Background: To investigate the kinetics and prognostic value of pancreatic stone protein (PSP) and mid-regional proadrenomedullin (MR-proADM) during episodes of febrile neutropenia (FN) in children with haematological malignancies.
Material and methods: We evaluated prospectively a total of 70 FN episodes in 70 children with acute leukemias and lymphomas. Levels of CRP, PSP and MR-proADM were measured at the onset of the febrile episode (day 1), on day 3 and on day 7. The outcome and survival of children were evaluated during the study period until day 28. The performance of each marker in identifying sepsis or severe sepsis was assessed as area under a receiver operating characteristic (ROC) curve. For each biomarker, ROC curves were used to derive cut-offs for sensitivity and specificity in distinguishing sepsis from non-sepsis.
Results: During the 2-year study period, 70 febrile neutropenia episodes in 70 children with haematological malignancies were enrolled. Of 70 episodes of febrile neutropenia, in 17 (24%) a bacterial/fungal infection was documented. Criteria for sepsis were fulfilled for 31 (44%) and 7 (10%) patients were admitted to PICU. The median values of all biomarkers were higher on day 1 and differed significantly between patients with and without sepsis. The specificity of PSP, MR-proADM, and CRP were 0.82, 0.70, and 0.57, respectively. The sensitivity of PSP, MR-proADM and CRP were 0.84, 0.74, and 0.88, respectively.
Conclusions: Both PSP and MR-proADM are promising biomarkers for early diagnosis of sepsis during FN episodes in children with haematological malignancies. PSP has the higher sensitivity and specificity.
{"title":"KINETICS AND ROLE OF PANCREATIC STONE PROTEIN AND MIDREGIONAL PROADRENOMEDULLIN AS PREDICTORS OF SEPSIS AND BACTEREMIA IN CHILDREN WITH HAEMATOLOGICAL MALIGNANCIES.","authors":"Vasiliki Antari, Lemonia Skoura, Athanasios Tragiannidis, Emmanuel Hatzipantelis, Vasiliki-Regina Tsinopoulou, Konstantina Papakonstantinou, Efthimia Protonotariou, Assimina Galli-Tsinopoulou","doi":"10.4084/mjhid.2023.065","DOIUrl":"https://doi.org/10.4084/mjhid.2023.065","url":null,"abstract":"Background: To investigate the kinetics and prognostic value of pancreatic stone protein (PSP) and mid-regional proadrenomedullin (MR-proADM) during episodes of febrile neutropenia (FN) in children with haematological malignancies.
 Material and methods: We evaluated prospectively a total of 70 FN episodes in 70 children with acute leukemias and lymphomas. Levels of CRP, PSP and MR-proADM were measured at the onset of the febrile episode (day 1), on day 3 and on day 7. The outcome and survival of children were evaluated during the study period until day 28. The performance of each marker in identifying sepsis or severe sepsis was assessed as area under a receiver operating characteristic (ROC) curve. For each biomarker, ROC curves were used to derive cut-offs for sensitivity and specificity in distinguishing sepsis from non-sepsis.
 Results: During the 2-year study period, 70 febrile neutropenia episodes in 70 children with haematological malignancies were enrolled. Of 70 episodes of febrile neutropenia, in 17 (24%) a bacterial/fungal infection was documented. Criteria for sepsis were fulfilled for 31 (44%) and 7 (10%) patients were admitted to PICU. The median values of all biomarkers were higher on day 1 and differed significantly between patients with and without sepsis. The specificity of PSP, MR-proADM, and CRP were 0.82, 0.70, and 0.57, respectively. The sensitivity of PSP, MR-proADM and CRP were 0.84, 0.74, and 0.88, respectively.
 Conclusions: Both PSP and MR-proADM are promising biomarkers for early diagnosis of sepsis during FN episodes in children with haematological malignancies. PSP has the higher sensitivity and specificity.","PeriodicalId":18498,"journal":{"name":"Mediterranean Journal of Hematology and Infectious Diseases","volume":"422 ","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136068976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kelvin Lynch, Andrea Mega, Andrea Piccin, Massimo Daves, Helen Fogarty
In patients with SCD, chronic liver damage is a common manifestation. More than 50% of SCD patients have elevated liver enzymes. Common underlying aetiologies include sickle cell hepatic crisis, viral hepatitis, sickle cell intrahepatic cholestasis and hepatic sequestration in the acute setting, and cholelithiasis and iron overload in the chronic setting. Autoimmune hepatitis (AIH) is a rare disease that appears to occur more commonly in the sickle cell disease (SCD) population than in the general population. There are many schools of thought as to why this is the case, including the phosphatidylserine hypothesis, the heme inflammatory hypothesis, the complement generation hypothesis, and the transfusion alloimmunization hypothesis. Due to the natural history of the two illnesses, SCD is almost always diagnosed first in cases of dual pathology. Symptoms such as jaundice, fatigue, and abdominal pain are common in SCD, as are abnormal liver function tests (LFTs). These abnormalities, attributed to the other more frequent liver involvements in SCD, can lead to delays in AIH diagnosis in this population. Corticosteroids, sometimes with other immunosuppressive agents, such as azathioprine, are the cornerstone of acute AIH treatment (4). However, corticosteroid use in the SCD population has been shown to carry an increased risk of vaso-occlusive crises (1, 5), providing a treatment dilemma. The following is a review of AIH in the SCD population, where we explore the pathophysiology behind the association between the two disorders, discuss an approach to investigating abnormal LFTs in SCD, and examine treatment options in this population with co-existing diseases.
