Identification of the new allele HLA-C*04:01:01:186 in a Greek individual using next generation sequencing.

The newly discovered HLA-C*04:01:01:186 allele differs from HLA-C*04:01:01:01 by a single nucleotide substitution in intron 3.

Identification of the new allele HLA-A*24:632 in a Greek individual using next generation sequencing.

The HLA-Α*24:632 allele differs from HLA-A*24:02:01:01 by a single nucleotide substitution in exon 2.

Pediococcus pentosaceus Endocarditis in a Patient With Recent Transcatheter Aortic Valve Implantation and Liver Cirrhosis: A Case Report and Review of the Literature.

Transcatheter aortic valve implantation (TAVI) is increasingly being used in the management of severe aortic stenosis, mainly in older and/or medically compromised patients, due to its minimally invasive nature. As in any valve replacement procedure, endocarditis is a recognized complication, more so in TAVI patients, in whom comorbidities are highly prevalent. We report the case of a 70-year-old male with a history of liver cirrhosis and a recent TAVI, who presented with recurrent fever and sustainedPediococcus pentosaceus bacteremia. The diagnosis of endocarditis was delayed, as the microorganism was initially discarded as a contaminant, given that Pediococci are rarely described as human pathogens. However, in cirrhotic patients, microbiota may cause intermittent bacteremia and thereby affect prosthetic valves. Transthoracic echocardiography was not helpful in validating the diagnosis, as is often the case in TAVI patients. Transesophageal echocardiography was deemed perilous, due to esophageal varices complicating the underlying cirrhosis. Therefore, endocarditis diagnosis was based on sustained bacteremia and Duke's criteria, including the presence of high fever, a predisposing cardiac lesion, splenic infarction, and the exclusion of an alternative diagnosis. Moreover, cirrhosis enhanced the side effects of treatment and led to the need for regimen changes and prolonged hospitalization. Given the precariousness of the situation, confirmation of treatment success by 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography-computed tomography (18F-FDG PET-CT) scan was sought. This is the first reported case of Pediococcus TAVI endocarditis in a cirrhotic patient, highlighting the unique challenges in the diagnosis and management of TAVI endocarditis in patients with co-existing conditions.

Intussuscepted Polypoid Meckel's Diverticulum Presenting With Gastrointestinal Bleeding in a Young Adult.

A 22-year-old female patient with a recent hospitalization for gastrointestinal bleeding presented with recurrent hematochezia and a positive shock index. Previous investigations, including endoscopy and wireless small bowel capsule, were non-diagnostic. CT angiography revealed extravasation in the ileum. Initial tests like technetium-99m scintigraphy and ileocolonoscopy were negative. Repeat wireless small bowel capsule identified a partially ulcerated polypoid mass in the distal ileum. At surgical exploration, an intussuscepted Meckel's diverticulum was identified and resected. A histopathologic examination confirmed the diagnosis. Meckel's diverticulum is a rare cause of gastrointestinal bleeding in adults. Preoperative diagnosis can be challenging. Reports of a polypoid morphology are very scarce in indexed literature and mostly derive from investigation with device-assisted enteroscopy. We report this extremely rare finding at capsule endoscopy to raise clinician awareness and to discuss diagnostic difficulties associated with similar cases, such as the negative scintigraphy result and the optimal timing of repeat capsule endoscopy.

Assessment of hemostatic profile in neonates with necrotizing enterocolitis using Rotational Thromboelastometry (ROTEM).

BACKGROUND: This study aimed to explore the hemostatic profile of neonates with necrotizing enterocolitis (NEC) using Rotational Thromboelastometry (ROTEM) and to investigate if ROTEM parameters have the capacity to play a role in the differentiation of NEC from sepsis at the disease onset. METHODS: This observational study included 62 neonates (mean gestational age 31.6 weeks and mean birth weight 1620g) hospitalized in a neonatal intensive care unit. The neonates were categorized in three groups: neonates with NEC (Bell stage II and above), neonates with sepsis and healthy neonates and they were matched 1:1:1 with regards to gestational age, delivery mode, and sex. Clinical, laboratory data as well as measurements of ROTEM parameters at disease onset were recorded. RESULTS: ROTEM parameters differed between neonates with NEC and neonates with sepsis, indicating that NEC results in accelerated clot formation and higher clot strength compared to sepsis. The EXTEM CFT and A10 parameters demonstrated the highest diagnostic performance for NEC in terms of discrimination between NEC and sepsis (AUC, 0.997; 95% CI: 0.991-1.000 and 0.973; 95% CI: 0.932-1.000, respectively). CONCLUSIONS: Neonates with NEC manifested accelerated clot formation and higher clot strength compared to septic and healthy neonates, as these were expressed by ROTEM parameters. IMPACT: This work reports data on the hemostatic profile of neonates with necrotizing enterocolitis (NEC) using Rotational Thromboelastometry (ROTEM) and the capacity of ROTEM parameters in differentiating of NEC from sepsis at the disease onset. Neonates with NEC present acceleration of coagulation and exhibit a hypercoagulable profile, as this is expressed by ROTEM parameters, in comparison to septic and healthy neonates. ROTEM parameters demonstrated a good diagnostic capacity in differentiating NEC from sepsis at the disease onset.

