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AbstractTumor lysis syndrome (TLS) in childhood leukemia was assessed retrospectively in 252 patients in a single tertiary center in Thailand during 2009–2019. Fifty-one (20.2%) developed TLS during their induction chemotherapy; 60.7% (31/51) were spontaneous TLS and 47% (24/51) developed clinical TLS. The predictive score model consisted of white blood cell (WBC) count more than 50,000 cells/mm3, glomerular filtration rate less than 90, and aspartate transaminase more than 44 units/L. The TLS development rates were 11.1%, 46.2%, and 78.5% in the low, intermediate, and high-risk groups, respectively. Death during the first induction phase in patients with TLS was significantly higher than in the patients without TLS. However, the 5-year overall survival rates for the children with and without TLS were not significantly different. [ABSTRACT FROM AUTHOR]

This article provides a summary of current data on the use of diuretic therapy in critically ill patients. Diuretics are commonly prescribed to remove excess fluid and can be used alone or in combination with other drugs. Common indications for diuretic use in critically ill patients include conditions where fluid accumulation negatively impacts organ function, situations where continued fluid administration is necessary despite the risk of fluid accumulation, and adjunctive management of hypertension. The goal of diuretic therapy is to increase urine output and decrease fluid pressure in the body. Monitoring diuretic therapy involves assessing the balance between effectiveness and safety, with indicators of effectiveness including improved respiratory status, decreased levels of natriuretic peptides, improved organ function, and resolution of congestion on imaging. Diuretic efficacy may decrease in the setting of hypovolemia, refractory venous congestion, inadequate concentrations at sites of action, and insufficient renal function. Adverse effects of diuretics can include electrolyte imbalances and metabolic disturbances. Continuous infusion of diuretics may be more effective than intermittent dosing, and combining diuretics with albumin may improve effectiveness. The furosemide stress test is a diagnostic tool to evaluate tubular function and can be used to assess diuretic response in patients with acute kidney injury. Diuretic resistance may occur due to various factors, and management involves addressing contributing factors and considering combination therapy or extracorporeal methods if necessary. [Extracted from the article]

Natural killer (NK) cell-based therapies have made great progress in treating both hematological and solid tumors. Their unique mechanism of action does not rely on antigen presentation to recognize and eliminate tumor cells, making them a promising approach for cancer immunotherapy. In this review, we present a comprehensive summary of the latest clinical data of the novel NK cell-based therapies from the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, highlighting the potential of these advancements to revolutionize the treatment of hematologic malignancies and solid tumors. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T-cell therapy has achieved substantial clinical outcomes for tumors, especially for hematological malignancies. However, extending the duration of remission, reduction of relapse for hematological malignancies and improvement of the anti-tumor efficacy for solid tumors are challenges for CAR-T cells immunotherapy. Besides the endeavors to enhance the functionality of CAR-T cell per se, optimization of the infusion and delivery strategies facilitates the breakthrough of the hurdles that limited the efficacy of this cancer immunotherapy. Here, we summarized the infusion and delivery strategies of CAR-T cell therapies under pre-clinical study, clinical trials and on-market status, through which the improvements of safety and efficacy for hematological and solid tumors were analyzed. Of note, novel infusion and delivery strategies, including local-regional infusion, biomaterials bearing the CAR-T cells and multiple infusion technique, overcome many limitations of CAR-T cell therapy. This review provides hints to determine infusion and delivery strategies of CAR-T cell cancer immunotherapy to maximize clinical benefits. [ABSTRACT FROM AUTHOR]

Summary Twenty years after the conceptual revolution that occurred in the millennium turnaround upon the introduction of PET/CT in lymphoma staging, restaging, and prognostication, a number of new parameters for PET reading have been proposed: (1) the shift from a qualitative to a semi‐quantitative reading for PET reporting, (2) an international consensus on these novel interpretation keys, (3) a standardized and agreed procedure to measure the total metabolic tumour volume (TMTV), and (4) the proposition of new indexes to portray the tumour spread: (D‐Max and Total Lesion Surface –TLS). These proved to be very powerful prognosticators, able to revolutionize the traditional Ann Arbor four‐stage lymphoma staging. During the 17° Lugano meeting on lymphoma, one main question was asked to experts attending a closed workshop dedicated to new metrics for lymphoma diagnosis, staging, restaging, and prognostication: “Should the traditional 4‐stage anatomic staging system be simplified to a more clinically relevant 2‐stage system (e.g., limited vs. extensive disease)?” Early‐stage HL is an example of how these new metrics could fit with this proposal. [ABSTRACT FROM AUTHOR]

Introduction: Single, fixed-dose rasburicase administration has been evaluated as an effective strategy in the management of hyperuricemia in the hospital setting, but this has not yet been described within ambulatory community oncology practices. The objective of this study is to evaluate and optimize the dosing strategy for rasburicase in the management of tumor lysis syndrome (TLS)-associated hyperuricemia in The US Oncology Network (The Network). Methods: A network-wide guideline was revised to standardize rasburicase dosing from a previous recommended fixed doses of 4.5 or 7.5 mg to either 3 or 6 mg for outpatient rasburicase use in management and prevention of TLS. The primary outcome evaluated mean dose of rasburicase among all patients before and after guideline revision. A retrospective chart review evaluated secondary endpoints. Results: The primary analysis included 291 patients (128 pre-revised and 163 post-revised guideline implementation). The primary outcome, mean rasburicase dose, was reduced in the post-revision compared to the pre-revision population (mean 6.2 mg pre vs. 4.5 mg post, p < 0.00001) resulting in a reduced cost per rasburicase dose of $974. Fifty patients were included for the secondary analysis. Guideline concordance was identified in 12 (48%) and 16 patients (64%), and uric acid <8 mg/dL post-rasburicase administration occurred in 14 (56%) and 16 patients (64%) before and after guideline revision, respectively. Conclusions: Guideline revision and electronic health record modification resulted in a 27% reduction in the mean rasburicase dose and a 50% reduction in repeat rasburicase dosing without a negative impact on clinical efficacy. [ABSTRACT FROM AUTHOR]

