Assessment of hematological parameters in malarial suspected patients: Cross sectional study.

Background: Malaria is a Zoonotic disease, worldwide in distribution and caused by different species of plasmodium. It is a major cause of sickness and mortality in developing countries including Pakistan. This study was carried with the aim to find out the prevalence of malaria and to aware the people about this disease. Methods: The study was carried out in district charsadda. 120 blood samples were collected from suspects both male and female, during the period of March 2022 to September 2022 and were analyzed for CBC and for Microscopic examination. Results: Out of these 120 samples 12(10%) were found positive and 108(90%) were negative. The prevalence of malaria was more in the month of June and July. The infection was high in male (13.3%) as compared to female (6.6%). The prevalence was more in rural areas 8(13.3%) than in urban areas 4(6.6%). Conclusion: The Hemoglobin, Hematocrit, Platelets and Red Blood Cells were found more affected in positive samples as compared to other parameters. The present study will help the malarial control programs to focus on rural areas. The Plasmodium vivax is more common in the study area.

From the mechanism of action to clinical management: A review of cardiovascular toxicity in adult treated with CAR-T therapy.

Chimeric antigen receptor T-cell therapy represents an innovative approach to immunotherapy and currently stands out, particularly for oncohematological patients refractory to traditional treatments. Ongoing trials are further expanding its clinical use for new oncological and non-oncological indications, potentially leading to newer treatment options soon. This new approach, however, also presents challenges, including cardiovascular toxicity. Little is reported in pivotal studies, and some recent retrospective observations suggest a non-negligible incidence of side effects with presentation ranging from mild adverse cardiovascular events to fatal complications in which, in most cases, there is a direct or indirect association with cytokine release syndrome. In this literature review, the hypotheses of an important interface between cytokine release syndrome and cardiotoxicity by chimeric antigen receptor T-cell therapy will be addressed, as will current knowledge about risk factors for cardiotoxicity and recommendations for pre-therapy evaluation, post-infusion monitoring and clinical management of these complications.

Understanding innate and adaptive responses during radiation combined burn injuries.

The occurrence of incidents involving radiation-combined burn injuries (RCBI) poses a significant risk to public health. Understanding the immunological and physiological responses associated with such injuries is crucial for developing care triage to counter the mortality that occurs due to the synergistic effects of radiation and burn injuries. The core focus of this narrative review lies in unraveling the immune response against RCBI. Langerhans cells, mast cells, keratinocytes, and fibroblasts, which induce innate immunity, have been explored for their response to radiation, burns, and combined injuries. In the case of adaptive immune response, exploring behavioral changes in T regulatory (Treg) cells, T helper cells (Th1, Th2, and Th17), and immunoglobulin results in delayed healing compared to burn and radiation injury. The review also includes the function of complement system components such as neutrophils, acute phase proteins (CRP, C3, and C5), and cytokines for their role in RCBI. Combined insults resulting in a reduction in the cell population of immune cells display variation in response based on radiation doses, burn injury types, and their intrinsic radiosensitivity. The lack of approved countermeasures against RCBI poses a significant challenge. Drug repurposing might help to balance immune cell alteration, resulting in fast recovery and decreasing mortality, which gives it clinical significance for its implication on the site of such incidence. However, the exact immune response in RCBI remains insufficiently explored in pre-clinical and clinical stages, which might be due to the non-availability of in vitro models, standard animal models, or human subjects, warranting further research.

In the realm of public health, RCBI presents significant risks and obstacles. This hazard is quite serious, and it might get worse in the future as evidenced by incidents like nuclear meltdowns and medical mistakes. Diagnosis and treatment become more challenging when serious injuries, particularly burns, are combined with radiation exposure. Features like early shock, poor wound healing, and hematopoietic instability call for advancements in both diagnosis and therapy. Furthermore, the immune system's response to RCBI is complicated and involves changes in cytokine concentrations, immune cell activity, and adaptive immune responses compared to single injuries. Immune cell radiosensitivity varies depending on the type of cell, radiation dose, and length of exposure, so it's important to understand. Repurposing drugs is one of the potential techniques to reduce mortality and speed up healing which are discussed in the manuscript. Still, more research is needed. To effectively tackle RCBI, more investigation into molecular processes, treatment strategy optimization, and information gap closure are essential.

