Body composition, physical activity, and quality of life in pediatric patients with inflammatory bowel disease on anti-TNF therapy-an observational follow-up study.

BACKGROUND: Poor outcome of inflammatory bowel disease (IBD) is associated with malnutrition. Our aim was to compare body composition (BC) and physical activity (PA) between patients with IBD and healthy controls, and to assess the changes in BC, PA and health related quality of life (HRQoL) in children with IBD during anti-TNF therapy. METHODS: 32 children with IBD (21 with Crohn's disease (CD), (age: 15.2 ± 2.6 years, 9 male) and 11 with ulcerative colitis (UC), (age: 16.4 ± 2.2 years, 5 male) participated in this prospective, observational follow up study conducted at Semmelweis University, Hungary. As control population, 307 children (age: 14.3 ± 2.1) (mean ± SD) were included. We assessed BC via bioelectric impedance, PA and HRQoL by questionnaires at initiation of anti-TNF therapy, and at two and six months later. The general linear model and Friedman test were applied to track changes in each variable. RESULTS: During follow-up, the fat-free mass Z score of children with CD increased significantly (-0.3 vs 0.1, p = 0.04), while the BC of patients with UC did not change. PA of CD patients was lower at baseline compared to healthy controls (1.1 vs. 2.4), but by the end of the follow up the difference disappeared. CONCLUSIONS: The fat-free mass as well as PA of CD patients increased during the first six months of anti-TNF treatment. As malnutrition and inactivity affects children with IBD during an important physical and mental developmental period, encouraging them to engage in more physical activity, and monitoring nutritional status should be an important goal in patient care.

Graft Arterial Dissection and Thrombosis After Kidney Transplantation With Undiagnosed Fibromuscular Dysplasia From a Deceased Donor: Case Report and Review.

BACKGROUND: Fibromuscular dysplasia (FMD), a relatively frequent arterial deformity with an estimated prevalence of 2% to 6% has been sporadically reported during deceased donor kidney donations. Only 8 case reports are available in the previous literature. CASE PRESENTATION: In our work, implantation of 2 kidneys from the same deceased donor with macroscopically evident and later histologically confirmed FMD are presented, one of which ended up as acute arterial complication. Renal arteries were cut short to allow safe implantation, but arterial dissection and thrombosis led to graft loss in the early perioperative period in the latter case. CONCLUSIONS: Although resection of the arterial segments affected by FMD as a routine may allow implantation, macroscopically healthy-looking arteries might still be affected and thus carry elevated postoperative risk. The aim of our case report is to make proposal for an onsite diagnosis of FMD in case of clinical suspicion.

The Importance of Arterial Stiffness Assessment in Patients with Familial Hypercholesterolemia.

Cardiovascular diseases are still the leading cause of mortality due to increased atherosclerosis worldwide. In the background of accelerated atherosclerosis, the most important risk factors include hypertension, age, male gender, hereditary predisposition, diabetes, obesity, smoking and lipid metabolism disorder. Arterial stiffness is a firmly established, independent predictor of cardiovascular risk. Patients with familial hypercholesterolemia are at very high cardiovascular risk. Non-invasive measurement of arterial stiffness is suitable for screening vascular dysfunction at subclinical stage in this severe inherited disorder. Some former studies found stiffer arteries in patients with familial hypercholesterolemia compared to healthy controls, while statin treatment has a beneficial effect on it. If conventional drug therapy fails in patients with severe familial hypercholesterolemia, PCSK9 inhibitor therapy should be administered; if these agents are not available, performing selective LDL apheresis could be considered. The impact of recent therapeutic approaches on vascular stiffness is not widely studied yet, even though the degree of accelerated athero and arteriosclerosis correlates with cardiovascular risk. The authors provide an overview of the diagnosis of familial hypercholesterolemia and the findings of studies on arterial dysfunction in patients with familial hypercholesterolemia, in addition to presenting the latest therapeutic options and their effects on arterial elasticity parameters.

