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BACKGROUND: With transesophageal echocardiography (TEE), were evaluated morphological characteristics and early hemodynamic parameters of stentless three leaflets pericardial patch in patients with aortic stenosis (AS) undergoing aortic valve (AV) surgery. AIM: The aim of the study was to point the importance of two-dimensional and three-dimensional TEE imaging intra and early postoperatively. METHODS: At Zan Mitrev Clinic, 2002–2020, were included 377 patients following the actual guidelines of European Society of Cardiology for valvular disease, whereas patients with dilatation of aortic annulus, rheumatoid arthritis, and chronic program on hemodialysis were excluded from the study. Instead of using a standard prosthesis, we made a reconstructive surgery implanting three new created leaflets using bovine/equine pericardium by replacing destroyed valve cusps. Leaflets were implanted separately, using continuous sutures with two supported stitches and that is how real stentless AV without any stent or sowing ring was created. Intraoperative and post-operative TEE was performed. RESULTS: 377 pts with aortic valvular disease (211–56% male, and 166–44% female; 82–21, 75% with AS, 32–8, 49% with aortic insufficiency, and 263–69, 76% with combined stenosis and insufficiency) were included in the study. Post-operative TEE showed aortic morphology close to normal AV, average pressure gradient was 8 mmHg. 121 pts got a combination with aortocoronary bypass (2.3 grafts per pts). 4 patients were re-operated. Mortality rate was 12.46% (44 pts). Follow-up period was 18 years. CONCLUSIONS: Real stentless aortic bioprosthesis is with a close morphology and hemodynamic parameters as a normal valve. TEE such as tool for assessment of AV morphology, anatomy of aortic root, pre-, and intra-operative plays a pivotal role in guiding case selection, surgical planning, and in evaluating procedural success.

Aims The present observational cohort study evaluated the association between the AKR1D1*36 (rs1872930) allele and the risk of major adverse cardiovascular and cerebrovascular events (MACCE) in clopidogrel treated patients. Methods We screened 198 consecutive cardiovascular patients on clopidogrel therapy admitted in October to November 2010 with cardiovascular or cerebrovascular symptoms; of these 118 met the study protocol entry criteria; the median age of the cohort was 62.5 years (IQR 57-66 years), and 55% were females. Results The median follow up time was 38.5 (IQR 24-48) months; Kaplan-Meier/Log-rank analysis showed that patients carrying the AKR1D1*36 allelic variant have a shorter event-free-survival compared to wild type patients, hazard ratio = 2.193 (95% CI, 1.091 to 4.406); p = 0.0155. Multivariable Cox regression analysis confirmed the AKR1D1*36 allele as an independent risk factor (HR = 2.36; 95% CI, 1.34 to 4.18) and identified 3 other risk factors for MACCE; previous percutaneous interventions (PCI), HR = 2.78; (95% CI, 1.34 to 5.78), and a history of myocardial infarction, HR = 2.62; (95% CI, 1.48 to 4.64) at baseline and the previously reported CYP2C19*2 polymorphism (HR = 2.33; 95% CI, 1.33 to 4.06). Conclusion The AKR1D1*36 (rs1872930) variant is independently associated with a higher risk for MACCE and shorter event-free survival time.

Introduction Coronavirus disease 2019 (COVID-19) is associated with significant acute clinical manifestations, and reports indicate that some patients experience prolonged symptomatology and morbidity. These late clinical manifestations have been termed Post-Acute Sequelae of COVID-19 (PASC) and hypothesised to be associated with clinical severity in the acute infection phase and biochemical abnormalities. Aim Evaluate the incidence of PASC in previously hospitalised COVID-19 patients and compare the admission and follow-up levels of biochemical parameters stratified according to baseline clinical severity. Methods N = 168 COVID-19 patients previously hospitalised at the Zan Mitrev Clinic in Skopje, North Macedonia, with matched laboratory data at baseline and follow-up clinical visit > 30 days post-discharge, were stratified according to National Institute of Health clinical severity guidelines as mild, moderate, severe or critical according to admission clinical presentation. We assessed the incidence of PASC and compared the biochemical profile. Results The median hospitalisation and clinical follow-up period were 11 (9-20) and 53 (30-105) days. The overall incidence of PASC was 56.5% (95/168); most PASC cases were confined to the severe sub-group (61/101, 61.4%). Contrary to mild and moderate cases and a healthy “non-COVID-19” control cohort, we observed that severe COVID-19 cases experienced sustained biochemical disturbances, most notably elevated D-dimers and Ferritin of 600 ng/ml (283-1168) and 432 ng/ml (170-916), respectively. Conclusions Previously hospitalised severe COVID-19 patients are more likely to experience Post-Acute Sequelae of COVID-19 and prolonged biochemical disturbances, evident by abnormal values of D-dimers and Ferritin.

Introduction: Severe coronavirus disease 2019 (COVID-19) is characterised by hyperinflammatory state, systemic coagulopathies, and multiorgan involvement, especially acute respiratory distress syndrome (ARDS). We here describe our preliminary clinical experience with COVID-19 patients treated via an early initiation of extracorporeal blood purification combined with systemic heparinisation and respiratory support. Methods: Fifteen patients were included; several biomarkers associated with COVID-19 severity were monitored. Personalised treatment was tailored according to the levels of interleukin (IL)-6, IL-8, tumour necrosis factor alpha, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio, thrombocyte counts, D-dimers, and fibrinogen. Treatment consisted of respiratory support, extracorporeal blood purification using the AN69ST (oXiris®) hemofilter, and 300 U/kg heparin to maintain activation clotting time ≥ 180 seconds. Results: Ten patients presented with severe to critical disease (dyspnoea, hypoxia, respiratory rate > 30/min, peripheral oxygen saturation < 90%, or > 50% lung involvement on X-ray imaging). The median intensive care unit length of stay was 9.3 days (interquartile range 5.3-10.1); two patients developed ARDS and died after 5 and 26 days. Clinical improvement was associated with normalisation (increase) of thrombocytes and white blood cells, stable levels of IL-6 (< 50 ng/mL), and a decrease of CRP and fibrinogen. Conclusion: Continuous monitoring of COVID-19 severity biomarkers and radiological imaging is crucial to assess disease progression, uncontrolled inflammation, and to avert irreversible multiorgan failure. The combination of systemic heparin anticoagulation regimens and extracorporeal blood purification using cytokine-adsorbing hemofilters may reduce hyperinflammation, prevent coagulopathy, and support clinical recovery.

