, this study has some limitations. Our small sample led to a low event rate and hampered the statistical power with which to show differences between subgroups. In addition, though pulmonary vascular remodeling is known to be more pronounced in the venous bed ,45, the Pulmonary vascular remodeling evaluated with echocardiography, right heart catheterization, and pulmonary OCT were not associated with prognosis in this selected sample of adults evaluated for an HT. The clinical utility of OCT cannot be ruled out given the small size, absence of significant PH, and low event rate in this sample.


Primary aldosteronism (PA) is a pathological condition characterized by an excessive aldosterone secretion; once thought to be rare, PA is now recognized as the most common cause of secondary hypertension. Its prevalence increases with the severity of hypertension, reaching up to 29.1% in patients with resistant hypertension (RH). Both PA and RH are “high-risk phenotypes”, associated with increased cardiovascular morbidity and mortality compared to non-PA and non-RH patients. Aldosterone excess, as occurs in PA, can contribute to the development of a RH phenotype through several mechanisms. First, inappropriate aldosterone levels with respect to the hydro-electrolytic status of the individual can cause salt retention and volume expansion by inducing sodium and water reabsorption in the kidney. Moreover, a growing body of evidence has highlighted the detrimental consequences of “non-classical” effects of aldosterone in several target tissues. Aldosterone-induced vascular remodeling, sympathetic overactivity, insulin resistance, and adipose tissue dysfunction can further contribute to the worsening of arterial hypertension and to the development of drug-resistance. In addition, the pro-oxidative, pro-fibrotic, and pro-inflammatory effects of aldosterone may aggravate end-organ damage, thereby perpetuating a vicious cycle that eventually leads to a more severe hypertensive phenotype. Finally, neither the pathophysiological mechanisms mediating aldosterone-driven blood pressure rise, nor those mediating aldosterone-driven end-organ damage, are specifically blocked by standard first-line anti-hypertensive drugs, which might further account for the drug-resistant phenotype that frequently characterizes PA patients. Physiologically, aldosterone is a key hormone in the regulation of blood pressure and electrolyte homeostasis ,2. HowevThe detrimental role of aldosterone excess depends not only on its well-known effects on water and sodium reabsorption in the kidney, but also on its pro-fibrotic, pro-inflammatory, and pro-oxidative action in several target tissues ,11. In tIn physiological conditions, aldosterone is a key regulator of blood pressure, electrolyte balance and volume status and its actions are closely integrated with that of the renin-angiotensin-aldosterone system (RAAS) ,2. The mIn addition, aldosterone secretion is also regulated by other angiotensin-independent molecular mechanisms. The most important is represented by extracellular potassium levels , which dShifting the focus on aldosterone actions, aldosterone fulfills its function on several target tissues via activation of the mineralocorticoid receptor (MR), an intracellular transcription factor that can modulate the transcription of effector proteins as well as initiate rapid non-genomic, or extra-nuclear, events through various signaling pathways .The primary effect of aldosterone is exerted on the kidney, where it increases the expression of epithelial sodium channels (ENaC) in the luminal membrane of the principal cells in the collecting tubules ,25; thisAlthough the kidney represents the main target organ for aldosterone action, aldosterone also binds to the MR in various other tissues, inducing pleiotropic effects. In fact, the MR has been identified in a wide variety of different cell types, most notably in the cardiovascular system  ,34,35,36As discussed previously, aldosterone plays a central role in the physiological regulation of blood pressure, stimulating several responses in various target cells in order to maintain hydro-electrolytic homeostasis. High aldosterone levels are not pathological “per se”, and do not necessarily determine arterial hypertension, as long as they are appropriate to the sodium/volume status of the individual. An outstanding example of this is provided by Yanomamo Indians, a tribe inhabiting the tropical rainforest between northern Brazil and southern Venezuela, which was renowned for living on a diet with an extremely low content of salt (approximately 10 mmol per day) . These iIn most cases, PA is sporadic, and the underlying cause is represented either by an aldosterone-producing adenoma (APA) or by bilateral adrenal hyperplasia (BAH) ,44,45,46Once thought to be rare, PA is now recognized as the most common cause of secondary hypertension; its prevalence increases with the severity of