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We retrospectively compared the impact of the conditioning regimen in adult patients with acute myeloid leukemia (AML) in first complete remission (CR1) that received high-dose myeloablative chemotherapy followed by autologous stem cell transplantation (ASCT) from 2010 to 2021 with either high-dose cytarabine, etoposide and busulfan (BEA), busulfan with cyclophosphamide (BUCY) or busulfan and high-dose melphalan (BUMEL) registered in the EBMT database. Overall 1560 patients underwent ASCT, of which 156, 1143 and 261 received BEA, BUCY and BUMEL, respectively. Compared to BUCY and BUMEL, BEA patients were younger (p < 0.001) and less frequently had NPM1 mutations (p = 0.03). Transplant outcomes at 5 years with BEA, BUCY and BUMEL were: cumulative incidence of relapse 41.8%, 46.6% and 51.6%; non-relapse mortality (NRM) 1.5%, 5.2% and 7.3%; probability of leukemia-free survival (LFS) 56.7%, 48.2% and 41.1%; and overall survival (OS) 71.3%, 62.3% and 56%, respectively. In multivariable analysis the BEA regimen showed significant improvement in OS compared to BUCY (hazard ratio [HR] 0.65; 95% CI, 0.42-0.83; p = 0.048) and BUMEL (HR 0.59; 95% CI, 0.37-0.94; p = 0.029). In conclusion, high-dose myeloablative combination chemotherapy with BEA offered improved outcomes compared to classical BUCY or BUMEL in patients with AML in CR1 undergoing ASCT., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Myelofibrosis (MF) is a clonal disorder of hematopoietic stem cells characterized by altered bone marrow function and fibrosis. The aim of this narrative review is to report on the most recent epidemiologic data and to discuss features of MF and current strategies for the management of this condition in clinical practice. MF features covered by our review will include: characteristics of patients with MF; myeloproliferative and myelodepletive phenotypes; MF-associated thrombosis and bleeding; risk of infections; prefibrotic and overt PMF; secondary MF. Finally, we will discuss a few aspects of MF management in clinical practice and suggest strategies for its optimization and standardization. The focus of our paper is on Italy, but relevant data from other countries will also be reviewed. [ABSTRACT FROM AUTHOR]

Donor-derived hematological malignancies have been recognized as rare but serious late complications in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Most cases in the literature were diagnosed as myelodysplastic syndrome or acute leukemia, with very few malignant lymphoma reported. We herein present another case of donor-derived Burkitt lymphoma that occurred 9 years after allo-HSCT under continued administration of immunosuppressants for chronic graft-versus-host disease (GVHD). The patient achieved a partial response after rituximab-combined intensive chemotherapy. To reduce the risk of relapse and to avoid organ toxicities due to repeated chemotherapies, we performed upfront high-dose chemotherapy followed by stem cell rescue using donor-derived CD34 + cells, called pseudo-autologous HSCT (pASCT), and adjusted immunosuppressants appropriately. The patient remained disease-free for 23 months after pASCT without exacerbation of cGVHD. Although the observation period has been relatively short and longer follow-up is needed, pASCT may be a feasible option for donor-derived lymphoma even in patients with active cGVHD., (© 2022. Japanese Society of Hematology.)

Background: The therapeutic status of allogeneic stem cell transplantation (allo-SCT) as a post-remission treatment for patients with high-risk acute myeloid leukemia (AML) was well-accepted. However, the optimal treatment for patients with low/favorable- or intermediate-risk AML who achieve complete remission has remained controversial. Therefore, we conducted a network meta-analysis to discuss this disputed problem. Methods: We compared the effects of treatment strategies including allo-SCT, autologous stem cell transplantation (auto-SCT) and consolidation chemotherapy (CT) for patients with low/favorable- or intermediate-risk AML. The pooled HRs and 95% CIs for overall survival and disease-free survival were estimated with Stata12 and R software. Thirty clinical studies with 6682 patients were included in the meta-analysis. Results: The results indicated that the treatment outcome of allo-SCT was the best, followed by auto-SCT, and CT was likely the worst in the total AML patients. In patients with low/favorable-risk AML, the treatment outcome of auto-SCT was likely ranked first, followed by allo-SCT, and CT was the worst. In patients with intermediate-risk AML, the treatment outcome of haploidentical stem cell transplantation (haplo-SCT) was the best, followed by allo-SCT (excluding haplo-SCT), and auto-SCT and CT were the worst. However, the median age of the haplo-SCT group was much younger than that of the control group, which may be one of the reasons for the better prognosis of the haplo-SCT group. Conclusions: Patients with low/favorable- and intermediate-risk (non-high-risk) AML should prioritize allo-SCT if they are eligible for transplantation, and auto-SCT is optional. However, in the subgroup analysis, auto-SCT was the optimal treatment choice for patients with low/favorable-risk AML, and allo-SCT was the priority selection for patients with intermediate-risk AML, especially young patients. These findings could provide references for clinical practice. [ABSTRACT FROM AUTHOR]

