Major Clinical Complications Research Articles

Viral hepatitis in persons living with HIV in the post-COVID era.

Coinfection with hepatitis viruses A to E is frequent in persons living with HIV (PLWH) and causes significant morbidity and mortality. Oro-fecal transmissible hepatitis A and E mostly produce acute self-limited episodes in poor income regions and in non-vaccinated travelers. In high-income countries, outbreaks of hepatitis A occur in men having sex with men (MSM) and chronic hepatitis E is occasionally reported among PLWH with severe immunodeficiency. Chronic hepatitis B, C, and D are frequent in PLWH in highly endemic regions and globally in persons who inject drugs (PWID) and MSM. Progression to liver cirrhosis and development of hepatocellular carcinoma (HCC) is major clinical complications in coinfected patients. Current estimates for PLWH are of 38 million worldwide. Roughly 12% have chronic viral hepatitis (5 million). Coinfection figures are of 5-10% for HBV (2-4 million), 4% for HCV (1.5 million), and 15% of HBsAg+ for HDV (0.5 million). Oral direct-acting antivirals (DAA) cure almost all treated patients with hepatitis C. However, given that there is no protective HCV immunity, PLWH with high-risk behaviors may experience HCV reinfection episodes. Tenofovir is the drug of choice in PLWH with chronic hepatitis B, given its dual effect on HIV and HBV. Lifelong oral tenofovir suppresses HBV replication and ameliorate liver damage. However, the risk of HCC persists even in the absence of cirrhosis. Finally, HDV causes the worst of viral hepatitis with faster progression to cirrhosis and HCC. An entry inhibitor, bulevirtide, has recently been approved and another drug, lonafarnib, is completing Phase 3 trials. Combination antiviral therapy for hepatitis D could improve dramatically the poor prognosis of HIV-HDV coinfected patients. The resumption of good medical practices in PLWH after the big disruption caused by COVID-19 will reduce the burden of viral hepatitis coinfections. Renewed efforts on HAV and HBV vaccination of susceptible individuals and earlier and wider prescription of antiviral therapy for HBV, HCV, and/or HDV coinfection should be prioritized in PLWH. The benefits of innovative strategies for viral hepatitis, including pre-exposure prophylaxis or use of long-acting antivirals, warrant further consideration in PLWH.

Fractional and Microablative CO2 LASER and Radiofrequency in the Treatment of Genitourinary Syndrome of Menopause: A Descriptive Study.

Objectives: This study aimed to evaluate the vagina clinically, cytologically, and histologically before and after treating genitourinary syndrome of menopause (GSM) with fractional microablative carbon dioxide LASER (CO2L), radiofrequency (RF), and estrogen vaginal cream (CT). Methods: Women with moderate-to-severe symptoms of GSM, denoted by a GSM Visual analog scale (VAS) score of >4, were eligible for this study. The patients were randomized into treatment groups. In the energy groups, three vulvovaginal applications were administered monthly. The CT group used 0.5 mg vaginal estriol cream for 14 consecutive days, followed by twice a week for 4 months. The follow-up visits occurred 120 days after the beginning of the treatments. The same parameters obtained at the first visit were re-evaluated: GSM VAS score, Incontinence Quality of Life Questionnaire (I-QOL), gynecological examination determining Vaginal Health Index (VHI), vaginal smear for Vaginal Maturation Value (VMV), and vaginal biopsy. Results: Seventy-one women were included, 48 completed the study and provided adequate samples for analysis (CO2L [21 patients], RF [15 patients], and CT [12 patients]). GSM symptoms, I-QOL, and VHI significantly improved after all proposed treatments, with no significant differences between them. VMV did not change after any treatment; however, only 22.9% of the patients presented with cytological atrophy before treatment. Histological vaginal atrophy was identified in 6 (12.5%) pretreated vaginal samples. After the intervention, all histological parameters were normalized, no tissue damage was observed, and no major clinical complications were observed. Conclusion: CO2L and RF seem to be good alternatives to CT for GSM treatment, with no tissue damage.