hypertension and can be estimated approximately as 5% in primary care practice ,54,55,56The most important mechanisms that lead to an abnormal increase in blood pressure levels in patients with PA are those exerted on the kidney. At a renal level, in fact, aldosterone excess determines an inappropriately high distal tubular resorption of sodium, which prevails on the actual sodium/volume status and leads to extracellular volume expansion ,25,26,27RH is defined as uncontrolled blood pressure despite appropriate lifestyle measures and treatment with ≥3 anti-hypertensive agents of different classes at maximal or maximally tolerated doses, including a diuretic and, typically, a calcium-channel blocker (CCB) and a blocker of the renin-angiotensin system  . RH is aPA and RH frequently coexist. In a recent study by our group, which enrolled 110 consecutive patients with true RH, PA was diagnosed in 32 cases (29.1%) ; similarThe high prevalence of PA in patients with RH strongly suggests a role for aldosterone excess in the development of resistance to antihypertensive medications. Moreover, it is now well established that add-on treatment with a MRA in patients with RH, even in the absence of a clear diagnosis of PA, is effective in lowering blood pressure, as highlighted in the PATHWAY-2 study, the first randomized controlled trial comparing different antihypertensive treatments in patients with RH . In thisAldosterone excess can contribute to the development of severe hypertension and resistance to antihypertensive treatment through several mechanisms.The most straightforward mechanism by which aldosterone excess can contribute to the development of RH is the chronic expansion of blood volume and enhanced salt retention ,45,47,48The relevance of body sodium content and water retention as a determinant of blood pressure levels has been demonstrated by clinical studies, in which lifestyle interventions decreasing daily salt intake have been shown to significantly improve blood pressure control, even without changes in prescribed medications . Sodium In conclusion, inappropriate fluid retention secondary to high dietary sodium intake and aldosterone excess is an important mediator of antihypertensive treatment resistance that is best overcome by the natriuretic and diuretic effects of spironolactone in patients with RH . CoherenAs we have already mentioned, aldosterone excess has been shown to have detrimental effects on many target organs that go beyond its action on water and sodium reabsorption and that can also contribute to the development of a RH phenotype. The deleterious effects of aldosterone excess at a vascular level  ,82,83,84One way by which aldosterone promotes inflammation is by increasing the generation of reactive oxygen species (ROS), which in turn activate pro-inflammatory transcription factors such as nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB). Aldosterone can increase oxidative stress through several mechanisms. First of all, it can induce the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in several organs  . MoreoveAldosterone-induced oxidative stress and inflammation can promote endothelial dysfunction and increase the expression of pro-fibrotic molecules, such as transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), placental growth factor (PGF), endothelin 1 (ET1), osteopontin and galectin-3, eventually leading to fibrosis in the heart, kidney and vasculature . The mecAldosterone excess can cause endothelial dysfunction by determining an imbalance between vasoconstrictors and vasodilators. First of all, aldosterone impairs NO formation via a MR-dependent pathway by causing a reduction of cofactor BH4, by determining the dephosphorylation of endothelial NOS, and by increasing the production of ROS and impairing ROS scavenging capacity, thus reducing the bioavailability of NO ,92. MoreThe MR is expressed not only in endothelial cells, but also in VSMCs. In the presence of endothelial damage, which can be cause by mechanical injury or by hypertension, dyslipidemia, diabetes and smoking, VSMC are capable of proliferating and producing extracellular matrix thereby contributing to vascular fibrosis and vessel wall thickening and stiffening, a process known as vascular remodeling. Studies on VSMC-MR knockout mice have shown that VSMC-MR is essential for aldosterone-mediated vascular fibrosis and stiffening, since in the absence of VSMC-MR aldosterone does not mediate its detrimental effects on the vasculature . In animAt a vascular level, aldosterone-mediated oxidative stress, inflammation, endothelial dysfunction, and fibrosis  lead to Aldosterone pro-oxidative, pro-inflammatory, and pro-fibrotic effects have also been demonstrated in the kidney. In animal models, aldosterone excess has been shown to induce sodium-dependent hypertrophy and hyperplasia of distal tubule cells ,86, as wThe relationship between CKD and RH is bilateral: on the one