Extracorporeal Blood Purification in Moderate and Severe COVID-19 Patients: A Prospective Cohort Study.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is characterized by hyperinflammation and coagulopathy. Severe cases often develop respiratory distress, requiring mechanical ventilation and with critical cases progressing to acute respiratory distress syndrome. 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 evaluated the longitudinal changes of systemic inflammatory markers in critically ill COVID-19 patients treated with blood purification using AN69ST (oXiris®) haemofilter. METHODS: We performed a time-series analysis of 44 consecutive COVID-19 cases treated with the AN69ST (oXiris®) cytokine adsorbing haemofilter (CAH) according to local practice; we visualize longitudinal results of biochemical, inflammatory, blood gas, and vital sign parameters focussing on systemic levels of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin. RESULTS: All patients were treated with ≥1 cycle extracorporeal continuous venovenous haemofiltration (CVVH) with CAH; of these, 30 severe patients received CVVH-CAH within 4-12 h of admission after recognizing a hyper-inflammatory state. Another 14 patients admitted with mild-to-moderate symptoms progressed to severe disease and were placed on EBP during hospitalization. The treatment was associated with a reduction of ferritin, CRP, fibrinogen, several inflammatory markers, and a resolution of numerous cytopenias. The observed mortality across the cohort was 36.3%. CONCLUSION: EBP with CAH was associated with a decrease in CRP, and control of IL-6 and procalcitonin.

Outcomes with Ventricular Assist Device Therapy for Advanced Heart Failure in North Macedonia: First Annual Report

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.

Cardiac autotransplantation and ex vivo surgical repair of giant left atrium: a case presentation.

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.

Effectiveness of a multidimensional approach for prevention of ventilator-associated pneumonia in adult intensive care units from 14 developing countries of four continents: findings of the International Nosocomial Infection Control Consortium.

OBJECTIVES: The aim of this study was to analyze the effect of the International Nosocomial Infection Control Consortium's multidimensional approach on the reduction of ventilator-associated pneumonia in patients hospitalized in intensive care units. DESIGN: A prospective active surveillance before-after study. The study was divided into two phases. During phase 1, the infection control team at each intensive care unit conducted active prospective surveillance of ventilator-associated pneumonia by applying the definitions of the Centers for Disease Control and Prevention National Health Safety Network, and the methodology of International Nosocomial Infection Control Consortium. During phase 2, the multidimensional approach for ventilator-associated pneumonia was implemented at each intensive care unit, in addition to the active surveillance. SETTING: Forty-four adult intensive care units in 38 hospitals, members of the International Nosocomial Infection Control Consortium, from 31 cities of the following 14 developing countries: Argentina, Brazil, China, Colombia, Costa Rica, Cuba, India, Lebanon, Macedonia, Mexico, Morocco, Panama, Peru, and Turkey. PATIENTS: A total of 55,507 adult patients admitted to 44 intensive care units in 38 hospitals. INTERVENTIONS: The International Nosocomial Infection Control Consortium ventilator-associated pneumonia multidimensional approach included the following measures: 1) bundle of infection-control interventions; 2) education; 3) outcome surveillance; 4) process surveillance; 5) feedback of ventilator-associated pneumonia rates; and 6) performance feedback of infection-control practices. MEASUREMENTS: The ventilator-associated pneumonia rates obtained in phase 1 were compared with the rates obtained in phase 2. We performed a time-series analysis to analyze the impact of our intervention. MAIN RESULT: During phase 1, we recorded 10,292 mechanical ventilator days, and during phase 2, with the implementation of the multidimensional approach, we recorded 127,374 mechanical ventilator days. The rate of ventilator-associated pneumonia was 22.0 per 1,000 mechanical ventilator days during phase 1, and 17.2 per 1,000 mechanical ventilator days during phase 2.The adjusted model of linear trend shows a 55.83% reduction in the rate of ventilator-associated pneumonia at the end of the study period; that is, the ventilator-associated pneumonia rate was 55.83% lower than it was at the beginning of the study. CONCLUSION: The implementation the International Nosocomial Infection Control Consortium multidimensional approach for ventilator-associated pneumonia was associated with a significant reduction in the ventilator-associated pneumonia rate in the adult intensive care units setting of developing countries.