Association between affective temperaments and arterial stiffness index in chronic hypertensive patients. / Az affektív temperamentumok és az artériás érfalmerevségi index kapcsolata krónikus hypertoniás betegekben.

Összefoglaló. Bevezetés: Az affektív temperamentumok (depresszív, cyclothym, hyperthym, ingerlékeny, szorongó) a személyiségnek olyan genetikailag meghatározott, felnottkorban stabil részei, amelyekkel jellemezhetok a környezeti ingerekre adott érzelmi válaszok. Az artériás érfalmerevségi index megmutatja, hogy az adott egyénnek a valóságban mért és az elvárt pulzushullám-terjedési sebessége (PWV) milyen arányban áll egymással; pozitív értéke számít kórosnak. Célkituzés: Célunk az volt, hogy az affektív temperamentumok kapcsolatát vizsgáljuk az artériás érfalmerevségi indexszel krónikus hypertoniás betegekben. Módszer: A bevont betegeknél tonometriás eszközzel (PulsePen) mértük a carotis-femoralis PWV-t, mely az artériás érfalmerevség legelfogadottabb markere. Az artériás érfalmerevségi indexet a mért és az elvárt PWV arányában határoztuk meg. Az affektív temperamentumokat a Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire kérdoív (TEMPS-A) segítségével objektivizáltuk. Eredmények: Vizsgálatunkba 185 beteget vontunk be, életkoruk 61,6 (49,5-69,8) év volt. Kortól, nemtol, diabetestol, alkoholfogyasztástól, dohányzástól, BMI-tol, systolés vérnyomástól, összkoleszterinszinttol és GFR-tol független kapcsolatot találtunk az artériás érfalmerevségi index és a depresszív (B = 0,009, 95% CI: 0,002-0,017, p = 0,018), a cyclothym (B = 0,009, 95% CI: 0,002-0,016, p = 0,012), az ingerlékeny (B = 0,013, 95% CI: 0,005-0,021, p<0,001) és a szorongó (B = 0,008, 95% CI: 0,003-0,013, p<0,001) temperamentum között. Következtetés: Újabb kapcsolatot sikerült kimutatni egy cardiovascularis rizikót jelzo paraméter és az affektív temperamentumok között, ami megerosíti ezen személyiségjegyek meghatározásának jelentoségét cardiovascularis prevenciós szempontból is az ismert pszichopatológiai vonatkozások mellett. Orv Hetil. 2022; 163(8): 312-318. INTRODUCTION: Affective temperaments (depressive, anxious, cyclothymic, hyperthymic, irritable) are genetically determined, adult-stable parts of the personality that characterize emotional responses to environmental stimuli. The arterial stiffness index demonstrates the ratio of the actually measured and expected pulse wave velocity (PWV) of a given individual. The positive value is considered to be abnormal. OBJECTIVE: The aim of this study was to investigate the relationship between affective temperaments and arterial stiffness index in chronic hypertensive patients. METHOD: Carotid-femoral PWV, the most accepted marker of arterial stiffness, was measured using a tonometric device (PulsePen). The arterial stiffness index was determined as the ratio of measured and expected PWVs. Affective temperaments were evaluated by the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A). RESULTS: The study included 185 patients, with a mean age of 61.6 (49.5-69.8) years. We found association between arterial stiffness index and depressive (B = 0.009, 95% CI: 0.009-0.017, p = 0.018), cyclothymic (B = 0.009, 95% CI: 0.002-0.016, p = 0.012), irritable (B = 0.013, 95% CI: 0.005-0.021, p = 0.001), and anxious (B = 0.008, 95% CI: 0.003-0.013, p = 0.001) temperaments independent of age, sex, diabetes, alcohol consumption, smoking, BMI, systolic blood pressure, total cholesterol, and GFR. CONCLUSION: An additional relationship between a cardiovascular risk measure and affective temperaments has been demonstrated, confirming the importance of determining these personality traits aiming cardiovascular prevention in addition to their known psychopathological aspects. Orv Hetil. 2022; 163(8): 312-318.