#926 Qatar's Assisted Home Hemodialysis Program (AHHD): a new challenge to reach better outcomes for elderly patients

Abstract Background and Aims There are a growing number of patients supported by dialysis in older age. In Qatar, 58% of haemodialysis patients are above 60 years. The dialysis care of these patients can be challenging due to frailty, chronic health conditions, diminished QOL, and function. One important reason to favor Assisted Home Haemodialysis (AHHD), especially in the older population is the greater flexibility in conducting dialysis sessions. Our aim is to assess the efficacy of AHHD program in comparison to in-center dialysis. Method This is retrospective study to evaluate AHHD program in Qatar between July 2021 to December 2023 and compare to in-center haemodialysis in complications, compliance, infectivity and cost. Results The AHHD population increased gradually to 122 patients in December 2023. Patients and families reported great satisfaction 98.9% with the AHHD experience as they reported less fatigue post dialysis, eliminated the burden of transportation, and improved quality of life by having HD provided in a home environment. AHHD patients had a significantly lower infection rate (5%) during the COVID-19 outbreak than those receiving in-center dialysis. AHHD freed up crucial slots in hemodialysis centers, increasing the availability of dialysis slots by 10%. Mortality rate was 20.6% while 5 % of patient returned back to in-center dialysis. No major clinical or technical complications had been reported during follow up. The program had resulted in 25% reduction in total cost mainly due to reduction in ambulance use. Conclusion AHHD service increases access to hemodialysis care for elderly patients. The AHHD in Qatar showed great success over 30 months and there was a remarkable increase in the number of patients who started the AHHD with better outcomes regard to QOL and infectivity. It was cost-effective and showed an obvious outcome of reducing ambulance transport utilization and improving patients’ QOL and satisfaction.

Evaluation of short and mid-term clinical outcomes in patients with aortic coarctation treated with self-expandable stents

The present study aimed to evaluate the outcomes of percutaneous treatment of aortic coarctation using self-expandable uncovered Nitinol stents. We conducted a retrospective clinical data review of all patients with aortic coarctation and treated with self-expandable uncovered Nitinol stents at our institution between 2009 and 2019. The gradient pressure across the coarctation site was measured using aortography. Follow-up echocardiography and computed tomography angiography were performed to assess possible stent complications. A total of 127 stents were successfully implanted in 125 patients (64.8% males) with a mean age of 35.36 ± 11.9 years. The gradient across the coarctation site decreased significantly from 67.48 ± 14.79 to 5.04 ± 3.01 mmHg (P < 0.001) after self-expandable stent implantation. Systolic blood pressure (SBP) decreased significantly from 175.53 ± 15.99 to 147.22 ± 12.83 mmHg (P < 0.001) after self-expandable stenting. There were no major technical or clinical complications, including balloon rupture, aneurysmal formation, infection, secondary stent migration, thrombosis, death during the procedure, and in-hospital mortality. On a mean follow-up of 48 ± 23.6 months (12–120 months), the gradient [from 59.43 ± 15.42 to 3.72 ± 1.38 mmHg (P < 0.001)] and SBP [from 175.53 ± 15.99 to 127.99 ± 7.82 mmHg (P < 0.001)] decreased significantly. There was no mortality, aneurysmal formation in the stent site, dislocation, or aortic re-stenosis requiring intervention during mid-term follow-up. Treatment of aortic coarctation using a self-expandable uncovered nitinol stent is safe and effective with promising mid-term outcomes.

Transcatheter mitral valve repair with MitraClip: comparison of NT, NTr, and XTr Devices.

Transcatheter edge-to-edge repair (TEER) has become an established minimally invasive treatment for significant mitral regurgitation. Ongoing refinements and the availability of different clipping devices have expanded the indications for and effectiveness of TEER, but comprehensive comparative data on this issue are lacking. In this study, we compared NT, NTr, and XTr MitraClip devices (Abbot) for TEER. Details on patient, imaging, and procedural details, as well as short- and long-term outcomes, were sought from a national prospective clinical registry on TEER with MitraClip. The primary outcome of interest was discharge after procedural success without major clinical complications. A total of 2236 patients were included, 1228 (54.9%) in whom NT implantation only was attempted, 233 (10.4%) in whom NTr but not XTr implantation was attempted, and 775 (34.7%) in whom XTr implantation was attempted. Clinical and imaging features differed substantially across the groups, reflecting expanding indications with NTr and XTr devices. In-hospital outcomes were largely similar among the 3 groups, including death. Long-term unadjusted estimates of effect showed significant differences in several outcomes, including death, rehospitalization, and their composite, which demonstrated that NT was associated with more unfavorable outcomes compared with the other devices (all P less than .05). However, most differences depended on baseline features, as adjusted analysis showed no significant differences for early as well as long-term outcomes, including long-term death, rehospitalization, and their composite (all P greater than .05). New-generation MitraClip devices are associated with favorable procedural and clinical outcomes, despite being used in patients with more adverse features, when compared with patients treated with previous devices.