A Case of Scleroderma With Coexisting Multiple Myeloma and Bullous Pemphigoid.

An 83-year-old female patient presented to our nephrology outpatient clinic with complaints of weakness, edema, abdominal pain, and constipation, with a preliminary diagnosis of chronic kidney failure related to heart failure. The patient had undergone mitral valve replacement surgery 10 years prior and was diagnosed with chronic renal failure six years prior. Laboratory tests revealed mild normochromic normocytic anemia, consistently high erythrocyte sedimentation rate (ESR) above 100 mm/h, and nephrotic-range proteinuria, prompting suspicion of multiple myeloma. Further investigations, including bone marrow aspiration, confirmed the diagnosis of multiple myeloma. During follow-up, the patient began to complain of difficulty swallowing and symptoms of microstomia. Upon further questioning, it was discovered that these symptoms had been present for more than 10 years. Immunoblot tests revealed positive centromere protein B (CENP-B), suggesting a diagnosis of scleroderma. Subsequently, during follow-up, bullous lesions appeared on the patient's chest. Biopsy samples confirmed a diagnosis of bullous pemphigoid (BP). The co-occurrence of scleroderma, multiple myeloma, and superimposed BP represents a rare and noteworthy case for publication.

Retrospective comparative analysis of two medical evacuation systems for Ukrainian patients affected by war.

INTRODUCTION: Coordinated medical evacuations represent an important strategy for emergency response when healthcare systems are impaired by armed conflict, particularly for patients diagnosed with life-threatening conditions such as cancer. In this study, we compare the experiences of two parallel medical evacuation systems developed to meet the medical needs of Ukrainians affected by war. METHODS: This retrospective study compared outcomes of two medical evacuation systems, developed by the European Union Emergency Response Coordination Centre (ERCC) and Supporting Action for Emergency Response in Ukraine (SAFER Ukraine) collaborative, in the first 10 months after the war's intensification in Ukraine (February 24 to December 21, 2022). Each groups' respective registries served as data sources. Patient demographics and allocation data were summarized descriptively. Median time for patient referral were analyzed statistically. RESULTS: The ERCC pathway evacuated 1385 patients (median age: 36 [0 - 85] years) to 16 European countries; 78.7 % (n = 1091) suffered from trauma-related injuries and 13.4 % (n = 185) from cancer. SAFER Ukraine evacuated 550 patients (median age: 9 [0 - 22] years) to 14 European and North American countries; 97.1 % (n = 534) were children diagnosed with cancer or blood disorders. The median evacuation time for the SAFER Ukraine cohort was shorter than the ERCC cohort (p < 0.001), though comparable (six versus seven days). CONCLUSION: The ERCC and SAFER Ukraine collaborative successfully developed medical evacuation pathways to meet the needs of Ukrainian patients impacted by war. System comparison provides opportunity to identify strategies for parallel system harmonization and a pragmatic example of how to anticipate support of these patients in future armed conflicts.

Investigating the Impact of Cold Agglutinins on Red Blood Cell Parameters in a Trauma Patient.

Cold agglutinins are autoantibodies that can cause primary hemolytic anemia and RBC agglutination syndrome. Secondary agglutination of RBCs may be found in hypothermia, as well as in cancers, infections, and traumatic injuries. This report presents the case of a 37-year-old man who suffered multiple injuries in a motorcycle accident. On admission, the patient's laboratory tests showed a high concentration of cold agglutinins associated with low RBC count, hemoglobin, and hematocrit, and elevated mean corpuscular hemoglobin and mean corpuscular volume. Intravenous immunoglobulin treatment was effective at reversing the abnormal blood parameters to normal. Unlike acute blood loss, which typically manifests with normal hemoglobin and hematocrit levels initially due to proportional loss of plasma and red cells, the presence of cold agglutinins can lead to abnormal agglutination and sequestration of RBCs, with low hemoglobin and hematocrit. The findings of this case report highlight the importance of recognizing cold agglutinins in trauma patients to avoid misdiagnosis and misinterpretation of laboratory results.

Monoclonal Gammopathy of Renal Significance With Preexisting Connective Tissue Disease: A Case Report.

