Progressive Insufficiency Research Articles

GSDMD Mediates Ang II-Induced Hypertensive Nephropathy by Regulating the GATA2/AQP4 Signaling Pathway.

Hypertensive nephropathy is a common complication of hypertension. However, no effective measures are currently available to prevent the progression of renal insufficiency. Gasdermin D (GSDMD) is a crucial mediator of pyroptosis that induces an excessive inflammatory response. In the present study, we aimed to determine the effect of GSDMD on the pathogenesis of hypertensive nephropathy, which may provide new insights into the treatment of hypertensive nephropathy. C57BL/6 (wild-type, WT) and Gsdmd knockout (Gsdmd-/-) mice were subcutaneously infused with angiotensin II (Ang II) via osmotic mini-pumps to establish a hypertensive renal injury model. Recombinant adeno-associated virus serotype 9 (AAV9) carrying GSDMD cDNA was used to overexpress GSDMD. Renal function biomarkers, histopathological changes, and inflammation and fibrosis indices were assessed. Transcriptome sequencing (RNA-seq) and cleavage under targets and mentation (CUT & Tag) experiments were performed to identify the downstream pathogenic mechanisms of GSDMD in hypertensive nephropathy. GSDMD was activated in the kidneys of mice induced by Ang II (P < 0.001). This activation was primarily observed in the renal tubular epithelial cells (P < 0.0001). GSDMD deficiency attenuated renal injury and fibrosis induced by Ang II (P < 0.0001), whereas Gsdmd overexpression promoted renal injury and fibrosis (P < 0.01). Mechanistically, GSDMD increased Ang II-induced GATA binding protein 2 (GATA2) transcription factor expression (P < 0.01). GATA2 also bound to the aquaporin 4 (Aqp4) promoter sequence and facilitated Aqp4 transcription (P < 0.001), leading to renal injury and fibrosis. Moreover, treatment with GI-Y1, an inhibitor of GSDMD, alleviated Ang II-induced renal injury and fibrosis (P < 0.01). GSDMD plays an important role in the development of hypertensive nephropathy. Targeting GSDMD may be a therapeutic strategy for the treatment of hypertensive nephropathy.

Surgical Treatment of Unusual Anatomy of the Tricuspid Valve in Ebstein’s Anomaly

Ebstein’s anomaly is a congenital heart disease in which the septal and posterior leaflets of the tricuspid valve are displaced to the apex of the right ventricle, forming its atrialization. In contrast, the anatomical position of the anterior leaflet usually remains normal. The aim. To present and analyze a case of surgical treatment of Ebstein’s anomaly with a rare anatomy – isolated displacement of the anterior leaflet of the tricuspid valve. Case report. We present a rare clinical case of isolated displacement of the anterior leaflet of the tricuspid valve into the right ventricular cavity with the formation of a right atrial aneurysm. The diagnosis was made prenatally and confirmed after the birth of the child by echocardiography. Surgical intervention was postponed and successfully performed at the age of six years due to the progression of tricuspid insufficiency and increase in the right atrial aneurysm. We achieved a reduction in the size of the right atrium (diameter 31 mm, volume 25 ml and area 10 cm2) and minimized insufficiency at the tricuspid valve. The total duration of the surgical intervention was 270 minutes. The intra- and postoperative periods were uneventful. The duration of the patient’s stay in the intensive care unit was 4 days. We believe that this pathology of the anterior leaflet of the tricuspid valve should be interpreted as a variant of Ebstein’s anomaly. Conclusion. Isolated tricuspid valve anterior leaflet displacement with right atrial aneurysm is amenable to surgical correction with good immediate and long-term results.

Adrenoleukodystrophy an Overview

Adrenoleukodystrophy (ALD) is a rare X-linked peroxisomal oxidation disease caused by mutations in ABCD1. It presents with various clinical manifestations, including cerebral ALD, myelopathy, and primary adrenal insufficiency. About 80% of ALD patients suffer from adrenal insufficiency, and cerebral ALD affects one-third of boys under twelve, progressing to total impairment and death without treatment. Hematopoietic stem cell transplantation (HSCT) is the only disease-modifying treatment for early-stage cerebral ALD, but it does not halt adrenal insufficiency progression and carries significant morbidity and mortality risks. A recent gene therapy clinical trial showed short-term MRI and neurological outcomes equivalent to past HSCT treatments without the adverse side effects. Additionally, over a dozen states have initiated newborn screening (NBS) for ALD, with the number expected to triple by 2020. Genetic testing of NBS-positive newborns has identified novel variations of unknown significance, raising questions about monitoring and treating preclinical or moderate adrenal insufficiency or cerebral involvement. This presents further opportunities for genetic characterization. The availability of matching donors, transplant centers, and specialists will impact prompt treatment for those diagnosed with ALD at birth. As NBS and gene therapy trials improve ALD's clinical management and prognosis, endocrine management of presymptomatic and subclinical adrenal insufficiency will become increasingly important.