Background: Severe pneumonia is one of the most important causes of mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Adenovirus (ADV) is a significant cause of severe viral pneumonia after allo-HSCT, and we aimed to identify the clinical manifestations, prognostic factors, and outcomes of ADV pneumonia after allo-HSCT. Methods: Twenty-nine patients who underwent allo-HSCT at the Peking University Institute of Hematology and who experienced ADV pneumonia after allo-HSCT were enrolled in this study. The Kaplan–Meier method was used to estimate the probability of overall survival (OS). Potential prognostic factors for 100-day OS after ADV pneumonia were evaluated through univariate and multivariate Cox regression analyses. Results: The incidence rate of ADV pneumonia after allo-HSCT was approximately 0.71%. The median time from allo-HSCT to the occurrence of ADV pneumonia was 99 days (range 17–609 days). The most common clinical manifestations were fever (86.2%), cough (34.5%) and dyspnea (31.0%). The 100-day probabilities of ADV-related mortality and OS were 40.4% (95% CI 21.1%-59.7%) and 40.5% (95% CI 25.2%-64.9%), respectively. Patients with low-level ADV DNAemia had lower ADV-related mortality and better OS than did those with high-level (≥ 106 copies/ml in plasma) ADV DNAemia. According to the multivariate analysis, high-level ADV DNAemia was the only risk factor for intensive care unit admission, invasive mechanical ventilation, ADV-related mortality, and OS after ADV pneumonia. Conclusions: We first reported the prognostic factors and confirmed the poor outcomes of patients with ADV pneumonia after allo-HSCT. Patients with high-level ADV DNAemia should receive immediate and intensive therapy. [ABSTRACT FROM AUTHOR]

HHV-6B reactivation affects approximately half of all allogeneic hematopoietic cell transplant (HCT) recipients. HHV-6B is the most frequent infectious cause of encephalitis following HCT and is associated with pleiotropic manifestations in this setting, including graft-versus-host disease, myelosuppression, pneumonitis, and CMV reactivation, although the causal link is not always clear. When the virus inserts its genome in chromosomes of germ cells, the chromosomally integrated form (ciHHV6) is inherited by offspring. The condition of ciHHV6 is characterized by the persistent detection of HHV-6 DNA, often confounding diagnosis of reactivation and disease—this has also been associated with adverse outcomes. Recent changes in clinical practice in the field of cellular therapies, including a wider use of post-HCT cyclophosphamide, the advent of letermovir for CMV prophylaxis, and the rapid expansion of novel cellular therapies require contemporary epidemiological studies to determine the pathogenic role and spectrum of disease of HHV-6B in the current era. Research into the epidemiology and clinical significance of HHV-6B in chimeric antigen receptor T cell (CAR-T cell) therapy recipients is in its infancy. No controlled trials have determined the optimal treatment for HHV-6B. Treatment is reserved for end-organ disease, and the choice of antiviral agent is influenced by expected toxicities. Virus-specific T cells may provide a novel, less toxic therapeutic modality but is more logistically challenging. Preventive strategies are hindered by the high toxicity of current antivirals. Ongoing study is needed to keep up with the evolving epidemiology and impact of HHV-6 in diverse and expanding immunocompromised patient populations. [ABSTRACT FROM AUTHOR]

Background: The occurrence of myeloproliferative neoplasms (MPNs) that evolve into each other is well-described, as is this occurrence of lymphoproliferative neoplasms (LPNs). However, less is known about rare MPN/LPN coexistence, and the aim of our study was to analyze charachteristics of these patients after long term follow-up. Methods: Fourteen patients with MPN/LPN coexistence were diagnosed and treated according to guidelines at a single university center across two decades. Results: The overall median age was 53 years (22–69). MPNs patients with subsequent LPNs had a shorter period of second malignancy development and a more aggressive course of LPN, which can cause fatal outcomes. Polycythemia vera and chronic lymphocytic leukemia were most commonly associated (36%). The JAK2V617F mutation had 2/3 and cytogenetic abnormalities occurred in 1/3 of patients. MPN/LPN coexistence cases had significantly higher thrombotic potential (42.8%) and a higher third malignancy accruement frequency (21.4%) versus those without such malignancies. Conclusions: Considering the younger ages at MPN diagnosis, it is recommended to check regularly for blood lymphocytosis or lymphadenopathy occurrences and organomegaly progression faster than expected for MPN, with the aim of timely LPN diagnoses. The presence of molecular-cytogenetic abnormalities in a majority of patients indicate possible genetic instability and increased risk of development of multiple neoplasms, thus elevating thrombotic risk. [ABSTRACT FROM AUTHOR]

Global trade and globalization have driven growth and diversification in the horticultural industry. Fresh grapes, a key product, face challenges of market volatility, trade barriers, and logistics. Market diversification is essential for stability and competitiveness in international trade. This research focused on analyzing market diversification in Peru's fresh grape exports during the 2013–2022 period, exploring its implications for international trade. A quantitative methodology was used, along with the analysis of publicly recorded data on the website of the National Superintendence of Customs and Tax Administration, specifically exports from companies shipping under the national subheading for Grapes (0806.10.00.00). Diversification was analyzed using the Herfindahl–Hirschman concentration index (HHI), and competitiveness through the Balassa index. The main findings were that between 2013 and 2022, Peruvian grape exports grew in value (CAGR of 12.02%) and volume (CAGR of 12.13%). The sector expanded with an average of 151.2 companies and 59.1 destination markets. Diversification varied: the USA (12.4%), the Netherlands (1.6%), Hong Kong (4.2%), and Mexico (63.2%). The Herfindahl–Hirschman index showed concentration in the USA (4533 in 2020, 4519 in 2022) and stability in companies (2318 in 2014, 2450 in 2022). Finally, it is recommended to strengthen the Peruvian viticultural sector by maintaining geographic diversification through policies seeking new markets, monitoring global trends, constantly analyzing market concentration, and promoting fair competition among participating companies, allowing new ones to enter this sector. [ABSTRACT FROM AUTHOR]