Preoperative Left Ventricular Global Longitudinal Strain Identifies Aortic Stenosis Patients with Improved Postoperative Recovery of Left Ventricular Geometry: A Prospective Cohort Study.

INTRODUCTION: The left ventricular ejection fraction (LVEF) is commonly used as a marker of aortic stenosis (AS) disease severity and to indicate surgical intervention. However, an LVEF <50% identifies mainly advanced disease. Hence, earlier detection of subclinical LV systolic dysfunction may improve clinical decision-making. The global longitudinal strain (GLS) can identify subclinical systolic dysfunction at earlier stages of AS progression even in the presence of preserved LVEF. To this end, we evaluated the preoperative prognostic significance of the LVGLS to identify patients who will undergo a more extensive postoperative LV reverse remodeling as a surrogate marker for clinical recovery. METHODS: We performed a prospective observational study based on detailed pre- and postoperative 2D transthoracic echocardiographic examinations, including strain analysis with speckle tracking. We screened 60 consecutive patients with severe AS and a preoperative LVEF ≥50% indicated for surgery; 39 patients met the study entry criteria and consented to their participation. RESULTS: The median age was 67 (range 30-79) years; 56.4% were female. At baseline, the GLS was 61.64±7.22%. Surgery led to an improvement in the GLS; the mean difference was 3.23% [95% CI=1.96 to 4.49%] during a median follow up time of 5 (interquartile range 4-6) months. The preoperative GLS correlated with the postoperative LV mass index (LVMI) r=0.526, P=0.001 and the intraventricular septal thickness in diastole (IVSd) r=0.462, P=0.003. Furthermore, patients with a normal GLS (≤-18.9%) at baseline experienced a better recovery of their LV morphology and systolic function during the postoperative course compared to those with an abnormal GLS (>-18.9%). The effect size, hedges g, was at least >0.75 for the LVMI, IVSd, intraventricular septal thickness in systole (IVSs), left ventricular posterior wall thickness in diastole (LVPWd) and LVEF, suggesting a clinically significant difference between subgroups at follow-up. CONCLUSION: A normal preoperative left ventricular global longitudinal strain is associated with an improved left ventricular reverse remodeling and systolic function following surgery to resolve aortic stenosis.

Aortic Valve Neocuspidization Using Xenologous Pericardium Versus Bioprosthetic Valve Replacement.

BACKGROUND: Surgical aortic valve replacement (SAVR) for patients with aortic valve stenosis (AS) with small aortic root is associated with a higher rate of prosthesis-patient mismatch and suboptimal clinical outcomes. Aortic valve neocuspidization using xenologous pericardium (xAVNeo) has shown a favorable hemodynamic performance. The aim was to compare 6-year clinical outcomes of xAVNeo with SAVR. METHODS: Between 2003 and 2018, 412 patients with severe AS and small aortic root received either xAVNeo (n = 114) or bioprosthesis (n = 298). After propensity matching the cohort included 222 patients. The primary endpoints were early mortality, 6-year mortality, and freedom from reoperation. Mean follow-up averaged 3.4 ± 3.1 years and was 95% complete. RESULTS: Early mortality was 8.1% for the SAVR group versus 9.9% for the xAVNeo group (odds ratio, 1.25; 95% confidence interval, 0.51-2.89). The estimated survival probabilities at 6 years for the SAVR and xAVNeo cohorts were 89.9% and 88.8%, respectively (odds ratio, 1.07; 95% confidence interval, 0.49-2.34). Progressive degeneration of the neocusps resulted in a mean gradient increase from 6.1 ± 2.3 mm Hg to 22.7 ± 11.5 mm Hg (P < .0001); cusp sclerosis was the most common indication for reoperation in the xAVNeo group with a linearized rate of 1.92% versus 0.26% per patient-year (rate ratio, 7.41; 95% confidence interval, 0.95-333.7). The freedom from reoperation was 84.8% at 6 years, inferior to that of the SAVR group (100%). CONCLUSIONS: Early clinical outcomes and 6-year survival rates after xAVNeo and SAVR were comparable. However xAVNeo using bovine pericardium was associated with a higher rate of structural valve deterioration and inferior freedom from reoperation when compared with SAVR.