The Budd-Chiari Syndrome as a Complication of Paroxysmal Nocturnal Hemoglobinuria (Clinical Case)

Among the main causes of recurrent thrombosis in young patients there is paroxysmal nocturnal hemoglobinuria (PNH), a complication of which is Budd-Chiari syndrome (BCS), characterized by thrombosis of the hepatic veins and/or inferior vena cava. Detection of PNH is an extremely important task, because its untimely diagnosis leads to recurrent thrombosis, deterioration of the patient’s quality of life, and increased mortality from complications which accompany PNH. The article analyzes a clinical case of PNH in a young patient with recurrent BCS, which illustrates the relevance and timely diagnosis of this disease. As a result of unsuccessful pharmacological treatment and progression of liver insufficiency, the patient had liver transplantation. After surgery and standard post-transplantation therapy the patient’s condition improved, but after some time a recurrence of hepatic vein thrombosis was developed. After hematologist consultation and performing flow cytometry, the patient was diagnosed PNH. However, on the background of recurrent hepatic vein thrombosis, immunosuppressive therapy, and the lack of targeted treatment for PNH, multiple organ failure was developed, which led to the patient’s death. PNG is one of the orphan diseases, which is characterized by a severe, chronic, progressive course and accompanied by the formation of degenerative changes in the body, a decrease in the quality and shortening of the patient’s life. Targeted therapy can reduce the risk of thrombosis, red blood cell transfusions and improve the quality of life of patients with PNH.

Management of aortic valve insufficiency in patients with continuous-flow left ventricular assist device: a republication of the review published in Japanese Journal of Artificial Organs.

Since 2011, implantable ventricular assist devices have been a standard treatment for severe heart failure alongside heart transplantation in Japan. However, the limited availability of donors has led to a prolonged wait for transplants, now averaging 1719days, intensifying the issue of aortic insufficiency in patients with continuous flow ventricular assist devices. These devices limit the opening of the aortic valve, leading to sustained closure and increased shear stress, which accelerates valve degradation. Risk factors for aortic insufficiency include having a smaller body surface area, being of advanced age, and the presence of mild aortic insufficiency prior to device implantation. In patients presenting with mild or moderate aortic regurgitation at the time of ventricular assist device implantation, interventions such as aortic valve repair or bioprosthetic valve replacement are performed with the aim of halting its progression. The choice of surgical procedure should be tailored to each patient's individual condition. The management of de novo aortic insufficiency in patients with continuous flow ventricular assist devices remains challenging, with no clear consensus on when to intervene. Interventions for significant aortic insufficiency typically consider the patient's symptoms and aortic insufficiency severity. De novo aortic insufficiency progression in continuous flow ventricular assist devices patients necessitates careful monitoring and intervention based on individual patient assessments and valve condition. This review was created based on a translation of the Japanese review written in the Japanese Journal of Artificial Organs in 2023 (Vol. 52, No. 1, pp. 77-80), with some modifications.

Anatomical-functional state of surface lymphatic system of lower extremities in chronic vein diseases according to fluorescence lymphograph

Despite the large arsenal of diagnostic methods for studying the lymphatic system, there are isolated works on its morpho-functional state in chronic venous insufluciency. The purpose of the study was to study the anatomical and physiological state of the surface lymphatic system of the lower extremities in persons with different clinical classes of chronic vein diseases using fluorescence lifography. The study was conducted in 105 patients divided into six groups according to the clinical class of chronic diseases of the veins of the lower extremities according to the CEAP classiffication. We used fluorescent lymphography using sodium fluorescein to study the anatomical and functional capabilities of the lymphotone. The study revealed that morphofunctional changes in superficial lymphatic vessels in chronic lower extremity vein diseases depend on venous system decompensation. With an increase in the clinical class of chronic diseases of the veins of the lower extremities, the rate of lymph flow through the superficial lymphatic vessels is statistically significantly reduced. At the same time, the antegrade lymph cell is completely absent in С5-С6, with the appearance of retrograde outflow and discharge of the lymph into the deep lymph vessels. Thus, the progression of chronic venous insufficiency leads to proportional progression of morphofunctional changes in the superficial lymphatic system, which leads to the formation of lymphovenous insufficiency.