hand, uncontrolled blood pressure leads to the development of renal complications; on the other hand, CKD is recognized as a frequent cause of RH in the general hypertensive population. RH is a common finding among patients with CKD: in a study by De Nicola et al., evaluating 436 hypertensive CKD patients, true RH had a prevalence of 22.9% . SeveralMarked neuroadrenergic activation and baroreflex dysfunction have been shown in patients with true RH as compared with apparent RH and essential hypertension ,115. At Several studies in literature have suggested that the effect of aldosterone on SNS activity may be also dependent on MR-mediated effects of aldosterone in the central nervous system. In a study by Wray et al., the authors reported a significant reduction in SNS activity after six months of therapy with MRAs, which was obtained without a change in end-organ alpha-adrenergic responsiveness, implicating a central mechanism for the reduced autonomic activity . ExpressAldosterone excess might promote and sustain a rise in blood pressure also through some additional indirect pathways involving adipose tissue dysfunction. In fact, there is some evidence supporting a possible role of PA in the pathogenesis of insulin-resistance and metabolic syndrome, which are per se well-known risk factors and substrates for the development and sustenance of hypertension . The preAldosterone excess and obesity also have a causative role in the development of obstructive sleep apnea (OSA), a condition that appears to be strongly related to RH: in a study on 41 patients with RH, Logan et al. diagnosed OSA in 83% of cases; moreover, the severity of OSA was correlated with the presence of RH . FurtherThe specific pathophysiology of hypertension in patients with PA also influences the efficacy of standard first-line anti-hypertensive medications. In fact, the pathophysiological mechanisms underlying the development of hypertension in patients with PA are persistent and sustained even during treatment with a conventional 3-drug combination regimen ; the driving mechanisms of sodium retention and volume expansion that characterize the pathophysiology of hypertension in PA are not specifically hampered by standard first-line anti-hypertensive drugs, and this might decrease their efficacy in blood pressure control ,71,137. In addition, non-specific anti-hypertensive treatment has been demonstrated to be insufficient to provide optimal organ protection in patients with PA; the available evidence, in fact, highlights that the benefit of a specific surgical or medical treatment of PA is significantly higher than the one of non-specific anti-hypertensive medications, both in terms of clinical outcomes and end-organ damage ,138,139.The overall summary of the main pathophysiological mechanisms by which PA may determine a resistant-hypertensive phenotype is reported in In this review we have summarized the current evidence regarding the potential pathophysiological link between aldosterone excess, as occurs in PA, and RH.The most important mechanisms leading to the development and maintenance of arterial hypertension and RH in patients with PA are those exerted on the kidney, with increased sodium retention and volume expansion. These mechanisms are believed to play a key role in the pathophysiology of RH even in non-PA patients. Moreover, there is a growing body of evidence showing that the excessive activation of MR in other tissues may also play a role, mostly through vascular remodeling, increased sympathetic outflow, and additional indirect pathways involving insulin-resistance and adipose tissue dysfunction. The pro-oxidative, pro-fibrotic and pro-inflammatory effects of aldosterone may also contribute to the worsening of end-organ damage, thereby perpetuating a vicious cycle that eventually leads to a more severe hypertensive phenotype. Finally, neither the pathophysiological mechanisms mediating aldosterone-driven blood pressure rise, nor those mediating aldosterone-driven end-organ damage, are specifically blocked by standard first-line anti-hypertensive drugs, which might further account for the drug-resistant phenotype that frequently characterizes PA patients.Both PA and RH are “high-risk phenotypes”, associated with increased cardiovascular morbidity and mortality compared to non-PA and non-RH patients. Given the high prevalence of PA in patients with RH, an accurate screening of PA in this population is essential, to ensure to all PA patients a timely diagnosis and a specific surgical or medical treatment, whose benefits are by far greater than those of non-specific anti-hypertensive medications, both in terms of blood pressure control and of cardiovascular damage prevention. Moreover, acknowledging the role of aldosterone excess in the development of RH even in the absence of a clear diagnosis of PA has important implications for the choice of the most effective add-on antihypertensive medications.