Monoclonal gammopathy of renal significance (MGRS) has lately drawn the interest of physicians and pathologists due to the ability of these monoclonal proteins to cause end-organ damage. The early detection of this monoclonal protein along with hematological studies and renal biopsy are essential to establish the associated nephropathological diagnosis. We herein describe the case of a patient with MGRS and the diagnostic entity involved. She responded well to the treatment as co-managed by a multidisciplinary team of nephrologists, hematologists, and renal pathologists.

Extreme Reactive Thrombocytosis Caused by Obstructive Nephrolithiasis and Pyelonephritis.

Platelet counts in reactive thrombocytosis rarely exceed 1000 × 109/L. We present the case of a male patient, aged 80 years, with quiescent rheumatoid arthritis who was found to have a platelet count of 1011 × 109/L on routine laboratory testing. The patient was initially asymptomatic but developed leukocytosis to 23.1 × 109/L on hospital day 2. Diagnostic work-up revealed obstructive nephrolithiasis and pyelonephritis, and the thrombocytosis and leukocytosis gradually resolved with empiric antibiotic treatment and ureteral stent placement. Tests for myeloproliferative disorders, including JAK-2V617F mutation, BCR-ABL for chronic myeloid leukemia and acute lymphocytic leukemia, and myeloproliferative neoplasms (MPL/CALR), were negative. Physicians should be aware that in rare cases reactive thrombocytosis can exceed 1000 × 109/L, and that markedly elevated platelet counts in the setting of urinary tract infections may be an early sign of obstructive uropathy.

Somatic RAP1B gain-of-function variant underlies isolated thrombocytopenia and immunodeficiency.

The ubiquitously expressed small GTPase Ras-related protein 1B (RAP1B) acts as a molecular switch that regulates cell signaling, cytoskeletal remodeling, and cell trafficking and activates integrins in platelets and lymphocytes. The residue G12 in the P-loop is required for the RAP1B-GTPase conformational switch. Heterozygous germline RAP1B variants have been described in patients with syndromic thrombocytopenia. However, the causality and pathophysiological impact remained unexplored. We report a boy with neonatal thrombocytopenia, combined immunodeficiency, neutropenia, and monocytopenia caused by a heterozygous de novo single nucleotide substitution, c.35G>A (p.G12E) in RAP1B. We demonstrate that G12E and the previously described G12V and G60R were gain-of-function variants that increased RAP1B activation, talin recruitment, and integrin activation, thereby modifying late responses such as platelet activation, T cell proliferation, and migration. We show that in our patient, G12E was a somatic variant whose allele frequency decreased over time in the peripheral immune compartment, but remained stable in bone marrow cells, suggesting a differential effect in distinct cell populations. Allogeneic hematopoietic stem cell transplantation fully restored the patient's hemato-immunological phenotype. Our findings define monoallelic RAP1B gain-of-function variants as a cause for constitutive immunodeficiency and thrombocytopenia. The phenotypic spectrum ranged from isolated hematological manifestations in our patient with somatic mosaicism to complex syndromic features in patients with reported germline RAP1B variants.

Alterations in hematologic, coagulation, and inflammatory markers based on fever status in hospitalized COVID-19 patients: A retrospective study.

Background: Laboratory markers like lymphopenia, thrombocytopenia, elevated D-dimer, and C-reactive protein (CRP) predict worse outcomes in coronavirus disease 2019 (COVID-19). However, a comprehensive analysis of hematologic and coagulation parameter alterations based on fever status is lacking. Methods: This retrospective study analyzed 300 COVID-19 patients hospitalized from March to December 2020. Demographic, clinical, and laboratory data were extracted from electronic medical records. Patients were stratified into fever (n = 200) and no fever (n = 100) groups. Hematologic, coagulation, and inflammatory markers were compared between groups using appropriate statistical tests. Multivariate regression identified independent predictors of fever. Results: Fever was associated with leukocytosis, neutrophilia, lymphopenia, thrombocytopenia, elevated CRP, D-dimer, procalcitonin, interleukin-6, neutrophil to lymphocyte ratio (NLR), and ferritin compared to no fever (all P < 0.05). D-dimer (r = 0.42), CRP (r = 0.52), NLR (r = 0.48), and interleukin-6 (r = 0.46) demonstrated the strongest correlation with fever (P < 0.001). High D-dimer >1000 ng/mL (adjusted odds ratio 2.7), CRP >100 mg/L (3.1), lymphopenia <1.0 × 109/L (2.8), NLR >4 (2.9), and thrombocytopenia <150 × 109/L (2.7) were significant independent predictors of fever status (P < 0.005). These parameters had moderate sensitivity (40-60%) and high specificity (74-88%) for discriminating febrile patients with AUC of 0.85. Conclusions: Marked alterations in hematologic, coagulation, and inflammatory markers occur in COVID-19 based on fever. Routine laboratory parameters can facilitate diagnosis and risk stratification.