Resveratrol-βcd inhibited premature ovarian insufficiency progression by regulating granulosa cell autophagy

BackgroundThe ovarian environment of premature ovarian insufficiency (POI) patients exhibits immune dysregulation, which leads to excessive secretion of numerous proinflammatory cytokines that affect ovarian function. An abnormal level of macrophage polarization directly or indirectly inhibits the differentiation of ovarian granulosa cells and steroid hormone production, ultimately leading to POI. Resveratrol, as a health supplement, has been widely recognized for its safety. There is a substantial amount of evidence indicating that resveratrol and its analogs possess significant immune-regulatory functions. It has also been reported that resveratrol can effectively inhibit the progression of POI. However, the underlying immunological and molecular mechanisms through which resveratrol inhibits the progression of POI are still unclear.ResultsOur preliminary reports have shown that resveratrol-βcd, the beta-cyclodextrin complex of resveratrol, significantly enhances the stability of resveratrol. Resveratrol-βcd could regulate the dysfunctional immune status of macrophages and T cells in the tumor microenvironment. In this study, we treated busulfan and cyclophosphamide (B/C)-treated mice, which were used as a POI model, with resveratrol-βcd. After resveratrol-βcd treatment, the levels of IL-6 in the ovaries were significantly increased, and the progression of POI was suppressed. IL-6 activated granulosa cells (GCs) through soluble IL-6R (sIL-6R), promoting autophagy in GCs. Resveratrol-βcd and IL-6 had a synergistic effect on enhancing autophagy in GCs and promoting E2 secretion.ConclusionsWe partially elucidated the immune mechanism by which resveratrol inhibits the progression of POI and the autophagy-regulating function of GCs. This provides a theoretical basis for using resveratrol to prevent POI in future studies and clinical guidance.

Combined effects of sodium-glucose cotransporter 2 inhibitor and angiotensin receptor-neprilysin inhibitor on renal function in cardiovascular disease patients with type 2 diabetes mellitus: a retrospective cohort study.

Angiotensin receptor/neprilysin inhibitor (ARNI) and sodium-glucose cotransporter 2 inhibitor (SGLT2i) have shown a significant protective role against cardiovascular diseases and type 2 diabetes mellitus (T2DM), and there is a growing proportion of patients who are undergoing combined therapy with the two drugs. However, the effect of this combination treatment on renal function has not yet been determined. This study included 539 patients who were diagnosed with cardiovascular disease combined with T2DM. According to the use of SGLT2i and ARNI, patients were divided into the combination treatment group, SGLT2i group, ARNI group and control group. Primary outcomes were serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) changes in the 6th month and 12th month. In the ARNI group, no significant changes in Scr or eGFR were observed during the follow-up period, while the above indicators showed a trend of deterioration in the other three groups. The univariate analysis results showed that at 6 months of follow-up, the renal function indicators of patients treated with ARNI (either alone or in combination) were better than those treated with SGLT2i alone. After 12 months of follow-up, the Scr results were the same as before, while the difference in eGFR between groups disappeared. After multivariate analysis, in terms of delaying the progression of Scr, the ARNI group was superior to the other groups at the end of follow-up. No significant difference in eGFR was observed between groups during follow-up. In patients with cardiovascular disease and T2DM, combination therapy with ARNI and SGLT2i did not show an advantage over monotherapy in delaying renal insufficiency progression, and renal function seems to be better preserved in patients treated with ARNI alone. clinicaltrials.gov, identifier NCT05922852.

Effect of a Low Salt Diet on the Progression of Chronic Kidney Disease: A Prospective, Open-Label, Randomized Controlled Trial.