Seroconversion after anti-SARS-CoV-2 mRNA vaccinations among moderate-to-severe psoriatic patients receiving systemic biologicals-Prospective observational cohort study.

It is unclear whether biological antipsoriatic therapies affect seroconversion after messenger ribonucleic acid (mRNA)-based antisevere acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) vaccinations. To assess antibody formation and the incidence of side effects after anti-SARS-CoV-2 mRNA vaccinations in psoriatic patients receiving different biologicals compared to healthy controls. 102 moderate-to-severe psoriatic patients (56.2 [±13.5] years) and 55 age-matched healthy (56.4 ± 13.6 years) volunteers were included in our study. Ten to 21 days after the administration of the second dosage of BNT162b2 or mRNA-1273 vaccine, antibody levels specific to the SARS-CoV-2 spike (S) protein receptor binding domain were monitored. The incidence of postvaccination side effects was recorded and compared to real-life data in the literature. Of the 102 patients, 57 (55.88%) received tumor necrosis factor (TNF), 28 (27.45%) received interleukin (IL)-12/23, 16 (15.68%) received IL-17, and 1 (0.99%) received IL-23 inhibitors. No significant differences in the median serum level of anti-SARS-CoV-2S antibody were observed between the study population and the control group (median IQR range: 1681.0 U/mL (600.0-4844.0) versus 1984.0 U/mL (1000.0-3136.0; p = 0.82). The most frequent side effects of the mRNA vaccines within 7 days after the administration of both dosages were arm pain on the side of injection (23.53% and 23.53%), fatigue (9.80% and 13.72%), headache (4.9% and 5.88%), and chills or shivering (4.9% and 8.82%). Detectable antibodies against SARS-CoV-2S protein appear 10-21 days after the administration of the second dosage of BNT162b2 or mRNA-1273 vaccines in moderate-to-severe psoriatic patients receiving biologicals, similar to those of healthy controls.

Oxygenated End-Hypothermic Machine Perfusion in Expanded Criteria Donor Kidney Transplant: A Randomized Clinical Trial.

Importance: Continuous hypothermic machine perfusion during organ preservation has a beneficial effect on graft function and survival in kidney transplant when compared with static cold storage (SCS). Objective: To compare the effect of short-term oxygenated hypothermic machine perfusion preservation (end-HMPo2) after SCS vs SCS alone on 1-year graft survival in expanded criteria donor kidneys from donors who are brain dead. Design, Setting, and Participants: In a prospective, randomized, multicenter trial, kidneys from expanded criteria donors were randomized to either SCS alone or SCS followed by end-HMPo2 prior to implantation with a minimum machine perfusion time of 120 minutes. Kidneys were randomized between January 2015 and May 2018, and analysis began May 2019. Analysis was intention to treat. Interventions: On randomization and before implantation, deceased donor kidneys were either kept on SCS or placed on HMPo2. Main Outcome and Measures: Primary end point was 1-year graft survival, with delayed graft function, primary nonfunction, acute rejection, estimated glomerular filtration rate, and patient survival as secondary end points. Results: Centers in 5 European countries randomized 305 kidneys (median [range] donor age, 64 [50-84] years), of which 262 kidneys (127 [48.5%] in the end-HMPo2 group vs 135 [51.5%] in the SCS group) were successfully transplanted. Median (range) cold ischemia time was 13.2 (5.1-28.7) hours in the end-HMPo2 group and 12.9 (4-29.2) hours in the SCS group; median (range) duration in the end-HMPo2 group was 4.7 (0.8-17.1) hours. One-year graft survival was 92.1% (n = 117) in the end-HMPo2 group vs 93.3% (n = 126) in the SCS group (95% CI, -7.5 to 5.1; P = .71). The secondary end point analysis showed no significant between-group differences for delayed graft function, primary nonfunction, estimated glomerular filtration rate, and acute rejection. Conclusions and Relevance: Reconditioning of expanded criteria donor kidneys from donors who are brain dead using end-HMPo2 after SCS does not improve graft survival or function compared with SCS alone. This study is underpowered owing to the high overall graft survival rate, limiting interpretation. Trial Registration: isrctn.org Identifier: ISRCTN63852508.