Dengue virus infection in hematopoietic stem cell transplant recipients: A case series and comparative literature review from dengue endemic region.

This case series describes the wide spectrum of clinical presentation, laboratory findings, and morbidity/mortality associated with dengue fever in hematopoietic stem cell transplant recipients, treated in a dengue endemic region. The risk of acquiring viral infections increases manifold after transplant due to the severely immunocompromised state amid conditioning toxicity and immunosuppressive therapy. The classical warning signs of dengue viremia are often masked in posttransplant patients, leading to a missed diagnosis of dengue and grave consequences observed in some of the patients. Accurate and timely diagnosis of dengue fever especially in dengue prevalent areas can prevent the unwarranted complications and reduce the morbidity and mortality associated with dengue in allogeneic/autologous transplant recipients.

Cancer Therapy and Exercise Intolerance: The Heart Is But a Part: JACC: CardioOncology State-of-the-Art Review.

The landscape of cancer therapeutics is continually evolving, with successes in improved survivorship and reduced disease progression for many patients with cancer. Improved cancer outcomes expose competing comorbidities, some of which may be exacerbated by cancer therapies. The leading cause of disability and death for many early-stage cancers is cardiovascular disease (CVD), which is often attributed to direct or indirect cardiac injury from cancer therapy. In this review, the authors propose that toxicities related to conventional and novel cancer therapeutics should be considered beyond the heart. The authors provide a framework using the oxygen pathway to understand the impact of cancer treatment on peak oxygen uptake, a marker of integrative cardiopulmonary function and CVD risk. Peripheral toxicities and the impact on oxygen transport are discussed. Consideration for the broad effects of cancer therapies will improve the prediction and identification of cancer survivors at risk for CVD, functional disability, and premature mortality and those who would benefit from therapeutic intervention, ultimately improving patient outcomes.

Construction of platelet count-optical method reflex test rules using Micro-RBC#, Macro-RBC%, "PLT clumps?" flag, and "PLT abnormal histogram" flag on the Mindray BC-6800plus hematology analyzer in clinical practice.

OBJECTIVES: Utilizing RBC or PLT-related parameters to establish rules for the PLT-O reflex test can assist laboratories in quickly identifying specimens with interfered PLT-I that require PLT-O retesting. METHODS: Prospective PLT-I and PLT-O testing was performed on 6857 EDTA-anticoagulated whole blood samples, split randomly into training and validation cohorts at a 2:3 ratio. Reflex and non-reflex groups were distinguished based on the differences between PLT-I and PLT-O results. By comparing RBC and PLT parameter differences and flags in the training set, we pinpointed factors linked to PLT-O reflex testing. Utilizing Lasso regression, then refining through univariate and multivariate logistic regression, candidate parameters were selected. A predictive nomogram was constructed from these parameters and subsequently validated using the validation set. ROC curves were also plotted. RESULTS: Significant differences were observed between the reflex and non-reflex groups for 19 parameters including RBC, MCV, MCH, MCHC, RDW-CV, RDW-SD, Micro-RBC#, Micro-RBC%, Macro-RBC#, Macro-RBC%, MPV, PCT, P-LCC, P-LCR, PLR,"PLT clumps?" flag, "PLT abnormal histogram" flag, "IDA Anemia?" flag, and "RBC abnormal histogram" flag. After further analysis, Micro-RBC#, Macro-RBC%,"PLT clumps?", and "PLT abnormal histogram" flag were identified as candidate parameters to develop a nomogram with an AUC of 0.636 (95 %CI: 0.622-0.650), sensitivity of 42.9 % (95 %CI: 37.8-48.1 %), and specificity of 90.5 % (95 %C1: 89.6-91.3 %). CONCLUSIONS: The established rules may help laboratories improve efficiency and increase accuracy in determining platelet counts as a supplement to ICSH41 guidelines.