{"title":"LIVER DISEASE & SICKLE CELL DISEASE: AUTOIMMUNE HEPATITIS MORE THAN A COINCIDENCE; A SYSTEMATIC LITERATURE REVIEW.","authors":"Kelvin Lynch, Andrea Mega, Andrea Piccin, Massimo Daves, Helen Fogarty","doi":"10.4084/mjhid.2023.060","DOIUrl":"https://doi.org/10.4084/mjhid.2023.060","url":null,"abstract":"In patients with SCD, chronic liver damage is a common manifestation. More than 50% of SCD patients have elevated liver enzymes. Common underlying aetiologies include sickle cell hepatic crisis, viral hepatitis, sickle cell intrahepatic cholestasis and hepatic sequestration in the acute setting, and cholelithiasis and iron overload in the chronic setting. Autoimmune hepatitis (AIH) is a rare disease that appears to occur more commonly in the sickle cell disease (SCD) population than in the general population. There are many schools of thought as to why this is the case, including the phosphatidylserine hypothesis, the heme inflammatory hypothesis, the complement generation hypothesis, and the transfusion alloimmunization hypothesis. Due to the natural history of the two illnesses, SCD is almost always diagnosed first in cases of dual pathology. Symptoms such as jaundice, fatigue, and abdominal pain are common in SCD, as are abnormal liver function tests (LFTs). These abnormalities, attributed to the other more frequent liver involvements in SCD, can lead to delays in AIH diagnosis in this population. Corticosteroids, sometimes with other immunosuppressive agents, such as azathioprine, are the cornerstone of acute AIH treatment (4). However, corticosteroid use in the SCD population has been shown to carry an increased risk of vaso-occlusive crises (1, 5), providing a treatment dilemma. The following is a review of AIH in the SCD population, where we explore the pathophysiology behind the association between the two disorders, discuss an approach to investigating abnormal LFTs in SCD, and examine treatment options in this population with co-existing diseases.","PeriodicalId":18498,"journal":{"name":"Mediterranean Journal of Hematology and Infectious Diseases","volume":"204 ","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136069586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: To analyze the significance of lung ultrasound score (LUS) combined with serum inflammatory indexes in different severities of severe pneumonia and and its clinical value on prognosis.
Methods: A total of 100 patients with severe pneumonia who were treated in the Gansu Provincial Hospital from June 2017 to June 2021 were selected as the research objects. According to the acute physiology and chronic health (APACHE II) score, they were divided into low-risk group (28 cases) and medium-risk group (39 cases) and high-risk group (33 cases). The general clinical data of the patients (age, gender, smoking history, and underlying diseases) were collected, the lung ultrasound score (LUS) of the patients was measured, and the serum inflammatory indicators (IL-6, IL-10, TNF-α, CRP and NLR) levels; pearson correlation analysis to evaluate the correlation between LUS score, serum inflammatory index levels and disease severity; receiver operating characteristic (ROC) curve analysis to evaluate the prognostic value of the combined diagnosis of LUS score and serum inflammatory index for the severity of severe pneumonia.
Results: With the increase of the severity of severe pneumonia, the LUS score and the level of inflammation in the body continued to increase, and LUS combined with serum inflammatory indexes could distinguish the severity of low-risk, medium-risk and high-risk of severe pneumonia, and had high diagnostic value. In addition, the combined diagnosis of LUS and serum inflammatory markers is also closely related to the prognosis of patients with severe pneumonia, which can distinguish the prognosis.
Conclusion: LUS combined with serum inflammatory indicators (IL-6, IL-10, TNF-α, CRP and NLR) can differentiate the severity and prognosis of severe pneumonia, which may be a new direction for the diagnosis of severe pneumonia and guide early clinical intervention.