Background The pathogenesis of cardiovascular diseases (CVD) is sustained by persistent low-grade systemic inflammation. Lipid deposition, atherosclerotic plaque formation, toll-like receptor activation, leukocyte infiltration and secretion of pro-inflammatory mediators collectively promote chronic low-grade inflammation which drives CVD-progression. Despite the well-described inflammatory processes in CVD, its perioperative clinical significance in cardiac surgery is ill-defined. Aim To evaluate the association between the preoperative chronic inflammation and postoperative outcome. We hypothesized that an elevated systemic inflammation predisposes patients to adverse postoperative outcome. Methods A retrospective analysis of 1251 consecutive adults undergoing cardiac surgery between July 2018 and Dec 2019. We used the systemic-immune-inflammation index (SII) as a marker for chronic inflammation and was calculated as follows: “platelet counts x (Neutrophil/Lymphocyte ratio)”. A Receiver Operating Characteristic (ROC) curve was generated by plotting the SII values for in-hospital mortality cases vs successfully discharged patients, the Wilcoxon estimate of area under ROC curve = 0.67; an optimum cut-off point of 647 (sensitivity = 0.72, specificity = 0.59) was chosen to classify patients with an elevated inflammatory status. We used the Fisher's exact test to assess whether the preoperative SII was related with adverse outcome. Finally, we included the SII in a multivariable logistic regression controlling for 11 established cardiac surgery mortality risk-factors. Results The median age was 65 years (range 18–88), 361 (29%) were females. The mean ACEF II operative mortality was 3.49%. The median SII before surgery was 576 (IQR 402 - 855). In comparison, the SII of a healthy control non-surgical cohort (N=60) was 434 (IQR 290–559), median difference = 142 [CI95% 84 to 223), p Sub-group analysis revealed that patients who passed away during hospitalisation were admitted with a significantly higher preoperative SII (= 824), median difference 255 [CI95% 143–388], p Contrary to patients with low-grade systemic inflammation (= SII Multivariable logistic regression revealed that an SII ≥647 is an independent risk factor for in-hospital mortality, adjusted OR 2.67, p=0.004. Conclusion A high SII (≥647) is independently associated with postoperative morbidity and mortality following cardiac surgery. The SII may support clinical decision making and stratification of high-risk patients undergoing cardiac surgery. Funding Acknowledgement Type of funding source: None

Severe coronavirus disease 2019 (COVID-19) is characterised by hyperinflammatory state, systemic coagulopathies, and multiorgan involvement, especially acute respiratory distress syndrome (ARDS). We here describe our preliminary clinical experience with COVID-19 patients treated via an early initiation of extracorporeal blood purification combined with systemic heparinisation and respiratory support.Fifteen patients were included; several biomarkers associated with COVID-19 severity were monitored. Personalised treatment was tailored according to the levels of interleukin (IL)-6, IL-8, tumour necrosis factor alpha, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio, thrombocyte counts, D-dimers, and fibrinogen. Treatment consisted of respiratory support, extracorporeal blood purification using the AN69ST (oXiris®) hemofilter, and 300 U/kg heparin to maintain activation clotting time ≥ 180 seconds.Ten patients presented with severe to critical disease (dyspnoea, hypoxia, respiratory rate30/min, peripheral oxygen saturation90%, or50% lung involvement on X-ray imaging). The median intensive care unit length of stay was 9.3 days (interquartile range 5.3-10.1); two patients developed ARDS and died after 5 and 26 days. Clinical improvement was associated with normalisation (increase) of thrombocytes and white blood cells, stable levels of IL-6 (50 ng/mL), and a decrease of CRP and fibrinogen.Continuous monitoring of COVID-19 severity biomarkers and radiological imaging is crucial to assess disease progression, uncontrolled inflammation, and to avert irreversible multiorgan failure. The combination of systemic heparin anticoagulation regimens and extracorporeal blood purification using cytokine-adsorbing hemofilters may reduce hyperinflammation, prevent coagulopathy, and support clinical recovery.

IntroductionCOVID-19 is characterised by hyperinflammation and coagulopathy. Severe cases often develop respiratory distress, requiring mechanical ventilation and critical cases progressing to ARDS. Control of hyperinflammation has been proposed as a possible therapeutic avenue for COVID-19; extracorporeal blood purification (EBP) modalities offer an attractive mean to ameliorate maladaptive inflammation.With this work, we describe the longitudinal variation of parameters of systemic inflammation in critically ill COVID-19 patients treated with blood purification using AN69ST (oXiris®) hemodiafilter.MethodsWe performed a time-series analysis of 44 consecutive COVID-19 cases treated with the AN69ST (oXiris®) cytokine adsorbing hemodiafilter; we visualise longitudinal results of biochemical, inflammatory, blood gas- and vital sign parameters.ResultsBlood purification was indicated for suspected hyperinflammation or hypercoagulation, (= CRP ≥ 100 mg/L and/or IL-6 ≥ 40 pg/mL and/or Ferritin ≥ 500 ng/mL and/or Lactate Dehydrogenase > 365 U/L or D-dimers > 2000 ng/mL). All patients were treated with ≥ 1 cycle extracorporeal continuous venovenous hemofiltration (CVVHF) with cytokine adsorbing hemodiafilter (CAH); of these, 30 severe patients received CVVHF-CAH within 4 – 12 hours of hospitalisation. Another 14 patients admitted with mild-to-moderate symptoms progressed to severe disease and placed on EBP during the course of hospitalisation. The treatment was associated with a reduction of Ferritin, C-reactive protein, Fibrinogen, several inflammatory markers and a resolution of numerous cytopenias. The observed mortality across the cohort was 36.3% across the cohort.ConclusionExtracorporeal blood purification with cytokine adsorbing hemofilter was associated with a decrease in the acute phase proteins CRP, Ferritin, and resolution of numerous cytopenias. Repetitive hemofiltration has been associated with lower levels of IL-6 in COVID-19 patients.

