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OBJECTIVE: The aim of this study is to investigate the temporal relationship between the first occurrence of thromboembolic events (TEE) and the timing of myeloproliferative neoplasm (MPN) diagnosis and to determine risk factors for TEE-related mortality in MPN. PATIENTS AND METHODS: A total of 138 BCR-ABL-negative MPN patients with TEE, diagnosed from January 2010 to December 2019, were included in this retrospective cohort. Patients were compared according to mortality and subjects were classified into three groups with respect to having suffered index TEE before, during, or after MPN diagnosis. RESULTS: The mean age of surviving patients was 57.5±13.8, while those who had died had a mean age of 72.0±9.0 (p<0.001). Males represented 56.5% of patients with mortality and 60.9% of those without mortality (p=0.876). TEE was detected in 26.0% of MPN patients, and TEE-related mortality rate was 16.7%. There was no relationship between mortality and the classification of patients according to index TEE (p =0.884). High age (p<0.001) and danazol use (p=0.014) were independently associated with TEE-related mortality. CONCLUSIONS: The temporal relationship between TEE and MPN diagnosis was not found to influence mortality. Older patients and danazol recipients should be considered to have a higher risk of TEE-related mortality. [ABSTRACT FROM AUTHOR]

The detection of lymph node metastases is essential for breast cancer staging, although it is a tedious and time-consuming task where the sensitivity of pathologists is suboptimal. Artificial intelligence (AI) can help pathologists detect lymph node metastases, which could help alleviate workload issues. We studied how pathologists' performance varied when aided by AI. An AI algorithm was trained using more than 32 000 breast sentinel lymph node whole slide images (WSIs) matched with their corresponding pathology reports from more than 8000 patients. The algorithm highlighted areas suspicious of harboring metastasis. Three pathologists were asked to review a dataset comprising 167 breast sentinel lymph node WSIs, of which 69 harbored cancer metastases of different sizes, enriched for challenging cases. Ninety-eight slides were benign. The pathologists read the dataset twice, both digitally, with and without AI assistance, randomized for slide and reading orders to reduce bias, separated by a 3-week washout period. Their slide-level diagnosis was recorded, and they were timed during their reads. The average reading time per slide was 129 seconds during the unassisted phase versus 58 seconds during the AI-assisted phase, resulting in an overall efficiency gain of 55% ( P <0.001). These efficiency gains are applied to both benign and malignant WSIs. Two of the 3 reading pathologists experienced significant sensitivity improvements, from 74.5% to 93.5% ( P ≤0.006). This study highlights that AI can help pathologists shorten their reading times by more than half and also improve their metastasis detection rate., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: To investigate inflammation indices and erythropoietin levels for their potential role in distinguishing polycythemia vera from secondary polycythemia and to compare different parameter combinations in terms of the diagnostic accuracy., Methods: This retrospective cohort was created from patients assessed for polycythemia from January 2020 to December 2023. Polycythemia vera diagnosis was made according to the 2016 World Health Organization criteria ( n = 145). Those who did not fulfill the criteria were defined as having secondary polycythemia ( n = 84)., Results: The neutrophil lymphocyte ratio, platelet lymphocyte ratio and systemic immune-inflammation index were significantly higher in the polycythemia vera group ( p < 0.001 for all). Erythropoietin had the highest area under the curve in the analysis to distinguish groups, followed by the systemic immune-inflammation index. The platelet lymphocyte ratio (≥135) had the highest specificity to detect polycythemia vera, followed closely by the systemic immune-inflammation index. The sensitivity for polycythemia vera detection was highest with the erythropoietin and systemic immune-inflammation index combination, followed by erythropoietin and the neutrophil lymphocyte ratio. All the single and combinatory variables exhibited significant performance in predicting polycythemia vera after adjusting for age and sex. However, the erythropoietin and systemic immune-inflammation index combination had the highest odds ratio, followed by erythropoietin alone., Conclusion: These are promising findings supporting the usability of these biomarkers, especially the systemic immune-inflammation index, as minor criteria in the diagnosis of polycythemia vera. It is especially crucial to note that using erythropoietin in combination with these markers may improve diagnostic accuracy.

A multicenter, retrospective, observational study was conducted to explore effectiveness and safety of ixazomib plus lenalidomide with dexamethasone (IRd) in relapsed/refractory multiple myeloma (RRMM) patients following at least ≥ two lines of therapy. Patients' treatment responses, overall response rate, progression-free survival rate, and adverse events were recorded. Mean age of 54 patients was 66.5 ± 9.1 years. There were 20 patients (37.0%) with progression. Median progression-free survival was 13 months in patients who received a median of three therapy lines in a 7.5-month follow-up period. Overall response rate was 38.5%. Of 54 patients, 19 (40.4%) had at least one adverse event, and nine (19.1%) had an adverse event of at least grade 3 or more. Of 72 adverse events observed in 47 patients, 68% were grade 1 or 2. Treatment was not stopped in any patient due to adverse events. IRd combination therapy was effective and safe in heavily treated RRMM patients.