A review of the perioperative management of direct oral anticoagulants for pediatric anesthesiologists.

BACKGROUND: Although direct oral anticoagulants (DOACs) have been used in the adult population for over a decade, DOACs use has begun to rise in pediatric populations since FDA approval of rivaroxaban and dabigatran, DOACs offer several advantages for pediatric patients, to other anticoagulants, including a similar safety profile, minimal lab monitoring, and ease of administration. The rise in DOAC use has led to an increasing number of pediatric patients managed on DOACs presenting for elective and urgent procedures. Perioperative management of anticoagulation is often challenging for providers due to the lack of expert consensus guidelines and the difficulty in balancing a patient's thrombotic risk with bleeding risk for a given procedure. AIMS: Using the most up to date literature, we provide a focused review on the perioperative management of DOACs in pediatric patients. CONCLUSIONS: This work presents a focused review for pediatric anesthesiologists on clinically available DOACs, perioperative monitoring and management of DOACs, as well as options and indications for reversal. While consensus expert practice guidelines are still needed, we hope this work will familiarize perioperative physicians with these agents, recommended uses, and potential perioperative management.

Clinical and hematological profile of patients with pancytopenia at a tertiary medical center in Ethiopia.

BACKGROUND: Pancytopenia is an important hematological problem encountered in routine clinical practice associated with a multitude of disease states. The possible causes of pancytopenia can be influenced by geography, socioeconomic conditions, and endemic illnesses. Information regarding the underlying clinical conditions and morphologic features of blood cells of pancytopenia is limited and varied across different regions. Thus, this study was designed to assess the peripheral morphologic features of blood cells and the underlying clinical causes of pancytopenia. METHODS: A facility-based cross-sectional study was conducted at the Jimma Medical Center hematology laboratory from June 13 to November 13, 2022. A total of 3 mL of whole blood was collected from each subject for complete blood count analysis and peripheral blood morphology examination. Data on sociodemographic and clinical conditions were collected from medical records using a checklist. The data were analyzed using Statistical Package for the Social Sciences version 26. RESULTS: A total of 163 patients with pancytopenia were identified within the 5 months. Hyper-reactive malarial splenomegaly was the most prevalent cause (29.4%), followed by megaloblastic anemia (20.2%), chronic liver disease (10.4%), and acute leukemia (8.6%). Anisocytosis was the predominant peripheral blood morphology finding (82.2%), along with microcytosis (49.7%), ovalocytosis (31.3%), and macrocytosis (30.7%). Severe anemia was observed in 57% of cases, whereas the majority (92%) exhibited moderate leukopenia. A significant proportion (42.3%) had a platelet count below 50,000/µL. CONCLUSION: Unlike previous studies conducted in other parts of the world, this study showed that hyperreactive malarial splenomegaly was the leading cause of pancytopenia. This emphasizes the necessity of considering this condition as a possible cause for pancytopenia, particularly in malaria-endemic areas. The findings of the hematological profiles and peripheral blood morphology strongly suggest that early identification and prompt management of patients with pancytopenia require collaboration between clinical and laboratory investigations.

The significance of CD49f expression in pediatric B-cell acute lymphoblastic leukemia.

OBJECTIVES: CD49f is an adhesion molecule present on malignant lymphoblasts in B-cell acute lymphoblastic leukemia; it is associated with a poor prognosis. CD49f expression has been proposed as a marker for measurable residual disease (MRD) marker, but this marker has yet to be implemented in clinical practice. METHODS: In this study, we used flow cytometry to detect CD49f expression by leukemic blasts in paired bone marrow and cerebrospinal fluid samples at diagnosis and bone marrow at day 15 of treatment. RESULTS: At diagnosis, 93% of bone marrow and 100% of cerebrospinal fluid lymphoblasts expressed CD49f. The intensity of CD49f expression statistically significantly increased during treatment (P < .001). In MRD-negative end-of-treatment samples, only a small population of hematogones expressed CD49f. Interestingly, the intensity of CD49f expression varied among the different groups of recurrent genetic abnormalities. The ETV6::RUNX1 fusion and ETV6::RUNX1 combined with the high hyperdiploid group were associated with increased expression, whereas the Philadelphia-like group showed low CD49f expression. The lower CD49f expression at diagnosis predicted a lower MRD rate at day 15 of treatment. CONCLUSIONS: We concluded that CD49f can be used as an MRD marker and possible prognostic factor in B-cell acute lymphoblastic leukemia.

