Blood transfusions in non-major burns patients.

BACKGROUND: Blood transfusions are essential to treating anaemia of burn injuries. It has recently been observed that patients with non-major burns < 20%TBSA may also develop anaemia requiring transfusion of blood products. Due to the morbidity and mortality rate associated with blood transfusions better understanding of risk factors may guide clinical practices to improve patient care. OBJECTIVE: To determine risk factors for transfusion of blood products in patients with non-major burn injuries and assess transfusion practices to establish impact on patient outcome. METHOD: Our study included 182 adult patients with non-major burn injuries, < 20%TBSA admitted over a 3-year period at the Department of Plastic Surgery and Burns Unit of the Emergency County Hospital Cluj-Napoca. We analysed patient and injury characteristics: age, gender, %TBSA burn, %FT burn, burn site, mechanism of injury, inhalation injury, Hb lab determinations throughout admission and surgical management. Charlson comorbidities index has been determined based on cardiovascular, neurological, gastrointestinal and renal comorbidities as well as diabetes mellitus. We selected blood transfusions, wound infections and length of hospital stay as outcome for our analysis. RESULTS: 37.9% of patients included in our study developed anaemia throughout admission and 7.7% underwent blood transfusions. Mean Hb levels triggering blood transfusions have been recorded at 7.4 (IQR=8.8-9.9) g/dL. Patients who received transfusions were older, presented with higher %TBSA and associated a higher comorbidity index. They also tended to develop coagulopathy and underwent more surgical procedures to achieve wound closure. In transfused patients who associate comorbidities we observed a higher rate of wound infections and longer hospital stay. CONCLUSIONS: Patient related comorbidities correlate with higher transfusion rates in non-major burn injuries. Due to the risk associated with the use of blood products decision to transfuse should adhere to current guideline practices and be tailored to specific patient requirements.

Design and preclinical testing of an anti-CD41 CAR T cell for the treatment of acute megakaryoblastic leukaemia.

Acute megakaryoblastic leukaemia (AMkL) is a rare subtype of acute myeloid leukaemia (AML) representing 5% of all reported cases, and frequently diagnosed in children with Down syndrome. Patients diagnosed with AMkL have low overall survival and have poor outcome to treatment, thus novel therapies such as CAR T cell therapy could represent an alternative in treating AMkL. We investigated the effect of a new CAR T cell which targets CD41, a specific surface antigen for M7-AMkL, against an in vitro model for AMkL, DAMI Luc2 cell line. The performed flow cytometry evaluation highlighted a percentage of 93.8% CAR T cells eGFP-positive and a limited acute effect on lowering the target cell population. However, the interaction between effector and target (E:T) cells, at a low ratio, lowered the cell membrane integrity, and reduced the M7-AMkL cell population after 24 h of co-culture, while the cytotoxic effect was not significant in groups with higher E:T ratio. Our findings suggest that the anti-CD41 CAR T cells are efficient for a limited time spawn and the cytotoxic effect is visible in all experimental groups with low E:T ratio.

A Survival Analysis of Acute Myeloid Leukemia Patients Treated With Intensive Chemotherapy: A Single Center Experience.

INTRODUCTION: Acute myeloid leukaemia (AML) is a haematological disease associated with a dismal prognosis, despite major progress made in recent years in terms of antileukemic agents and supportive care. METHODS: We investigated the results of the intensive treatment of 133 fit AML patients (de novo and secondary) from a referral cancer centre in Romania, treated between January 2015 and December 2021. RESULTS: We included 79 male and 54 female patients with a median age of 53 years (range 18-70). Molecular biology analysis was available for 82.7% of patients, whereas karyotype analysis was only available for 33% of patients. The median overall survival (OS) was 8.7 months, and the disease-free survival rate was 26.3% at a median follow-up of 33.7 months. The complete remission (CR) rate after induction was 48.9% for all patients and 61.9% for patients who were assessable (excluding patients who died before being assessed for response). Twelve patients underwent allogeneic bone marrow transplantation (BMT), with the median OS not reached. Early mortality (EM), defined as death during the first 30 days after admission, was 17.3%, with the main cause of death being septic shock (78.3%). Elderly patients (≥60 years of age) had a lower OS, more primary refractory disease, and higher rates of early mortality. CONCLUSION: Complete remission rates and OS in our cohort were lower than in other reports. Early mortality was unexpectedly high, mainly due to infections, which were the main causes of death in our cohort.