A causal relationship exists between salt intake and hypertension, stroke, and kidney disease. However, whether or not reduced salt intake slows progression of renal diseases has been intensely debated. In this prospective, open-label, randomized controlled trial, we examined the impact of a low salt diet on renal function, blood pressure, and other metabolic parameters. Herein, 194 patients with chronic kidney disease (CKD) stages 1 to 3 were randomized in low salt (intervention) and control groups. The intervention group was provided a low salt diet (1.5 g/day) for 3 months. The control group consumed their usual diet, and daily food intake was recorded in the control group. Renal function tests, 24-h urinary sodium excretion, urinary protein, serum calcium, phosphorus, and electrolyte levels were recorded monthly. After 3 months, the mean reduction in estimated glomerular filtration rate was significantly higher in the control group (mean reduction in eGFR, -3.011 mL/min/1.73 m2; 95% confidence interval (CI) = -5.367, -0.656, P = .013). Blood pressure (BP) decreased significantly in both groups; systolic and diastolic BP reduction at 3 months was significantly greater in the intervention group (systolic BP mean reduction -6.57/-4.29 mmHg; 95% CI = -10.24, -2.89) and diastolic BP mean reduction -6.95, -1.64 mmHg) compared with the control group (systolic BP mean reduction -0.58/-2.63 mmHg; 95%, CI = -4.33, 3.17 and diastolic BP mean reduction -5.34, -0.08 mmHg). The mean reduction in 24-h urine sodium excretion was greater in the intervention group, reaching a significant level at month 2 (-14.45 mmol/day; 95% CI = -27.63, -1.22). Overall, salt restriction can help slow the progression of renal insufficiency and results in statistically significant and clinically important reductions in BP among patients with CKD. NCT05716386 on 28/01/2023.

The Role of the Vegfa C936t Polymorphism in the Development of Chronic Venous Insufficiency of the Legs And Its Analysis

In 98 patients, an analysis of the genetic risk factor for the development of chronic venous insufficiency was carried out by studying the frequency of distribution of alleles and genotypes of the C936T polymorphism in the VEGFA gene. In both groups, the actual distribution of C807T polymorphism genotypes corresponded to those expected under the Hardy-Weinberg equilibrium (p&#x0D; &lt;0.05). A significant relationship was established between the risk of developing chronic venous insufficiency and the distribution of predisposing/protective variants of the C807T polymorphism genotypes in the VEGFA gene. These data allow us to suggest testing this locus to predict the risk of occurrence and progression of chronic venous insufficiency&gt;

Phosphate Toxicity and Vascular Calcification in Chronic Kidney Disease: A Closer Look Utilizing Transmission Electron Microscopy.

Hyperphosphatemia is independently linked with vascular calcification, cardiovascular disease, bone-mineral disease, progression of renal insufficiency, and all-cause mortality in chronic kidney disease (CKD) and end-stage renal disease (ESRD). The emerging importance of fibroblast growth factor-23 (FGF-23) and its co-factor Klotho play very important roles as phosphaturic hormones; however, phosphate levels rise due to a loss of renal Klotho production and the phosphaturic effects of the FGF-23/Klotho axis. Hyperphosphatemia is also associated with calciphylaxis, acceleration of renal tubulointerstitial disease, renal osteodystrophy, and uremic cardiomyopathy. This review incorporates ultrastructural remodeling of the thoracic aorta to provide a different perspective on vascular calcification. Nine-week-old male heterozygous (mRen2) 27 (Ren2) rat models of hypertension, insulin resistance, vascular oxidative stress and albuminuria are utilized to demonstrate aortic remodeling associated with vascular calcification. Nine-week-old male Zucker obese (fa/fa) rat models are utilized to better understand nephrolith formation. Phosphate homeostasis, toxicity, multiple metabolic and uremic toxicities, renal osteodystrophy, and vascular calcification are also discussed. Additionally, the role of the endothelium, vascular smooth muscle cells, inflammatory monocytes/macrophages and mast cells, pericytes, oxidative stress, hydrogen sulfide, and extraosseous calcification in the kidney are discussed as they relate to CKD, ESRD and calciphylaxis.

No More Venous Ulcers-What More Can We Do?