{"title":"Diagnosis and prognosis evaluation of severe pneumonia by lung ultrasound score combined with serum inflammatory markers","authors":"Bo Fu, Peng Zhang, JunHua Zhang","doi":"10.4084/mjhid.2023.057","DOIUrl":"https://doi.org/10.4084/mjhid.2023.057","url":null,"abstract":"Objective: To analyze the significance of lung ultrasound score (LUS) combined with serum inflammatory indexes in different severities of severe pneumonia and and its clinical value on prognosis.
 Methods: A total of 100 patients with severe pneumonia who were treated in the Gansu Provincial Hospital from June 2017 to June 2021 were selected as the research objects. According to the acute physiology and chronic health (APACHE II) score, they were divided into low-risk group (28 cases) and medium-risk group (39 cases) and high-risk group (33 cases). The general clinical data of the patients (age, gender, smoking history, and underlying diseases) were collected, the lung ultrasound score (LUS) of the patients was measured, and the serum inflammatory indicators (IL-6, IL-10, TNF-α, CRP and NLR) levels; pearson correlation analysis to evaluate the correlation between LUS score, serum inflammatory index levels and disease severity; receiver operating characteristic (ROC) curve analysis to evaluate the prognostic value of the combined diagnosis of LUS score and serum inflammatory index for the severity of severe pneumonia.
 Results: With the increase of the severity of severe pneumonia, the LUS score and the level of inflammation in the body continued to increase, and LUS combined with serum inflammatory indexes could distinguish the severity of low-risk, medium-risk and high-risk of severe pneumonia, and had high diagnostic value. In addition, the combined diagnosis of LUS and serum inflammatory markers is also closely related to the prognosis of patients with severe pneumonia, which can distinguish the prognosis.
 Conclusion: LUS combined with serum inflammatory indicators (IL-6, IL-10, TNF-α, CRP and NLR) can differentiate the severity and prognosis of severe pneumonia, which may be a new direction for the diagnosis of severe pneumonia and guide early clinical intervention.","PeriodicalId":18498,"journal":{"name":"Mediterranean Journal of Hematology and Infectious Diseases","volume":"75 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136023232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R.A. Stuurman, E. Jong, P.C.R. Godschalk, M.F. Corsten, J.E. Nagtegaal
Abstract
Objectives
The Antibiotic Stewardship Team of Meander Medical Centre (Meander MC) instigated a revaluation of its treatment protocol for hematologic patients admitted with febrile neutropenia. The current hospital protocol advises administering meropenem for 72 hours, followed by antibiotic therapy guided by microbiological cultures. In order to responsibly adjust the current empiric regimen, this study aimed to determine the frequency of bacteria resistant to alternative antibiotics, namely ceftazidime and piperacillin/tazobactam, in both surveillance and diagnostic cultures.
Methods
This retrospective, observational, single-centre study included adult patients with a hematologic malignancy and febrile neutropenia admitted between October 2018 and June 2021. Collected metadata included patient characteristics, surveillance and diagnostic culture results, and antibiotic use.
Results
A total of 100 patients were included. One or more bacteria resistant to ceftazidime or piperacillin/tazobactam were identified in blood and urine cultures in seven (7%) and one (1%) patients respectively.
Conclusions
Our results support the safe reduction of the use of meropenem by changing the empiric treatment protocol for patients with hematologic malignancy and febrile neutropenia. As this study showed a lower resistance frequency to piperacillin/tazobactam than to ceftazidime, this antibiotic is the recommended alternative.
{"title":"Evaluating the use of meropenem in hematologic patients with febrile neutropenia","authors":"R.A. Stuurman, E. Jong, P.C.R. Godschalk, M.F. Corsten, J.E. Nagtegaal","doi":"10.4084/mjhid.2023.067","DOIUrl":"https://doi.org/10.4084/mjhid.2023.067","url":null,"abstract":"Abstract
 Objectives 
 The Antibiotic Stewardship Team of Meander Medical Centre (Meander MC) instigated a revaluation of its treatment protocol for hematologic patients admitted with febrile neutropenia. The current hospital protocol advises administering meropenem for 72 hours, followed by antibiotic therapy guided by microbiological cultures. In order to responsibly adjust the current empiric regimen, this study aimed to determine the frequency of bacteria resistant to alternative antibiotics, namely ceftazidime and piperacillin/tazobactam, in both surveillance and diagnostic cultures.
 Methods
 This retrospective, observational, single-centre study included adult patients with a hematologic malignancy and febrile neutropenia admitted between October 2018 and June 2021. Collected metadata included patient characteristics, surveillance and diagnostic culture results, and antibiotic use.
 Results
 A total of 100 patients were included. One or more bacteria resistant to ceftazidime or piperacillin/tazobactam were identified in blood and urine cultures in seven (7%) and one (1%) patients respectively.
