Coexistence of HHV-8-Associated Plasmacytic Multicentric Castleman Disease, Kaposi's Sarcoma, and Multiple Myeloma in a HIV-Negative Patient.

Background: Multicentric Castleman disease (MCD) is a rare, aggressive lymphoproliferative disorder. Human herpesvirus-8 (HHV-8) has an important role in the pathogenesis of the disease and its association with Kaposi's sarcoma has been reported, especially in people living with human immunodeficiency virus (HIV). In this report, we present the case of HHV-8 positive MCD accompanied by Kaposi's sarcoma and multiple myeloma in an HIV-negative patient. Case Report: A 78-year-old man with Kaposi's sarcoma presented with B symptoms, pancytopenia, lymphadenopathy, and splenomegaly. The bone marrow biopsy demonstrated 70% lambda-restricted monotypic plasma cell infiltration consistent with plasma dyscrasia. Also, the patient was diagnosed with HHV-8 positive MCD as a result of inguinal lymph node excisional biopsy. Treatment was initiated including ganciclovir and methylprednisolone and followed by rituximab. The patient passed away at the 24th hour of rituximab infusion due to shock. Conclusions: MCD and associated malignancies are difficult to treat and have a poor prognosis. More studies and data are needed to manage these patients. LEARNING POINTS: Multicentric Castleman disease (MCD), often linked with human herpesvirus-8 (HHV-8) and Kaposi's sarcoma, is rare and aggressive condition, particularly in human immunodeficiency virus (HIV)-positive patients.The coexistence of MCD, Kaposi's sarcoma, and multiple myeloma is exceptionally rare in HIV-negative, immunocompetent patient.This case highlights the challenges in diagnosing and managing complex presentations of MCD and related malignancies, with poor outcomes despite treatment.

Lipotoxicity-Related Hematological Disorders in Obesity.

Lipotoxicity can mediate endothelial dysfunction in obesity. Altered endothelial cell phenotype during the pathobiological course of the lipotoxicity may lead to hemostatic abnormalities, which is a hallmark of several hematological disorders. Impaired hemostasis could also be directly related to numerous metabolic diseases such as hypertension, diabetes, and atherosclerosis. On the other hand, the local hematopoietic bone marrow (BM) renin-angiotensin system (RAS) contributes to the development of atherosclerosis via acting on the lipotoxicity processes. Local BM RAS, principally an autocrine/paracrine/intracrine hematological system, is located at the crossroads of cellular regulation, molecular interactions, and lipotoxicity-mediated vascular endothelial dysfunction. The positive regulatory role of plasma LDL on AT1 receptor-mediated hematopoietic stem cell (HSC) differentiation and the production of pro-atherogenic monocytes have been described. LDL-regulated HSC function may explain in part hypercholesterolemia-induced inflammation as well as the anti-inflammatory and anti-atherosclerotic effects of AT1 receptor blockers. The role of local adipose tissue RAS is directly related to the pathogenesis of metabolic derangements in obesity. There may be a crosstalk between local BM RAS and local adipose tissue RAS at the genomics and transcriptomics levels. This chapter aims to review hematological alterations propagating the pathological influences of lipotoxicity on the vascular endothelium.

Prognostic gene biomarkers for c-Src inhibitor Si162 sensitivity in melanoma cells.