Bilateral Acute Proptosis With Papilledema and Sub-retinal Fluid As Initial Manifestations of Acute Lymphoblastic Leukemia in a Child.

A five-year-old boy presented with bilateral acute proptosis, papilledema, and sub-retinal fluid. Notably, choroidal thickening exceeded 600 microns. These ocular findings were the initial manifestations of acute lymphoblastic leukemia. This case underscores the importance of recognizing uncommon ocular presentations in pediatric leukemia for timely diagnosis and management.

[To construct Chinese hematology community].

The development of hematology in China has gradually begun since the 1950s. After several generations of hard work, it has grown into a young but vibrant discipline. The development of Chinese hematology has experienced rapid rise and steady growth, but there is still a gap with the international level of hematology development. Only by constructing a Chinese community of hematology and forming a joint force to promote the development of hematology can we better realize the Chinese Dream in the field of hematology.

Pharmaceutical care in the screening process of phase I oncohaematological clinical trials.

OBJECTIVE: To determine the pharmaceutical interventions in patients eligible for phase I cancer clinical trials, focusing specifically on exclusion criteria related to medication or relevant interactions. METHOD: Descriptive, observational study conducted at a comprehensive cancer centre. Patients undergoing screening for phase I clinical trials (March 2019-December 2022) were included. The pharmacist reviewed concomitant medication and provided a recommendation. RESULTS: The concomitant medication of 512 patients eligible to participate in 84 phase I clinical trials was analysed. In 230 (44.9%) patients, the clinical trial treatment included oral medication. The median number of concomitant medications was 5 (IQR 3-8) per patient.A total of 280 pharmaceutical interventions were performed in 140 (27.3%) patients: 240 (85.7%) were due to interactions in 124 (24.2%) patients, and 40 (14.3%) were due to exclusion criteria in 34 (6.6%) patients. Interactions and exclusion criteria were detected in 18 (3.5%) patients. The main groups of drugs involved were 68 (24.3%) antacids and antiulcer drugs, 28 (10.0%) antidepressants and 26 (9.3%) opioids. Acceptance analysis of the recommendation was applicable in 215 cases; in 208 (96.7%), the pharmaceutical intervention was accepted.Differences were identified for exclusion criteria (7 vs 27) and interactions (37 vs 87) between parenteral and oral clinical trial medication (p<0.001). CONCLUSION: The pharmacist's review of concomitant medication during the screening period in phase I clinical trials enables the detection of prohibited medication or relevant interactions, potentially avoiding screening failures and increasing the efficacy and safety of treatments.

An automated method for thrombocyte counting in capillary microsamples.

INTRODUCTION: We aimed to develop an automated, low-volume method for thrombocyte counting in capillary blood using the Sysmex predilution (PD) mode. METHODS: Microsamples were prepared by resuspension of 50 µL blood in 300 µL DCL CellPack. Thrombocyte counting was done in the impedance (PLT-I) and fluorescence (PLT-F) channels. The imprecision and bias was evaluated in >394 microsamples from adult blood. Preanalytical factors (skin-piercing, storage, and transportation in our pneumatic tube system) was assessed, and studies on pediatric microsamples were made for comparison. The improvement in analytical quality and turnaround time was examined. RESULTS: For PLT-F, the imprecision was 1.1%-3.7%, and the bias was 10.1% (95% CI: 8.8-11.3). After skin-piercing, the bias was 8.1% (95% CI: 5.6-10.6) and the imprecision 1.9% (95% CI: 1.3-2.5). Thrombocyte counts kept stable after 4 h at room temperature (94.8% [95% CI: 93.2-96.4]) and after pneumatic tube transportation [6.7% (95% CI: 4.8-8.6)]. The bias of the PD mode for pediatric microsamples was 13.0% (95% CI: -8.4-34.4) in the PLT-F channel. The automated method had a considerably lower imprecision than the existing manual thrombocyte counting method and reduced turnaround times. CONCLUSION: The automated microsample method offers a low-volume alternative for measurement of thrombocytes. The method appears useful also in pediatric samples.