DOP88 Lipids drive myofibroblast activation and the epithelial-mesenchymal transition process in Crohn’s Disease

Abstract Background Fibrostenosis represents one of the major clinical complications of Crohn’s Disease (CD). However, the molecular mechanisms underlying intestinal fibrogenesis remain poorly understood and anti-fibrotic therapy has not yet been developed. Growing evidences supports that oxidative stress and the epithelial-mesenchymal transition (EMT) process contribute to the development and progression of fibrosis. Here, we assessed the role of lipids in fibrogenesis and whether mitochondria dysfunction can support fibrosis formation. Methods Spatial metabolomics analysis and adipophilin (ADFP) staining were performed on surgical specimens from fibrotic ileum and the surrounding region (healthy) derived from CD patients. Fibroblasts isolated from fibrotic and healthy ileum and human induced pluripotent stem cell-derived intestinal organoids (iHOs) were treated for 1-3 weeks with lipid mix (2%) and analyzed by RNA sequencing. Pathways significantly modulated were validated by RT-PCR, WB, FACS analysis, and proliferative, migratory and contraction assays, and mitochondrial functions by Seahorse analyzer. Results Spatial metabolomics revealed a significant accumulation of lipids characterized by very long-chain fatty acids in the fibrotic area compared to surrounding healthy regions, which was further confirmed by ADFP staining. RNA-seq analysis showed overlapping dysregulated pathways between healthy fibroblasts stimulated with lipids and fibrotic fibroblasts, in particular genes related to cell cycle, cytoskeletal reorganization, migration, contractility and cell metabolism (oxidative stress) which were further confirmed by functional assays. Among the genes related to oxidative stress, lipid stimulation significantly decreased NFE2L2 and promoted an increase in CPT1A, gene encoding for a fatty oxidation mediator. Moreover, lipid-stimulated fibroblasts showed a reduction in mitochondrial respiration, particularly basal and maximal respiration, and spare respiratory capacity by Seahorse analysis. On the other hand, long exposure of iHOs to lipids promoted the EMT process through the upregulation of TWIST, ZEB, VIM, and S100a4. Conclusion Lipid stimulation induced myofibroblast activation through oxidative stress and alteration of mitochondrial metabolism, and increased the expression of EMT transcription factors in intestinal epithelial cells (iHOs) that may support fibroblast-mediated pro-fibrotic activity. These data indicate that regulators of fatty acid oxidation involved in the fibrotic process may represent new potential targets for the treatment of fibrostenotic CD patients.

Early Diagnosis of Risks and Management of Cardiometabolic Diseases: A Case Study

The case study presented underscores the importance of early identification of metabolic risks, effective management, and lifestyle modifications in preventing clinical complications associated with cardiometabolic diseases (CMDs). The individual in the study, a South Asian immigrant, experienced the development of essential hypertension in his mid-50s, leading to left ventricular hypertrophy (LVH) and mild diastolic dysfunction. However, through proactive measures such as early diagnosis of metabolic risks, robust management of cardiovascular disease (CVD), adherence to a heart-healthy diet, and lifestyle changes, he was able to avoid major clinical complications of diabetes and maintain overall well-being until the age of 87. The key takeaways from this case study align with broader public health initiatives aimed at addressing the global epidemic of metabolic diseases. The multifaceted and intricate nature of this problem requires a comprehensive approach that considers various factors contributing to the rising prevalence of these diseases. Primary prevention strategies, which focus on identifying and mitigating risk factors for CMDs before the onset of vascular disease, play a crucial role in curbing the epidemic. The success observed in this case study, highlights the potential impact of proactive management and lifestyle interventions, in preventing and mitigating the progression of cardiometabolic diseases. It emphasizes the need for increased awareness, early screening, and ongoing monitoring of individuals at risk. Additionally, promoting heart-healthy diets and encouraging lifestyle modifications, such as regular physical activity and stress reduction, are essential components of a holistic approach to cardiometabolic health. Despite the positive outcomes demonstrated in this case, the article acknowledges that the global response to preventing both communicable and non-communicable diseases has been tepid, with varying levels of enthusiasm for developing primary prevention strategies across different nations. Addressing this challenge requires coordinated efforts at the individual, community, and policy levels to promote a culture of preventive healthcare. In conclusion, the findings of this case study contribute to the growing body of evidence supporting the efficacy of early diagnosis of metabolic risks, effective management, and lifestyle modifications in preventing clinical complications associated with cardiometabolic diseases. The lessons learned from individual cases can inform broader public health initiatives and underscore the importance of a proactive and comprehensive approach to address the escalating prevalence of metabolic diseases globally

Impact of non-driver gene mutations on thrombo-haemorrhagic events in ET patients.