Background/aim: Early detection and treatment are crucial in combating malignant melanoma. Src is an important therapeutic target in melanoma due to its association with cancer progression. However, developing effective Src-targeting drugs remains challenging and personalized medicine relies on biomarkers and targeted therapies for precise and effective treatment. This study focuses on Si162, a newly synthesized c-Src inhibitor, to identify reliable biomarkers for predicting Si162 sensitivity and explore associated biological characteristics and pathways in melanoma cells. Materials and methods: Primary melanoma cells (M1, M21, M24, M84, M133, M307, and M2025) were obtained from patients diagnosed with melanoma. Si162 cytotoxicity tests were performed using luminescent adenosine triphosphate detection and the half-maximal inhibitory concentration (IC50) values were calculated. Gene expression profiles were analyzed using microarray-based gene expression data. Differentially expressed genes between the resistant and sensitive groups were identified using Pearson correlation analysis. Gene coexpression, interactions, and pathways were investigated through clustering, network, and pathway analyses. Biological functions were examined using the Database for Annotation, Visualization, and Integrated Discovery. Molecular pathways associated with different responses to Si162 were identified using gene set enrichment analysis. The gene expressions were validated using reverse transcription-quantitative polymerase chain reaction. Results: The cells revealed significant differences in response to Si162 based on the IC50 values (p < 0.05). A total of 36 differentially expressed genes associated with Si162 susceptibility were identified. Distinct expression patterns between the sensitive and resistant groups were observed in 9 genes (LRBA, MGMT, CAND1, ADD1, SETD2, CNTN6, FGF18, C18orf25, and RPL13). Coexpression among the differentially expressed genes was highlighted, and 9 genes associated with molecular pathways, including EMT, transforming growth factor-beta (TGF-ß) signaling, and ribosomal protein synthesis, between groups. Genes involved in dysregulated immune response were observed in the resistant group. The involvement of 5 genes (ADD1, CNTN6, FGF18, C18orf25, and RPL13) in Si162 resistance was confirmed through qRT-PCR validation. Conclusion: These findings contribute to our understanding of the underlying biological differences among melanoma cells and suggest potential biomarkers and pathways associated with Si162 response and resistance.

Single agent vemurafenib or rituximab-vemurafenib combination for the treatment of relapsed/refractory hairy cell leukemia, a multicenter experience.

BACKGROUND: Hairy cell leukemia (HCL) is a rare mature B-cell malignancy that is primarily treated with purine analogues. However, relapse remains a significant challenge, prompting the search for alternative therapies. The BRAF V600E mutation prevalent in HCL patients provides a target for treatment with vemurafenib. PATIENTS AND METHODS: This multicenter retrospective study included nine patients with relapsed/refractory (R/R) HCL from six different centers. Patient data included demographics, prior treatments, clinical outcomes, and adverse events. RESULTS: Patients received different treatment regimens between centers, including vemurafenib alone or in combination with rituximab. Despite the differences in protocols, all patients achieved at least a partial response, with seven patients achieving a complete response. Adverse events were generally mild with manageable side effects. The absence of myelotoxic effects and manageable side effects make BRAF inhibitors attractive, especially for patients ineligible for purine analogues or those with severe neutropenia. CONCLUSION: Single agent vemurafenib or in combination with rituximab appears to be a promising therapeutic option for R/R HCL. Further research is needed to establish standardized treatment protocols and to investigate long-term outcomes.

Tigecycline-associated hypofibrinogenemia: A single center, retrospective, controlled study.

BACKGROUND: Tigecycline-associated hypofibrinogenemia has been reported as an important adverse effect in recent years, but controlled studies minimizing confounding factors are needed. The objective of our study was to assess changes in fibrinogen levels in patients for hospitalization, comparing two antibiotic episodes (tigecycline and other) within the same patients. METHODS: The retrospective, self-controlled case series study was conducted at our University Hospitals. The study compared the change in fibrinogen levels during the patient's hospitalization for tigecycline (TigePer) and another antibiotic period (OtherPer). In addition, bleeding events, bleeding risk (determined by the IMPROVE bleeding risk score), as well as 15- and 30-day mortality rates between TigePer and OtherPer were compared. RESULTS: The study enrolled 50 patients with 100 episodes of antibiotic treatment. The median age (interquartile range) of the patients was 68.5 (21.5) years, and 38 % were female. As compared to OtherPer, TigePer had a statistically significant reduction in fibrinogen levels (p < 0.001), with a hypofibrinogenemia rate of 40 % in TigePer as compared to 2 % in OtherPer (p < 0.001). TigePer demonstrated a significantly higher 15-day mortality rate (p = 0.006). No significant differences were observed between the two periods in terms of bleeding risk, rate of bleeding events, and 30-day mortality rate (p > 0.05). CONCLUSION: Hypofibrinogenemia and other coagulopathies, without associated bleeding events, are more frequently observed in patients receiving tigecycline. Therefore, it is crucial for clinicians to monitor fibrinogen levels during tigecycline use.

Enterotoxins A and B produced by Staphylococcus aureus increase cell proliferation, invasion and cytarabine resistance in acute myeloid leukemia cell lines.