Venous leg ulcers (VLUs) are the most severe complication caused by the progression of chronic venous insufficiency. They account for approximately 70-90% of all chronic leg ulcers (CLUs). A total of 1% of the Western population will suffer at some time in their lives from a VLU. Furthermore, most CLUs are VLUs, defined as chronic leg wounds that show no tendency to heal after three months of appropriate treatment or are still not fully healed at 12 months. The essential feature of VLUs is their recurrence. VLUs also significantly impact quality of life and could cause social isolation and depression. They also have a significant avoidable economic burden. It is estimated that the treatment of venous ulceration accounts for around 3% of the total expenditure on healthcare. A VLU-free world is a highly desirable aim but could be challenging to achieve with the current knowledge of the pathophysiology and diagnostic and therapeutical protocols. To decrease the incidence of VLUs, the long-term goal must be to identify high-risk patients at an early stage of chronic venous disease and initiate appropriate preventive measures. This review discusses the epidemiology, socioeconomic burden, pathophysiology, diagnosis, modes of conservative and invasive treatment, and prevention of VLUs.

Safety and efficacy of aortic valvuloplasty for de novo aortic insufficiency in patients with a left-ventricular assist device.

Progression of aortic insufficiency during left-ventricular assist device (LVAD) support is a crucial topic. One treatment option is aortic valvuloplasty (AVP); however, there is controversy regarding its safety and efficacy. We investigated the safety and efficacy of AVP using the coaptation stitch method (Park's stitch) performed for de novo aortic insufficiency. Between 2013 and 2020, 175 consecutive patients underwent LVAD implantation, of which 7 patients [men, 2 (28.6%); median age, 55years] underwent late-stage AVP. Two patients underwent AVP within 2weeks, and the remaining six patients underwent AVP 3, 19, 24, 28, 42, and 49months, respectively, after LVAD implantation. Preoperatively, the degree of aortic insufficiency was moderate in 6 (85.7%) patients and severe in 1 (14.3%) patient. AVP was technically successful in 6 (85.7%) patients, while one case of failed plasty was subsequently treated with bioprosthetic valve replacement. A 1-year post-AVP right heart catheterization study revealed a median pulmonary artery wedge pressure of 10.0mmHg. No deaths or heart failure admissions occurred during the follow-up (median, 38.0months). There was no aortic insufficiency in 2 (28.6%) patients; however, trivial AI was observed in 3 (42.8%) patients, and mild AI was observed in 1 (14.3%) patient 2years postoperatively. However, at the 3-year follow-up, two patients developed an increase in AI grade from trivial to mild. AVP using Park's stitch was safe. It is critical to carefully observe the aortic valve during AVP surgery to ensure that AVP is appropriate.

Epidemiology and Diagnosis of Post-Thrombotic Syndrome: Qualitative Synthesis with a Systematic Review.

Background: Post-thrombotic syndrome (PTS) is a common and debilitating sequela of lower limb deep vein thrombosis (DVT). There is significant heterogeneity in reported PTS incidence due to lack of standardised diagnostic criteria. This review aimed to develop diagnostic criteria for PTS and subsequently refine the reported incidence and severity. Methods: PRISMA principles were followed; however, the review was not registered. The Cochrane CENTRAL database, MEDLINE, Embase, the NHS NICE Healthcare Databases Advanced Search interface, and trial registers including isrctn.com and clinicaltrials.gov were searched for studies addressing areas of interest (PTS definition, epidemiology, assessment). An experienced Clinical Librarian undertook the systematic searches, and two independent reviewers agreed on the relevance of the papers. Conflicts were resolved through panel review. Evidence quality was assessed using a modified Coleman scoring system and weighted according to their relevance to the aforementioned areas of interest. Results: A total of 339 abstracts were retrieved. A total of 33 full-text papers were included in this review. Following qualitative analysis, four criteria were proposed to define PTS: (1) a proven thrombotic event on radiological assessment; (2) a minimum 24-month follow-up period after an index DVT; (3) assessment with a validated score; and (4) evidence of progression of venous insufficiency from baseline. Four papers conformed to our PTS definition criteria, and the incidence of mild to moderate PTS ranged from 7 to 36%. On reviewing the studies which utilised the recommended Villalta scale, PTS incidence narrowed further to 23-36%. Incidence and severity reached a plateau at 24 months. Conclusions: Four diagnostic criteria were developed from qualitative synthesis. When these criteria were applied to the literature, the range of reported PTS incidence narrowed. These four criteria may standardise PTS diagnosis in future studies, facilitating the pooling of data for meta-analysis and synthesis of higher levels of evidence.

Transcatheter closure of a ruptured sinus of valsalva: a systematic review of the literature.