For patients with acute myeloid leukemia (AML) who are not candidates for allogeneic stem cell transplantation (SCT) or do not have a human leukocyte antigen (HLA)-matched donor, it is unclear whether autologous SCT (ASCT) has a better prognosis after the first complete response (CR1) compared to further chemotherapy treatment. A meta-analysis evaluating ASCT compared to further chemotherapy for AML patients in CR1 was performed. The Medline, Embase, Cochrane Controlled Trials Registry, Cochrane Library, Web of Science, and National Knowledge Infrastructure of China databases were searched for relevant literature as of May 26, 2023. Eligible studies included prospectively enrolled adults with AML and randomized first-time respondent patients who did not have a matched sibling donor. Fourteen randomized controlled trials were identified and included 4281 participants, of which 1499 patients received ASCT and 2782 underwent chemotherapy and continued follow-up. In patients with AML in CR1, a lower relapse rate was associated with ASCT compared to chemotherapy [odds ratio (OR) = 0.49, 95% confidence interval (CI) = 0.41-0.57]. Significant disease-free survival (DFS; OR = 1.37, 95% CI = 1.02-1.84) and relapse-free survival (RFS; OR = 2.78, 95% CI = 1.28-6.02) ASCT benefits were documented, and there was no difference in the overall survival (OS) when the studies were pooled (OR = 1.12, 95% CI = 0.85-1.48). The study results indicated that after the first remission, AML patients receiving autologous stem cell transplantation had higher DFS and RFS, similar OS, and lower relapse compared to patients undergoing chemotherapy treatment. This indicated that autologous stem cell transplantation may have a better prognosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Copyright of Turkish Journal of Hematology is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a crucial treatment option for children with M2 subtype acute myeloid leukemia (AML). Human herpesvirus 6 (HHV-6) encephalitis following transplantation is a rare postoperative complication, with a poor prognosis and a high fatality rate in allo-HSCT recipients. In this report, a juvenile patient with AMLwas successfully treated after developing visual impairment as a result of HHV-6B encephalitis during allo-HSCT therapy. HHV-6 encephalitis-associated visual impairment after transplantation is rare, and clinical diagnosis and treatment are challenging, requiring more attention in the future., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Copyright of Journal of Modern Medicine & Health is the property of Journal of Modern Medicine & Health and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Kamezaki K, Shimoda K, Numata A, Aoki K, Kato K, Takase K, Nakajima H, Ihara K, Haro T, Ishikawa F, Imamura R, Miyamoto T, Nagafuji K, Gondo H, Hara T, Harada M. The lipocalin 24p3, which is an essential molecule in IL-3 withdrawal-induced apoptosis, is not involved in the G-CSF withdrawal-induced apoptosis. Eur J Haematol 2003: 71: 412–417. © Blackwell Munksgaard 2003. Many hematopoietic cells undergo apoptosis when deprived of specific cytokines. Lipocalin 24p3, reported to be induced in hematopoietic cells by interleukin 3 (IL-3) depletion, induces hematopoietic cell apoptosis despite the presence of IL-3. As granulocyte colony stimulating factor (G-CSF) depletion also induces the apoptosis of G-CSF-dependent cell line cells, we examined the effect of 24p3 on the apoptotic function induced by G-CSF depletion. 24p3 was induced by the depletion of IL-3, but not G-CSF, in cytokine-dependent cell lines. Although 24p3 suppressed growth induced by IL-3, it did not influence G-CSF-dependent cell growth. These observations show that 24p3 is not involved in the G-CSF withdrawal-induced apoptosis, although it is essential in IL-3 withdrawal-induced apoptosis. [ABSTRACT FROM AUTHOR]

It is crucial to ensure food security to continue the sustainable nutrition of the world population. Food losses in the global food supply chain pose a significant risk to food security. Especially foods that require cold chain logistics are prone to deterioration and eventually food losses. Therefore, cold chain logistics processes require operational expertise and specialized equipment. Reefer (refrigerated) container is the most used cold chain transport equipment for perishable foods requiring atmospheric control. Analyzing operational and hardware‐related causes and implementing relevant countermeasures are necessary to prevent food losses in reefer containers. With this motivation in the study, the relationships between the factors causing food losses in the reefer containers were evaluated qualitatively and quantitatively via the model built using the Fuzzy Bayesian network method. The findings indicate that the most critical root causes of food losses in reefer containers are excessive time off‐power, inappropriate preload conditions, and refrigerant faults, respectively. Moreover, the riskiest combination of factors that causes food loss consists of excessive time‐off power, refrigerant faults, and adverse weather conditions during navigation and in port. When the existing legal framework and professional practices are examined, in light of the results of the study, the following will be recommended: Establishing minimum standard and maintenance arrangements for cooling systems, ensuring safety margin in the shelf life of the foods carried in the reefer containers, making mandatory the automatic temperature recordings systems, and increasing the number of personnel specialized in product types and transportation. The study results will benefit supply chain stakeholders for process planning and implementation to mitigate the risk of food losses in reefer containers. Practical applications: This study examines the factors causing food losses in reefer containers from loading to discharge. The findings indicate that the most critical root causes of food losses in reefer containers are excessive time off‐power, inappropriate preload conditions, and refrigerant faults, respectively. When the existing legal framework and professional practices are examined, in light of the results of the study, the following will be recommended: Establishing minimum standard and maintenance arrangements for cooling systems, ensuring safety margin in the shelf life of the foods carried in the reefer containers, making mandatory the automatic temperature recordings systems, and increasing the number of personnel specialized in product types and transportation. [ABSTRACT FROM AUTHOR]