Transplantation of kidneys from hepatitis C-infected donors to hepatitis C-negative recipients: Single center experience.

Our aim was to evaluate the safety of transplanting kidneys from HCV-infected donors in HCV-uninfected recipients. Data collected from 53 recipients in a single center, observational study included donor and recipient characteristics, liver and kidney graft function, new infections and de novo donor-specific antibodies and renal histology. Treatment with a direct-acting antiviral regimen was initiated when HCV RNA was detected. The mean ± SD age of recipients was 53 ± 11 years, 34% were female, 19% and 79% of recipients were white and African American, respectively. The median and interquartile range (IQR) time between transplant and treatment initiation was 76 (IQR: 68-88) days. All 53 recipients became viremic (genotype: 1a [N = 34], 1b [N = 1], 2 [N = 3], and 3 [N = 15]). The majority (81%) of recipients did not experience clinically significant increases (>3 times higher than upper limit of the normal value) in aminotransferase levels and their HCV RNA levels were in the 5 to 6 log range. One patient developed fibrosing cholestatic hepatitis with complete resolution. All recipients completed antiviral treatment and 100% were HCV RNA-negative and achieved 12-week sustained virologic response. The estimated GFRs at end of treatment and 12-week posttreatment were 67 ± 21 mL/min/1.73 m2 and 67 ± 17 mL/min/1.73 m2 , respectively. Four recipients developed acute rejection. Kidney transplantation from HCV-infected donors to HCV-negative recipients should be considered in all eligible patients.

Shear-wave elastography for the assessment of liver fibrosis in liver transplant recipients treated for hepatitis C virus recurrence.

OBJECTIVES: Direct-acting antiviral agents have revolutionized hepatitis C therapy, and are also found to be effective in the liver transplant setting. The extent of liver fibrosis influences patient management and is used to monitor therapeutic effects. Shear-wave elastography (SWE) is a relatively new imaging-based method that has not yet been studied extensively in liver transplant patients. Our aim was to study the effect of direct-acting antivirals in heaptitis C recurrence on liver stiffness determined by SWE. PATIENTS AND METHODS: A total of 23 liver transplant patients with hepatitis C recurrence were enrolled in this prospective study. The patients underwent 24 weeks of ombitasvir/paritaprevir/ritonavir+dasabuvir±ribavirin combination therapy. Elastographic examinations, serological tests and laboratory tests were performed, and serum biomarkers of liver fibrosis were calculated the day before treatment (baseline) and at the end of the treatment. RESULTS: All our patients became hepatitis C virus RNA negative by the end of the treatment. Median liver stiffness values decreased significantly after treatment compared with baseline (8.72±3.77 vs. 7.19±2.4 kPa; P<0.001). Among the studied laboratory values, a significant decrease was observed in the levels of alanine aminotransferase, aspartate aminotransferase and γ-glutamyltransferase, whereas international normalized ratio levels increased. Serum biomarkers, namely aspartate aminotransferase-to-platelet ratio index and Fibrosis-4, decreased significantly after treatment compared with baseline. CONCLUSION: In the present study, SWE was succesfully used to monitor the beneficial therapeutic effects of direct-acting antivirals in hepatitis C recurrence following liver transplantation. We believe that SWE is a useful noninvasive diagnostic tool in the follow-up of hepatitis C treatment in liver transplant patients.

Association of affective temperaments with blood pressure and arterial stiffness in hypertensive patients: a cross-sectional study.