Coronavirus disease 2019 (COVID-19) has swept the world, unlike any other pandemic in the last 50 years. Our understanding of the disease has evolved rapidly since the outbreak; disease prognosis is influenced mainly by multi-organ involvement. Acute respiratory distress syndrome, heart failure, renal failure, liver damage, shock and multi-organ failure are strongly associated with morbidity and mortality. The COVID-19 disease pathology is plausibly linked to the hyperinflammatory response of the body characterized by pathological cytokine levels. The term ‘cytokine storm syndrome’ is perhaps one of the critical hallmarks of COVID-19 disease severity. In this review, we highlight prominent cytokine families and their potential role in COVID-19, the type I and II interferons, tumour necrosis factor and members of the Interleukin family. We address various changes in cellular components of the immune response corroborating with changes in cytokine levels while discussing cytokine sources and biological functions. Finally, we discuss in brief potential therapies attempting to modulate the cytokine storm.

Background: Transthoracic device closure (TTDC), also known as a Hybrid procedure, has been proposed as an alternative, less invasive approach compared to open-heart surgery for the treatment of ventricular septal defect (VSD). Case Presentation: We present our first national case of TTDC in a 6-month-old female baby with a muscular 8mm ventricular septal defect, 3 mm atrial defect, enlarged right and left ventricle and a dilated pulmonary artery complicated by severe pulmonary hypertension.Treatment consisted of two pulmonary artery banding attempts at the age of 2 months to control pulmonary hypertension – the interventions were combined with diuretics and angiotensin-converting enzymes inhibitors. Yet, the initial approach was suboptimal as we noticed a failure to thrive continuous sweating and tachypnea. Because of the worsening condition at the age of 6 months, and a weight of 6.6 kg, we performed TTDC. After median sternotomy, a 10mm muscular VSD occluder was implanted under trans-oesophagal echocardiography guidance on the beating heart. The procedure lasted 90 min and was performed without incident; the hemodynamics were stable with only a minor residual VSD. The child was extubated after 2 hours and discharged after five days from the hospital.Conclusions: Transthoracic device closure (TTDC) is a promising treatment modality for large muscular VSD in small infants with low weight. TTDC is feasible in cases with heavy myocardial right ventricle trabeculae and who previously underwent open-heart surgery.

Introduction: Our understanding of the COVID-19 disease has been steadily evolving since the original outbreak in December 2019. Advanced disease is characterised by a hyperinflammatory state, systemic coagulopathies and multiorgan involvement, in particular respiratory distress. We here describe our initial experience with treating of COVID-19 patients based on early initiation of extracorporeal blood purification, systemic heparinisation and respiratory support.Methods: 15 patients were included; 2 were females. We monitored real-time several biochemical, immunological and coagulation biomarkers associated with disease severity following admission to our dedicated COVID-19 intensive care unit. To guide personalised treatment, we monitored among others levels of IL-6, IL-8, TNF-α, C-Reactive Protein (CRP), Neutrophil-to-Lymphocyte ratios, Thrombocyte counts, D-Dimers, Fibrinogen, and Activation Clotting time (ACT).Treatment consisted of individualised respiratory support supplemented with 1 - 4 cycles of 24-hour Extracorporeal Organ Support (ECOS) and Blood Purification using the AN69ST (oXiris®) hemofilter. We administered heparin (300 U/kg) to counter suspected hypercoagulability (= elevated Fibrinogen or D-dimers) states to maintain ACT ≥ 180 seconds.Results: N = 10 presented with severe to critical disease (= dyspnoea, hypoxia, respiratory rate > 30/min, peripheral oxygen saturation < 90%, or > 50% lung involvement on X-ray imaging). A single case was admitted with a critical condition (= respiratory failure). One patient died after 5 days of hospitalisation after developing Acute Respiratory Syndrome. 8 Patients have been discharged - average ICU length-of-stay was 9.9 ± 2.4 days. Clinical improvement was associated with normalisation (increase) of thrombocytes, white blood cells, stable levels of IL-6 (< 50 ng/mL) and a decrease of CRP and Fibrinogen. Conclusion: Means to monitor COVID-19 disease severity during hospitalisation are crucial to control disease progression and prevent hyperinflammation and irreversible multiorgan failure. We present here a real-time monitoring system accounting for biochemical, immunological, coagulation parameters and radiological imaging. The combination of systemic heparin anticoagulation regimens and blood purification may prevent hyperinflammation, thromboembolism during hospitalisation and thus support clinical recovery.

To enable the implementation of precise genomics in a local healthcare system, we devised a pipeline for filtering and reporting of relevant genetic information to healthy individuals based on exome or genome data. In our analytical pipeline, the first tier of filtering is variant-centric, and it is based on the selection of annotated pathogenic, protective, risk factor, and drug response variants, and their one-by-one detailed evaluation. This is followed by a second-tier gene-centric deconstruction and filtering of virtual gene lists associated with diseases, and VUS-centric filtering according to ACMG pathogenicity criteria and pre-defined deleteriousness criteria. By applying this filtering protocol, we were able to provide valuable insights regarding the carrier status, pharmacogenetic profile, actionable cardiovascular and cancer predispositions, and potentially pathogenic variants of unknown significance to our patients. Our experience demonstrates that genomic profiling can be implemented into routine healthcare and provide information of medical significance.

Introduction: Mechanical circulatory support by a continuous-flow ventricular assist device (VAD) improves survival and quality of life in selected patients with advanced heart failure. Developing countries have been struggling to construct a contemporary and effective health care system to manage advanced heart failure. This observation represents the first annual report on clinical outcomes with VAD for patients with advanced heart failure in the Republic of North Macedonia. Methods: Data from all patients with VAD implantations between November 2018 and December 2019 were collected. The etiology of the heart failure was dilated cardiomyopathy in 4 patients (57%), ischemic cardiomyopathy in 2 (28%), and hypertrophic cardiomyopathy in 1 (14%). The primary outcome was survival; secondary outcomes included adverse events defined according to the Interagency Registry for Mechanically Assisted Circulatory Support. Results: A total of 7 patients (85% males, median age 56 years) received a VAD; 5 of them received left VAD, and the remaining 2 received biventricular VAD. There were no deaths. Observed morbidity during a mean follow-up of 216 days included 3 bleeding events in 1 patient, 2 patients with superficial driveline infection, and 1 minor stroke and a pump thrombosis, which were treated with VAD exchange. Significant improvement in quality of life, as assessed by the Kansas City Cardiomyopathy Questionnaire and the Functional Independence Measure™ instrument, was seen with all patients. Conclusions: Our results demonstrate a successful initiation of the VAD program in the Republic of North Macedonia. Proper training of a dedicated HF team supports the reproducibility of this treatment in developing countries.