As in the case of cancer, the risk of infection increases when the host's immune system is not working properly. It has been shown that toxins produced by the bacteria responsible for bacterial infections can alter the properties of cancer cells as well as their sensitivity to chemotherapy agents. Staphylococcus aureus (S. aureus) is one of the most prevalent pathogens in acute myeloid leukemia (AML) patients and it produces several virulence factors, including Staphylococcal enterotoxin A (SEA) and Staphylococcal enterotoxin B (SEB). Cytotoxicity, transwell migration, invasion assays, and various transcriptomic and gene set enrichment (GSE) analyses were used to determine how SEA and SEB alter cell proliferation, migration, invasion, and Cytarabine (Cyt) resistance in AML cell lines. The treatment of AML cell lines with SEA/SEB caused an increase in cell proliferation and Cyt resistance. Toxins enhanced the proclivity of cells to migrate and invade, with around 50% of cells in the presence of SEA and SEB. Transcriptomic and gene set enrichment analyses, and subsequent PCR validations showed dysregulation of immune related genes and genesets. Apparently, this allows AML cells to escape and survive the undesirable environment created by toxins, possibly via the ER stress signaling pathway. Therefore, SEA and SEB can significantly alter the characteristics of AML cancer cells and evaluation of alterations in responsible immune genes and pathways may be crucial for controlling the progression of cancer. In addition, our results suggest that there may be a strong interaction between the immune related pathways and the ER signaling pathway.

The probiotic-induced disregulation of immune-related genes in colon cells and relation with colorectal cancer.

Supplemental probiotics available without a doctor's prescription have become a booming global market in past few years. Medical research has shown that probiotics may benefit both healthy people and cancer patients by improving their immune systems and digestive health. Even though they seldom produce serious side effects, it's important to note that they are generally safe to use. But further investigation into the role of probiotics and gut microbes in the etiology of colorectal cancer is required. Here we used computational methods to identify the transcriptome alterations induced by probiotic treatment of colon cells. The impacts of genes with substantially altered expression were assessed in relation to the progression of colorectal cancer. Following probiotic treatment, substantial and high-level changes in the expression of genes were determined. BATF2, XCL2/XCL1, RCVRN and, FAM46B were up-regulated while IL13RA2, CEMIP, CUL9, Cand XCL6, PTCH2 were down-regulated in probiotic-treated colonic tissue and tumor samples. Also, immune-related pathways were determined that contribute to colorectal cancer formation and progression, as well as genes with opposing roles. This suggests that the length and dosage of probiotic use, in addition to the specific bacterial strain, maybe the most important determinants in the association between probiotics and colorectal cancer.

Hypophosphatemia related to the use of ibrutinib.

INTRODUCTION: Tyrosine kinase inhibitors (TKis) and Bruton's TKi (BTKis) constitute broadly used antitumor drug groups with almost completely tolerable and manageable side-effect profiles. Mainly side effects are cardiovascular and gastrointestinal for the TKi group. Hypophosphatemia is documented frequently in many studies with TKis but rarely mentioned with ibrutinib use up to the present. CASE REPORT: A 61-year-old patient with the diagnosis of chronic lymphocytic leukemia had hypophosphatemia-related complaints and symptoms when ibrutinib use was preferred for his second relapse of the disease. After drug discontinuation, we started ibrutinib again with an alternating dose. We managed to control hypophosphatemia, and the patient has been following up for 2 years in remission status without any support or a second drug need. MANAGEMENT AND OUTCOME: We have presented here a chronic lymphocytic leukemia case that developed mild-severe hypophosphatemia associated with ibrutinib use. By using an alternating dose of ibrutinib, we managed to control the disease and drug side effects. DISCUSSION: TKis and BTKis are widely in use for different indications. Hypophosphatemia is rare but it can cause drug discontinuation or change if it is not manageable. It is mentioned that hypophosphatemia can be seen due to a common group effect with the mechanism of causing secondary hyperparathyroidism and renal tubulopathy. In our case, we could explain the side effect of hypophosphatemia with secondary hyperparathyroidism and renal tubulopathy. Prospective, large-group studies are needed to explain the hypophosphatemia and other side effects of ibrutinib and new BTKis in detail.

A single-center experience of haploidentical stem cell transplantation in hematological malignancies.