Risk-adapted therapy is recommended to prevent major clinical complications, such as thrombo-haemorrhagic events, in patients with essential thrombocythaemia (ET). In this study, we analysed the association between non-driver gene mutations and thrombo-haemorrhagic events in 579 patients with ET. ASXL1 and TP53 mutations were frequently identified in patients with ET complicated by thrombosis (22.7% and 23.1%, respectively), and the DNMT3A mutation was frequently identified in patients who experienced haemorrhage (15.2%). Multivariate analyses of thrombosis-free survival (TFS) revealed that ASXL1 and TP53 mutations are associated with thrombosis (hazard ratio [HR] = 3.140 and 3.752 respectively). Patients harbouring the ASXL1 or TP53 mutation had significantly worse TFS rates than those without mutation (p = 0.002 and p < 0.001 respectively). Furthermore, JAK2V617F-mutated patients with accompanying ASXL1 mutations showed significantly shorter TFS compared with those without ASXL1 mutations (p = 0.003). Multivariate analyses of haemorrhage-free survival (HFS) revealed that the DNMT3A mutation (HR = 2.784) is associated with haemorrhage. DNMT3A-mutated patients showed significantly shorter HFS than those without the mutation (p = 0.026). Non-driver gene mutations should be considered in treatment strategies and may provide important information for personalised treatment approaches.

P111 RADIAL ACCESS FOR THE PERCUTANEOUS TREATMENT OF CHRONIC CORONARY OCCLUSIONS: A SINGLE CENTER EXPERIENCE

Abstract Background In the last years the improvement of interventional techniques for the treatment of coronary total occlusions (CTO) trough percutaneous coronary intervention (PCI) allowed a significant increase of the number and success rate of these procedures. At the same time, transradial access is increasingly being used for CTO–PCI even though there are concerns about its efficacy in this setting because of the higher procedural complexity. Aim of our study was to review the procedural success of all the CTO–PCI performed in our center according to the vascular access utilized. Methods We retrospectively evaluated all the CTO–PCI performed in our center from January 2018 to December 2019. These procedures were divided in two groups according to the vascular access employed: all femoral access procedures (Group 1) or procedures with at least one radial access (Group 2). The primary end–point of the study was the procedural success. Major procedural complications, the duration of the procedure and the volume of contrast used were also evaluated. Results A total of 66 CTO procedures have been performed: 15 procedures in Group 1 (66 ± 14 years, 80% males) and 51 in Group 2 (66 ± 9 years; 80% males, P= NS). In Group 2, 14 procedures were performed using only radial access whereas in 38 procedures a combination of radial and femoral access have been utilized. There were no significant differences in the main cardiovascular risk factors between the two groups. In Group 2, 5 procedures were performed by retrograde approach while in Group 1 all procedures were performed by antegrade approach. There were no significant differences between Group 1 and Group 2 in terms of contrast volume used (376 ± 137 mL and 345 ± 101 mL respectively, P=0.40) or in terms of procedure time duration (132 ± 49 min and 149 ± 71 min respectively, p=0.13). Procedural success was similar in the two groups: 86% in Group 1 and 80% in Group 2 ( P=0.86). There was one only major clinical complications in group 1 ( one stroke) and no complications in Group 2. Conclusion In our experience, the use of radial access alone or in combination with a single femoral access is safe and effective to perform CTO–PCI.

Diet-related complications according to the timing of enteral nutrition support in patients who recovered from out-of-hospital cardiac arrest: a propensity score matched analysis.

A proper nutritional plan for resuscitated patients is important in intensive care; however, specific nutritional guidelines have not yet been established. This study aimed to determine the incidence of diet-related complications that were affected by the timing of enteral nutrition in resuscitated patients after cardiac arrest. This retrospective and 1:1 propensity score matching study involved patients who recovered after nontraumatic, out-of-hospital cardiac arrest at a tertiary hospital. Patients were divided into an early nutrition support (ENS) group and a delayed nutrition support (DNS) group according to the nutritional support time within 48 hours after admission. The incidence of major clinical complications was compared between the groups. A total of 46 patients (ENS: 23, DNS: 23) were enrolled in the study. There were no differences in body mass index, comorbidity, and time of cardiopulmonary resuscitation between the two groups. There were 9 patients (ENS: 4, DNS: 5) with aspiration pneumonia; 4 patients (ENS: 2, DNS: 2) with regurgitation; 1 patient (ENS: 0, DNS: 1) with ileus; 21 patients (ENS: 10, DNS: 11) with fever; 13 patients (ENS: 8, DNS: 5) with hypoglycemia; and 20 patients (ENS: 11, DNS: 9) with hyperglycemia. The relative risk of each complication during post-resuscitation care was no different between groups. There was a similar incidence of diet-related complications during post cardiac arrest care according to the timing of enteral nutrition.