Background: In recent years, it has been shown that many of the pervasive genetic defects in cancer occur in chromatin modifiers. In order to obtain insights in regards to their biology and clinical relevance in cancer, we analyzed the distribution and mutual relationships of genetic aberrations in relevant chromatin modifiers in tens of thousands of publicly available cancer datasets. Results: We observed that in general, they are mutually exclusive, and their prevalence is higher in some types of cancers compared to others. Moreover, we observed a strong association between aberrations in selected chromatin modifiers and tumor mutational burden, leading to an improved response to checkpoint immunotherapy. Conclusion: All in all, this study uncovered interesting relationships between chromatin factors and features of cancer in regards to cancer biology, and cancer therapy. These insights could set the stage for follow up functional and clinical studies.

Targeted gene panel testing has the power to interrogate hundreds of genes and evaluate the genetic risk for many types of hereditary cancers simultaneously. We screened a 13-year-old male patient diagnosed with glioblastoma multiforme with the aim to get further insights into the biology of his condition. Herein, we applied gene panel sequencing and identified a heterozygous frameshift mutation c.333_334delTC; p.His112CysfsTer9 in the MLH1 gene in blood and tumor tissue accompanied by a known heterozygous missense variant of unknown significance c.847C > T; p.Arg283Cys in the TP53 gene. Parental screening revealed the presence of the same TP53 variant in the father and the same MLH1 variant in the mother, who was in fact undergoing treatment for early-stage breast cancer at the time of her son’s unfortunate diagnosis. This case reports for the first time the co-occurrence of a genetic mutation in the MLH1 gene of the mismatch repair pathway, commonly associated with the Lynch syndrome, accompanied by a rare variant in the TP53 gene. This report underlines the need for broad panel gene testing in lieu of single-gene or syndrome-focused gene screening and evaluation of the effects of multiple pathogenic or modifier variants on the phenotypic spectrum of the disease.

Hasan, M. Shahnaz/0000-0002-7493-7416; Abouqal, Redouane/0000-0002-6117-4341; Altindis, Mustafa/0000-0003-0411-9669; Masjedi, Mansoor/0000-0001-6175-9289; Popescu, Roxana/0000-0002-9387-1141; Mikaszewska-Sokolewicz, Malgorzata A/0000-0002-1148-7817; Meco, Basak Ceyda/0000-0003-2951-9634; Kumar, Perikala Vijayananda/0000-0001-8315-7000; Zand, Farid/0000-0003-3489-3372; Maghsoudi, Behzad/0000-0002-1279-8799; KAMARUL ZAMAN, MAZUIN/0000-0002-7920-6399; Gan, Chin Seng/0000-0002-6758-4798; Horoz, Ozden Ozgur/0000-0001-7590-650X; Medeiros, Eduardo A/0000-0002-6205-259X; Sabetian, Golnar/0000-0001-8764-2150; UNAL, SERHAT/0000-0003-1184-4711; Gan, Chin Seng/0000-0002-6758-4798; Delia, Muntean/0000-0001-9100-4530; Yalcin, Ata Nevzat/0000-0002-7243-7354; Leblebicioglu, Hakan/0000-0002-6033-8543; Horhat, Florin George/0000-0001-6133-0204; Yousef, Reham H. A./0000-0003-4004-3008; Delgado Aguirre, Hector Alberto/0000-0001-5448-7975; El Kholy, Amani/0000-0002-0645-7664; Rodriguez Ferrer, Marena Luz/0000-0002-8053-8454; Sanaei Dashti, Anahita/0000-0002-2827-3575; KARABAY, OGUZ/0000-0003-1514-1685; Barahona G., Nayide/0000-0003-3559-6900; Stagnaro, Juan Pablo/0000-0003-3836-9957; Alexandru Florin, Rogobete/0000-0003-1286-4431; KAYA, ZEYNEP/0000-0002-8468-2103; Dragan, Barbara/0000-0003-3108-4211; alvarez Moreno, carlos Arturo/0000-0001-5419-4494; Gonzalez Martinez, Marisela del Rocio/0000-0003-1474-736X; Jayatilleke, Kushlani/0000-0002-3931-6630; Unal, Necmettin/0000-0002-9440-7893; Duszynska, Wieslawa/0000-0002-5880-4904; Ngo, Quy Chau/0000-0002-6787-2757; Elmanakhly, Arwa/0000-0001-8557-0536; yildizdas, dincer/0000-0003-0739-5108; Kanj, Souha/0000-0001-6413-3396; Gupta, Umesh/0000-0001-7717-1404 WOS: 000392626300014 PubMed: 27742143 Background: We report the results of International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2010-December 2015 in 703 intensive care units (ICUs) in Latin America, Europe, Eastern Mediterranean, Southeast Asia, and Western Pacific. Methods: During the 6-year study period, using Centers for Disease Control and Prevention National Healthcare Safety Network (CDC-NHSN) definitions for device-associated health care-associated infection (DAHAI), we collected prospective data from861,284 patients hospitalized in INICC hospital ICUs for an aggregate of 3,506,562 days. Results: Although device use in INICC ICUs was similar to that reported from CDC-NHSN ICUs, DA-HAI rates were higher in the INICC ICUs: in the INICC medical-surgical ICUs, the pooled rate of central lineassociated bloodstream infection, 4.1 per 1,000 central line-days, was nearly 5-fold higher than the 0.8 per 1,000 central line-days reported from comparable US ICUs, the overall rate of ventilator-associated pneumonia was also higher, 13.1 versus 0.9 per 1,000 ventilator-days, as was the rate of catheterassociated urinary tract infection, 5.07 versus 1.7 per 1,000 catheter-days. From blood cultures samples, frequencies of resistance of Pseudomonas isolates to amikacin (29.87% vs 10%) and to imipenem (44.3% vs 26.1%), and of Klebsiella pneumoniae isolates to ceftazidime (73.2% vs 28.8%) and to imipenem (43.27% vs 12.8%) were also higher in the INICC ICUs compared with CDC-NHSN ICUs. Conclusions: Although DA-HAIs in INICC ICU patients continue to be higher than the rates reported in CDC-NSHN ICUs representing the developed world, we have observed a significant trend toward the reduction of DA-HAI rates in INICC ICUs as shown in each international report. It is INICC's main goal to continue facilitating education, training, and basic and cost-effective tools and resources, such as standardized forms and an online platform, to tackle this problem effectively and systematically. (C) 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. VDR; Foundation to Fight against Nosocomial Infections The funding for design, development, maintenance, technical support, data validation, and report generation of the Surveillance Online System, and the activities carried out at International Nosocomial Infection Control Consortium headquarters, were provided by VDR and the Foundation to Fight against Nosocomial Infections.