BACKGROUND: Since well-designed prospective comparative trials are lacking, haploidentical hematopoietic stem cell transplantations approach should be based on the expertise of a particular center. In this study, we aimed to report the results and outcomes of patients who underwent haploidentical hematopoietic stem cell transplantation. METHODS: : Thirty-nine patients who underwent transplantation in our clinic between 2015 and 2022 were retrospectively analyzed. Primary end point of this study is to find out the survival rates of the patients. RESULTS: The overall survival of patients was 29.9 ± 4.9 months. The disease-free survival of the patients was 37.8 ± 5.7 months. The 3-year overall survival rate of the patients was %50 and the 3-year disease-free survival rate of the patients was %53. Nineteen patients were nonsurvivors among a total of 39 patients. Busulfan-fludarabine-thiotepa was the most frequently used conditioning regimen for transplantation. Busulfan-fludarabin-antithymocyte globulin regimen is the second preferred conditioning regimen. Cyclosporine- cyclophosphamide-mycophenolate mofetil was the most widely used graft-versus-host disease prophylaxis regimen. Sixteen patients had graft-versus-host disease, 28% of the patients had acute graft-versus-host disease, and 13% had chronic graft-versus-host disease. Gastrointestinal system consists of the most involved organs in graft-versus-host disease since 15% of the patients had gastrointestinal graft-versus-host disease. First-degree relatives (parent/child) were the most frequent donor source for haploidentical hematopoietic stem cell transplantation. Sepsis was the most frequent reason of death among transplant patients. DISCUSSION: In our center, we prefer to use high dose posttransplantation cyclophosphamide after haploidentical hematopoietic stem cell transplantation for graft-versus-host disease prophylaxis. With this approach, our center's overall survival and disease-free survival rates are comparable and compatible with the literature findings.

Pathobiological alterations affecting the distinct clinical courses of pediatric versus adult COVID-19 syndrome.

Background/aim: The clinical presentation of pediatric coronavirus disease 2019 (COVID-19) is associated with a milder disease course than the adult COVID-19 syndrome. The disease course of COVID-19 has three clinicobiological phases: initiation, propagation, and complication. This study aimed to assess the pathobiological alterations affecting the distinct clinical courses of COVID-19 in pediatric age groups versus the adult population. We hypothesized that critical biogenomic marker expressions drive the mild clinical presentations of pediatric COVID-19. Materials and methods: Blood samples were obtained from 72 patients with COVID-19 hospitalized at Ankara City Hospital between March and July 2021. Peripheral blood mononuclear cells were isolated using Ficoll-Paque and density-gradient sedimentation. The groups were compared using a t-test and limma analyses. Mean standardized gene expression levels were used to hierarchically cluster genes employing Euclidean Gene Cluster 3.0. The expression levels of identified genes were determined using reverse transcription-polymerase chain reaction. Results: This study found that ANPEP gene expression was significantly downregulated in the pediatric group (p < 0.05, FC: 1.57) and IGF2R gene expression was significantly upregulated in the adult group (p < 0.05, FC: 2.98). The study results indicated that the expression of critical biogenomic markers, such as the first-phase (ACE2 and ANPEP) and second-phase (EGFR and IGF2R) receptor genes, was crucial in the genesis of mild clinical presentations of pediatric COVID-19. ANPEP gene expression was lower in pediatric COVID-19. Conclusion: The interrelationship between the ANPEP and ACE2 genes may prevent the progression of COVID-19 from initiation to the propagating phase in pediatric patients. High IGF2R gene expression could potentially contribute to a protective effect and may be a contributing factor for the mild clinical course observed in pediatric patients.

Comment on Zamfir et al. Hematologic Malignancies Diagnosed in the Context of the mRNA COVID-19 Vaccination Campaign: A Report of Two Cases. Medicina 2022, 58, 874.

The SARS-CoV-2 spike protein mRNA-based vaccines have prevented countless mortality and morbidity, and have an excellent risk/benefit ratio. However, various adverse events may rarely occur after the BNT162b2 vaccine, like any other medical intervention. The COVID-19 itself and the spike protein produced endogenously by mRNA vaccines may have immunological, microenvironmental, prothrombotic, and neoplastic effects. As a contribution to the published report, we would like to share our experience regarding four cases in which myeloid neoplasms emerged following the vaccination. Conclusions: There is no doubt that vaccination could continue along the lines of established universal recommendations. Meanwhile, all hematological adverse events must be closely monitored and reported. Further efforts should be focused on the probable pathobiological mechanisms and causalities of spike protein-related toxicity and clonal myeloid disorders.