Flow Cytometry of CD5-Positive Hairy Cell Leukemia.

BACKGROUND AND OBJECTIVE: Hairy cell leukemia (HCL) is a chronic lymphoproliferative disorder for which diagnosis is typically straightforward, based on bone marrow morphology and flow cytometry (FC) or immunohistochemistry. Nevertheless, variants present atypical expressions of cell surface markers, as is the case of CD5, for which the differential diagnosis can be more difficult. The aim of the current paper was to describe diagnosis of HCL with atypical CD5 expression, with an emphasis on FC. METHODS: The detailed diagnostic methodology for HCL with atypical CD5 expression is presented, including differential diagnosis from other lymphoproliferative diseases with similar pathologic features, by FC analysis of the bone marrow aspirate. RESULTS: Diagnosis of HCL by means of FC started by gating all events based on side scatter (SSC) versus CD45 and B lymphocytes were selected from the lymphocytes gate as CD45/CD19 positive. The gated cells were positive for CD25, CD11c, CD20, and CD103, while CD10 proved to be dim to negative. Moreover, cells positive for CD3, CD4, and CD8, the three pan-T markers, as well as CD19, showed a bright expression of CD5. The atypical CD5 expression is usually correlated with a negative prognosis and thus chemotherapy with cladribine should be initiated. CONCLUSION: HCL is an indolent chronic lymphoproliferative disorder and diagnosis is usually straightforward. However, atypical expression of CD5 renders its differential diagnosis more difficult, but FC is a useful tool that allows an optimal classification of the disease and allows initiation of timely satisfactory therapy.

Implementing change in the care of the complex cardiac patient.

PURPOSE OF REVIEW: Development of advanced and minimally invasive surgical procedures is providing treatment opportunities to older and higher risk patients. This has also led to highly specialized physicians and a need for better communication and planning with the patients and within the care team. RECENT FINDINGS: In the field of cardiac surgery, the heart team model has been advocated and implemented as a vehicle to optimize decision making prior to procedure, care during the procedure and in the recovery process. The goal is to provide a treatment path that prioritizes the patient's goals and to anticipate and minimize complications. SUMMARY: In this review, we discuss the concepts of shared decision making (SDM) and implementation science in the context of the complex cardiac patient. We also review the most recent evidence for their use in cardiac surgery. We argue that a team model not only bridges knowledge gaps but provides a multidisciplinary environment for the practice of SDM and implementation of evidence-based practices. Be believe this will provide patients with a better experience as they navigate their care and improve their medical outcomes as well.

COVID-19 Impact on Chronic Myeloid Leukemia Patients.

(1) Background: Chronic myeloid leukemia (CML) is a blood dyscrasia that accounts for about 20% of all leukemia cases. Tyrosine kinase inhibitors (TKIs) are used as first line treatment of CML. The 2019 SARS-CoV-2 outbreak raised new concerns for CML patients, such as whether CML increases the risk of contracting COVID-19, whether TKIs increase that risk, whether these drugs are safe to use during the infection, and whether any other hematologic parameters influence infection outcomes. (2) Methods: In our study we addressed these intriguing questions by using a retrospective analysis of 51 CML patients treated at the Ion Chiricuta Cancer Center, Cluj-Napoca, Romania. Furthermore, we investigated the effects of currently approved COVID-19 vaccines in our CML patients treated with tyrosine kinase inhibitors. (3) Results: Our results have shown that hemoglobin level upon diagnosis of CML has been the only hematologic parameter correlated to the risk of contracting COVID-19 in our CML patients. (4) Conclusions: TKI treatment did not negatively influence COVID-19 risk or the response to the vaccine in our patients. The safety profile of the currently approved COVID-19 vaccines was similar to that of the general population.