Decreased Platelet Specific Receptor Expression of P-Selectin and GPIIb/IIIa Predict Future Non-Surgical Bleeding in Patients after Left Ventricular Assist Device Implantation.

Non-surgical bleeding (NSB) is one of the major clinical complications in patients under continuous-flow left ventricular assist device (LVAD) support. The increased shear stress leads to an altered platelet receptor composition. Whether these changes increase the risk for NSB is unclear. Thus, we compared the platelet receptor composition of patients with (bleeder group, n = 18) and without NSB (non-bleeder group, n = 18) prior to LVAD implantation. Blood samples were obtained prior to LVAD implantation and after bleeding complications in the post-implant period. Platelet receptor expression of GPIbα, GPIIb/IIIa, P-selectin and CD63 as well as intra-platelet oxidative stress levels were quantified by flow cytometry. Bleeders and non-bleeders were comparable regarding clinical characteristics, von Willebrand factor diagnostics and the aggregation capacity before and after LVAD implantation (p > 0.05). LVAD patients in the bleeder group suffered from gastrointestinal bleeding (33%; n = 6), epistaxis (22%; n = 4), hematuria or hematoma (17%; n = 3, respectively) and cerebral bleeding (11%; n = 2). Prior to LVAD implantation, a restricted surface expression of the platelet receptors P-selectin and GPIIb/IIIa was observed in the bleeder group (P-selectin: 7.2 ± 2.6%; GPIIb/IIIa: 26,900 ± 13,608 U) compared to non-bleeders (P-selectin: 12.4 ± 8.1%, p = 0.02; GPIIb/IIIa: 36,259 ± 9914 U; p = 0.02). We hypothesized that the reduced platelet receptor expression of P-selectin and GPIIb/IIIa prior to LVAD implantation may be linked to LVAD-related NSB.

Mothers with hypertensive disorders of pregnancy increased risk of periventricular leukomalacia in extremely preterm or extremely low birth weight infants: A propensity score analysis.

BackgroundAt present, the conclusions about the impact of hypertensive disorders of pregnancy (HDP) on the clinical outcomes of preterm infants are inconsistent. This study used the propensity score matching (PSM) analysis to evaluate the effect of HDP on clinical outcomes of extremely preterm or extremely low birth weight (EP/ELBW) infants.MethodsRetrospective analysis was performed on the EP/ELBW infants discharged from 26 tertiary neonatal intensive care units or died during hospitalization from 2008 to 2017, who were divided into HDP group and non-HDP group. The six covariates including sex, gestational age, birth weight, twin or multiple pregnancy, antenatal steroids administration, and conception method were matched through the PSM method at a ratio of 1:1. The survival rate at discharge and the major clinical complications were compared between the two groups.ResultsAfter matching the six covariates, compared with the non-HDP group, there was no significant difference in the survival rate at discharge (64 vs. 63.2%, p > 0.05), the incidence of bronchopulmonary dysplasia (BPD) or moderate to severe BPD in the HDP group (58.3 vs. 54.9%, p > 0.05; 5.2 vs. 6.2%, p > 0.05). The incidence of periventricular leukomalacia (PVL) in the HDP group was significantly increased (5.7 vs. 1.9%, p < 0.05).ConclusionsHDP increased the risk of PVL in EP/ELBW infants, but had no significant effect on the survival rate at discharge, or the occurrence of other complications.

'Breast Cancer Resistance Likelihood and Personalized Treatment Through Integrated Multiomics'.