Purpose: Although outcomes of children with acute myeloid leukemia (AML) have improved over the last decades, around one-third of patients relapse. Measurable (or minimal) residual disease (MRD) monitoring may guide therapy adjustments or pre-emptive treatments before overt hematological relapse. Methods: In this study, we review 297 bone marrow samples from 20 real-life pediatric AML patients using three MRD monitoring methods: multiparametric flow cytometry (MFC), fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR). Results: Patients showed a 3-year overall survival of 73% and a 3-year event-free survival of 68%. Global relapse rate was of 25%. All relapses were preceded by the reappearance of MRD detection by: (1) MFC (p = 0.001), (2) PCR and/or FISH in patients with an identifiable chromosomal translocation (p = 0.03) and/or (3) one log increase of Wilms tumor gene 1 (WT1) expression in two consecutive samples (p = 0.02). The median times from MRD detection to relapse were 26, 111, and 140 days for MFC, specific PCR and FISH, and a one log increment of WT1, respectively. Conclusions: MFC, FISH and PCR are complementary methods that can anticipate relapse of childhood AML by weeks to several months. However, in our series, pre-emptive therapies were not able to prevent disease progression. Therefore, more sensitive MRD monitoring methods that further anticipate relapse and more effective pre-emptive therapies are needed. [ABSTRACT FROM AUTHOR]

Introduction: This systematic review aimed to retrieve patients diagnosed with de novo immune thrombocytopenic purpura (ITP) after COVID‐19 immunization to determine their epidemiological characteristics, clinical course, therapeutic strategies, and outcome. Materials and Methods: We conducted the review using four major databases, comprising PubMed, Scopus, Web of Science, and the Cochrane library, until April 2022. A systematic search was performed in duplicate to access eligible articles in English. Furthermore, a manual search was applied to the chosen papers' references to enhance the search sensitivity. Data were extracted and analyzed with the SPSS 20.1 software. Results: A total of 77 patients with de novo COVID‐19 vaccine‐associated ITP were identified from 41 studies, including 31 case reports and 10 case series. The median age of patients who developed COVID‐19 vaccine‐associated ITP was 54 years (IQR 36–72 years). The mRNA‐based COVID‐19 vaccines, including BNT16B2b2 and mRNA‐1273, were most implicated (75.4%). Those were followed by the adenovirus vector‐based vaccines, inclusive of ChAdOx1 nCoV‐19 and vAd26.COV2.S. No report was found relating ITP to other COVID‐19 vaccines. Most cases (79.2%) developed ITP after the first dose of COVID‐19 vaccination. 75% of the patients developed ITP within 12 days of vaccination, indicating a shorter lag time compared to ITP after routine childhood vaccinations. Sixty‐seven patients (87%) patients were hospitalized. The management pattern was similar to primary ITP, and systemic glucocorticoids, IVIg, or both were the basis of the treatment in most patients. Most patients achieved therapeutic goals; only two individuals required a secondary admission, and one patient who presented with intracranial hemorrhage died of the complication. Conclusions: De novo ITP is a rare complication of COVID‐19 vaccination, and corresponding reports belong to mRNA‐based and adenovirus vector‐based vaccines, in order of frequency. This frequency pattern may be related to the scale of administration of individual vaccines and their potency in inducing autoimmunity. The more the COVID‐19 vaccine is potent to induce antigenic challenge, the shorter the lag time would be. Most patients had a benign course and responded to typical treatments of primary ITP. [ABSTRACT FROM AUTHOR]

The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating, and categorizing indications for the evidence‐based use of therapeutic apheresis (TA) in human disease. In the Ninth Edition, the JCA Special Issue Writing Committee has incorporated systematic review and evidence‐based approaches in the grading of evidence and categorization of apheresis indications to make recommendations on the use of apheresis in a wide variety of diseases and conditions. This edition has largely maintained the general layout and concept of a fact sheet introduced in the Fourth Edition (2007). Each fact sheet succinctly summarizes the evidence for the use of TA in a specific disease or medical condition. The Ninth Edition of the JCA Special Issue comprises 91 fact sheets and 166 graded and categorized indications. This includes seven new fact sheets, nine new indications on existing fact sheets, and eight changes in the category for existing indications. The Ninth Edition of the JCA Special Issue seeks to continue to serve as a key resource that guides the utilization of TA in the treatment of human disease. [ABSTRACT FROM AUTHOR]

Shipping containers are used globally for the domestic distribution and export of several products. In this study, we compared the efficacy of controlled atmosphere (CA) containers to reefer containers based on the quality of 41 fresh fruits and vegetables exported from Japan to Singapore. We used instrumental analysis and sensory evaluation to compare the quality of fruits and vegetables transported in these two container types. Thirteen types of produce showed higher quality in the CA container than in the reefer container. Two types of fruits deteriorated in flavor due to abnormal maturation under CA conditions. Six types of produce showed higher quality in the reefer containers than in the CA containers. The CA containers were particularly effective in improving the quality of leafy vegetables, root vegetables, and fresh legumes; thus, CA containers are excellent for exporting these types of produce. Practical applications: The export of fresh fruits and vegetables by CA containers is expanding year after year, but their operation is difficult because the optimal storage environment for fruits and vegetables varies from item to item. This study showed the effectiveness of CA containers in improving the quality of leafy vegetables, root vegetables, and fresh legumes during their export from Japan to Singapore. These findings would contribute to the expansion of exports using CA containers in the future. [ABSTRACT FROM AUTHOR]

A systematic review and network meta‐analysis was performed to provide evidence for the best polishing protocol for different types of resin composites to minimize surface roughness. A search was performed in PubMed, Scopus, Web of Science, LILACS, BBO, EMBASE, and Cochrane Library on July 2, 2019 (updated in December, 2020). In vitro studies that included at least two systems for polishing resin composites and analyzed surface roughness were included. The risk of bias was evaluated. A random‐effects Bayesian‐mixed treatment comparison model was used to compare surface roughness in resin composites with the different types of polishers. Surface under the cumulative ranking curve (SUCRA) analysis was performed to rank the probability for the best polishing system. After removal of duplicates, title and abstract screening yielded 34 studies. Network meta‐analysis was not possible for hybrid and microhybrid composites. SUCRA analysis showed that abrasive paper discs allowed greater surface smoothness for nanohybrid and nanofill composites to a probability of between 83% and 91.6%. Silicon carbide brush had a 78.2% probability of being the best system for microfill composites. The use of abrasive paper disc polishers showed a favorable result in nanofill and nanohybrid resin composites. Silicon carbide brush has a greater chance of promoting a smoother surface for microfill resin composites. [ABSTRACT FROM AUTHOR]