Mechanistic Insights in Hemophagocytic Lymphohistiocytosis: Subsequent Acute Hepatic Failure in a Multiple Myeloma Patient Following Therapy with Ixazomib-Lenalidomide-Dexamethasone.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, elusive, and life-threatening condition that is characterized by the pathologic and uncontrolled secondary activation of the cytotoxic T-cells, natural killer cells (NK-cells), and macrophages of the innate immune system. This condition can develop in sporadic or familial contexts associated with hematological malignancies, as a paraneoplastic syndrome, or linked to an infection related to immune system deficiency. This leads to the systemic inflammation responsible for the overall clinical manifestations. Diagnosis should be thorough, and treatment should be initiated as soon as possible. In the current manuscript, we focus on classifying the HLH spectrum, describing the pathophysiology and the tools needed to search for and correctly identify HLH, and the current therapeutic opportunities. We also present the first case of a multiple myeloma patient that developed HLH following therapy with the ixazomib-lenalidomide-dexamethasone protocol.

Current therapeutic approaches in the management of hemophilia-a consensus view by the Romanian Society of Hematology.

Hemophilia A (HA) and hemophilia B (HB) are rare disorders, being caused by the total lack or under-expression of two factors from the coagulation cascade coded by genes of the X chromosome. Thus, in hemophilic patients, the blood does not clot properly. This results in spontaneous bleeding episodes after an injury or surgical intervention. A patient-centered regimen is considered optimal. Age, pharmacokinetics, bleeding phenotype, joint status, adherence, physical activity, personal goals are all factors that should be considered when individualizing therapy. In the past 10 years, many innovations in the diagnostic and treatment options were presented as being either approved or in development, thus helping clinicians to improve the standard-of-care for patients with hemophilia. Recombinant factors still remain the standard of care in hemophilia, however they pose a challenge to treatment adherence because they have short half-life, which where the extended half-life (EHL) factors come with the solution, increasing the half-life to 96 hours. Gene therapies have a promising future with proven beneficial effects in clinical trials. We present and critically analyze in the current manuscript the pros and cons of all the major discoveries in the diagnosis and treatment of HA and HB, as well as identify key areas of hemophilia research where improvements are needed.

A narrative review of central nervous system involvement in acute leukemias.

Acute leukemias (both myeloid and lymphoblastic) are a group of diseases for which each year more successful therapies are implemented. However, in a subset of cases the overall survival (OS) is still exceptionally low due to the infiltration of leukemic cells in the central nervous system (CNS) and the subsequent formation of brain tumors. The CNS involvement is more common in acute lymphocytic leukemia (ALL), than in adult acute myeloid leukemia (AML), although the rates for the second case might be underestimated. The main reasons for CNS invasion are related to the expression of specific adhesion molecules (VLA-4, ICAM-1, VCAM, L-selectin, PECAM-1, CD18, LFA-1, CD58, CD44, CXCL12) by a subpopulation of leukemic cells, called "sticky cells" which have the ability to interact and adhere to endothelial cells. Moreover, the microenvironment becomes hypoxic and together with secretion of VEGF-A by ALL or AML cells the permeability of vasculature in the bone marrow increases, coupled with the disruption of blood brain barrier. There is a single subpopulation of leukemia cells, called leukemia stem cells (LSCs) that is able to resist in the new microenvironment due to its high adaptability. The LCSs enter into the arachnoid, migrate, and intensively proliferate in cerebrospinal fluid (CSF) and consequently infiltrate perivascular spaces and brain parenchyma. Moreover, the CNS is an immune privileged site that also protects leukemic cells from chemotherapy. CD56/NCAM is the most important surface molecule often overexpressed by leukemic stem cells that offers them the ability to infiltrate in the CNS. Although asymptomatic or with unspecific symptoms, CNS leukemia should be assessed in both AML/ALL patients, through a combination of flow cytometry and cytological analysis of CSF. Intrathecal therapy (ITT) is a preventive measure for CNS involvement in AML and ALL, still much research is needed in finding the appropriate target that would dramatically lower CNS involvement in acute leukemia.