The correlation between cuff inflatable hypertension and the difference in interarm diastolic pressure induced by single arm ischemia is investigated. A total of 126 patients undergoing coronary angiography in our hospital from January 2020 to January 2021 are selected and divided into the non-pseudohypertension (non-PHT) group (64 cases) and the PHT group (62 cases) according to the difference between systolic blood pressure and diastolic blood pressure measured directly and indirectly. The patients are subjected to the beam arm ischemia test and blood pressure measurement. The diastolic pressure differences between the patients before and after the beam arm are analyzed, and endothelial function and imaging indicators are compared. The risk factors for PHT are analyzed by binary logistic regression, and the diagnostic efficacy of diastolic blood pressure difference interarms (DBPI-r) for PHT patients is analyzed by receiver operating characteristic (ROC) curve. The experimental results show that the diastolic pressure difference induced by single arm ischemia can be used in the diagnosis of cuff inflatable hypertension. Hypertension is a relatively common chronic disease with a high prevalence and easy to induce cardiovascular and cerebrovascular diseases , 2. PseuAt present, there is still a lack of good noninvasive detection methods for clinical diagnosis of PHT. Studies have shown that the beam arm ischemia test is a good way to test vascular endothelial function, and the degree of arterial stiffness can also be detected . The cufThe rest of this study is organized as follows: PHT referred to actual normal blood pressure, which was caused by local arterial stiffness or neuromediated pressure, resulting in the illusion of elevated blood pressure during detection . Among tP < 0.05. An analysis of its mechanism was that patients with cuff hypertension have lower interbrachial diastolic pressure, which may be caused by impaired endothelial function. The principle of interbrachial diastolic pressure behind the banding arm was similar to that of FMD. The lower interbrachial diastolic pressure indicates poor vascular elasticity and impaired endothelial function. A higher interarm diastolic pressure indicates better elasticity [Domestic research studies by Fan et al.  showed tasticity .P > 0.05). Compared with the non-PHT group, the PHT group had more patients with left ventricular diastolic dysfunction, accounting for 70.97% (P < 0.05). Analysis of the reason is that in patients with hypertension with cuff inflatable cuff, a one-arm ischemia test will cause increased blood pressure and abnormal hemodynamics, thus affecting endothelial function and arterial vascular dilation, resulting in small differences in diastolic blood pressure between arms, thus weakening left ventricular diastolic function. This is similar to the research results of Xu et al. [It was found that there were no significant differences in the data of left ventricular end-systolic diameter, left ventricular end-diastolic diameter, septal thickness, and carotid artery intima thickness .A total of 126 patients who underwent coronary angiography in our hospital from January 2020 to January 2021 are selected according to the diagnostic criteria of PHT (systolic or diastolic blood pressure difference >10 mmHg), and the patients are divided into the non-PHT group (64 cases) and the PHT group (62 cases). The mean age of the PHT group is (56.32 ± 6.45) years old, with 33 males and 29 females. The mean age of the non-PHT group is (58.97 ± 7.28) years, with 34 males and 30 females. There are no significant differences in baseline data such as age and gender between the 2 groups (Instruments and equipment: Omron sphygmomanometer (German HEM-7330), mercury sphygmomanometer, pressure sensor, ECG monitor, ET kit, NO kit, and ONOO kit.The experimental procedure of bundle arm ischemia is performed on the patients . The speAn invasive blood pressure test is performed on the patient , 21, witSBPI-r and DBPI-r differences before and after single-arm ischemiaDifferences in endothelial function-related indicatorsDifferences in imaging indicatorsBinary logistic regression analysis of risk factors for PHTAnalyze the utility of DBPI-r in clinical diagnosis of PHT after beam armThe observed indicators of this study are as follows:t-test is adopted. The statistical data are expressed in percentage (%), the x2 test is used, binary logistic regression is used to analyze the risk factors affecting PHT, and ROC curve is used to plot the diagnostic efficiency, if P < 0.05 proved to be statistically significant.The data in this study are processed by SPSS 26.0 software , 23. Alla” represents P < 0.05 compared to baseline; “b” represents P < 0.05 compared with the non-PHT group. Through the above experimental results, it can be observed that there is no significant difference in SBPI-r and DBPI-r levels at baseline and no significant difference in SBPI-r levels after single-arm ischemia (P > 0.05). After single-arm ischemia, DBPI-r is significantly increased, and compared with the non-PHT group, DBPI-R in the PHT group is lower.a” stands for P < 0.05 compared with before beam arms of the same group; “b” stands for comparison between groups, P < 0.05. It can be seen from P < 0.05). ET level in the PHT group increased significantly than in the non-PHT group before and after beam arm (P < 0.05).P < 0.05.P < 0.05 are included as independent variables, including DBPI-r behind the beam arm, NO before the beam arm, NO after the beam arm, ET before the beam arm, and ET after the beam arm. According to the above statistical analysis results, indicators with ROC curve is applied to analyze the utility of DBPI-r in diagnosing PHT behind the arm. The correlation between cuff inflatable hypertension and the difference in interarm diastolic pressure induced by single arm ischemia is investigated. The diastolic pressure difference induced by single arm ischemia can be used to evaluate cuff inflatable hypertension. It is simple and noninvasive and can be a simple and effective indicator for cuff inflatable hypertension. The results of the study can be applied in clinical diagnosis, which can greatly enhance the identification and screening of PHT and reduce the occurrence of diagnostic errors.