In recent times, enormous progress has been made in improving the diagnosis and therapeutic strategies for breast carcinoma, yet it remains the most prevalent cancer and second highest contributor to cancer-related deaths in women. Breast cancer (BC) affects one in eight females globally. In 2018 alone, 1.4 million cases were identified worldwide in postmenopausal women and 645,000 cases in premenopausal females, and this burden is constantly increasing. This shows that still a lot of efforts are required to discover therapeutic remedies for this disease. One of the major clinical complications associated with the treatment of breast carcinoma is the development of therapeutic resistance. Multidrug resistance (MDR) and consequent relapse on therapy are prevalent issues related to breast carcinoma; it is due to our incomplete understanding of the molecular mechanisms of breast carcinoma disease. Therefore, elucidating the molecular mechanisms involved in drug resistance is critical. For management of breast carcinoma, the treatment decision not only depends on the assessment of prognosis factors but also on the evaluation of pathological and clinical factors. Integrated data assessments of these multiple factors of breast carcinoma through multiomics can provide significant insight and hope for making therapeutic decisions. This omics approach is particularly helpful since it identifies the biomarkers of disease progression and treatment progress by collective characterization and quantification of pools of biological molecules within and among the cancerous cells. The scrupulous understanding of cancer and its treatment at the molecular level led to the concept of a personalized approach, which is one of the most significant advancements in modern oncology. Likewise, there are certain genetic and non-genetic tests available for BC which can help in personalized therapy. Genetically inherited risks can be screened for personal predisposition to BC, and genetic changes or variations (mutations) can also be identified to decide on the best treatment. Ultimately, further understanding of BC at the molecular level (multiomics) will define more precise choices in personalized medicine. In this review, we have summarized therapeutic resistance associated with BC and the techniques used for its management.

Gastrointestinal Bleeding After LVAD Implantation: Is It Predictable?

Purpose Non-surgical bleeding (NSB) is one of the major clinical complications in patients under continuous-flow left ventricular assist device (LVAD) support. Previous studies showed an altered platelet receptor composition in response to increased shear stress and bleeding events in LVAD patients. We investigated if the platelet receptor composition of patients with bleeding complications differs from patients without bleeding complications prior to LVAD implantation. Methods Blood samples were obtained prior to LVAD implantation and at regular follow up-visits after LVAD implantation. The bleeder group consisted of 18 consecutive LVAD patients with postoperative NSB that were matched by age and gender with LVAD patients without NSB (non-bleeder group, n=18). Platelet receptor expression of GPIbα, GPIIb/IIIa, P-selectin and CD63 as well as intra-platelet oxidative stress levels were quantified by flow cytometry. Further we documented clinical characteristics, aggregation capacity and von Willebrand factor (vWF) diagnostic of all patients. Results Bleeders and non-bleeders were comparable regarding their age at study begin, gender, LVAD type, vWF antigen, vWF activity, vWF collagen-binding activity, and the aggregation capacity before and after LVAD implantation (p>0.05). LVAD patients in the bleeder group suffered from gastrointestinal bleeding (44%; n=8), epistaxis (28%; n=5), hematuria (28%; n=5), and from cerebral bleeding (11%; n=2). The analysis of platelet receptor expression showed that the percentage of P-selectin-positive platelets and the relative quantity of GPIIb/IIIa molecules on platelets were decreased in bleeders (GPIIb/IIIa: 26.900 ± 13.608 U; P-selectin: 7.2 ± 2.6%) compared to non-bleeders (GPIIb/IIIa: 36.259 ± 9.914 U; p = 0.024; P-selectin: 12.4 ± 8.1%; p = 0.016) prior to LVAD implantation. Conclusion In this pilot study, we observed a restricted surface expression of the two platelet receptors P-selectin and GPIIb/IIIa prior to LVAD implantation in patients who suffer from NSB during LVAD support. We hypothesized that P-selectin and GPIIb/IIIa may be suitable markers to identify patients at risk for LVAD-related NSB prior to LVAD implantation. Non-surgical bleeding (NSB) is one of the major clinical complications in patients under continuous-flow left ventricular assist device (LVAD) support. Previous studies showed an altered platelet receptor composition in response to increased shear stress and bleeding events in LVAD patients. We investigated if the platelet receptor composition of patients with bleeding complications differs from patients without bleeding complications prior to LVAD implantation. Blood samples were obtained prior to LVAD implantation and at regular follow up-visits after LVAD implantation. The bleeder group consisted of 18 consecutive LVAD patients with postoperative NSB that were matched by age and gender with LVAD patients without NSB (non-bleeder group, n=18). Platelet receptor expression of GPIbα, GPIIb/IIIa, P-selectin and CD63 as well as intra-platelet oxidative stress levels were quantified by flow cytometry. Further we documented clinical characteristics, aggregation capacity and von Willebrand factor (vWF) diagnostic of all patients. Bleeders and non-bleeders were comparable regarding their age at study begin, gender, LVAD type, vWF antigen, vWF activity, vWF collagen-binding activity, and the aggregation capacity before and after LVAD implantation (p>0.05). LVAD patients in the bleeder group suffered from gastrointestinal bleeding (44%; n=8), epistaxis (28%; n=5), hematuria (28%; n=5), and from cerebral bleeding (11%; n=2). The analysis of platelet receptor expression showed that the percentage of P-selectin-positive platelets and the relative quantity of GPIIb/IIIa molecules on platelets were decreased in bleeders (GPIIb/IIIa: 26.900 ± 13.608 U; P-selectin: 7.2 ± 2.6%) compared to non-bleeders (GPIIb/IIIa: 36.259 ± 9.914 U; p = 0.024; P-selectin: 12.4 ± 8.1%; p = 0.016) prior to LVAD implantation. In this pilot study, we observed a restricted surface expression of the two platelet receptors P-selectin and GPIIb/IIIa prior to LVAD implantation in patients who suffer from NSB during LVAD support. We hypothesized that P-selectin and GPIIb/IIIa may be suitable markers to identify patients at risk for LVAD-related NSB prior to LVAD implantation.