Fibrinolysis shutdown and elevated D-dimer levels have high prognostic capacity for postoperative thromboembolic complications in patients with bone tumors.

Surgical resection of malignant bone tumors is associated with a high risk of venous thromboembolism (VTE). The purpose of this study was to evaluate the association between rotational thromboelastometry (ROTEM) parameters and VTE following oncologic resections, and to evaluate their prognostic capacity for this complication. A prospective observational study was conducted including 113 patients who underwent surgical resection of malignant bone tumors. ROTEM analysis and conventional coagulation studies were performed preoperatively and on the 2nd postoperative day, while patients were followed for the development of VTE. Logistic regression was used to assess the association between ROTEM parameters and occurrence of VTE. The area under the receiver operating characteristic curve (AUC), sensitivity and specificity were calculated as measures of discrimination and predictive accuracy. Fourteen patients (12.4%) developed symptomatic VTE. Development of VTE was associated with shortened INTEM CFT (Odds Ratio [OR] 0.90, 95% Confidence Interval [CI] 0.84 - 0.96, p = 0.004), higher INTEM A10 (OR 1.21, 95% CI 1.07 - 1.36, p = 0.002), higher INTEM MCF (OR 1.22, 95% CI 1.08 - 1.37, p = 0.001) and higher INTEM LI60 (OR 2.10, 95% CI 1.38 - 3.21, p = 0.001). An INTEM LI60 value indicative of fibrinolysis shutdown (≥ 98%) had the best predictive accuracy for VTE (AUC = 0.887, 95% CI 0.824 - 0.951, sensitivity = 100%, specificity = 67.0%), higher than that of D-dimer levels (p = 0.028). ROTEM parameters were promising predictors of symptomatic VTE. Fibrinolysis shutdown as reflected by ROTEM LI60 and high D-dimer levels can aid the identification of high-risk patients. Future studies should evaluate whether the addition of ROTEM findings to an expanded risk-assessing model can improve the predictive capacity and provide better guidance in thromboprophylaxis.

Sepsis-Induced Coagulopathy: An Update on Pathophysiology, Biomarkers, and Current Guidelines.

Significant cross talk occurs between inflammation and coagulation. Thus, coagulopathy is common in sepsis, potentially aggravating the prognosis. Initially, septic patients tend to exhibit a prothrombotic state through extrinsic pathway activation, cytokine-induced coagulation amplification, anticoagulant pathways suppression, and fibrinolysis impairment. In late sepsis stages, with the establishment of disseminated intravascular coagulation (DIC), hypocoagulability ensues. Traditional laboratory findings of sepsis, including thrombocytopenia, increased prothrombin time (PT) and fibrin degradation products (FDPs), and decreased fibrinogen, only present late in the course of sepsis. A recently introduced definition of sepsis-induced coagulopathy (SIC) aims to identify patients at an earlier stage when changes to coagulation status are still reversible. Nonconventional assays, such as the measurement of anticoagulant proteins and nuclear material levels, and viscoelastic studies, have shown promising sensitivity and specificity in detecting patients at risk for DIC, allowing for timely therapeutic interventions. This review outlines current insights into the pathophysiological mechanisms and diagnostic options of SIC.

Pathogen Reduction Technologies and Their Impact on Metabolic and Functional Properties of Treated Platelet Concentrates: A Systematic Review.

Pathogen reduction technologies (PRTs) such as Mirasol and Intercept were developed to eliminate transfusion-transmitted infections. The impact of PRTs on platelet function during the storage period, their effect on platelet storage lesions, and the optimal storage duration following PRTs have not been clearly defined. The aim of this study was to systematically review the existing literature and investigate the impact of PRTs on functional alterations of PRT-treated platelets during the storage period. The authors identified 68 studies suitable to be included in this review. Despite the high heterogeneity in the literature, the results of the published studies indicate that PRTs may increase platelet metabolic activity, accelerate cell apoptosis, and enhance platelet activation, which can subsequently lead to a late exhaustion of activation potential and reduced aggregation response. However, these effects have a minor impact on platelet function during the early storage period and become more prominent beyond the fifth day of the storage period. Large in vivo trials are required to evaluate the effectiveness of PRT-treated platelets during the storage period and investigate whether their storage can be safely extended to more than 5 days, and up to the traditional 7-day storage period.