Inherited chromosomally integrated human herpesvirus 6 (iciHHV-6) is a condition in which the complete HHV-6 genome is integrated into the chromosomes of the host germ cell and is vertically transmitted. The aims of this study were to identify iciHHV-6 prevalence in hospitalized patients and clinical features in individuals carrying this integration. HHV-6 PCR on hair follicles was used to confirm iciHHV-6 status when the blood viral load was more than 5 Log10 copies/mL. From January 2012 to June 2022, HHV-6 DNAemia was investigated in 2019 patients. In particular, 49 had a viral load higher than 6 Log10 copies/mL and HHV-6 DNA in hair follicles was positive. A viral load between 5.0 and 5.9 Log10 copies/mL was observed in 10 patients: 6 infants with acute HHV-6 infection and 4 patients with leukopenia and HHV-6 integration. Therefore, the iciHHV-6 prevalence in our population was 2.6% (53/2019). Adult patients with integration presented hematological (24%), autoimmune (11%), autoimmune neurological (19%), not-autoimmune neurological (22%), and other diseases (19%), whereas 5% had no clinically relevant disease. Although in our study population a high percentage of iciHHV-6 adult hospitalized patients presented a specific pathology, it is still unknown whether the integration is responsible for, or contributes to, the disease development. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the microhardness, surface roughness, and field emission scanning electron microscopes (FE-SEM) images of three different single-shade composites (Essentia Universal, Omnichroma, and Vittra APS Unique) in food simulation liquids such as ethanol, citric acid, and distilled water. Materials and Methods: Three single-shade universal composites were selected for this study. For each composite resin group, 92 samples (5-mm diameter and 2-mm depth) were prepared in plexiglass molds (N = 276). Then, samples were separated into four groups randomly consisting of 23 samples each (10 for hardness, 10 for roughness, and 3 for FE-SEM analysis). Three groups were immersed in food-simulating liquids (FSL)--citric acid (0.02N), distilled water, and 75% ethanol stored in a glass at 37°C for the next 7 days to simulate a wet oral environment. Control samples were stored in an opaque-light-proof box at room temperature. After the conditioning period, roughness and microhardness were measured, and FE-SEM analysis was performed. For statistical analysis, the two-way analysis of variance and Tukey honestly significant difference tests were used to evaluate roughness and microhardness (P < 0.05). Results: There was a statistically significant difference between the composites in terms of roughness and hardness averages (P = 0.001; P < 0.05). Omnichroma showed the most surface changes in ethanol storage, whereas Vittra Unique showed the most surface changes in citric acid storage such as Essentia. Conclusion: FSL that mimic various oral environments affect single-shade universal resin composite restorations. [ABSTRACT FROM AUTHOR]

Objective: The study aims to evaluate the color adjustment potential (CAP-I, CAP-V) of different single-shade resin composites. Materials and methods: The shades of 40 human incisors were determined using a spectrophotometer, with the teeth divided into four groups of the same shade (n = 10). The following single-shade resin composites were tested: Omnichroma, Charisma Diamond One, Vittra Unique, and Essentia Universal. The specimens were prepared as "dual" and "single." Standardized cavity preparations (diameter, 7 mm; depth, 2 mm) were prepared in human incisor teeth and then restored for dual specimens. Composite duplicates of human incisors were prepared with resin composites for single specimens (n = 10). The color match of these specimens to that of unrestored human incisors was compared, and the color difference (ΔE*) was calculated. Independent observers conducted a visual evaluation of the specimens and scored them. CAP-I and CAP-V values were determined. A one-way analysis of variance test was used for statistical analysis (p < 0.05). Results: There was no statistically significant difference between the CAP-V and CAP-I values of the tested single-shade resin composites (p > 0.05). All the materials tested had acceptable color-matching potential. Conclusions: In terms of color matching, there were no significant differences between the different tooth shades of all the tested resin composites. Clinical relevance: Single-shade resin composites have acceptable CAP. The use of single-shade resin composites can reduce in-chair clinical times by minimizing the time spent on shade selection. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, 17 acute myeloid leukemia (AML) patients were identified to pose a pericentric inv(3) aberration with breakpoints at 3p23 (n = 11), 3p25 (n = 3), 3p21 (n = 2) and 3p13 (n = 1) on 3p and 3q26.2 on 3q, leading to MECOM rearrangement (MECOM-R). These pericentric inv(3)s were overlooked by karyotyping initially in 16 of 17 cases and later detected by metaphase FISH analysis. Compared to AML patients with classic/paracentric inv(3)(q21q26.2), our patients with pericentric inv(3)s also exhibited frequent cytopenia, morphological dysplasia (especially megakaryocytes), −7/del(7q) and dismal outcomes (median overall survival: 14 months). However, the patients in this cohort also exhibited certain unique features: high frequencies of thrombocytopenia (n = 15, 88%) and monocytosis in peripheral blood (n = 15, 88%) and decreased megakaryocytes (n = 11, 65%). In summary, the pericentric inv(3)s are often subtle/cryptic by chromosomal analysis. A reflex FISH analysis for MECOM-R is recommended in myeloid neoplasms showing −7/del(7q). MECOM rearrangement (MECOM-R) resulting from 3q26.2 aberrations is often associated with myeloid neoplasms and inferior prognosis in affected patients. Uncommonly, certain 3q26.2/MECOM-R can be subtle/cryptic and consequently overlooked by karyotyping. We identified 17 acute myeloid leukemia (AML) patients (male/female: 13/4 with a median age of 67 years, range 42 to 85 years) with a pericentric inv(3) leading to MECOM-R, with breakpoints at 3p23 (n = 11), 3p25 (n = 3), 3p21 (n = 2) and 3p13 (n = 1) on 3p and 3q26.2 on 3q. These pericentric inv(3)s were overlooked by karyotyping initially in 16 of 17 cases and later detected by metaphase FISH analysis. Similar to the patients with classic/paracentric inv(3)(q21q26.2), patients with pericentric inv(3) exhibited frequent cytopenia, morphological dysplasia (especially megakaryocytes), −7/del(7q), frequent NRAS (n = 6), RUNX1 (n = 5) and FLT-3 (n = 4) mutations and dismal outcomes (median overall survival: 14 months). However, patients with pericentric inv(3) more frequently had AML with thrombocytopenia (n = 15, 88%), relative monocytosis in peripheral blood (n = 15, 88%), decreased megakaryocytes (n = 11, 65%), and lower SF3B1 mutation. We conclude that AML with pericentric inv(3) shares some similarities with AML associated with classic/paracentric inv(3)/GATA2::MECOM but also shows certain unique features. Pericentric inv(3)s are often subtle/cryptic by chromosomal analysis. A reflex FISH analysis for MECOM-R is recommended in myeloid neoplasms showing −7/del(7q). [ABSTRACT FROM AUTHOR]