Background and aims The decision for general anesthesia (GA) vs regional anesthesia (RA) for staged carotid endarterectomy (CEA) is an ongoing debate 1 2 and should be done on an individual basis.3 We present a case of a highly-comorbid patient with dilated cardiomyopathy (DCM) undergoing staged CEA using RA. Methods A 72-year-old patient with previous stroke and soft carotid bifurcation plaque was admitted for right CEA. He experienced an infarction 4 years previously, left untreated, thus developing dilated cardiomyopathy, diabetic with an GFR of 43.7 mL/min/1.73 m2. Preoperative evaluation showed dyspnea at rest NYHA IV; and intermittent chest pain CCS IV. We opted for staged CEA shortly followed by coronary revascularization. Due to minimal invasiveness, RA was chosen because of the high-risk of myocardial infarction, intraoperative stroke and renal insufficiency. Deep cervical plexus block was performed, from C2 to C4 using 10 ml 0,5% bupivacaine and 10 ml 1% lidocaine [4]. Surgery was uneventful and pain free, with stable hemodynamics, using eversion endarterectomy and no shunt. Results Postoperative recovery was uneventful, patient was discharged on the 2nd day following surgery. Conclusions Staged CEA in high risk coronary patients can be safely performed using minimal invasive RA. Our ongoing study for RA vs GA in this patient will give definitive answer.

Background and aims Malnutrition and cachexia are frequent in head and neck cancer (HNC) patients. These complications occur as a result of the cancer but are worsened by surgery, radiotherapy or chemotherapy that further challenge oral intake but also airway obstruction. Methods We present case of 82-year-old male with nasopharyngeal carcinoma, severe malnutrition following multimodality therapy and difficult airway. He was unable to consume solid foods and liquids, developing severe cachexia due to esophageal stricture, confirmed during an unsuccessful gastroscopy. Refused by several hospitals, we opted for surgical gastrostomy under regional anesthesia, using epidural catheter placed T10/T11 and continuous 5% bupivacaine. Results The procedure was uneventful and pain free. The epidural catheter was removed on the 2nd postoperative day; patient discharged on the 4th postop day, with functional gastrostomy. First follow up showed increase in body weight. Conclusions Regional anesthesia and surgical gastrostomy can be successfully performed in a frail geriatric patient when the underlying disease cause severe airway obstruction.

Background We describe a combinatorial intensive care approach and discuss the critical factors that allowed us to successfully manage a life-threatening case of acute anaerobic septic shock triggered by descending necrotizing mediastinitis. Case presentation We admitted a 38-year-old critically ill Kosovar Albanian man to our intensive care unit because of clinical manifestations of severe sepsis. His condition had worsened in the previous 2 weeks following unsuccessful antibiotic therapy for tonsillitis complicated by retropharyngeal abscesses. Computed tomography and intraoperative observations identified abscesses in the anterior and middle mediastinum regions and the distal part of the neck, directly on the border with the left lobe of the thyroid gland. Cultures indicated infections with α-hemolytic Streptococcus and Clostridium species: High procalcitonin and lactate levels, blood gas analysis, poor peripheral capillary oxygen saturation, and severe hemodynamic instability pointed to a case of acute septic shock. The entire treatment consisted of an aggressive antibiotic regimen, transthoracic and mediastinal surgical evacuation of the abscess, vacuum sealing drainage with a pleural chest tube, continuous venovenous hemodiafiltration using cytokine-adsorbing hemofilters, and extracorporeal blood hyperoxygenation. Conclusions Efficient treatment of severe anaerobic sepsis resulting from descending necrotizing mediastinitis should build on a multidisciplinary approach. In support of first-line therapies with targeted antibiotics and surgical debridement, clinicians should consider alternative therapies such as continuous venovenous hemodiafiltration with cytokine-adsorbing hemofilters and hyperoxygenation. Electronic supplementary material The online version of this article (10.1186/s13256-019-2123-7) contains supplementary material, which is available to authorized users.

Background Chronic Mitral Valve disease is strongly associated with Left atrial enlargement; the condition has a high mortality risk. Clinical manifestations include atrial fibrillation, pulmonary hypertension, thromboembolic events, and in cases of Giant Left Atrium (GLA) and a distorted cardiac silhouette. Full sternotomy, conventional open-heart surgery, reductive atrioplasty and atrioventricular valve repair are required to resolve symptoms. However, these procedures can be complicated due to the posterior location of the GLA and concomitant right lateral protrusion. Cardiac autotransplantation is superior under these conditions; it provides improved visual access to the posterior atrial wall and mitral valve, hence, facilitates corrective surgical procedures. We aimed to assess the clinical outcome of patients undergoing cardiac autotransplantation as the primary treatment modality to resolve GLA. Moreover, we evaluated the procedural safety profile and technical feasibility. Case presentation Four patients, mean EuroSCORE II of 23.7% ± 7.7%, presented with heart failure, atrial fibrillation, left atrial diameter > 6.5 cm and a severe distorted cardiac silhouette; X-ray showed prominent right lateral protrusion. We performed cardiac autotransplantation using continuous retrograde perfusion with warm blood supplemented with glucose followed by atrioplasty, atrial plication, valve annuloplasty and valve repair on the explanted beating heart. The surgical approach reduced the left atrial area, mean reduction was − 90.71 cm2 [CI95% -153.3 cm2 to − 28.8 cm2, p = 0.02], and normalized pulmonary arterial pressure, mean decrease − 11.25 mmHg [CI95% -15.23 mmHg to − 7.272 mmHg, p = 0.003]. 3 out of 4 patients experienced an uneventful postoperative course; 2 out of 4 patients experienced a transient return to sinus rhythm following surgery. One was operated on in 2017 and is still in good condition; two other patients survived for more than 10 years; Kaplan-Meier determined median survival is 10.5 years. Conclusions Cardiac autotransplantation is an elegant surgical procedure that facilitates the surgical remodelling of Giant Left Atrium. Surgical repair on the ex vivo beating heart, under continuous warm blood perfusion, is a safe procedure applicable also to high-risk patients.