Overview of the Side-Effects of FDA- and/or EMA-Approved Targeted Therapies for the Treatment of Hematological Malignancies.

In the last decade there has been tremendous effort in offering better therapeutic management strategies to patients with hematologic malignancies. These efforts have ranged from biological to clinical approaches and resulted in the rapid development of new approaches. The main "problem" that comes with the high influx of newly approved drugs, which not only influences hematologists that frequently work with these drugs but also affects other healthcare professionals that work with hematologists in patient management, including intensive care unit (ICU) physicians, is they have to keep up within their specialty and, in addition, with the side-effects that can occur when encountering hematology-specific therapies. Nonetheless, there are few people that have an in-depth understanding of a specialty outside theirs. Thus, this manuscript offers an overview of the most common side-effects caused by therapies used in hematology nowadays, or that are currently being investigated in clinical trials, with the purpose to serve as an aid to other specialties. Nevertheless, because of the high amount of information on this subject, each chapter will offer an overview of the side-effects of a drug class with each reference of the section being intended as further reading.

Paraneoplastic hypereosinophilia in a patient with peripheral T cell lymphoma, not otherwise specified.

Under normal physiological conditions, the bone marrow (BM) will have between 1% and 6% eosinophils, translating into a peripheral count of 0.05 - 0.5 ×109/L eosinophils in the blood smear. This process is coordinated by transcription factors with specific roles in differentiation and activation. Secondary eosinophilia may be a paraneoplastic syndrome, related to the presence of a subsequent malignancy, as presented in this case report. Such paraneoplastic manifestations should be addressed properly in order for the patient to receive the best treatment of choice. Even if eosinophilia was associated with B-cell malignancies before, this is a report associating this symptom to a peripheral T-cell lymphoma, not other specified, thus emphasizing the importance of a complex approach for the management of the oncological patient.

Persistent Basophilia May Suggest an "Accelerated Phase" in the Evolution of CALR-Positive Primary Myelofibrosis Toward Acute Myeloid Leukemia.

Basophils are white blood cells that play an important role in the human immune system. These cells physiologically increase in number in immune response to certain allergies, chronic inflammation, and parasitic infections. Basophils are also a significant indicator for the presence of certain malignancies such as chronic myeloproliferative neoplasms and acute myeloid leukemia. In the current manuscript we present a statistically significant correlation between persistent basophilia in primary myelofibrosis (PMF) and the risk for the subsequent development of acute myeloid leukemia. We have retrospectively identified in the files of the Department of Hematology, Ion Chiricuta Clinical Cancer Center in Cluj Napoca, Romania 623 consecutive patients diagnosed with AML over a period spanning from 2008 to 2018. We afterwards identified 32 patients with AML diagnosis following a previous diagnosis of myelofibrosis (either post-PV, post-ET, or post-PMF). All the patients were diagnosed according to the WHO criteria. We subsequently established a control group consisting of 32 patients with underlying BCR-ABL-negative MPN who did not develop AML (AML-negative group). Following this, we assessed whether the AML-negative patients from our control group also had a persistent (>3 months) absolute basophilia. When comparing both groups of patients with myelofibrosis, the group with subsequent AML development and the one without AML, the follow-up did not present statistically significant differences between the two groups. In the univariate analysis, patients who progressed to AML had more frequently basophilia, longer basophilia duration, higher pre-therapy absolute, and relative basophil count and presented more frequently calreticulin (CALR) mutations. In the current study, we emphasize the need for a closer clinical monitoring for chronic MPNs with marked basophilia, with an important potential clinical impact.

Approach to the Adult Acute Lymphoblastic Leukemia Patient.