NK-cell dysfunction of acute myeloid leukemia in relation to the renin-angiotensin system and neurotransmitter genes.

Acute myeloid leukemia (AML) is the most heterogeneous hematological disorder and blast cells need to fight against immune system. Natural killer (NK) cells can elicit fast anti-tumor responses in response to surface receptors of tumor cells. NK-cell activity is often impaired in the disease, and there is a risk of insufficient tumor suppression and progression. The aim of this study is to assess the dysfunction of NK cells in AML patients via focusing on two important pathways. We obtained single-cell RNA-sequencing data from NK cells obtained from healthy donors and AML patients. The data were used to perform a wide variety of approaches, including DESeq2 (version 3.9), limma (version 3.26.8) power differential expression analyses, hierarchical clustering, gene set enrichment, and pathway analysis. ATP6AP2, LNPEP, PREP, IGF2R, CTSA, and THOP1 genes were found to be related to the renin-angiotensin system (RAS) family, while DPP3, GLRA3, CRCP, CHRNA5, CHRNE, and CHRNB1 genes were associated with the neurotransmitter pathways. The determined genes are expressed within different patterns in the AML and healthy groups. The relevant molecular pathways and clusters of genes were identified, as well. The cross-talks of NK-cell dysfunction in relation to the RAS and neurotransmitters seem to be important in the genesis of AML.

Efficacy of eltrombopag in thrombocytopenia after hematopoietic stem celltransplantation.

BACKGROUND: Thrombocytopenia is a common complication following hematopoietic stem cell transplantation (HSCT). Eltrombopag has been used in thrombocytopenia treatment after HSCT in recent years. Herein, we present our experience of 25 patients treated with eltrombopag for post-HSCT thrombocytopenia. METHODS: Fifteen autologous hematopoietic stem cell transplantation (AHSCT) and 10 allogenic hematopoietic stem cell transplantation (allo-HSCT) recipients treated with eltrombopag for treatment of prolonged isolated thrombocytopenia (PIT) or secondary failure of platelet recovery (SFPR) in the stem cell transplantation unit of Hacettepe University Hematology Department between 2017 and 2021 were included in the study. The primary endpoint of this study is eltrombopag response in patients diagnosed with PIT or SFPR. Platelet count above 50,000/mm3 for five consecutive days without platelet transfusion was considered as eltrombopag response. Overall survival (OS) analyses were calculated based on the time between HSCT and death from any cause. The patients who were alive at the last follow-up were censored at this time for calculation of OS analyses. RESULTS: AHSCT (66.7% (10/15)) and allo-HSCT (50% (5/10)) recipients responded to eltrombopag for the treatment of post-HSCT thrombocytopenia. There was no excess toxicity related to the eltrombopag use. The median response duration of allo-HSCT recipients and AHSCT recipients were 41 (13-104) days and 50 (7-342) days, respectively. There was a statistically significant OS duration difference between the responders and nonresponders in allo-HSCT and AHSCT recipients with p values of 0.005 and 0.02, respectively. DISCUSSION: Eltrombopag is promising for the treatment of thrombocytopenia after AHSCT and allo-HSCT in terms of efficacy and safety.

Antineoplastic Effects of Ankaferd Hemostat.

Materials and Methods: Up to June 2022, literature searches were performed using the internet search engines Medline, Google Scholar, and Embase: Ankaferd. PRISMA flow diagram described the Ankaferd search. Results: ABS have important effects in several cellular processes, like control of the cell cycle, apoptosis, angiogenesis, signal transduction, inflammation, immunologic, and metabolic mechanisms. The molecular basis of antineoplastic roles of ABS depends on its proteomics, metabolomics, and transcriptomics features. ABS has antineoplastic effects on solid tumors like colon, bladder, breast, and osteosarcoma cancer cells. Also, ABS effects renal tubular apoptosis and has antitumoral roles on malign melanoma cells. ABS inhibits hematological tumors like myeloma and lymphoid cells. ABS induces apoptosis in retinal cells and has inhibitory effects on mesenchymal stem cells. It has an antiproliferative role on gastrointestinal tumors like hepatocellular carcinoma cells. Moreover, ABS has a treatment supportive role in cancer since it can prevent oxidative DNA damage and decrease the intestinal damage in necrotizing enterocolitis. Furthermore, it has chemopreventive and hepatoprotective features and can be used for prophylaxis and treatment of oral mucositis. Conclusion: ABS alters cell metabolism and cell cycle. ABS has antineoplastic role on cancer cells. The expanding context of ABS compromises anti-infective, antineoplastic, and wound healing features. ABS may also be used for the palliative, adjuvant, neoadjuvant, or supportive use by interventional radiology procedures for the treatment of solid tumors. Future controlled studies are necessary to clarify the pleiotropic role of ABS like antineoplastic, antithrombotic, anti-inflammatory, anti-infective, antifungal, and antioxidative effects.