BACKGROUND: Affective temperaments (anxious, depressive, cyclothymic, irritable and hyperthymic) measure subclinical manifestations of major mood disorders. Furthermore, cumulating evidence suggests their involvement in somatic disorders as well. We aimed to assess associations between affective temperament scores and blood pressure and arterial stiffness parameters in hypertensive patients. METHODS: In this cross-sectional study, 173 patients with well-controlled or grade 1 chronic hypertension, with no history of depression, completed the TEMPS-A, Beck Depression Inventory (BDI) and Hamilton Anxiety Scale (HAM-A) questionnaires in three GP practices. Arterial stiffness was measured with tonometry (PulsePen). RESULTS: According to multiple linear regression analysis, cyclothymic temperament score was positively associated with brachial systolic blood pressure independently of age, sex, total cholesterol, brachial diastolic blood pressure, BDI, HAM-A and the use of alprazolam (ß = 0.529, p = 0.042), while hyperthymic temperament score was negatively related to augmentation index independent of age, sex, smoking, heart rate, BDI, HAM-A and the use of alprazolam (ß = -0.612, p = 0.013). A significant interaction was found between cyclothymic temperament score and sex in predicting brachial systolic blood pressure (p = 0.025), between irritable and anxious temperament scores and sex in predicting pulse wave velocity (p = 0.021, p = 0.023, respectively) and an interaction with borderline significance between hyperthymic temperament score and sex in predicting augmentation index (p = 0.052). CONCLUSIONS: The present findings highlight elevated blood pressure among subjects with high cyclothymic temperament as well as an increased level of arterial stiffening in subjects with low hyperthymic scores suggesting that affective temperaments may play a role in the development of hypertension and arterial stiffening and may thus represent markers of cardiovascular risk. Sex differences were also present in these associations.

Mycophenolate Mofetil Therapy in Children With Idiopathic Nephrotic Syndrome: Does Therapeutic Drug Monitoring Make a Difference?

BACKGROUND: Idiopathic nephrotic syndrome (INS) necessitates administration of corticosteroids or corticoid-sparing agents in 60% of the cases for prolonged periods resulting in serious adverse effects. METHODS: To avoid these complications, we investigated the efficacy and safety of mycophenolate mofetil (MMF) in our retrospective single-center study with 15 patients presenting with complicated courses of INS and aspired to estimate a cutoff level for mycophenolic acid-area under the curve (MPA-AUC) values, which can predict relapses with high sensitivity. RESULTS: Seven of 15 patients stayed in remission while receiving MMF. Average frequency of relapses was 1.39 (0.28-2.5) per year. In case of relapses, patients had lower predose and estimated AUC0-12 levels of MPA (P = 0.02 and 0.001, respectively). Based on the results of receiver operating characteristic analysis, we consider an estimated MPA-AUC0-12 lower than 44.6 mg·h·L(-1) as a risk factor for future relapses (91% sensitivity, 57% specificity, P = 0.06) because the prevalence of relapse is significantly lower (0.07 versus 0.5, P = 0.02), if the estimated MPA-AUC0-12 is >44.6 mg·h·L(-1). During MMF administration, we did not detect any adverse event requiring discontinuation of treatment. CONCLUSIONS: In conclusion, we demonstrate MMF as an alternative treatment for children with complicated INS to maintain remission without serious side effects. Furthermore, we propose a higher therapeutic target range of MPA-AUC0-12 (>45 mg·h·L(-1)) than used in transplanted children underlining the crucial role of therapeutic drug monitoring.

Voiding urosonography with second-generation contrast agent versus voiding cystourethrography.