P=0.006), s-suPAR at 2 months after initiating IST (s-suPAR (2M); HR for every 500 pg/mL increase: 1.13, P=0.015), urinary protein-to-creatinine ratio (u-PCR) (u-PCR (2M); HR for every 1.0 g/gCr increase: 2.94, P=0.003), and urinary liver-type fatty acid-binding protein (u-L-FABP) (u-L-FABP (2M); HR for every 1.0 μg/gCr increase: 1.14, P=0.006). All four factors exhibited high predictive accuracy for cumulative incidence of 40% reduction in the eGFR up to 8 years after initiating IST, with areas under the receiver operating characteristic curve of 0.92 for Δs-suPAR (2M), 0.87 for s-suPAR (2M), 0.93 for u-PCR (2M), and 0.93 for u-L-FABP (2M). These findings suggest that Δs-suPAR (2M), s-suPAR (2M), u-PCR (2M), and u-L-FABP (2M) could be useful indicators of initial therapeutic response for predicting kidney prognosis in primary NS.This retrospective exploratory study aimed to identify early clinical indicators of kidney prognosis in primary nephrotic syndrome (NS). Univariate Cox proportional hazards regression analysis identified clinical parameters in the 2-month period after initiating immunosuppressive therapy (IST); it predicted 40% reduction in the estimated glomerular filtration rate (eGFR) in 36 patients with primary NS. Time-dependent receiver operating characteristic curve analysis was used to evaluate the performance of the predictors for the cumulative incidence of 40% reduction in the eGFR up to 8 years after initiating IST. The mean follow-up period was 71.9 months. The eGFR was reduced by 40% in four patients. Significant predictors for time to 40% reduction in the eGFR were as follows: an increase in the serum soluble urokinase plasminogen activator receptor (s-suPAR) 2 months after initiating IST (Δs-suPAR (2M); hazard ratio (HR) for every 500 pg/mL increase: 1.36,  The status of nephrotic syndrome  at 6 months after initiating immunosuppressive therapy (IST) is an important factor for predicting kidney prognosis in NS cases –3. In a In this regard, indiscriminately administering primary treatment for 6 months only to identify intractable NS can be insufficient. In clinical practice, kidney prognosis should be predicted using valuable biomarkers at 1-2 months after commencing treatment to determine the effectiveness of each patient's management plan . HoweverIn this retrospective exploratory study, we evaluated 47 patients with primary NS who were diagnosed using kidney biopsy at our hospital between January 2006 and December 2017. After excluding 11 patients who did not receive IST ), 36 patients who received IST were included in the final analysis. Of these, 18 had minimal-change NS (MCNS), seven had focal segmental glomerulosclerosis, nine had MN, and two had membranoproliferative glomerulonephritis. The patients' clinical data were obtained from their medical records and laboratory test reports, all of which were stored in an electronic medical record system.This study was approved by the Kanazawa Medical University Ethics Committee (No. I285) and conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. All patients provided written informed consent for participation.In 29 (80.6%) patients, the IST protocol was methylprednisolone (MP) pulse + prednisolone (PSL) + cyclosporine (CyA) and involved the administration of PSL and CyA after MP pulse (500 mg/day for 3 days). The IST protocols were PSL alone in three (8.2%), MP pulse + PSL + mizoribine in two (5.6%), and MP pulse + PSL in two (5.6%) patients.Daily urinary protein level was estimated as the urinary protein-to-creatinine ratio (u-PCR) in voided urine. Proteinuria remission was categorized as complete remission , incomplete remission type 1 , and incomplete remission type 2 . Intractable NS was defined as NS in which u-PCR does not decrease to <1 g/gCr despite treatments, including steroids and immunosuppressors, for 6 months. These definitions were based on the NS clinical practice guidelines of the Japanese Society of Nephrology .The eGFR in adult Japanese patients aged at least 18 years was calculated using the following equation: eGFR = 194 × age (year) − 0.287 × serum creatinine (mg/dL) − 1.094 × 0.739  . suPAR iFor the main analysis, the time to 40% reduction in the eGFR, which is a surrogate marker of ESKD –10, was In the secondary analysis, the outcome