Background Ischemic stroke is the second leading cause of death in North Macedonia. Posterior circulation disease, caused by vertebral artery (VA) ostium (VAo) stenosis, is a common cause of ischemic stroke. We established a treatment approach using surgical revascularization of posterior circulation disease. In the present observational study, we assessed the outcome after surgical revascularization of the posterior circulation ischemia caused by VAo stenosis. Methods A retrospective analysis of 20 consecutive patients who had undergone surgery from January 2017 to December 2019. The VA was accessed through a 3-cm incision in the upper medial clavicle. The corrective procedures consisted of resection and anastomosis (15 of 20), VA to subclavian artery transposition (16 of 20), endarterectomy (10 of 20), vein graft interposition techniques (4 of 20), and vein graft bypass (1 of 20). Results The cohort included 9 acute cases. The mean patient age was 66.5 years (range 46–77). Of the 20 patients, 8 were women and 12 were men. Left-sided VA pathology was present in 75% of the cases. We observed rapid clinical improvement in 19 patients (95%). The total study period was 321 patient-months, with a median follow-up of 18 months (interquartile range, 5–24 months). One patient had died of an unknown cause after 12 months. During the follow-up period, 15 patients (75%) had reported permanent clinical improvement with no significant relapse of symptoms. Conclusions Minimally invasive surgical revascularization of the posterior brain circulation is a clinically effective therapeutic approach to manage ischemia caused by VAo stenosis. It can be performed safely, promote long-lasting symptom relief, and prevent recurrent strokes.

INTRODUCTION: Myocardial infarction is a rare medical event in young people. The main reasons include congenital coronary abnormalities, coronary artery spasm, and coronary thrombosis due to hypercoagulable states (hereditary and acquired).AIM: We present a case of a young male adult with myocardial infarction caused by a combination of gene mutations and anticoagulation protein deficiency.CASE PRESENTATION: A 19 years old young man was admitted to our hospital complaining of chest pain during the last two weeks. The patient did not have any known cardiovascular risk factors, except a positive family anamnesis. Subacute inferior nonST segment myocardial infarction was diagnosed according to the patient’s history, electrocardiographic and laboratory findings. Coronary angiography revealed suboclusive thrombus in the proximal, medial and distal part of the right coronary artery (TIMI 2). Percutaneous coronary intervention was performed. Anticoagulant and antiagregant therapy (heparin, acetilsalicilic acid and clopidogrel) according to protocol was started. The hospital stay was uneventful. Homozygous endothelial nitric oxid synthase (eNOS) T-786-C mutation, heterozygote prothrombin gene mutation (G-20210-A), and protein S deficiency were verified from the thrombophilia testing. Other trombophilic tests were normal. Three months after discharge from hospital another coronary angiography was performed. It revealed normal coronary arteries. Four years after the attack, the patient is free of symptoms and another cardiovascular event.CONCLUSION: Combination of genetic mutations and anticoagulation protein deficiency could be a reasonable cause for myocardial infarction in a very young male adult without any other cardiovascular risk factors.

Exome sequencing can interrogate thousands of genes simultaneously and it is becoming a first line diagnostic tool in genomic medicine. Herein, we applied trio clinical exome sequencing in a patient presenting with undiagnosed skeletal disorder, minor facial abnormalities, and kidney hypoplasia; her parents were asymptomatic. Testing the proband and her parents led to the identification of a de novo mutation c.188C>T (p.Pro63Leu) in the MAFB gene, which is known to cause multicentric carpotarsal osteolysis syndrome (MCTO). The c.188C>T mutation lies in a hotspot amino acid stretch within the transactivation domain of MAFB, which is a negative regulator of RANKL-induced osteoclastogenesis. MCTO is an extremely rare autosomal dominant (AD) disorder that typically arises spontaneously and causes carpotarsal osteolysis, often followed by nephropathy. To the best of our knowledge, this is the first study reporting genetically diagnosed multicentric carpotarsal osteolysis syndrome in the Balkans.

Urgent sorgely, is part of a daily practice on cardiovascular units, and it may be required in patients with conditions such as acute coronary syndrome, endocarditis and valvular diseases, trauma, acute aOl1ic dissection as well as acute vascular embolisations and Leriche syndrome. In emergency situation, preoperative patient work-up for cardia-vascular surgery is quite different from the elective setting.

Thoracic great vessel and cardiac trauma are characterized by anatomic location and mechanism of injury: blunt or penetrating. Management strategies are also directed by the extent and mechanism of injury. Advances in imaging and catheter-based technologies have allowed easier and more accurate diagnosis and less-invasive treatments. Although the advantages of endovascular techniques are attractive, open surgical repair remains the definitive treatment for many of these thoracic injuries. Given the increasing sophistication of these technologies and the demonstrated usefulness of a disease-oriented approach toward patient management, trauma centers have adopted a multidisciplinary team model for management of multitrauma victims. In this review, the authors detail the diagnosis and management of blunt or puncture aortic, non-aortic great vessel, blunt cardiac, and penetrating cardiac injuries.

Background: Atrial septal defect (ASD) is a common congenital heart disorder (CHD). While conventional open surgical treatment is the standard procedure in our country, percutaneous device closure with implantation of an atrial septal defect occluder is a promising alternative with very few peri and post procedural complications.Aim: The aim of the study was to present the rate of success and complications in percutaneous ASD closure with the implantation of an atrial septal defect occluder.Material and Methods: We treated 153 patients (ages 2-76; 65% female) with ASD secundum with percutaneous trans catheter closure using a septal occluder. Follow up was on a 3 month interval and assessment included clinical, electrophysiological and echocardiographic status. Results: The mean diameter of ASD obtained via balloon sizing was 16 ± 16 mm. Multiple ASDs were found in 20 (13%) patients and deficitary aortic and anterior rim (< 5 mm) was present in 16 (10%) patients. Due to inadequate placement and/or sizing, the device was removed and replaced in seven patients (5%). During follow up, trivial shunt was present in 4 (2.6%) patients. The diameter of the right ventricle corrected for age was reduced by an average of 20% by the first month and in 130 (86%) of patients it had normalized by one year of follow up. During follow up, 16 (10%) patients reported transient headaches and 3 (1.9%) patients had transient atrial fibrillation (AF).Conclusion: In conclusion, the implantation of a septal occluder was found to be a safe procedure that resulted in improved hemodynamic parameters that result from right ventricular volume overload with favorable short- and mid-term results.