During recent decades, understanding of the molecular mechanisms of acute lymphoblastic leukemia (ALL) has improved considerably, resulting in better risk stratification of patients and increased survival rates. Age, white blood cell count (WBC), and specific genetic abnormalities are the most important factors that define risk groups for ALL. State-of-the-art diagnosis of ALL requires cytological and cytogenetical analyses, as well as flow cytometry and high-throughput sequencing assays. An important aspect in the diagnostic characterization of patients with ALL is the identification of the Philadelphia (Ph) chromosome, which warrants the addition of tyrosine kinase inhibitors (TKI) to the chemotherapy backbone. Data that support the benefit of hematopoietic stem cell transplantation (HSCT) in high risk patient subsets or in late relapse patients are still questioned and have yet to be determined conclusive. This article presents the newly published data in ALL workup and treatment, putting it into perspective for the attending physician in hematology and oncology.

Clinical Approach to the Patient in Critical State Following Immunotherapy and/or Stem Cell Transplantation: Guideline for the On-Call Physician.

: The initial management of the hematology patient in a critical state is crucial and poses a great challenge both for the hematologist and the intensive care unit (ICU) physician. After years of clinical practice, there is still a delay in the proper recognition and treatment of critical situations, which leads to late admission to the ICU. There is a much-needed systematic ABC (Airway, Breathing, Circulation) approach for the patients being treated on the wards as well as in the high dependency units because the underlying hematological disorder, as well as disease-related complications, have an increasing frequency. Focusing on score-based decision-making on the wards (Modified Early Warning Score (MEWS), together with Quick Sofa score), active sepsis screening with inflammation markers (C-reactive protein, procalcitonin, and presepsin), and assessment of microcirculation, organ perfusion, and oxygen supply by using paraclinical parameters from the ICU setting (lactate, central venous oxygen saturation (ScVO2), and venous-to-arterial carbon dioxide difference), hematologists can manage the immediate critical patient and improve the overall outcome.

Pilot study using post-transplant cyclophosphamide (PTCy), tacrolimus and mycophenolate GVHD prophylaxis for older patients receiving 10/10 HLA-matched unrelated donor hematopoietic stem cell transplantation.

Allogeneic SCT for older patients remains challenging at least in part due to graft-versus-host disease (GVHD) and higher non-relapse mortality (NRM). We conducted a prospective pilot study primarily for older patients undergoing matched unrelated donor (MUD) SCT using a reduced-intensity (RIC) melphalan-based conditioning and post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis with tacrolimus and mycophenolate mofetil. Twenty-two patients (median age 64, IQR 58, 66) underwent RIC MUD SCT for high-risk hematological malignancies including AML/MDS (73%), CML/MPD (18%), and other (10%). Two (9%) patients had early death; the rest (100%) engrafted. After a median follow-up of 17 months, 11 patients were alive and disease-free with an estimated 2-year progression-free (PFS) and overall (OS) survival of 48%. The cumulative incidences of grades 2-4 and 3-4 acute GVHD (aGVHD) at day + 100 and 2-years were 32 and 4%, and 59 and 24%, respectively. No cases of chronic GVHD (cGVHD) were noted. However, late acute GVHD was observed in 6 (27%) patients. In conclusion, RIC MUD SCT with melphalan-based conditioning and PTCy-based GVHD-based prophylaxis for older patients appears effective in controlling relapse. While cGVHD was not seen and early aGVHD appears controllable, a significant proportion developed late aGVHD responsible for higher NRM seen in these patients.

Next-generation sequencing-based characterization of the invasion by anatomical contiguity in a primary osseous diffuse large B-cell lymphoma. Correlation between the genetic profile of the malignancy and the clinical outcome of the patient.