variable set was the achievement of ICR-1  by 6 months after initiating IST. The same clinical parameters used in the main analysis were used as explanatory variables in univariate logistic regression analysis to identify significant predictors of intractable NS. The performance (AUC) of the predictors for intractable NS identified in the secondary analysis was evaluated using ROC curve analysis, and the cutoff values were set to maximize the sum of sensitivity and specificity.P values were two-sided, and P < 0.05 was considered statistically significant. The P values reported in this manuscript are nominal values.Continuous variables are presented as means with standard deviation (SD) for normally distributed data and as the medians with interquartile range (IQR) for non-normally distributed data. All statistical analyses were performed using EZR  . All P v2. CyA was used for initial treatment in 29 (80.6%) patients.The mean patient age was 53.8 years, and the male-to-female ratio was 5 : 4. The baseline patient characteristics are summarized in X years after initiating IST . The cutoff value for each parameter is shown in The mean follow-up period in the study cohort was 71.9 months. There were four patients (11.1%) who showed 40% reduction in the eGFR; this was achieved at 80 months in a male patient in his 70s, at 17 months in an MCNS male patient in his 80s, and at 67 months in an MN male patient in his 70s and in an MN female patient in her 50s. In the main analysis, univariate Cox proportional hazards regression analysis showed that Δs-suPAR (2M), s-suPAR (2M), u-PCR (2M), and u-L-FABP (2M) were significant predictors of 40% reduction in the eGFR . No baseUsing the same clinical parameters used in the main analysis, Δs-suPAR (2M), s-suPAR (2M), u-PCR (2M), and u-L-FABP (2M) were found to be significant predictors of intractable NS  values to ICR-2, ICR-1, and CR levels could suppress the CI of 40% reduction in the eGFR by 2, 3–5, and 6–8 years after initiating IST, respectively. These findings suggest that reducing u-PCR (2M) to a lower level will reduce the long-term risk of kidney function deterioration. To the best of our knowledge, this study is the first to report on the feasibility of using Δs-suPAR (2M), s-suPAR (2M), u-PCR (2M), and u-L-FABP (2M) to define initial treatment response and predict long-term kidney prognosis in primary NS.β3 integrin-dependent podocyte injury and is involved in the onset of proteinuria in NS [Interestingly, this study revealed that a 3000 pg/mL cutoff value of s-suPAR (2M) predicted the occurrence of 40% reduction in the eGFR within 8 years of initiating IST, which was at the same level as the threshold of s-suPAR that induced podocyte injury in a previous study . s-suPARia in NS , 15; it ia in NS , 17. suPia in NS –17. In aia in NS , which iia in NS  that cauThis study demonstrated that serum (s-) suPAR, not urinary (u-), predicts kidney prognosis in primary NS. We hypothesize that this is because s-suPAR is the starting point of suPAR-induced kidney injury, which makes it superior to u-suPAR (which is only involved in part of the kidney injury mechanism) as a predictor of kidney prognosis. In other words, we believe that s-suPAR levels reflect both podocyte damage caused by s-suPAR and tubulointerstitial injury caused by u-suPAR, while u-suPAR levels reflect only the latter. Further, we found that the u-PCR and u-L-FABP were superior to s-suPAR as predictors of kidney prognosis. This could be because multiple humoral factors –23, inclThis study has several strengths. First, different statistical methods, namely, Cox proportional hazards regression analysis for 40% reduction in the eGFR –10 and lThis study also has certain limitations. First, it was a single-centre study with a small sample size and heterogenous causes of NS, which limits the generalizability of the results. Second, this was an exploratory study that was mainly intended to generate hypotheses. Therefore, prospective studies with larger sample sizes are needed to verify our results.In conclusion, Δs-suPAR (2M), s-suPAR (2M), u-PCR (2M), and u-L-FABP (2M) accurately predict 40% reduction in the eGFR. Thus, they may be useful noninvasive indicators for the early prediction of kidney prognosis after initial treatment in primary NS.