Infected aneurysm (or mycotic aneurysm) is defined as an infectious disease of the wall of an artery with formation of a blind, saccular out-pouching that is contiguous with the arterial lumen. Symptoms are frequently absent or nonspecific during the early stages. Once clinically presented, infected aneurysms are often at an advanced stage of development and associated with complications such as rupture. Nontreatment or delayed treatment of infected aneurysms has a poor outcome, with high morbidity and mortality rate via fulminant sepsis or hemorrhage. In clinically suspected cases, computed tomography is used for diagnosis. Urgent surgery, performed to prevent aortic rupture carries high morbidity and mortality rates.

Exploring the parenting styles, coping strategies and perceived stress in parents of children who have undergone cardiac intervention are challenging issues because they affect the whole family dynamics. Ten mothers of children who have undergone cardiac intervention and ten mothers of healthy children, aged 5 to 14 were administered three questionnaires: Parenting styl es Questionnaire, Cope and Perceived stress Questionnaire. The testing was conducted at the final day of their five-day summer camp in June 2011.Exploration of psychosocial characteristics of parents living with the diagnosis of cardiac disease in their child is crucial for the entire team of those providing healthcare. Adequate medical as well as psychological diagnosis can provide adequate psychotherapeutic interventions which can have multi-faceted benefits both for the parents and children in the process of coping.

There is evidence that body mass index (BMI) is related to some extent to the health related quality of life (HRQoL) in diffe rent populations. The purpose of our study was to investigate the relationship between the BMI and the HRQoL in patients awaiting coronary angiography. The sample consisted of 100 patients (68 males and 32 females) with symptomatology indicated for coronary angiography. For all of them BMI was calculated. They were also administered Duke Health profile questionnaire which measures adult self-reported functional health status. The findings reveal that BMI is related to some aspects of HRQoL. Considering this, health counseling directed at regulating body weight as part of the positive health behavior can benefit and improve some domains of the HRQoL and the QoL per se of the individuals having health problems.

BACKGROUND: Percutaneous transcatheter closure (PTC) of patent foramen ovale (PFO) is implicated in cryptogenic stroke, transitional ischemic attack (TIA) and treatment of a migraine.AIM: Our goal was to present our experience in the interventional treatment of PFO, as well as to evaluate the short and mid-term results in patients with closed PFO.MATERIAL AND METHODS: Transcatheter closure of PFO was performed in 52 patients (67.3% women, mean age 40.7 ± 11.7 years). Patients were interviewed for subjective grading of the intensity of headaches before and after the PFO closure.RESULTS: During 2 years of follow-up, there was no incidence of new stroke, TIA and/or syncope. Follow-up TCD performed in 35 patients showed complete PFO closure in 20 patients (57.1%). Out of 35 patients, 22 (62.9%) reported having a migraine before the procedure with an intensity of headaches at 8.1 ± 1.9 on a scale from 1 to 10. During 2 years of follow-up, symptoms of a migraine disappeared in 4 (18.2%) and the remaining 18 patients reported the significant decrease in intensity 4.8 ± 2.04 (p = 0.0001). In addition, following PFO closure the incidence of the headaches decreased significantly (p = 0.0001).CONCLUSIONS: Percutaneous transcatheter closure of PFO is a safe and effective procedure showing mid-term relief of neurological symptoms in patients as well as significant reduction of migraine symptoms.

BACKGROUND: Percutaneous pulmonary valvuloplasty is well established treatment of choice in pulmonary valve stenosis. AIM: The aim of our study was to present our experience with the interventional technique, its immediate and mid-term effectiveness as well as its complication rate. MATERIAL AND METHODS: The study included 43 patients, where 33 (74%) of them were children between the age of 1 month and 15 years. RESULTS: The procedure was successful in 38 patients or 90%. Mean peak to peak transvalvular gradient was reduced from 91.2 mmHg (55-150 mmHg) to 39.1 mmHg (20-80 mmHg). Follow- up of patients was between 2 and 13 years and included echocardiographic evaluation of pulmonary valve gradient, right heart dimensions and function as well as assessment of pulmonary regurgitation. We experienced one major complication pericardial effusion in a 5 months old child that required pericardiocenthesis. Six patients (13.9%) required a second intervention. During the follow up period there was significant improvement of right heart function and echocardiography parameters. Mild pulmonary regurgitation was noted in 24 (55%) patients, and four (9%) patients developed moderate regurgitation, without affecting the function of the right ventricle. CONCLUSIONS: Percutaneous pulmonary valvuloplasty is an effective procedure in treatment of pulmonary stenosis with good short and mid-term results.

Background Patients with terminal ischemic heart disease (IHD), severely depressed pump function with large LV dyskinesis with or without fibrosis do not benefit from revascularization alone; in time they are listed for transplantation. The long waiting list and lack of organ donors have imposed implementation of Direct Circular Repair (DCR) with total revascularization as an alternative. Methods DCR was performed on 17 patients with terminal IHD, after total revascularisation. The resected dyskinetic tissue was pathohistologicaly examined. Transesophageal ultrasound was performed pre- and early post-operatively and hemodynamic parameters measured invasively. Results Pathohistology showed that even in macroscopically viable myocardium where only dyskinesia without fibrosis persists, there are irreversible lesions on the ultrastructural level. Along with revascularization, with the application of DCR the LV spherical geometry was reconstructed with hemodynamic improvement. Conclusion Total revascularisation with DCR offers an alternative to transplantation in patients with wide anterior wall dyskinesia with or without fibrosis due to terminal IHD, the most frequent group listed for transplantation.