Preparation of chitosan-tannic acid coating and its anti-osteoclast and antibacterial activities in titanium implants.

Bacterial infection and aseptic loosening caused by bone resorption at the implant interface are major clinical complications during bone defect implantation surgery, and surface modification of the implant to address the aforementioned problems has long been a research focus. In this paper, a chitosan (CTS)-tannic acid (TA) colloid coating with a negative charge and excellent hydrophilicity was prepared on a Ti6Al4V (TC4) surface using a layer-by-layer assembly method. The physical properties, anti-osteoclast activity, and antimicrobial activity of the coatings were investigated. The findings showed that when the pH value was 5 and the ratio of CTS:TA was 0.8, the carrying rate of TA was the best. Furthermore, the CTS-TA coating had no cytotoxicity on the morphology and proliferation of BMSCs cells and effectively inhibited the differentiation of RAW264.7 cells into osteoclasts and the proliferation of Staphylococcus aureus and Escherichia coli. With the increase in the immersion time of TC4 in CTS-TA colloid solution, the inhibitory effects will also enhance. Therefore, the preparation of the CTS-TA coating provides a revolutionary technique for implant surface modification to avoid postoperative bacterial infection and aseptic loosening.

Interaction between Sars-CoV-2 structural proteins and host cellular receptors: From basic mechanisms to clinical perspectives.

Severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) has caused a global pandemic that has affected the lives of billions of individuals. Sars-CoV-2 primarily infects human cells by binding of the viral spike protein to angiotensin-converting enzyme 2 (ACE2). In addition, novel means of viral entry are currently being investigated, including Neuropillin 1, toll-like receptors (TLRs), cluster of differentiation 147 (CD147), and integrin α5β1. Enriched expression of these proteins across metabolic regulatory organs/tissues, including the circulatory system, liver, pancreas, and intestine contributes to major clinical complications among COVID-19 patients, particularly the development of hypertension, myocardial injury, arrhythmia, acute coronary syndrome and increased coagulation in the circulatory system during and post-infection. Pre-existing metabolic disease, such as cardiovascular disease, obesity, diabetes, and non-alcoholic fatty liver disease, is associated with increased risk of hospitalization, persistent post-infection complications and worse outcomes in patients with COVID-19. This review overviews the biological features of Sars-CoV-2, highlights recent findings that delineate the pathological mechanisms of COVID-19 and the consequent clinical diseases.

The Effect of Curcumin on Iron Overload in Patients with Beta-Thalassemia Intermedia.

β-thalassemia is an inherited disorder that stems from a defect in beta-globin chain synthesis. Iron overload toxicity is one of the major clinical complications in β-thalassemia that may be due to a reduction in the hepcidin level. As a result, intestinal iron absorption increases and finally iron overload occurs. The current study aimed to investigate the effect of curcumin on serum iron status, ferritin, and transferrin in patients with β-thalas-semia intermedia. This study was a randomized, controlled, double-blind clinical trial. Before and after the intervention period with curcumin, 5 ml blood was taken for the measurement of the entire index related to iron status. Our results demonstrated the levels of serum iron (p-value < 0.001), ferritin (p-value = 0.002), and transferrin saturation (p-value < 0.001) significantly decreased in the curcumin group compared to placebo. The data presented in this article show that curcumin supplementation would be effective in alleviating iron overload in patients with β-thalassemia intermedia.