 Conclusions
 Our results support the safe reduction of the use of meropenem by changing the empiric treatment protocol for patients with hematologic malignancy and febrile neutropenia. As this study showed a lower resistance frequency to piperacillin/tazobactam than to ceftazidime, this antibiotic is the recommended alternative.","PeriodicalId":18498,"journal":{"name":"Mediterranean Journal of Hematology and Infectious Diseases","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136103423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emiliano Fabiani, Giulia Falconi, Antonio Cristiano, H. Hajrullaj, Giulia Falconi, Giuseppe Leone, Maria Teresa Voso
Therapy-related Myeloid Neoplasm (t-MN) represents one of the worst long-term consequences of cytotoxic therapy for primary tumors and autoimmune disease. Poor survival and refractoriness to current treatment strategies characterize affected patients from a clinical point of view. In our aging societies, where newer therapies and ameliorated cancer management protocols are improving the life expectancy of cancer patients, therapy-related Myeloid Neoplasms are an emerging problem. Although several research groups have contributed to characterizing the main risk factors in t-MN development, the multiplicity of primary tumors, in association with the different therapeutic strategies available and the new drugs in development, make interpreting the current data still complex. The main risk factors involved in t-MN pathogenesis can be subgrouped into patient-specific, inherited, and acquired predispositions. Although t-MN can occur at any age, the risk tends to increase with advancing age, and older patients, characterized by a higher number of comorbidities, are more likely to develop the disease. Thanks to the availability of deep sequencing techniques, germline variants have been reported in 15-20% of t-MN patients, highlighting their role in cancer predisposition. It is becoming increasingly evident that t-MN with driver gene mutations may arise in the background of Clonal Hematopoiesis of Indeterminate Potential (CHIP) under the positive selective pressure of chemo and/or radiation therapies. Although CHIP is generally considered benign, it has been associated with an increased risk of t-MN. In this context, the phenomenon of clonal evolution may be described as a dynamic process of expansion of preexisting clones, with or without acquisition of additional genetic alterations, that, by favoring the proliferation of more aggressive and/or resistant clones, may play a crucial role in the progression from preleukemic states to t-MN.
{"title":"THERAPY-RELATED MYELOID NEOPLASMS: PREDISPOSITION AND CLONAL EVOLUTION","authors":"Emiliano Fabiani, Giulia Falconi, Antonio Cristiano, H. Hajrullaj, Giulia Falconi, Giuseppe Leone, Maria Teresa Voso","doi":"10.4084/mjhid.2023.064","DOIUrl":"https://doi.org/10.4084/mjhid.2023.064","url":null,"abstract":"Therapy-related Myeloid Neoplasm (t-MN) represents one of the worst long-term consequences of cytotoxic therapy for primary tumors and autoimmune disease. Poor survival and refractoriness to current treatment strategies characterize affected patients from a clinical point of view. In our aging societies, where newer therapies and ameliorated cancer management protocols are improving the life expectancy of cancer patients, therapy-related Myeloid Neoplasms are an emerging problem. Although several research groups have contributed to characterizing the main risk factors in t-MN development, the multiplicity of primary tumors, in association with the different therapeutic strategies available and the new drugs in development, make interpreting the current data still complex. The main risk factors involved in t-MN pathogenesis can be subgrouped into patient-specific, inherited, and acquired predispositions. Although t-MN can occur at any age, the risk tends to increase with advancing age, and older patients, characterized by a higher number of comorbidities, are more likely to develop the disease. Thanks to the availability of deep sequencing techniques, germline variants have been reported in 15-20% of t-MN patients, highlighting their role in cancer predisposition. It is becoming increasingly evident that t-MN with driver gene mutations may arise in the background of Clonal Hematopoiesis of Indeterminate Potential (CHIP) under the positive selective pressure of chemo and/or radiation therapies. Although CHIP is generally considered benign, it has been associated with an increased risk of t-MN. In this context, the phenomenon of clonal evolution may be described as a dynamic process of expansion of preexisting clones, with or without acquisition of additional genetic alterations, that, by favoring the proliferation of more aggressive and/or resistant clones, may play a crucial role in the progression from preleukemic states to t-MN.","PeriodicalId":18498,"journal":{"name":"Mediterranean Journal of Hematology and Infectious Diseases","volume":"424 ","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136068971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract. Objective: To evaluate the age at menarche and menstrual characteristics in patients with transfusion-dependent thalassemia (TDT) who started early chelation therapy (≤ 3 years) with a variety of chelating agents. Design: A retrospective multicenter study promoted by International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A). Setting: Eight of 13 International Thalassemia Centers (61.5%) in the ICET-A Network participated. Patients: Fifty-seven female TDT patients, aged 11 to 26 years, were enrolled in the study. Seven patients were excluded, 4 who were still prepubertal (age 12-14 years) and 3 with primary amenorrhea. The remaining 50 patients were from Iran (33 patients), 9 from Bulgaria, 8 from Greece, 4 from Oman, 2 from Cyprus, and 1 from Italy. Results: At start of chelation therapy, 22 patients received desferrioxamine mesylate (DFO), 26 deferasirox (DFX) and 2 deferiprone (DFP). All fifty TDT patients developed spontaneous menarche at a mean age of 14.2 ± 2.24 years (range 9 – 20). A significant positive correlation was observed between age at menarche and serum ferritin (SF) levels (r: 0. 41, P: 0.005). Thirty-two patients (64%) reported regular menstrual cycles, 7 (14 %) oligomenorrhea, 3 (6%) short/light menses (hypomenorrhea), and 8 (16%) secondary amenorrhea (SA) (16%). Conclusions: Early chelation does not necessary correlate with efficient chelation during pubertal age. Delayed menarche, related to high SF levels, was still frequent in most Centers and was a forerunner of irregular menstrual cycles, SA and associated complications. Neglecting the importance of adherence to iron chelation therapy (ICT), despite innovative and expensive therapies, may lead to complications and decreased quality of life.