Case Report: Omicron BA.2 Subvariant of SARS-CoV-2 Outcompetes BA.1 in Two Co-infection Cases.

Trends from around the world suggest that the omicron BA.2 subvariant is increasing in proportion to the original BA.1 subvariant. Here we report two cases of co-infection with omicron BA.1 and omicron BA.2 in co-exposed individuals. In both individuals, genome sequencing and/or S-gene specific PCR identified omicron BA.1 at early time-points, which was replaced by omicron BA.2 at later time-points of the infection. The timeline of our data supports the proposition that BA.2 outcompetes BA.1 in a real-life scenario, and in time becomes the dominant variant in the upper respiratory tract of the host.

Early Initiation of Extracorporeal Blood Purification Using the AN69ST (oXiris®) Hemofilter as a Treatment Modality for COVID-19 Patients: a Single-Centre Case Series.

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.

Minimally Invasive Surgical Repair of Vertebral Artery Ostium Stenosis in Patients with Ischemic Stroke: A Single-Center Case Series.

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.

Hemodynamic monitoring for less invasive cardiovascular surgery.

Surgery does not start with the incision and end with skin suturing. Successful surgical outcome depends on close interaction between the anesthesiology, surgery and intensive care units (ICU). Adequate patient monitoring is essential part of all aforementioned departments. Using adequate hemodynamic and neurologic monitoring, less invasive anaesthesia with less invasive cardiac and vascular surgery can be performed safely, leading to better surgical results, greater patient comfort and satisfaction, and reduced hospital stay.

Cytokine storm and COVID-19: a chronicle of pro-inflammatory cytokines.

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.

Workflow for the Implementation of Precision Genomics in Healthcare.

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.

The influence of controlled limb reperfusion with PGE1 on reperfusion injury after prolonged ischemia.

BACKGROUND: Controlled reperfusion of ischemic limbs has been found to be protective in limiting ischemia-reperfusion injury. We aimed to analyze local hemodynamic effects of prostaglandin E1 (PGE1) administrated during controlled reperfusion in an in vivo setting. MATERIAL AND METHODS: Twenty-four pigs underwent exposure of the infrarenal aorta and iliac vessels. Pigs were observed for 7.5 h without limb ischemia (group I). In the others, limb ischemia was produced by clamping the aorta for 6 h. Reperfusion was conducted in uncontrolled (group II), controlled (group III), and controlled fashion with addition of PGE1 (group IV) for the initial 30 min. We evaluated regional blood flow in the left common iliac artery, cardiac output, systemic vascular resistance, oxygen and glucose consumption, muscle adenosine triphosphate (ATP), and potassium levels in iliac vein. RESULTS: Benefits after reperfusion were observed in group IV compared with group III regarding regional blood flow at 60 min (P < 0.01) and 90 min (P < 0.01), glucose consumption at 30 min, (P < 0.05) and potassium regulation at 30 (P < 0.05) and 90 min (P < 0.05). CONCLUSION: The addition of PGE1 to controlled reperfusion further reduces local hemodynamic effects of ischemia-reperfusion injury compared with standard controlled and uncontrolled reperfusion in an animal model.

Continuous venovenous hemodiafiltration using cytokine-adsorbing hemofilters as adjuvant therapy for anaerobic descending necrotizing mediastinitis: a case report.

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.

The AKR1D1*36 (rs1872930) Allelic Variant Is Independently Associated With Clopidogrel Treatment Outcome.

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.

A Pediatric Case of Glioblastoma Multiforme Associated With a Novel Germline p.His112CysfsTer9 Mutation in the MLH1 Gene Accompanied by a p.Arg283Cys Mutation in the TP53 Gene: A Case Report.