Context.—: Prostate cancer diagnosis rests on accurate assessment of tissue by a pathologist. The application of artificial intelligence (AI) to digitized whole slide images (WSIs) can aid pathologists in cancer diagnosis, but robust, diverse evidence in a simulated clinical setting is lacking., Objective.—: To compare the diagnostic accuracy of pathologists reading WSIs of prostatic biopsy specimens with and without AI assistance., Design.—: Eighteen pathologists, 2 of whom were genitourinary subspecialists, evaluated 610 prostate needle core biopsy WSIs prepared at 218 institutions, with the option for deferral. Two evaluations were performed sequentially for each WSI: initially without assistance, and immediately thereafter aided by Paige Prostate (PaPr), a deep learning-based system that provides a WSI-level binary classification of suspicious for cancer or benign and pinpoints the location that has the greatest probability of harboring cancer on suspicious WSIs. Pathologists' changes in sensitivity and specificity between the assisted and unassisted modalities were assessed, together with the impact of PaPr output on the assisted reads., Results.—: Using PaPr, pathologists improved their sensitivity and specificity across all histologic grades and tumor sizes. Accuracy gains on both benign and cancerous WSIs could be attributed to PaPr, which correctly classified 100% of the WSIs showing corrected diagnoses in the PaPr-assisted phase., Conclusions.—: This study demonstrates the effectiveness and safety of an AI tool for pathologists in simulated diagnostic practice, bridging the gap between computational pathology research and its clinical application, and resulted in the first US Food and Drug Administration authorization of an AI system in pathology., (© 2023 College of American Pathologists.)

Polycythemia vera (PV) diagnosis remains a difficult task despite various updates in the 2016 World Health Organization (WHO) diagnostic criteria compared to 2008 criteria. This study aimed to examine the biochemical and clinical features of patients diagnosed with PV using the WHO 2016 criteria but would have been missed by the WHO 2008 criteria, and to ascertain the impact of the lowered thresholds on PV diagnosis. A total of 229 patients with suspected myeloproliferative neoplasms were included in this cross sectional study. The study group was divided with regard to hemoglobin values. Group A consisted of 126 patients with hemoglobin values of ≤ 18.5 g/dL in males and ≤ 16.5 g/dL in females. Group B comprised 103 patients with hemoglobin values of > 18.5 g/dL in males and > 16.5 g/dL in females. The number of PV diagnoses increased to 145 from 87 (increased by 66.67%) when the 2016 diagnostic criteria were employed rather that the 2008 criteria. Mean age and the frequency of female subjects were lower in Group A compared to Group B. The groups were similar in terms of chronic obstructive pulmonary disease/obstructive sleep apnea syndrome, spleen status, smoking status, and mean corpuscular volume, white blood count, neutrophil, eosinophil and platelet values. red blood cells and lactate dehydrogenase values were significantly higher, while lymphocyte counts were significantly lower in Group B. With the introduction of WHO 2016 criteria, we found a significant increase in the number of patients who were candidates for PV testing and were ultimately diagnosed with PV. These findings support the diagnostic value of the 2016 WHO criteria, and by extension, the lowered thresholds for detection of patients requiring further analysis., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Patients with hematological malignancies have a high risk of mortality from coronavirus disease 2019 (COVID-19). This study aimed to investigate the impact of COVID-19 on mortality rates in patients with various hematological malignancies and to determine risk factors associated with all-cause mortality., Methods: A multicenter, observational retrospective analysis of patients with hematological malignancies infected with COVID-19 between July 2020 and December 2021 was performed. Demographic data, clinical characteristics, and laboratory parameters were recorded. Patients were grouped as non-survivors and survivors. All-cause mortality was the primary outcome of the study., Results: There were 569 patients with a median age of 59 years. Non-Hodgkin lymphoma (22.0%) and multiple myelomas (18.1%) were the two most frequent hematological malignancies. The all-cause mortality rate was 29.3%. The highest mortality rates were seen in patients with acute myeloid leukemia (44.3%), acute lymphoid leukemia (40.5%), and non-Hodgkin lymphoma (36.8%). The non-survivors were significantly older (p<0.001) and had more comorbidities (p<0.05). In addition, there were significantly more patients with low lymphocyte percentage (p<0.001), thrombocytopenia (p<0.001), and high CRP (p<0.001) in the non-survived patients. Age ≥ 65years (p=0.017), cardiac comorbidities (p=0.041), and continuation of ongoing active therapy for hematological cancer (p<0.001) were the independent risk factors for the prediction of mortality., Conclusions: In patients with hematological malignancies, coexistent COVID-19 leads to a higher mortality rate in elderly patients with more comorbidities. Acute myeloid and lymphoid leukemia and non-Hodgkin lymphoma have the highest mortality rates. Older age, cardiac diseases, and continuation of ongoing active therapy for hematological cancer are the independent risk factors for mortality in hematological malignancy patients with COVID-19., Competing Interests: Competing interests: The authors declare no conflict of Interest.