Body plethysmography (BP) is the standard pulmonary function test (PFT) in pulmonary emphysema diagnosis, but not all patients can cooperate to this procedure. An alternative PFT, impulse oscillometry (IOS), has not been investigated in emphysema diagnosis. We investigated the diagnostic accuracy of IOS in the diagnosis of emphysema. Eighty-eight patients from the pulmonary outpatient clinic at Lillebaelt Hospital, Vejle, Denmark, were included in this cross-sectional study. A BP and an IOS were performed in all patients. Computed tomography scan verified presence of emphysema in 20 patients. The diagnostic accuracy of BP and IOS for emphysema was evaluated with two multivariable logistic regression models: Model 1 (BP variables) and Model 2 (IOS variables). Model 1 had a cross-validated area under the ROC curve (CV-AUC) = 0.892 (95% CI: 0.654–0.943), a positive predictive value (PPV) = 59.3%, and a negative predictive value (NPV) = 95.0%. Model 2 had a CV-AUC = 0.839 (95% CI: 0.688–0.931), a PPV = 55.2%, and an NPV = 93.7%. We found no statistically significant difference between the AUC of the two models. IOS is quick and easy to perform, and it can be used as a reliable rule-out method for emphysema. Chronic obstructive pulmonary disease (COPD) is a disease characterized by airflow limitation and respiratory symptoms usually caused by exposure to noxious gases and particles . It is iThe role of pulmonary function tests (PFT) in diagnosing and monitoring the development of pulmonary emphysema is of great interest, as these tests hold the potential to reduce the need for CT scans. The most widely used and tested PFT is spirometry , and theImpulse oscillometry (IOS) is a PFT that measures airway resistance and reactance by oscillating sound waves of different frequencies through the respiratory system ,18. The IOS has been described in COPD ,27,28,29One hundred consecutive patients with pulmonary symptoms of all causes were included in a cross-sectional study to investigate the additional value of IOS in the investigation of pulmonary symptoms at the pulmonary outpatient clinic at Lillebaelt Hospital, Vejle, Denmark, between October 2018 and March 2019. A CT scan was performed in 88 of the patients. These 88 patients were included in the present study, which specifically investigates the diagnostic accuracy of IOS in emphysema. Data were collected retrospectively via patient records. A clinical assessment was performed in all patients on the day of inclusion, including disease history, a BP with hemoglobin-adjusted diffusing capacity for carbon monoxide (DLCOc % of predicted), and an IOS. BP was performed with the Jaeger MasterScreen Body, and IOS was performed with the Vyntus IOS, both combined with the SentrySuite software. Variables for symptoms were collected as binary variables (yes/no) according to presence or absence of the symptom. Comorbidities were collected in the same way, with one or more diseases within a defined domain resulting in a “yes”. Smoking history was defined as never smoker, former smoker, and current smoker. For this study, we have computed a binary variable of smoking history, where former and current smoker was combined and defined as having a positive smoking history.CT scans were performed either in relation to the present investigation or in relation to investigation of pulmonary symptoms prior to inclusion. Scans performed up to 3 years prior to study inclusion were included and evaluated by both a radiologist and an experienced pulmonologist (OH). They were visually scored for emphysema severity on a scale from 0 to 3 . For this study, we have computed a binary variable for the presence or absence of emphysema.t-test or Wilcoxon rank-sum test for continuous variables and Fischer’s exact test for categorical variables. The population was stratified based on the presence of emphysema on the CT scan. The two groups were compared using two-sample We considered a selected range of variables for multivariable logistic regression analyses based on relevance for the diagnosis of emphysema. The aim was to obtain simple, comparable, and generalizable models. Clinical variables were age, sex, body mass index (BMI), dyspnea, cough, and smoking history. BP variables were FEV1 % of predicted, FEV1/FVC, RV, TLC, and DLCOc % of predicted. IOS variables were R5 % of predicted, R5-20, Fres, X5, and Ax. The diagnostic accuracy of each of these variables was evaluated individually, with area under the ROC curve (AUC) for continuous variables and sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for categorical variables. For continuous variables, where higher values were associated with a lower probability of emphysema, the values were inverted.We then constructed two logistic regression models. Model 1 consisted of clinical variables and BP variables. Model 2 consisted of clinical variables and IOS variables. We included all considered