Key words: Transfusion-dependent thalassemia, menarche, menstrual cycles, iron chelation therapy (ICT), iron overload, adherence to treatment.
{"title":"A multicenter ICET-A study on age at menarche and menstrual cycles in patients with transfusion-dependent thalassemia (TDT) who started early chelation therapy with different chelating agents","authors":"SALVATORE DI MAIO, VINCENZO DE SANCTIS, PIERLUIGI MARZUILLO, CHRISTOS KATTAMIS, SHAHINA DAAR, MEHERAN KARIMI, SAKI FOROUGH, ATANAS BANKEV, VALERIA KALEVA, SOTEROULA CHRISTOU, CARMELO FORTUGNO, POLYXENI DELAPORTA, ASHRAF T SOLIMAN, PLOUTARCHOS TZOULIS","doi":"10.4084/mjhid.2023.058","DOIUrl":"https://doi.org/10.4084/mjhid.2023.058","url":null,"abstract":"Abstract. Objective: To evaluate the age at menarche and menstrual characteristics in patients with transfusion-dependent thalassemia (TDT) who started early chelation therapy (≤ 3 years) with a variety of chelating agents. Design: A retrospective multicenter study promoted by International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A). Setting: Eight of 13 International Thalassemia Centers (61.5%) in the ICET-A Network participated. Patients: Fifty-seven female TDT patients, aged 11 to 26 years, were enrolled in the study. Seven patients were excluded, 4 who were still prepubertal (age 12-14 years) and 3 with primary amenorrhea. The remaining 50 patients were from Iran (33 patients), 9 from Bulgaria, 8 from Greece, 4 from Oman, 2 from Cyprus, and 1 from Italy. Results: At start of chelation therapy, 22 patients received desferrioxamine mesylate (DFO), 26 deferasirox (DFX) and 2 deferiprone (DFP). All fifty TDT patients developed spontaneous menarche at a mean age of 14.2 ± 2.24 years (range 9 – 20). A significant positive correlation was observed between age at menarche and serum ferritin (SF) levels (r: 0. 41, P: 0.005). Thirty-two patients (64%) reported regular menstrual cycles, 7 (14 %) oligomenorrhea, 3 (6%) short/light menses (hypomenorrhea), and 8 (16%) secondary amenorrhea (SA) (16%). Conclusions: Early chelation does not necessary correlate with efficient chelation during pubertal age. Delayed menarche, related to high SF levels, was still frequent in most Centers and was a forerunner of irregular menstrual cycles, SA and associated complications. Neglecting the importance of adherence to iron chelation therapy (ICT), despite innovative and expensive therapies, may lead to complications and decreased quality of life.
 
 Key words: Transfusion-dependent thalassemia, menarche, menstrual cycles, iron chelation therapy (ICT), iron overload, adherence to treatment.","PeriodicalId":18498,"journal":{"name":"Mediterranean Journal of Hematology and Infectious Diseases","volume":"47 ","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136102296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ugo Testa, Germana Castelli, Giuseppe Leone, Elvira Pelosi, Germana Castelli, Stefan Hohaus
Large B-cell lymphomas (LBCLs) are among the most frequent (about 30%) non-Hodgkin’s lymphoma. Despite the aggressive behavior of these lymphomas, more than 60% of patients can be cured with first-line chemoimmunotherapy using the R-CHOP regimen. Patients with refractory or relapsing disease show a poor outcome even when treated with second-line therapies.