Prophylactic Central Nervous System Irradiation Is Not Indispensable in Adult Patients with Acute Lymphoblastic Leukemia: A Multicenter Retrospective Cohort Study

Objective: Studies comparing the efficacy and safety of prophylactic regimens for central nervous system (CNS) involvement in acute lymphoblastic leukemia (ALL) are scarce in adults. This multicenter retrospective study aimed to compare the efficacy of prophylactic regimens with and without CNS irradiation on the development of CNS relapse during follow-up. Materials and Methods: This was a multicenter comparative cohort study. A total of 203 patients were included from four tertiary care centers in Turkey. Patients were divided into two groups according to whether they received CNS irradiation or not. The groups were analyzed retrospectively regarding patient and disease characteristics, with the main focus being CNS relapse. Results: While 105 patients received chemotherapy-based prophylaxis, 98 patients received additional CNS irradiation. These groups were statistically comparable in terms of demographic characteristics and risk factors for CNS involvement. In the irradiation group, patients were younger and had more stem cell transplants. In a median of 23.8 (11.1-62.4) months, there was no difference between the two groups regarding CNS relapse-free survival (log-rank p=0.787). Conclusion: Craniospinal irradiation may not be indispensable for every adult patient with ALL, similarly to pediatric patients. It is crucial to avoid the long-term toxicities of radiation, especially in patients with long life expectancy. Craniospinal irradiation may be reserved for therapeutic use in cases of CNS relapse and prophylaxis for some high-risk patients.

Association of Human Leukocyte Antigen Genotypes with Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine-Induced Subacute Thyroiditis.

Background: Despite mass vaccination, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced subacute thyroiditis (SAT) is rarely seen as a complication. The reason why some individuals are susceptible to developing vaccine-induced SAT is not known. SAT develops in genetically predisposed individuals who carry specific human leukocyte antigen (HLA) haplotypes. It is unknown whether specific HLA alleles are associated with SARS-CoV-2 vaccine-induced SAT. Objective: This study compared the HLA profiles of patients with SARS-CoV-2 vaccine-induced SAT to controls, to assess whether there is an association between specific HLA genotypes and development of SAT. The relationship between HLA genotypes and the clinical course of SARS-CoV-2 vaccine-induced SAT was also evaluated. Methods: A case-control study was conducted in a Turkish tertiary care center. Fourteen patients with SARS-CoV-2 vaccine-induced SAT and 100 healthy controls were included. HLA-A, HLA-B, HLA-C, HLA-DQB1, and HLA-DRB1 frequencies were analyzed by next-generation sequencing. Results: The frequencies of HLA-B*35 and HLA-C*04 alleles were significantly higher in SARS-CoV-2 vaccine-induced SAT cohort when compared with controls (HLA-B*35: 13 [93%] vs. 40 [40%], p < 0.001; HLA-C*04: 13 [93%] vs. 43 [43%], p < 0.001, respectively). More severe thyrotoxicosis was seen in patients having HLA-B*35 and HLA-C*04 homozygous alleles (free thyroxine: 4.47 ng/dL [3.77-5.18] vs. 1.41 ng/dL [1.22-2.63], p = 0.048). Inflammation tended to be more severe in homozygous patients (C-reactive protein: 28.2 mg/dL [13.6-42.9] vs. 4.8 [1.2-10.5], p = 0.07). Conclusions: The frequencies of HLA-B*35 and HLA-C*04 alleles were higher in SARS-CoV-2 vaccine-induced SAT compared with controls. Homozygosity for HLA-B*35 and HLA-C*04 was associated with thyrotoxicosis and a greater inflammatory reaction. Our findings should be confirmed in studies of other populations.