variables and performed a stepwise backwards elimination, using likelihood ratio testing for nested models and Akaike Information Criterion (AIC) for non-nested model comparison. All clinical variables could be eliminated without affecting the models, except for smoking history in Model 2, and we included smoking history in both models.The remaining variables showed high multicollinearity, and we eliminated multicollinear variables based on AIC and link test for model specification. Overall goodness of fit was evaluated with Stukel’s test. In Model 1, we included the combined variable of RV/TLC, instead of RV and TLC individually. FEV1 % of predicted and FEV1/FVC were highly collinear, and we included only FEV1/FVC in the final model. In Model 2, R5 % of predicted and R5-20 were highly collinear. We included only R5 % of predicted based on lower AIC, better model specification, and a significantly higher AUC. Ax and X5 were highly collinear, and only Ax was included in the final model. We computed sensitivity, specificity, PPV, and NPV for both models, based on the cut-off point where sensitivity and specificity intersected. The AUCs were compared using the DeLong test for comparison of ROC curves. We then performed 5-fold cross-validated AUCs (CV-AUC). To explore potential bias in the exclusion of the 12 patients without a CT scan, we evaluated the difference in PFT parameters between the excluded patients and the included patients . Only DLSTATA 17 was used for all statistical analyses.Patient characteristics stratified by presence of emphysema can be seen in The diagnostic accuracy of all the individual variables considered for the regression models is displayed in The AUC for the BP parameters, FEV1 % of predicted, FEV1/FVC, RV/TLC, and DLCOc % of predicted, were 0.842 (95% CI: 0.728–0.955), 0.874 (95% CI: 0.766–0.981), 0.743 (95% CI: 0.621–0.865), and 0.795 (95% CI: 0.682–0.908), respectively. The AUC for the IOS parameters, R5 % of predicted, R5-20, X5, Fres, and Ax, were 0.592 (95% CI: 0.431–0.754), 0.718 (95% CI: 0.568–0.867), 0.630 (95% CI: 0.462–0.798), 0.742 (95% CI: 0.603–0.881), and 0.704 (95% CI: 0.537–0.870), respectively.p = 0.037).p = 0.37).The ROC curves for the regression models are shown in We have evaluated the diagnostic accuracy of IOS for pulmonary emphysema in a population of patients with respiratory symptoms of all causes. IOS was compared to BP, including oxygen diffusing capacity, and it showed an excellent discriminatory ability (AUC > 0.80) . AlthougIOS has mainly been investigated in asthma, especially in children, because of its minimal requirement for patient cooperation ,32. HoweA key feature of IOS is its effectiveness in the detection of small airways disease (SAD), which is highly related to emphysema , and it The inclusion of R5 % of predicted in Model 2 resulted in a significantly better AUC than when including R5-20. This contrasts with the univariate ROC curve analyses seen in Spirometry and BP have also been investigated in relation to emphysema. A systematic review from 2012 investigated the correlation between CT emphysema measurements and airway obstruction parameters in spirometry . Both FEIn our study population, 9 patients had mild emphysema, 8 had moderate emphysema, and 3 had severe emphysema. It is difficult to determine how this distribution could affect our results, as the literature on IOS in emphysematous copd is extremely limited. As IOS may be better in detecting SAD than spirometry, and SAD is linked to emphysema with SAD likely preceding emphysematous destruction of lung tissue , it may There are some limitations to this study. The small study sample increases the risk of type 2 errors, and the study population is heterogenous. The study includes 88 patients with pulmonary symptoms of different causes, and the results may not be directly applicable in a population of patients with COPD. However, this study also has several strengths. Because of the small study sample, we created diagnostic models that are small and simple, which enhances replicability and generalizability. This has the added value of being easily understandable and applicable by clinicians in the daily setting. Another strength of the study is the cross validation of the AUCs, which further enhances generalizability.In conclusion, IOS showed excellent diagnostic accuracy for emphysema. BP showed a higher AUC than did IOS in the discrimination between presence and absence of emphysema, but the difference was not statistically significant. IOS is both quick and easy to perform, and it can be used when BP is not possible and as a reliable rule-out method for emphysema in clinical settings where time and space is limited. IOS may be a helpful alternative tool in the detection and management of emphysematous COPD, and studies investigating these qualities in a selected population of patients with COPD may elevate the usefulness of IOS in COPD.