CD19-targeted chimeric antigen receptor (CAR) T-cells are emerging as an efficacious second-line treatment strategy for patients with LBCL. Three CD19-CAR-T-cell products received FDA and EMA approval. The use of CAR-T cell therapy has also been explored for the treatment of high-risk LBCL patients in the first-line setting and for patients with central nervous system involvement.
Although CD19-CAR-T therapy has transformed the care of refractory/relapsed LBCL, about 60% of these patients will ultimately progress or relapse following CD19-CAR-T: therefore, it is fundamental to identify predictive criteria of response to CAR-T therapy and to develop salvage therapies for patients relapsing after CD19-CAR-T therapies. Moreover, ongoing clinical trials are evaluating bispecific CAR-T cells targeting both CD19 and CD20 or CD19 and CD22 as a tool to improve the therapeutic efficacy and to reduce the number of refractory/relapsing patients.
大b细胞淋巴瘤(LBCLs)是最常见的非霍奇金淋巴瘤(约30%)。尽管这些淋巴瘤具有侵袭性，但超过60%的患者可以通过使用R-CHOP方案的一线化学免疫治疗治愈。难治性或复发性疾病患者即使接受二线治疗，预后也很差。
cd19靶向嵌合抗原受体(CAR) t细胞正在成为LBCL患者有效的二线治疗策略。三种cd19 - car - t细胞产品获得FDA和EMA批准。CAR-T细胞疗法也被用于一线高危LBCL患者和中枢神经系统受损伤患者的治疗。
尽管CD19-CAR-T治疗已经改变了难治性/复发性LBCL的治疗，但这些患者中约60%最终会在CD19-CAR-T治疗后进展或复发:因此，确定对CAR-T治疗反应的预测标准并为CD19-CAR-T治疗后复发的患者开发挽救性治疗是至关重要的。此外，正在进行的临床试验正在评估靶向CD19和CD20或CD19和CD22的双特异性CAR-T细胞作为提高治疗效果和减少难治性/复发患者数量的工具。
{"title":"CAR-T CELL THERAPY IN LARGE B CELL LYMPHOMA","authors":"Ugo Testa, Germana Castelli, Giuseppe Leone, Elvira Pelosi, Germana Castelli, Stefan Hohaus","doi":"10.4084/mjhid.2023.066","DOIUrl":"https://doi.org/10.4084/mjhid.2023.066","url":null,"abstract":"Large B-cell lymphomas (LBCLs) are among the most frequent (about 30%) non-Hodgkin’s lymphoma. Despite the aggressive behavior of these lymphomas, more than 60% of patients can be cured with first-line chemoimmunotherapy using the R-CHOP regimen. Patients with refractory or relapsing disease show a poor outcome even when treated with second-line therapies.
 CD19-targeted chimeric antigen receptor (CAR) T-cells are emerging as an efficacious second-line treatment strategy for patients with LBCL. Three CD19-CAR-T-cell products received FDA and EMA approval. The use of CAR-T cell therapy has also been explored for the treatment of high-risk LBCL patients in the first-line setting and for patients with central nervous system involvement.
 Although CD19-CAR-T therapy has transformed the care of refractory/relapsed LBCL, about 60% of these patients will ultimately progress or relapse following CD19-CAR-T: therefore, it is fundamental to identify predictive criteria of response to CAR-T therapy and to develop salvage therapies for patients relapsing after CD19-CAR-T therapies. Moreover, ongoing clinical trials are evaluating bispecific CAR-T cells targeting both CD19 and CD20 or CD19 and CD22 as a tool to improve the therapeutic efficacy and to reduce the number of refractory/relapsing patients.","PeriodicalId":18498,"journal":{"name":"Mediterranean Journal of Hematology and Infectious Diseases","volume":"69 6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136022973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Mutation in the genome of SARS-CoV-2 may play a role in immune evasion, pathogenicity and speed of its transmission. Our investigation aimed to evaluate the mutations that exist in the nsp2.
Materials and Method: RNA was extracted from nasopharyngeal swabs from 100 COVID-19 patients. RT-PCR was performed on all samples using nsp2 specific primers. Following gel electrophoresis, the bands were cut, purified, and sequenced using Sanger method. After sequencing, 90 sequences could be used for further analysis. Bioinformatics analysis was conducted to investigate the effect of mutations on protein structure, prediction of homology models, phylogeny tree.
Results: The patients' mean age wa
Background: Mutation in the genome of SARS-CoV-2 may play a role in immune evasion, pathogenicity and speed of its transmission. Our investigation aimed to evaluate the mutations that exist in the nsp2.