Therapeutic plasma exchange (TPE) is used to treat more than 60 diseases worldwide and has drawn growing interest. Little is known about the current situation of TPE activity in Turkey, so we developed a survey to obtain information about this timely topic. We collected data on TPE from 28 apheresis units throughout Turkey. We performed a total of 24,912 TPE procedures with 3203 patients over the past decade. Twenty years ago, the majority of procedures were performed for neurological and hematological disorders, and today, most TPE procedures are done for the same reasons. The only historical change has been an increase in TPE procedures in renal conditions. Currently, renal conditions were more frequently an indication for TPE than rheumatic conditions. Fresh frozen plasma was the most frequently used replacement fluid, followed by 5% albumin, used in 57.9% and 34.6% of procedures, respectively. The most frequently used anticoagulants in TPE were ACD-A and heparin/ACD-A, used with 1671 (52.2%) and 1164 (36.4%) patients, respectively. The frequency of adverse events (AEs) was 12.6%. The most common AEs were hypocalcemia-related symptoms, hypotension, and urticaria. We encountered no severe AEs that led to severe morbidity and mortality. Overall, more than two thirds of the patients showed improvement in the underlying disease. Here, we report on a nationwide survey on TPE activity in Turkey. We conclude that there has been a great increase in apheresis science, and the number of TPE procedures conducted in Turkey has increased steadily over time. Finally, we would like to point out that our past experiences and published international guidelines were the most important tools in gaining expertise regarding TPE., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aims: Before the era of tyrosine kinase inhibitors (TKIs), the presence of bone marrow fibrosis (MF) in patients with chronic myeloid leukaemia (CML) has been established as a poor prognostic factor. The aim of the present study was to evaluate the effects of imatinib treatment on MF and the prognostic significance of MF at this new era of CML therapy., Methods: The study cohort consisted of 135 patients with CML who were exposed to imatinib. The grades of MF pre and post imatinib together with cytogenetic and molecular responses were evaluated., Results: Severe MF (grade II-III) was observed in 44 (33%) patients prior to imatinib therapy, and in 8 (8%) after 12 months of imatinib treatment (p=0.001). The complete cytogenetic response (CCyR) rates at 12 months did not differ according to the pre-imatinib MF grades, and CCyR rates in patients with grades 0, I, II and III MF were 36/47 (76.5%), 26/33 (78.7%), 12/23 (52.1%) and 7/10 (70%), respectively (p=0.127). There was no significant difference between patients with or without CCyR at 12 months of imatinib regarding grades of MF (p=0.785). The distribution of the major molecular response rates at 18 months according to pre-treatment grades of MF were determined as grade 0 in 38/45 (84.4%), grade I in 21/28 (75%), grade II in 14/21 (66.6%) and grade III in 7/10 (70%) (p=0.112). There was no significant difference in overall survival rates between initial MF mild (grade 0-I) and severe (grade II-III) groups (p=0.278)., Conclusions: According to our findings, MF regresses with imatinib therapy over time, and the MF grades at diagnosis do not have a negative impact on the responses to imatinib treatment. Therefore, the adverse prognostic impact of the MF among patients with CML seems to disappear in the era of the TKIs., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Thrombotic thrombocytopenic purpura (TTP) or Moschcowitz's syndrome is characterized by platelet and von Willebrand factor (vWF) deposition in arterioles and capillaries throughout the body, which results in organ ischemia. The diagnostic pentad characterizing TTP consists of thrombocytopenia, microangiopathic hemolytic anemia (MAHA), fever, neurologic manifestations, and renal insufficiency. In terms of type, TTP can be either idiopathic or secondary. The causes of secondary TTP include pregnancy, infections, pancreatitis, collagen vascular disease, cancer, bone marrow transplantation, and drugs (including cephalosporins). Postoperative TTP has been reported after vascular surgery, renal and liver transplantations, and orthopedic, urologic, and abdominal surgical procedures. Therapeutic plasma exchange (TPE) therapy has reduced the mortality rates, but sometimes patients may have to receive immunosuppressive drugs including vincristine (VCR). This report describes a 42-year-old woman with TTP after prophylactic usage of cefuroxime axetil in relation to a liposuction procedure who was treated successfully with plasma exchange and VCR. The patient fully recovered after 17 TPEs and three doses of VCR. At this writing, her TTP still is in remission after 6 months of follow-up evaluation. To the authors' knowledge, this is the first report in the literature describing a patient with TTP after cefuroxime axetil administered in relation to a surgical procedure who was treated successfully with TPE and VCR.