Ruptured sinus of Valsalva (RSOV) is a rare pathology, and current data regarding its symptoms, anatomy, associated pathologies, and appropriate therapeutic approaches are scarce. Transcatheter closure (TCC) has been performed in multiple cases; however, the information on its success rate and complications is limited. Two independent reviewers performed an advanced search based on inclusion criteria on Scopus, PubMed, and Embase from January 1985 through July 2022. The main search terms were "Sinus of Valsalva", "Rupture/Aneurysm", and "Transcatheter/Catheter/Device". Totally, 1,017 relevant articles from the 3 databases were retrieved. After the final review and appraisal, 94 articles describing 407 patients who underwent the TCC of RSOV were included. Males comprised 65% of the studied patients, and the average age was 34.5 years. The total success rate of TCC was 95.6%. Forty-nine patients (12%) developed complications, the most significant of which were sustained residual shunts in 7 patients (1.7%), substantial new onset or progression of aortic insufficiency in 6 (1.5%), and RSOV recurrence in 6 (1.5%). Post-interventional mortality was reported in only 2 patients (0.5%). The present study is the first systematic review of available data regarding the TCC of RSOV principally comprising case series and case reports. Although TCC seems a good option, precise patient selection is mandatory.

The association between exocrine pancreatic insufficiency and changes in gut microbiota: a narrative review

Due to their physical proximity, the healthy pancreas and the gut microbiome are known to interact in a variety of ways. The gut microbiota has been recognized as a potential factor in the development and progression of exocrine pancreatic insufficiency through several mechanisms. Pancreatic diseases like chronic and acute pancreatitis or pancreatic cancer are frequently accompanied by pancreatic exocrine insufficiency which affects the gut microbiota. Firstly, the gut microbes are controlled by antimicrobial pancreatic secretions, while themselves induce the secretion of substances by the pancreas through metabolite production, such as short chain fatty acids. Secondly, dysbiosis, the alteration in the abundance and diversity of different species, has been observed in patients with pancreatic diseases. Dysbiosis influences carcinogenesis in pancreatic cancer in ways that are either procarcinogenic or anticarcinogenic and finding these connections will have clinical implications. Identifying microbial biomarkers allow for an earlier diagnosis, improved therapy and prognosis in pancreatic cancer. The gut microbiome has a role in the pathogenesis of pancreatitis by either a bacterial translocation or a host immune response mechanism. The disruption of the normal gut barrier is believed to be the primary source of bacteria in acute pancreatitis which leads to infected pancreatic necrosis.&#x0D; In this paper, we review the current data about the association between pancreatic diseases linked to exocrine insufficiency and gut microbiota.

Long-Term Results of Congenital Aortic Stenosis Treatment in the Era of Percutaneous Balloon Valvuloplasty: Up to 33 Years Follow-Up.

Background The goal of this study was to evaluate long-term results of percutaneous balloon valvuloplasty (BVPL) used exclusively for initial management of congenital aortic stenosis in children. Methods and Results A total of 409 consecutive pediatric patients (134 newborns, 275 older patients) who underwent BVPL as initial treatment of aortic stenosis in a single nationwide pediatric center were subjected to a retrospective follow-up study. The resulting follow-up time reached a median of 18.5 (interquartile range, 12.2-25.1) years. Successful BVPL was defined by residual Doppler gradient <70/40 (systolic/mean) mm Hg. The primary end point was death; secondary end points included any valve reintervention, balloon revalvuloplasty, any aortic valve surgery, and aortic valve replacement, respectively. BVPL effectively reduced the peak and mean gradient both immediately and at the latest follow-up (P<0.001). There was significant procedure-related progression of aortic insufficiency (P<0.001). Higher aortic annulus z score was predictive for severe aortic regurgitation (P<0.05) and lower z score for insufficient gradient reduction (P<0.05). The actuarial probability of survival/survival free from any valve reintervention was 89.9%/59.9%, 85.9%/35.2%, and 82.0%/26.7% at 10, 20, and 30 years after first BVPL, respectively. Left ventricular dysfunction or arterial duct dependency as the indication for BVPL was predictive of both worse survival and survival free from any reintervention (P<0.001). Lower aortic annulus z score and lower balloon-to-annulus ratio were predictive of a need for revalvuloplasty (P<0.001). Conclusions Percutaneous BVPL provides good initial palliation. In patients with hypoplastic annuli and left ventricular or mitral valve comorbidity, the results are less favorable.