Materials and Method: RNA was extracted from nasopharyngeal swabs from 100 COVID-19 patients. RT-PCR was performed on all samples using nsp2 specific primers. Following gel electrophoresis, the bands were cut, purified, and sequenced using Sanger method. After sequencing, 90 sequences could be used for further analysis. Bioinformatics analysis was conducted to investigate the effect of mutations on protein structure, prediction of homology models, phylogeny tree.
Results: The patients' mean age was 51.08. The results revealed that 8 of the 17 nsp2 mutations (R207C, T224I, G262V, T265I, K337D, N348S, G392D, and I431M) were missense. One deletion was also found in nsp2. Among nsp2 missense mutations studied, K337D and G392D increased structural stability while the others decreased it. The homology-designed models demonstrated that the homologies were comparable to the sequences of the Wuhan-HU-1 virus.
Conclusion: Our study suggested that the mutations as K337D and G392D modulate the stability of nsp2 and tracking viral evolution should be implemented and vaccine development updated.
s 51.08. The results revealed that 8 of the 17 nsp2 mutations (R207C, T224I, G262V, T265I, K337D, N348S, G392D, and I431M) were missense. One deletion was also found in nsp2. Among nsp2 missense mutations studied, K337D and G392D increased structural stability while the others decreased it. The homology-designed models demonstrated that the homologies were comparable to the sequences of the Wuhan-HU-1 virus.
Conclusion: Our study suggested that the mutations as K337D and G392D modulate the stability of nsp2 and tracking viral evolution should be implemented and vaccine development updated.
背景:SARS-CoV-2基因组突变可能与免疫逃避、致病性和传播速度有关。我们的研究旨在评估存在于nsp2.
材料和方法:从100例COVID-19患者鼻咽拭子中提取RNA。采用nsp2特异性引物对所有样品进行RT-PCR。凝胶电泳后，将条带剪切、纯化并使用Sanger法进行测序。测序后，90个序列可用于进一步分析。生物信息学分析研究突变对蛋白质结构的影响，预测同源模型，系统发育树。
结果:患者平均年龄为
背景:SARS-CoV-2基因组突变可能与免疫逃避、致病性和传播速度有关。我们的研究旨在评估存在于nsp2.
材料和方法:从100例COVID-19患者鼻咽拭子中提取RNA。采用nsp2特异性引物对所有样品进行RT-PCR。凝胶电泳后，将条带剪切、纯化并使用Sanger法进行测序。测序后，90个序列可用于进一步分析。生物信息学分析研究突变对蛋白质结构的影响，预测同源模型，系统发育树。
结果:患者平均年龄51.08岁。结果显示，17个nsp2突变中有8个(R207C、T224I、G262V、T265I、K337D、N348S、G392D和I431M)是错义突变。在nsp2中也发现了一个缺失。在研究的nsp2错义突变中，K337D和G392D增加了结构稳定性，而其他突变则降低了结构稳定性。同源性设计模型表明，这些同源性与武汉- hu -1病毒的序列相当。结论:我们的研究表明，K337D和G392D突变调节了nsp2的稳定性，应该跟踪病毒的进化并更新疫苗的开发。51.08 s。结果显示，17个nsp2突变中有8个(R207C、T224I、G262V、T265I、K337D、N348S、G392D和I431M)是错义突变。在nsp2中也发现了一个缺失。在研究的nsp2错义突变中，K337D和G392D增加了结构稳定性，而其他突变则降低了结构稳定性。同源性设计模型表明，这些同源性与武汉- hu -1病毒的序列相当。结论:我们的研究表明，K337D和G392D突变调节了nsp2的稳定性，应该跟踪病毒的进化并更新疫苗的开发。
{"title":"NOVEL MUTATIONS IN THE NON-STRUCTURE PROTEIN 2 OF SARS-CoV-2","authors":"Mohsen Nakhaei, Zohreh-Al-Sadat Ghoreshi, Mohammad Rezaei Zadeh Rukerd, Hedyeh Askarpour, None Nasir","doi":"10.4084/mjhid.2023.059","DOIUrl":"https://doi.org/10.4084/mjhid.2023.059","url":null,"abstract":"Background: Mutation in the genome of SARS-CoV-2 may play a role in immune evasion, pathogenicity and speed of its transmission. Our investigation aimed to evaluate the mutations that exist in the nsp2.
 Materials and Method: RNA was extracted from nasopharyngeal swabs from 100 COVID-19 patients. RT-PCR was performed on all samples using nsp2 specific primers. Following gel electrophoresis, the bands were cut, purified, and sequenced using Sanger method. After sequencing, 90 sequences could be used for further analysis. Bioinformatics analysis was conducted to investigate the effect of mutations on protein structure, prediction of homology models, phylogeny tree.