Abstract 14209: Natural History of Resolved Left Ventricular Thrombi

Introduction: Left ventricular thrombi (LVT) are associated with a significantly increased risk of systemic thromboembolism with its major clinical complications especially cerebrovascular stroke. Several societal guidelines recommend a duration of 3 to 6 months of anticoagulation (AC). However, evidence regarding LVT recurrence after AC discontinuation is lacking. Hypothesis: To determine the clinical characteristics associated with LVT recurrence in patients with resolved LVT after AC discontinuation. Methods: Follow-up data of 52 patients with resolved LVT derived from the Comparative Study of Oral Anticoagulation in Left Ventricular Thrombi (No-LVT Trial) was retrospectively analyzed. Results: 47 patients (90.38%) had no recurrence of LVT while 5 patients (9.61%) had LVT recurrence at a mean follow-up duration of 86.17±20.54 and 81±26.08 days, respectively. There was no statistically significant difference in age, gender, diabetes, hypertension, smoking or etiology of heart failure between the two groups. Baseline and follow-up left ventricular ejection fraction (LVEF) were lower in patients with recurrent LVT (32.4±5.37% and 40.34±4.08% respectively) compared to the no recurrence group (39.36±4.68% and 54.24±5.09% respectively) which was statically significant (p=value of 0.003*, &lt;0.0001* respectively). Conclusions: In patients with resolved LVT, low LVEF was the strongest predictor of LVT recurrence after AC discontinuation. Further research is required to determine clinical characteristics associated with LVT recurrence and indications for extended duration of AC in LVT treatment.

Development and Validation of a High-Fidelity Neonatal Pneumothorax Simulator

Neonatal pneumothorax is a clinical emergency procedure that - if not solved within minutes - can lead to major clinical complications, including death. For this reason, advanced management skills are required. High-fidelity simulation represents a valuable training tool for residents that allows to gain experience and confidence thus preserving patient safety. Nevertheless, systems now available on the market and literature prototypes provide poor anatomical and physiological features, thus limiting the realism of the simulation and the training. With the aim to overcome these limitations and allow the training of all aspects of the clinical procedure, an innovative high-fidelity neonatal pneumothorax simulator was realized by exploiting two airtight pressurized chambers coupled together with self-sealing needle insertion areas. The simulator assessment phase was carried out involving both expert neonatologists and residents. Before and after the clinical procedure, surveys were used for collecting subjective evaluations. Finally, procedural time was recorded. Based on the obtained results, neonatologists considered the simulator a valid teaching and retraining tool. Moreover, thanks to a simple setting and the possibility to provide real-time feedback, the simulator proved to be a valid tool for training also in critical conditions of personal distancing, e.g., Covid-19 pandemic, which often requires remote operation.

Retrograde chronic total occlusion percutaneous coronary intervention using single catheter: A single centre registry

ObjectivesTo analyse the feasibility, safety and procedural outcomes of percutaneous coronary intervention (PCI) for chronic total occlusions (CTO) through retrograde approach using single catheter. MethodsOur study was a retrospective observational study that enrolled patients who underwent retrograde CTO PCI using a single catheter between June 2016 and February 2020. Clinical success was defined as successful completion of CTO PCI without associated in-hospital major clinical complications like death, myocardial infarction, stroke or urgent revascularisation. Technical success was defined as successful completion of CTO PCI using single catheter and minimum diameter stenosis of <30% with thrombolysis in myocardial infarction (TIMI) flow grade 3, without significant side branch occlusion, flow-limiting dissection, distal embolization, or angiographic thrombus. ResultsTotally 102 patients underwent retrograde CTO PCI during the study period. Out of which, 15 cases were attempted using single catheter. Mean age of the population was 59.1 ± 8.9 years (males: 86.7%) and the left ventricular ejection fraction (LVEF) was (61% ± 9.1%). Mean number of diseased arteries was 2.1 ± 0.7, length of the CTO was 25.5 ± 7.4 mm and J-CTO score was 2.3 ± 0.7. We achieved a technical success rate of 73.3% using single catheter, and the overall clinical success (Including single catheter and ping pong) was obtained in 86.7% cases. One patient (6.7%) developed cardiac tamponade and none of study population required dialysis for contrast induced acute kidney injury (CI-AKI) ConclusionsRetrograde CTO PCI using single catheter is a technically challenging procedure when compared with other CTO PCI. Our study demonstrated acceptable outcomes which is comparable to other antegrade and retrograde CTO PCI registries.