Maghsoudi, Behzad/0000-0002-1279-8799; Kritsotakis, Evangelos/0000-0002-9526-3852; Yalcin, Ata Nevzat/0000-0002-7243-7354; Mikaszewska-Sokolewicz, Malgorzata A/0000-0002-1148-7817; ALDEMIR KOCABAS, Bilge/0000-0002-6396-5243; Masjedi, Mohammad Reza/0000-0002-6871-382X; Masjedi, Mansoor/0000-0001-6175-9289; Gan, Chin Seng/0000-0002-6758-4798; Oncul, Oral/0000-0002-1681-1866; Sabetian, Golnar/0000-0001-8764-2150; YAMAN, Ayhan/0000-0002-5651-1286; Ozdemir, Halil/0000-0002-7318-1688; Leon, Hector Armando Rincon/0000-0003-0715-200X; Delia, Muntean/0000-0001-9100-4530; Atasay, Fatma Begum/0000-0002-9114-5293; Zand, Farid/0000-0003-3489-3372; Kuchenbecker, Ricardo/0000-0002-4707-3683; Medeiros, Eduardo A/0000-0002-6205-259X; ROMERO LOPEZ-ALBERCA, CRISTINA/0000-0001-5856-8668; Salomao, Reinaldo/0000-0003-1149-4598; ozdemir, sonay incesoy/0000-0003-2863-901X; Meco, Basak Ceyda/0000-0003-2951-9634; Horoz, Ozden Ozgur/0000-0001-7590-650X; Horhat, Florin George/0000-0001-6133-0204; Kazi, Mohammad Mukhit/0000-0003-3824-5540; Ciftci, Ergin/0000-0002-4955-160X; Abouqal, Redouane/0000-0002-6117-4341; Leblebicioglu, Hakan/0000-0002-6033-8543; Garcell, Humberto Guanche/0000-0001-7279-0062; Kendirli, Tanil/0000-0001-9458-2803; de Souza, Maria Cecilia B V/0000-0003-0318-3087; Sanaei Dashti, Anahita/0000-0002-2827-3575; UNAL, SERHAT/0000-0003-1184-4711; alvarez Moreno, carlos Arturo/0000-0001-5419-4494; Barahona G., Nayide/0000-0003-3559-6900; Rodriguez Ferrer, Marena Luz/0000-0002-8053-8454; Karabay, Oguz/0000-0003-0502-432X; Kaya, Sehnaz/0000-0003-0002-1517; ERDEVE, OMER/0000-0002-3193-0812; Gonzalez Martinez, Marisela del Rocio/0000-0003-1474-736X; Gikas, Achilleas/0000-0002-8455-9631; Baylan, Orhan/0000-0002-6529-7824; Mitrev, Zan/0000-0001-7859-8821; yildizdas, dincer/0000-0003-0739-5108; Ngo, Quy Chau/0000-0002-6787-2757; Duszynska, Wieslawa/0000-0002-5880-4904; KAYA, ZEYNEP/0000-0002-8468-2103; Dragan, Barbara/0000-0003-3108-4211; Gupta, Umesh/0000-0001-7717-1404; Navarro Fuentes, Karla Reyna/0000-0002-6894-8872; zali, Mohammadreza/0000-0002-9027-4560; Morocho Tutillo, Diego Rolando/0000-0002-4974-7856; El Kholy, Amani/0000-0002-0645-7664; Kanj, Souha/0000-0001-6413-3396; Assiri, Abdullah/0000-0002-5605-2876; Unal, Necmettin/0000-0002-9440-7893; Jayatilleke, Kushlani/0000-0002-3931-6630; KARABAY, OGUZ/0000-0003-1514-1685 WOS: 000341307100001 PubMed: 25179325 We report the results of an International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2007-December 2012 in 503 intensive care units (ICUs) in Latin America, Asia, Africa, and Europe. During the 6-year study using the Centers for Disease Control and Prevention's (CDC) U.S. National Healthcare Safety Network (NHSN) definitions for device-associated health care-associated infection (DA-HAI), we collected prospective data from 605,310 patients hospitalized in the INICC's ICUs for an aggregate of 3,338,396 days. Although device utilization in the INICC's ICUs was similar to that reported from ICUs in the U.S. in the CDC's NHSN, rates of device-associated nosocomial infection were higher in the ICUs of the INICC hospitals: the pooled rate of central line-associated bloodstream infection in the INICC's ICUs, 4.9 per 1,000 central line days, is nearly 5-fold higher than the 0.9 per 1,000 central line days reported from comparable U. S. ICUs. The overall rate of ventilator-associated pneumonia was also higher (16.8 vs 1.1 per 1,000 ventilator days) as was the rate of catheter-associated urinary tract infection (5.5 vs 1.3 per 1,000 catheter days). Frequencies of resistance of Pseudomonas isolates to amikacin (42.8% vs 10%) and imipenem (42.4% vs 26.1%) and Klebsiella pneumoniae isolates to ceftazidime (71.2% vs 28.8%) and imipenem (19.6% vs 12.8%) were also higher in the INICC's ICUs compared with the ICUs of the CDC's NHSN. Copyright (C) 2014 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Methods In emergency situation, preoperative patient work-up for cardio-vascular surgery is quite different from the elective setting. Since 03/2000 till 01/2012 we have analyzed a consecutive series of 12 172 cases out of which 2214 underwent emergency procedures (18.19%). The most frequent problems requiring urgent intervention were thoracic aortic aneurysms (448 cases; 20.24%); coronary artery disease (1006 cases; 45.47%) abdominal aortic aneurysms (125 cases 66 with rupture; 2.96%), peripheral vascular (364 cases; 16.46%), and others (329 cases: 14.87%).

Background The native aortic valve can be explained with rules of the equal side triangle, and as a part of the aortic root it is wedged between the heart and the ascending aorta. Beside different types of aortic valve replacements, reconstructive techniques are increasingly performed to restore normal aortic valve function. Reconstructive techniques themselves can be divided into isolated reconstruction of aortic valve/root structures and the isolated replacement of one or more structures. With this study we evaluated clinical results of reconstructive surgery of the aortic root with 3 leaflets pericardial patch. Methods We created this reconstructive technique using bovine/ equine pericardium, replacing valve cusps on aortic fibrous ring of patient. The leaflets are made from same pericardium from which other biologic valve prosthesis are done. The ring of patient’s aorta was used as guide for sizing this valve. Leaflets are implanted separately; using continuous sutures with 2 supported stitches at newly created commissure, without a stent or sowing ring. Main including criteria was stenosis of the aortic valve and patients with aortic annuli ring dilatation had been excluded. Intraoperative and postoperative TEE was performed for every created valve. Results