The clinical course of COVID-19 in hematopoietic stem cell transplantation (HSCT) recipients

Background/aim: The disease caused by SARS-CoV-2 was named as COVID-19. There is as yet insufficient information about the effects of HSCT on the clinical course of COVID-19. In the present study, we aimed to investigate the clinical course of COVID-19 in patients who had undergone HSCT. Materials and methods: We analyzed baseline characteristics, clinical course and findings of COVID-19, hospitalization and death rates, overall survival, and case fatality rates of HSCT recipients diagnosed with COVID-19 retrospectively. Results: 57.6% of the patients underwent AHSCT, and 42.4% underwent allo-HSCT. 60.6%, 27.3%, and 12.1% of the patients had mild, moderate, and severe COVID-19 or critical illness, respectively. Overall, 45.5% were hospitalized, 12.1% required intensive care, and 9.1% necessitated invasive mechanical ventilation. The total CFR was 9.1% in HSCT recipients, 22.2% in patients with active hematologic malignancy, and 4.2% in patients without active hematologic malignancy. Conclusion: It can be concluded that mortality of HSCT recipients is lower in patients whose primary disease is in remission compared to ones that are not in remission. Further studies with larger group patients are needed in order to delineate the effects of COVID-19 on HSCT patients.

Hypercalcemia associated with the interaction between all trans retinoic acid and posaconazole in an acute promyelocytic leukemia case.

INTRODUCTION: All-trans retinoic acid (ATRA) is a physiological metabolite of vitamin A and it is used for the treatment of acute promyelocytic leukemia (APL). Hypercalcemia is a rare side effect of ATRA and it may be potentiated after interaction of ATRA with azole group antifungals. Herein, we have reported an APL case with hypercalcemia that is caused by the interaction of ATRA and posaconazole. CASE REPORT: A 49-year-old female patient was diagnosed as APL after the examinations performed upon the detection of pancytopenia when she had presented with the complaints of widespread bruising and fever. After the initiation of posaconazole and ATRA, her serum calcium levels begin to increase (10.3 to 11.1mg/dl). Her vitamin D level was 21.9 ng/ml and PTH 17.8 pg/ml, both were in the normal ranges. The Drug Interaction Probability Scale score of our case was calculated as 6, indicating that the probable adverse drug reaction. Therefore, the high level of serum calcium was attributed to the interaction between ATRA and posaconazole. MANAGEMENT & OUTCOME: Although hypercalcemia with ATRA and other antifungal agents have been previously reported in the literature, this is the first report of hypercalcemia with the concomitant use of ATRA and posaconazole. DISCUSSION: This case highlights the importance of monitoring ATRA's side effects when it is used in combination with drugs inhibiting the cytochrome P450 enzymes. In conclusion, the concomitant use of posaconazole and ATRA may lead to hypercalcemia and serum calcium levels return to normal ranges with the discontinuation of these drugs.

Current community transmission and future perspectives on the COVID-19 process

Background/aim: COVID-19 syndrome due to the SARS-CoV-2 virus is a currently challenging situation ongoing worldwide. Since the current pandemic of the SARS-CoV-2 virus is a great concern for everybody in the World, the frequently asked question is how and when the COVID-19 process will be concluded. The aim of this paper is to propose hypotheses in order to answer this essential question. As recently demonstrated, SARS-CoV-2 RNAs can be reverse-transcribed and integrated into the human genome. Our main hypothesis is that the ultimate aim of the SARS-CoV-2 virus is the incorporation to human genome and being an element of the intestinal virobiota. Materials and methods: We propose that the SARS-CoV-2 genomic incorporation to be a part of human virobiota is essentially based on three pathobiological phases which are called as the 'induction', 'consolidation', and 'maintenance phases'. The phase of 'recurrence' complicates any of these three disease phases based on the viral load, exposure time, and more contagious strains and/or mutants. We have performed the 'random walk model' in order to predict the community transmission kinetics of the virus. Results: Chimerism-mediated immunotherapy at the individual and community level with the help of vaccination seems to be the only option for ending the COVID-19 process. After the integration of SARS-CoV-2 virus into the human genome via the induction, consolidation, and maintenance phases as an element of intestinal virobiota, the chimerism would be concluded. The 'viral load', the 'genomic strain of the SARS-CoV-2', and 'host immune reaction against the SARS-CoV-2' are the hallmarks of this long journey. Conclusion: Elucidation of the functional viral dynamics will be helpful for disease management at the individual- and community- based long-term management strategies.