The Human Betaherpesviruses HHV-5 and HHV-6 are quite inimical in immunocompromised hosts individually. A co-infection of both has been surmised to be far more disastrous. This can be attributed to a synergetic effect of their combined pathologies. While there have been attempts to develop a vaccine against each virus, no efforts were made to contrive an effective prophylaxis for the highly detrimental co-infection. In this study, an ensemble of viral envelope glycoproteins from both the viruses was utilized to design a multi-epitope vaccine using immunoinformatics tools. A collection of bacterial protein toll-like receptor agonists (BPTAs) was screened to identify a highly immunogenic adjuvant for the vaccine construct. The constructed vaccine was analysed using an array of methodologies ranging from World population coverage analysis to Immune simulation, whose results indicate high vaccine efficacy and stability. Furthermore, codon optimization and in silico cloning analysis were performed to check for efficient expression in a bacterial system. Collectively, these findings demonstrate the potential of the constructed vaccine to elicit an immune response against HHV-5 and HHV-6, thus supporting the viability of in vitro and in vivo studies. [ABSTRACT FROM AUTHOR]

Summary: Available data have proved insufficient to develop consensus recommendations on the prevention of thrombosis and bleeding in myelofibrosis (MF). We evaluated the incidence and risk factors of vascular complications in 1613 patients from the Spanish Myelofibrosis Registry. Over a total of 6981 patient‐years at risk, 6.4% of the study population had at least one thrombotic event after MF diagnosis, amounting to an incidence rate of 1.65 per 100 patient‐years. Prior history of thrombosis, the JAK2 mutation, and the intermediate‐2/high‐risk International Prognostic Scoring System (IPSS) categories conferred an increased thrombotic risk after adjustment for the risk‐modifying effect of anti‐thrombotic and cytoreductive treatments. History of thrombosis and the JAK2 mutation allowed us to pinpoint a group of patients at higher risk of early thrombosis. No decreased incidence of thrombosis was observed while patients were on anti‐thrombotic or cytoreductive treatment. An increased risk of venous thrombosis was found during treatment with immunomodulatory agents. A total of 5.3% of patients had at least one episode of major bleeding, resulting in an incidence rate of 1.5 events per 100 patient‐years. Patients in the intermediate‐2/high‐risk IPSS categories treated with anti‐coagulants had an almost sevenfold increased risk of major bleeding. These findings should prove useful for guiding decision‐making in clinical practice. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with favorable-risk acute myeloid leukemia in first remission. Method: Twenty patients who received auto-HSCT at our center between January 2014 and January 2021 were retrospectively reviewed. Results: Until last follow-up, three patients in the cohort were dead due to relapse. The estimated 1-year and 5-year overall survival were 95.00% ± 4.87% and 83.82% ± 8.58%, respectively. The estimated 5-year RFS and CIR (cumulative incidence of relapse) were 85.00% ± 7.98% and 15.00% ±7.98%, respectively. Conclusion: The outcome of auto-HSCT in patients with favorable-risk acute myeloid leukemia in first remission was excellent and auto-HSCT could be an effective treatment for these patients. [ABSTRACT FROM AUTHOR]

Several cases of autoimmune encephalitis have been reported after ChAdOx1 nCoV‐19 (AZD1222) vaccination. We encountered a male patient who presented with generalized tonic‐clonic seizures, cognitive decline, and gait disturbance that occurred suddenly after the second dose of the ChAdOx1 nCoV‐19 vaccine. Clinical presentation and magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) test results were compatible with limbic encephalitis. Synaptic autoantibody tests confirmed serum and CSF GABA B receptor antibodies were present. The patient was treated with immunotherapy with intravenous immunoglobulin and rituximab. This GABA‐B receptor antibody encephalitis case occurred presumably due to transient autoantibody production following vaccine administration. [ABSTRACT FROM AUTHOR]