Contrast-enhanced voiding urosonography (VUS) is becoming more widely used for the diagnosis of vesicoureteric reflux (VUR). The purpose of this study was to evaluate the sensitivity of VUS using a second-generation ultrasound (US) contrast agent and compare it with standard fluoroscopic voiding cystourethrography (VCUG). A total of 183 children with 366 kidney-ureter units (KUUs) underwent VUS and VCUG in the same session with the same catheterization. VUS was performed after intravesical administration of 1 ml of a second-generation ultrasound contrast agent (UCA; SonoVue, Bracco, Italy). VUR was detected in 140 out of 366 cases (38%); in 89 (24.3%) by both methods, in 37 (10.1%) by VUS only, and in 14 (3.8%) by VCUG only. Although there was considerable agreement in the diagnosis of VUR by VUS and VCUG (κ=0.68, standard error [κ]=0.04), the difference in the detection rate of reflux between VUS and VCUG was significant (p<0.00001). The grade of VUR detected with VUS showed moderate agreement with grading by VCUG. Our findings suggest that contrast-enhanced harmonic VUS using a second-generation contrast agent is superior to VCUG in the detection and grading of VUR, and it should be the method of choice for this clinical indication.

Captopril-enhanced renal scintigraphy in the diagnosis of pediatric hypertension.

Hypertension in childhood is no longer a rare condition mainly secondary to renal, or renovascular diseases, as a growing proportion of children are obese and hypertensive, with the phenotype of metabolic syndrome. Thus, we need to reconsider our practice in the examination of the hypertensive child and redefine the place of non-invasive methods for screening of renovascular hypertension, and specifically, to evaluate the value of captopril-enhanced renal scintigraphy at the two ends of the palette: the obese child with hypertension and the severely hypertensive prepubertal child. Renal artery stenosis in children is mainly due to fibromuscular dysplasia and stenoses associated with syndromes involving single or multiple smaller branch vessels. This explains the low specificity and sensitivity of the color-Doppler ultrasound method and captopril renal scintigraphy. Even the more sophisticated computed tomography (CT) and magnetic resonance imaging (MRI) angiographic techniques are, at present, not sensitive enough to exclude stenoses of the small branches definitely. Thus, children in whom there is a strong suggestion of renovascular hypertension should undergo angiography with a view to endovascular treatment, as non-invasive imaging has no significant benefit and might lead to a delay in treatment. In the cases when the probability of renovascular disease is moderate a basic assessment of renal function and structure is sufficient. In the neonate, catheter-associated thromboembolic disease is among the most common causes hypertension. It should be controlled medically until the patient is old enough to undergo angiography and angioplasty successfully. Thus, in this age group, there is a place for functional imaging with renal sonography and angiotensin-converting enzyme inhibitor (ACEI) renography to detect hemodynamically significant renovascular disease, with the limitations mentioned above. However, the rapid technical evolution of non-invasive methods requires periodic re-consideration of the actual standpoints.

Effects of bone and mineral metabolism on arterial elasticity in chronic renal failure.

Arterial stiffness (Ast) individually predicts cardiovascular (CV) mortality. Ast increases via vascular calcification and can be characterized by pulse wave velocity (PWV). We assessed the influence of mineral and bone metabolism on Ast in dialyzed (D) and renal transplanted (Tx) children by measuring fetuin-A and bone markers [bone-specific alkaline phosphatase (BALP); beta-CrossLaps (beta)]. Normalized PWV/height (PWV/h) of 11 D and 17 Tx patients was measured by applanation tonometry. Levels of calcium (Ca), phosphate (P), fetuin-A, and bone markers were analyzed. Ca x P/fetuin-A ratio was calculated to characterize the balance of calcification and inhibition. Cumulative dose of calcitriol was also assessed. Fetuin-A was lower in D and Tx compared with healthy controls. Bone markers and Ca x P/ fetuin-A of D were significantly higher than those of Tx and controls. In D PWV/h correlated with Ca x P/fetuin-A and BALP (r=0.8; p=0.005, r=0.6, p=0.05, respectively); BALP correlated with Ca x P/fetuin-A (r=0.7, p=0.01). In Tx, there was a correlation between calcitriol administered before transplantation and PWV/h (r=0.5, p=0.04). Increased bone turnover was coupled with an increased potential of calcium-phosphate precipitation, as shown by the increased Ca x P/fetuin-A. It might explain the connection between disturbed mineral and bone metabolism and Ast. Tx might be beneficial on Ast, though follow-up studies are needed.