(284) Progression of Valvular Insufficiency with the Heartmate 3 Left Ventricular Assist Left Ventricular Assist Device: An Institutional Experience

(284) Progression of Valvular Insufficiency with the Heartmate 3 Left Ventricular Assist Left Ventricular Assist Device: An Institutional Experience

Thyroid dysfunction and the state of the GH/IGF-1 system in adolescents with type 1 diabetes mellitus

Purpose: to determine the relationship between the functional state of the pituitary-thyroid system and the growth hormone/insulin-like growth factor type 1 (GH/IGF-1) system in adolescents with type 1 diabetes mellitus (DM1) during puberty&#x0D; Material &amp; Methods: 165 children (85 girls (51,5%) and 80 boys (48,5%) aged 8 to 18 years old who have DM1 and are in the endocrinology department of the State Institution "Institute for Children and Adolescents Health Care at the National Academy of Medical Sciences of Ukraine" (SI "ICAHC NAMS"). The criterion for inclusion in the study was the duration of DM1 for more than one year (from 1 to 16 years). The level of thyrotropin (TSH), free fractions of thyroxin (fT4) and triiodothyronine (fT3), GH and IGF-1 was determined and the ratio (fT3/fT4 and TSH/fT4) was calculated. Study participants were divided into groups depending on the level of sexual development (T1-T4) at the time of the study, assessed by the Marshall &amp; Tanner scale (Marshall &amp; Tanner, 1969; Marshall &amp; Tanner, 1970); functional state of the pituitary-thyroid system: (euthyroidism (TSH/fТ4 &lt;0,19 c.u.), minimal thyroid insufficiency (0,19 c.u. ≤ TSH/fТ4 ≤0,29 c.u.), with subclinical hypothyroidism (TSH/fТ4 &gt;0,29 c.u.) (Turchina et al., 2016).&#x0D; Results: it was found that among adolescents with DM1, almost every child has signs of thyroid dysfunction. An increase in the fT3 level and the fT3/fT4 ratio were more often diagnosed. The frequency of increase in the level of TSH and the ratio of TSH/fT4 fluctuated widely and depended on the sexual development of the child. More often, signs of SGH were determined during early puberty (23,5%), which probably exceeded those in prepubertal (16%, Pφ&lt;0,05), proper (8,9%, Pφ&lt;0,05) and late puberty (6,1%, Pφ&lt;0,05). These changes indicate the tension of the thyroid system at the beginning of puberty, which is the basis not only for an increase in the risk of thyroid pathology in this period of puberty, but also for violations of physical and sexual development.&#x0D; Conclusions: almost a third of adolescents with DM1 had signs of thyroid insufficiency of varying degrees, which was most often determined during early puberty. The progression of thyroid insufficiency was accompanied by a decrease in the level of GH and IGF-1.

Blood pressure goals in chronic kidney disease : What is the optimal blood pressure for inhibition of progression and risk reduction?

Well-controlled blood pressure is an essential factor in inhibiting the progression of renal failure and also in controlling cardiovascular mortality and morbidity. For decades there has been an intensive search for the optimal blood pressure target values in order to reduce the progression of renal insufficiency to aphysiological level as far as possible. In the last few decades, very different target blood pressure values have been defined, which time and again contribute more to confusion than clarity in everyday clinical practice. The present work considers the relevant guidelines; it analyzes the basis on which the sometimes widely varying guidelines were created. All guidelines agree that blood pressure control with atarget of less than 140 mm Hg systolic should be achieved in patients with impaired renal function. The European guidelines recommend aiming for atarget of 130-140 mm Hg systolic. The American guidelines go one step further and specify asystolic blood pressure target of less than 130 mm Hg. The Kidney Disease: Improving Global Outcomes (KDIGO) organization is even more ambitious. It recommends ablood pressure target of less than 120 mm Hg, whereby in contrast to the European and American guidelines, the level of evidence required in the guidelines is considered to be very weak and the goals should also be achieved if automated, standardized blood pressure measurement is carried out, which is rarely available in everyday practice and may not be feasible. The present overview discusses the arguments for lowering blood pressure with different goals and presents the evidence. Of course, the blood pressure goals in the presence or absence of albuminuria should also be considered.