Primary bone lymphoma is now a well-described entity in the World Health Organization (WHO) Classification of Tumors of Soft Tissue and Bone as a malignancy of the lymphoid tissue, with at least one mass within bone, without involvement of supraregional lymph nodes or other extranodal sites. In the current paper, we describe the complete characterization of the mutational landscape of a diffuse large B cell non-Hodgkin's lymphoma (DLBLCL) of the tibial plateau. Currently, there is very little data about the genetic landscape of primary osseous lymphomas and about the genetic background of this type of malignancy, resistant to chemotherapy and invading the surrounding tissues. In the current paper, we describe the complete characterization of the mutational landscape of a DLBCL of the tibial plateau. Our data is consistent with already published data, that have shown that MKI67 activation is correlated with lymphoma progression. Along with a high Ki67 index, resistance to chemotherapy occurs with neurogenic locus notch homolog protein 1 (Notch) and KRAS activation. This is the first molecular characterization for the invasion by anatomical contiguity for a primary bone lymphoma and while we only characterized one case and further deep sequencing analyses are required, we can explain the clinical dismal evolution of the patient by correlating them with the genetic landscape of this type of lymphoma.

Protein dysregulation in graft versus host disease.

Allogeneic hematopoietic stem cell transplantation is a well-established treatment for many malignant and non-malignant hematological disorders. As a frequent complication in up to 50% of all patients, graft-versus-host disease is still the main cause for morbidity and non-relapse mortality. Diagnosis is usually done clinically, even though confirmation by pathology is often used to support the clinical findings. Effective treatment requires intensified immunosuppression as early as possible. Although several promising biomarkers have been proposed for an early diagnosis, no internationally-recognized consensus has yet been established. Protein-based biomarkers represent an interesting tool since they have been recently reported to be an important regulator of various cells, including immune cells such as T cells. Therefore, we assume that protein dysregulation is important in the pathogenesis of acute graft versus host disease and their detection might be an possibility in the early diagnosis and monitoring. In this review, we aim to summarize the previous reports of protein biomarkers, focusing on the pathogenesis of the disease and possible implications in diagnostic approaches.

Harnessing insulin- and leptin-induced oxidation of PTP1B for therapeutic development.

The protein tyrosine phosphatase PTP1B is a major regulator of glucose homeostasis and energy metabolism, and a validated target for therapeutic intervention in diabetes and obesity. Nevertheless, it is a challenging target for inhibitor development. Previously, we generated a recombinant antibody (scFv45) that recognizes selectively the oxidized, inactive conformation of PTP1B. Here, we provide a molecular basis for its interaction with reversibly oxidized PTP1B. Furthermore, we have identified a small molecule inhibitor that mimics the effects of scFv45. Our data provide proof-of-concept that stabilization of PTP1B in an inactive, oxidized conformation by small molecules can promote insulin and leptin signaling. This work illustrates a novel paradigm for inhibiting the signaling function of PTP1B that may be exploited for therapeutic intervention in diabetes and obesity.

Smoking and Smoking Cessation During Pregnancy. An Analysis of a Hospital Based Cohort of Women in Romania.

Perinatal smoking is associated with a wide range of negative reproductive and pregnancy outcomes. The aim of the current study was to examine the prevalence and characteristics of women who report smoking prenatally and quit during pregnancy in a large sample of Romanian women. Understanding which women are more likely to quit will contribute to public health knowledge that will help more women stop smoking prior to or during pregnancy and prevent relapse postpartum. This cross-sectional analysis was conducted based on cross-sectional data collected between May 2012 and April 2015 as part of a cohort study of pregnancy implemented in six clinical settings in central Romania (N = 2370). Approximately 28 % of the sample reported smoking in the 6 months prior to learning they were pregnant. Half of the women who reported smoking 6 months before learning of their pregnancy, also reported that they stopped smoking by the time of the interview. Overall, tobacco consumption decreased from a sample mode of 10 cigarettes/day (range: 1-30) before pregnancy, to a sample mode of 5 cigarettes/day (range: 1-25) at the time of the interview. Women who quit had a higher socioeconomic position, were more likely to live in urban areas, partnered, primigravid, nulliparous, and reported lower anxiety and more social support. The combination of a socioeconomic gradient, less anxiety, and more social support suggests that efforts should be increased to target lower income, less educated, multigravid, and multiparous women and to develop programs that heighten social support and alleviate anxiety.