Background: Autologous stem cell transplantation (ASCT) has gained growing consideration as a treatment option for favorable-risk acute myeloid leukemia (FR-AML) in first complete remission (CR1), compared with chemotherapy. Materials and Methods: We report the long-term outcomes of 117 consecutive patients with FR-AML fit for intensive chemotherapy diagnosed in our center between 1999 and 2020, who underwent ASCT. Results: Sixty-five of the 117 were eligible for intensive post-remission treatment, and 42 of those 65 received ASCT. Median follow up was 132 months. Overall survival (OS) and disease-free survival (DFS) were 75% and 76%. Higher doses of CD34 + stem cell infusions negatively impacted DFS in multivariate analysis. Core-binding factor (CBF) leukemia was an independent prognostic factor for improved DFS. No differences based on pre-transplant measurable residual disease (MRD) were observed. In CBF leukemia, 10-year DFS is 72% for MRD-positive patients versus 100% for MRD negative patients. Conclusions: ASCT is effective and safe in FR-AML patients. In CBF leukemia, ASCT provides excellent results regardless of achievement of bone marrow MRD negativity. In NPM1-mutated/FLT3-wild type (mNPM1) AML, early molecular response seems to have more impact on prognosis. Prospective investigation of the role of gemtuzumab ozogamicin in this setting is ongoing. [ABSTRACT FROM AUTHOR]

Genistein (GE) or 4′,5,7-trihydroxyflavone, a plant derived isoflavone, is a biologically active compound having several beneficial properties. Studies showed that GE possesses anti-neoplastic, anti-tumor, anti-helminthic, anti-oxidant, and anti-inflammatory activities. Herein, we investigated the neuroprotective effects of GE in a mouse model of hypoxia-induced amnesia. Mice were exposed to hypoxic conditions (10% O2) in a designated hypoxia chamber and co-treated with GE (10, 20, or 30 mg/kg) for 4 weeks. Following this, behavioral tests were performed to evaluate memory performance. We assessed microglial activation in the hippocampus, amygdala, and pre-frontal cortex (PFC) regions by evaluating the Iba-1 and GFAP transcript levels, and MIP-1β, Cox-2, and IL6 protein levels. Apoptosis was assessed by evaluating Bax, BAD, and Bcl-2 mRNA levels, and caspase-3 activity. To uncover the underlying molecular mechanism, we evaluated the levels of Nrf2, HO-1, and NQO1 in different brain regions of mice from all groups. Results showed that hypoxia-exposed mice have reduced performance in the behavioral tests and GE treatment enhanced the memory performance in hypoxia-exposed mice. Moreover, hypoxia-exposed mice showed increased expression of microglial activation markers and enhanced apoptosis in the hippocampus, amygdala, and PFC. GE treatment suppressed microglial activation and prevented apoptosis in the brain of hypoxia-exposed mice. Furthermore, hypoxia-exposure reduced the expression of Nrf2, NQO1, and HO-1 while GE treatment ameliorated this decrease in different regions of hypoxia-exposed mice brain. In conclusion, GE prevents cognitive dysfunction by suppressing microglial activation and inhibiting apoptosis in the hypoxia-exposed mice brain. [ABSTRACT FROM AUTHOR]

Beyond their pulmonary disease, many COVID-19 patients experience a complex constellation of characteristics, including hyperinflammatory responses, autoimmune disorders, and coagulopathies. However, the pathogenesis of these aspects of COVID-19 is obscure. More than 90% of people are latently infected with the lymphotropic herpesviruses Epstein–Barr Virus (EBV) and/or Human Herpesvirus-6 (HHV-6). Some of the inflammatory features of COVID-19 resemble clinical syndromes seen during EBV and HHV-6 infection, and these latent viruses can be reactivated by inflammatory mediators. We hypothesized that EBV and HHV-6 reactivation might be a common feature of early COVID-19, particularly in patients with more inflammation. We tested for EBV and HHV-6 reactivation in 67 patients acutely hospitalized with COVID-19 using previously validated quantitative PCR assays on the plasma. In our cohort, we found that 15/67 (22.4%) patients had detectable EBV and 3/67 (4.5%) had detectable HHV-6. This frequency of activation is somewhat more than the frequency reported for some healthy cohorts, such as blood donors and other healthy control cohorts. There was no association between EBV or HHV-6 and markers indicative of more inflammatory disease. We conclude that EBV and HHV-6 activation at about day 7 of hospitalization occurred in a modest fraction of our cohort of COVID-19 patients and was not associated with high levels of inflammation. In the modest fraction of patients, EBV and HHV-6 reactivation could contribute to some features of acute disease and pre-disposition to post-acute sequelae in a subset of patients. [ABSTRACT FROM AUTHOR]