Rotational Thromboelastometry Predicts Transfusion Requirements in Total Joint Arthroplasties.

The frequency of red blood cell (RBC) transfusions is high in total joint arthroplasties, and the hemorrhagic risk is associated with both surgery- and patient-related factors. This study aims to assess the ability of rotational thromboelastometry (ROTEM) to identify patients at high risk for transfusion and excessive bleeding. A prospective observational study was conducted including 206 patients who underwent total knee or hip arthroplasties. Assessment of the coagulation status was performed preoperatively and immediately postoperatively using ROTEM analysis and conventional coagulation tests. The number of RBC transfusions and the postoperative hemoglobin drop were recorded. ROTEM findings were compared between transfused and nontransfused patients, and also between patients with and without excessive bleeding. Higher values of postoperative FIBTEM maximum clot firmness (MCF) were associated with lower risks of transfusion (odds ration [OR]: 0.66, 95% confidence interval [CI]: 0.57-0.78, p<0.001) and excessive bleeding (OR: 0.58, 95% CI: 0.36-0.94, p=0.028). A postoperative FIBTEM MCF value ≤10mm had 80.1% (95% CI: 73.1-85.9%) sensitivity with 75.5% (95% CI: 60.4-87.1%) specificity to predict transfusion requirements, and 70.5% (95% CI: 63.6-76.8%) sensitivity with 88.8% (95% CI: 51.7-99.7%) specificity to predict excessive bleeding. The estimated average probability of transfusion in patients with FIBTEM MCF values of 0 to 4mm is 86.3%. ROTEM assay demonstrated high predictive ability for transfusion and excessive bleeding. Identification of patients at risk for transfusion could allow blood banks to ensure adequate blood supply, while also more intense blood-salvaging strategies could be implemented in these patients.

SARS-CoV-2 Infection and Outcomes in Children with Inflammatory Bowel Diseases: A Systematic Review.

The impact of COVID-19 on pediatric patients with inflammatory bowel disease (PIBD) is still not clear and the knowledge acquired over the last 2 years is still evolving. This study aims to investigate the risk and clinical outcomes of COVID-19 in patients with PIBD. A systematic search of PubMed and Scopus databases was conducted to identify studies published up until September 2022. Out of the 475 articles screened, 14 studies were included in the review. Of the 4006 children with PIBD included, 390 (9.7%) tested positive for COVID-19. Among those with COVID-19, 5.9% (0-16.7%) needed hospitalization, 0.6% (0-1%) were admitted to the pediatric intensive care unit (PICU), and no deaths were reported. Among the included studies, only four presented details regarding patients' symptoms, with 21% (0-25%) presenting gastrointestinal (GI) symptoms. An association between PIBD activity or specific treatment and COVID-19 outcome could not be established. The prevalence of COVID-19 in patients with PIBD was low; therefore, the initial concerns regarding higher infection risk and worse prognosis in this population are not supported by the currently available data. Further research is needed to determine the natural history of the infection and the optimal treatment for these patients. Much is still unclear and additional studies should be performed in order to optimize prevention and care for this special group of patients.

Assessment of agreement between EXTEM and NATEM thromboelastometry measurement assays in critically ill neonates.

OBJECTIVES: To investigate the agreement between the EXTEM and NATEM measurements. METHODS: In this retrospective observational study, EXTEM and NATEM analyses were performed on blood samples from 162 ill neonates, providing 324 paired measurements. The agreement between EXTEM and NATEM measurements was evaluated by the nonparametric spearman's rank correlation to assess the correlation between the paired measurements, by the Bland-Altman analysis for the graphical presentation of the agreement, and by the Deming regression model to assess the significance of the agreement. The agreement between the two methods for the detection of bleeding events was determined by kappa statistic. RESULTS: Strong correlations were found between EXTEM and NATEM measurements for A10, MCF. The Bland-Altman plots showed good agreement for A10, MCF, LI60, and alpha angle parameters, while CT showed a nearly linear slope indicating that bias increased with the mean. The highest agreement for bleeding events was found for the A10 parameter (κ = 0.70, p < .001), while the lowest for the CT parameter (κ = 0.36, p = .94). CONCLUSIONS: NATEM parameters that reflect clot firmness and fibrinolytic activity are strongly correlated with the corresponding EXTEM measurements with a good agreement between them, indicating that these two methods could be used interchangeably.