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.

Surgical plate fixation of multiple rib fractures: a case report.

BACKGROUND: The healthcare system in developing countries is limited; particularly, medical specialties such as emergency and trauma medicine are underdeveloped. Consequently, trauma injuries sustained in traffic accidents result in chronic morbidity more often than similar cases in developed countries. Multiple rib fractures induce significant patient morbidity. Current international guidelines recommend a multidisciplinary, surgery-based treatment approach to achieve optimal clinical benefit. CASE PRESENTATION: We admitted a 41-year-old Albanian man to our emergency department following a pedestrian-vehicle accident 5 days earlier. He presented with severe upper thoracic pain, chest deformity, dyspnea, tachycardia, subcutaneous emphysema, and hematoma. Chest radiography pointed to hypoventilated lung fields and a minor pleural effusion. Computed tomographic scans indicated displaced fractures of right lateral ribs 5 -11, hyperdensity regions from bone fragments, and pulmonary contusion. The treatment consisted of surgical fixation of ribs 7-10 using titanium reconstruction plates and cortical locking screws. The patient's clinical condition rapidly improved postoperatively. Follow-up at 6 weeks confirmed a full return to preoperative daily activities and a high quality of life. CONCLUSIONS: In this case report, we present a novel and promising development in the field of trauma medicine in the Republic of Macedonia. Trauma injuries can be treated via advanced multidisciplinary medical care according to international standards, allowing optimal health recovery.

Trio Clinical Exome Sequencing in a Patient With Multicentric Carpotarsal Osteolysis Syndrome: First Case Report in the Balkans.

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 (CES) 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 MCTO in the Balkans.

Preoperative Left Ventricular Global Longitudinal Strain Identifies Aortic Stenosis Patients with Improved Postoperative Recovery of Left Ventricular Geometry: A Prospective Cohort Study

Abstract Introduction: The left ventricular ejection fraction (LVEF) is commonly used as a marker of aortic stenosis (AS) disease severity and to indicate surgical intervention. However, an LVEF <50% identifies mainly advanced disease. Hence, earlier detection of subclinical LV systolic dysfunction may improve clinical decision-making. The global longitudinal strain (GLS) can identify subclinical systolic dysfunction at earlier stages of AS progression even in the presence of preserved LVEF. To this end, we evaluated the preoperative prognostic significance of the LVGLS to identify patients who will undergo a more extensive postoperative LV reverse remodeling as a surrogate marker for clinical recovery. Methods: We performed a prospective observational study based on detailed pre- and postoperative 2D transthoracic echocardiographic examinations, including strain analysis with speckle tracking. We screened 60 consecutive patients with severe AS and a preoperative LVEF ≥50% indicated for surgery; 39 patients met the study entry criteria and consented to their participation. Results: The median age was 67 (range 30-79) years; 56.4% were female. At baseline, the GLS was 61.64±7.22%. Surgery led to an improvement in the GLS; the mean difference was 3.23% [95% CI=1.96 to 4.49%] during a median follow up time of 5 (interquartile range 4-6) months. The preoperative GLS correlated with the postoperative LV mass index (LVMI) r=0.526, P=0.001 and the intraventricular septal thickness in diastole (IVSd) r=0.462, P=0.003. Furthermore, patients with a normal GLS (≤-18.9%) at baseline experienced a better recovery of their LV morphology and systolic function during the postoperative course compared to those with an abnormal GLS (>-18.9%). The effect size, hedges g, was at least >0.75 for the LVMI, IVSd, intraventricular septal thickness in systole (IVSs), left ventricular posterior wall thickness in diastole (LVPWd) and LVEF, suggesting a clinically significant difference between subgroups at follow-up. Conclusion: A normal preoperative left ventricular global longitudinal strain is associated with an improved left ventricular reverse remodeling and systolic function following surgery to resolve aortic stenosis.

Early Initiation of Extracorporeal Blood Purification Using the AN69ST (oXiris®) Hemofilter as a Treatment Modality for COVID-19 Patients: a Single-Centre Case Series

Abstract 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.