With the recent outbreak of the COVID-19 pandemic and emergency use authorization of anti-SARS-CoV-2 vaccines, reports of post-vaccine immune thrombocytopenia (ITP) have gained attention. With this systematic review, we aim to analyze the clinical characteristics, therapeutic strategies, and outcomes of patients presenting with ITP after receiving COVID-19 vaccination. Medline, Embase, and Ebsco databases were systematically explored from inception until 1 June 2022. Case reports and case series investigating the association between the anti-SARS-CoV-2 vaccine and ITP were included. We found a total of 66 patients. The mean age of presentation was 63 years with a female preponderance (60.6%). Sixteen patients had pre-existing ITP. The mean time from vaccine administration to symptom onset was 8.4 days. More ITP events were triggered by mRNA vaccines (BNT162b2 (n = 29) > mRNA-1273 (n = 13)) than with adenoviral vaccines (ChAdOx1-S AstraZeneca (n = 15) > Ad26.COV2-S (n = 9)). Most of the patients were treated with steroids or IVIG, or both. The overall outcome was promising, with no reported deaths. Our review attempts to increase awareness among physicians while evaluating patients presenting with thrombocytopenia after receiving the vaccine. In our solicited opinion, the rarity of these events and excellent outcomes for patients should not change views regarding the benefits provided by immunization. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to examine and compare the differences between droplet digital PCR (ddPCR) and metagenomic next-generation sequencing (mNGS) in the detection of human herpesvirus 6B (HHV-6B). Long-term monitoring of HHV-6B viral load in patients receiving chimeric antigen receptor-modified T-cell (CAR-T) therapy and hematopoietic stem cell transplantation (HSCT) can be used to identify immune effector cell-associated neurotoxicity syndrome (ICANS) and guide drug therapy. Methods: Twenty-seven patients with suspected HHV-6B infection who had both mNGS and ddPCR test results were analyzed retrospectively, including 19 patients who received CAR T-cell therapy and 8 who received HSCT. The HHV-6B probe and primers were designed, and the performance of the ddPCR assay was evaluated. Subsequently, ddPCR was performed utilizing blood and urine. Data on clinical information and mNGS investigations were collected. Results: The ddPCR test results correlated significantly with the mNGS test results (P < 0.001, R2 = 0.672). Of the 27 time-paired samples, ddPCR showed positive HHV-6B detection in 20 samples, while mNGS alone showed positive HHV-6B detection in 12 samples. ddPCR detected additional HHV-6B infections in 8 samples that would have been missed if only mNGS were used. In addition, the first HHV-6B infection event was detected at a median of 14 days after CAR T-cell infusion (range, 8 to 19 days). Longitudinal monitoring of HHV-6B by ddPCR was performed to assess the effectiveness of antiviral therapy. The data showed that with antiviral treatment HHV-6B viral load gradually decreased. Conclusion: Our results indicated that ddPCR improved the HHV-6B positive detection ratio and was an effective adjunct to mNGS methods. Furthermore, the longitudinal detection and quantification of HHV-6B viral load in patients undergoing CAR T-cell therapy and HSCT may serve as a guide for drug treatment. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Ege University School of Dentistry / Ege Üniversitesi Dis Hekimligi Fakültesi Dergisi is the property of Ege University Faculty of Dentistry and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

There are few prospective studies on patients with post-essential thrombocythemia myelofibrosis (PET-MF) and post-polycythemia vera myelofibrosis (PPV-MF). Therefore, we conducted a nationwide longitudinal prospective survey to clarify the clinical characteristics of these diseases. A total of 197 PET-MF and 117 PPV-MF patients diagnosed between 2012 and 2021 were analyzed. The median age at diagnosis was 70.0 years for both diseases. The time from diagnosis of ET or PV to that of MF was 9.6 and 10.4 years, respectively, with no significant difference. Patients with PPV-MF had higher hemoglobin levels and white blood cell counts than those with PET-MF, whereas those with PET-MF had higher platelet counts than those with PPV-MF. Although splenomegaly was more frequent in patients with PPV-MF at diagnosis, there was no difference in the frequency of constitutional symptoms. Ruxolitinib was the most common treatment administered to 74.6% and 83.8% of patients with PET-MF and PPV-MF, respectively. Patients with PET-MF and PPV-MF had similar prognoses, with 3-year overall survival (OS) of 0.742 in PET-MF and 0.768 in PPV-MF patients. In both diseases, leukemic transformation was the leading cause of death, followed by infection. The 3-year OS for patients with PET/PPV-MF and primary MF diagnosed during the same period was 0.754 and 0.626, respectively, with no significant difference. This survey provides real-world clinical features and prognostic data on secondary myelofibrosis in the ruxolitinib era., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Copyright of Shandong Medical Journal is the property of Shandong Medical Health Newspapers and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The present paper describes a compact point of care (POC) optical device for therapeutic drug monitoring (TDM). The core of the device is a disposable plastic chip where an immunoassay for the determination of immunosuppressants takes place. The chip is designed in order to have ten parallel microchannels allowing the simultaneous detection of more than one analyte with replicate measurements. The device is equipped with a microfluidic system, which provides sample mixing with the necessary chemicals and pumping samples, reagents and buffers into the measurement chip, and with integrated thin film amorphous silicon photodiodes for the fluorescence detection. Submicrometric fluorescent magnetic particles are used as support in the immunoassay in order to improve the efficiency of the assay. In particular, the magnetic feature is used to concentrate the antibody onto the sensing layer leading to a much faster implementation of the assay, while the fluorescent feature is used to increase the optical signal leading to a larger optical dynamic change and consequently a better sensitivity and a lower limit of detection. The design and development of the whole integrated optical device are here illustrated. In addition, detection of mycophenolic acid and cyclosporine A in spiked solutions and in microdialysate samples from patient blood with the implemented device are reported. [ABSTRACT FROM AUTHOR]

Coronavirus Disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is frequently complicated by thrombosis. In some cases of severe COVID-19, fibrinolysis may be markedly enhanced within a few days, resulting in fatal bleeding. In the treatment of COVID-19, attention should be paid to both coagulation activation and fibrinolytic activation. Various thromboses are known to occur after vaccination with SARS-CoV-2 vaccines. Vaccine-induced immune thrombotic thrombocytopenia (VITT) can occur after adenovirus-vectored vaccination, and is characterized by the detection of anti-platelet factor 4 antibodies by enzyme-linked immunosorbent assay and thrombosis in unusual locations such as cerebral venous sinuses and visceral veins. Treatment comprises high-dose immunoglobulin, argatroban, and fondaparinux. Some VITT cases show marked decreases in fibrinogen and platelets and marked increases in D-dimer, suggesting the presence of enhanced-fibrinolytic-type disseminated intravascular coagulation with a high risk of bleeding. In the treatment of VITT, evaluation of both coagulation activation and fibrinolytic activation is important, adjusting treatments accordingly to improve outcomes. [ABSTRACT FROM AUTHOR]