 Results: The patients' mean age wa
 Background: Mutation in the genome of SARS-CoV-2 may play a role in immune evasion, pathogenicity and speed of its transmission. Our investigation aimed to evaluate the mutations that exist in the nsp2.
 Materials and Method: RNA was extracted from nasopharyngeal swabs from 100 COVID-19 patients. RT-PCR was performed on all samples using nsp2 specific primers. Following gel electrophoresis, the bands were cut, purified, and sequenced using Sanger method. After sequencing, 90 sequences could be used for further analysis. Bioinformatics analysis was conducted to investigate the effect of mutations on protein structure, prediction of homology models, phylogeny tree.
 Results: The patients' mean age was 51.08. The results revealed that 8 of the 17 nsp2 mutations (R207C, T224I, G262V, T265I, K337D, N348S, G392D, and I431M) were missense. One deletion was also found in nsp2. Among nsp2 missense mutations studied, K337D and G392D increased structural stability while the others decreased it. The homology-designed models demonstrated that the homologies were comparable to the sequences of the Wuhan-HU-1 virus.
 Conclusion: Our study suggested that the mutations as K337D and G392D modulate the stability of nsp2 and tracking viral evolution should be implemented and vaccine development updated.
 s 51.08. The results revealed that 8 of the 17 nsp2 mutations (R207C, T224I, G262V, T265I, K337D, N348S, G392D, and I431M) were missense. One deletion was also found in nsp2. Among nsp2 missense mutations studied, K337D and G392D increased structural stability while the others decreased it. The homology-designed models demonstrated that the homologies were comparable to the sequences of the Wuhan-HU-1 virus.
 Conclusion: Our study suggested that the mutations as K337D and G392D modulate the stability of nsp2 and tracking viral evolution should be implemented and vaccine development updated.","PeriodicalId":18498,"journal":{"name":"Mediterranean Journal of Hematology and Infectious Diseases","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136183736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-01eCollection Date: 2023-01-01DOI: 10.4084/MJHID.2023.038
Ugo Testa, Germana Castelli, Elvira Pelosi
TP53-mutated myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) form a distinct and heterogeneous group of myeloid malignancies associated with poor outcomes. Studies carried out in the last years have in part elucidated the complex role played by TP53 mutations in the pathogenesis of these myeloid disorders and in the mechanisms of drug resistance. A consistent number of studies has shown that some molecular parameters, such as the presence of a single or multiple TP53 mutations, the presence of concomitant TP53 deletions, the association with co-occurring mutations, the clonal size of TP53 mutations, the involvement of a single (monoallelic) or of both TP53 alleles (biallelic) and the cytogenetic architecture of concomitant chromosome abnormalities are major determinants of outcomes of patients. The limited response of these patients to standard treatments, including induction chemotherapy, hypomethylating agents and venetoclax-based therapies and the discovery of an immune dysregulation have induced a shift to new emerging therapies, some of which being associated with promising efficacy. The main aim of these novel immune and nonimmune strategies consists in improving survival and in increasing the number of TP53-mutated MDS/AML patients in remission amenable to allogeneic stem cell transplantation.
{"title":"TP53-Mutated Myelodysplasia and Acute Myeloid Leukemia.","authors":"Ugo Testa, Germana Castelli, Elvira Pelosi","doi":"10.4084/MJHID.2023.038","DOIUrl":"10.4084/MJHID.2023.038","url":null,"abstract":"<p><p>TP53-mutated myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) form a distinct and heterogeneous group of myeloid malignancies associated with poor outcomes. Studies carried out in the last years have in part elucidated the complex role played by TP53 mutations in the pathogenesis of these myeloid disorders and in the mechanisms of drug resistance. A consistent number of studies has shown that some molecular parameters, such as the presence of a single or multiple TP53 mutations, the presence of concomitant TP53 deletions, the association with co-occurring mutations, the clonal size of TP53 mutations, the involvement of a single (monoallelic) or of both TP53 alleles (biallelic) and the cytogenetic architecture of concomitant chromosome abnormalities are major determinants of outcomes of patients. The limited response of these patients to standard treatments, including induction chemotherapy, hypomethylating agents and venetoclax-based therapies and the discovery of an immune dysregulation have induced a shift to new emerging therapies, some of which being associated with promising efficacy. The main aim of these novel immune and nonimmune strategies consists in improving survival and in increasing the number of TP53-mutated MDS/AML patients in remission amenable to allogeneic stem cell transplantation.</p>","PeriodicalId":18498,"journal":{"name":"Mediterranean Journal of Hematology and Infectious Diseases","volume":"15 1","pages":"e2023038"},"PeriodicalIF":2.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/87/c9/mjhid-15-1-e2023038.PMC10332352.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10353069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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