Summary: Methotrexate (MTX), although an indispensable part of contemporary treatment protocols for childhood acute lymphoblastic leukaemia (ALL)/lymphomas (LBL) in improving outcomes, can lead to serious neurotoxicity with long‐term consequences. The aetiopathogenesis, predisposing factors and treatment for MTX‐induced neurotoxicity are not yet well defined. The aim of our study was to detect the incidence, risk factors and to assess the overall outcomes of MTX‐induced neurotoxicity among large cohort of paediatric ALL/LBL patients treated on a uniform protocol. We conducted retrospective audit of medical records of 622 consecutive children (≤14 years) diagnosed with ALL and LBL between January 2018 and December 2022 and treated on modified BFM‐95 protocol at the Department of Pediatric Oncology, Regional Cancer Centre, Thiruvananthapuram. Risk factors predisposing to MTX‐induced neurotoxicity were identified using binary logistic regression analysis. Forty‐three children were diagnosed with MTX‐induced neurotoxicity with an incidence rate of 6.9%. More than two‐thirds of them had high‐grade MTX‐induced neurotoxicity CTCAE v5.0 with a median age of 9 years (range: 9 months to 14 years). Almost half of them developed MTX neurotoxicity during Protocol M followed by Phase‐Ib consolidation (15%). Majority of these patients (84%, 36/43) were challenged again with MTX, with 11% (4/36) developing recurrence. Fifteen per cent had persistent neurological deficits at last follow‐up. Univariate analysis found older age (age > 5 years) (p < 0.001), T‐cell phenotype (p = 0.040), tumour lysis syndrome during induction (p < 0.001), baseline renal problems prior to MTX exposure (p < 0.001) and CNS leukaemic involvement (p < 0.003) to be significantly associated with MTX neurotoxicity. On multivariate analysis, older age (>5 years), tumour lysis during induction and CNS leukaemia retained statistical significance (p < 0.05). Methotrexate‐induced neurotoxicity during paediatric acute lymphoblastic leukaemia/lymphoma therapy is a transient phenomenon in majority and re‐challenge with MTX is generally safe. Older age children who develop tumour lysis during induction and CNS leukaemic involvement are at increased risk for MTX‐induced neurotoxicity during ALL/LBL treatment. [ABSTRACT FROM AUTHOR]

Introduction: Kidney diseases frequently complicate cancer and its treatment, contributing to both morbidity and mortality. Malignancies can give rise to various kidney issues, such as glomerulonephritis and Chronic Kidney Disease (CKD). This association operates bidirectionally, with patients experiencing the development of renal diseases due to cancer, and CKD predisposing to cancer. Furthermore, nephrotoxicity induced by chemotherapy can result in Acute Tubular Injury (ATI) and necrosis, imposing limitations on its application. Aim: To evaluate the spectrum of renal pathology in autopsies of malignancies. Materials and Methods: This was a retrospective crosssectional study of complete autopsies of all cases of malignancies performed in the Department of Pathology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India. The study was carried out over a 5-year period from January 2015 to December 2019. Analysis of cases with respect to demographics, type of primary malignancy, gross and microscopic features, and the final cause of death was conducted. These findings were meticulously tabulated, with frequencies and percentages calculated for each category. Results: A total of 4392 autopsies were conducted throughout the study period, with 120 of them revealing the presence of malignancies. A total of 38 (31.6%) malignancies were diagnosed for the first time at autopsy. The commonest renal findings on gross were scars (superficial and deep) seen in 40 (33.33%), followed by cortical cysts in 25 (20.83%), granular contracted kidney in 15 (12.50%), mass lesions in 7 (5.83%), abscesses in 7 (5.83%), and swollen, oedematous kidneys in 6 (5%) autopsies. The most frequent renal pathology on microscopy were infective lesions seen in 43 (35.83%), Acute Tubular Necrosis (ATN) in 32 (26.66%), ATI in 30 (25%), followed by malignancies- primary and secondary in 11 (9.16%), tubular casts in 6 (5%), etc. Rare findings included membranous glomerulonephritis and Tumour Lysis Syndrome (TLS) (Acute urate nephropathy) in 1 (0.83%) each. The TLS case had classic histomorphological features of TLS, apart from laboratory parameters. Extensive deposits of uric acid crystals were seen obstructing the tubules as well as some of the glomeruli on microscopy. Conclusion: In one-third of the cases, the malignancy was exclusively discovered during the autopsy. The study revealed a diverse array of lesions, encompassing pyelonephritis, ATN, primary and metastatic renal tumours, cast nephropathy, membranous glomerulonephritis, and TLS. One-fifth of the cases had end-stage renal disease (advanced renal disease). A significant number of the cases exhibited tumour masses within the kidneys. One-fifth of the cases had renal pathology contributing to the final cause of death, further highlighting the association between malignancies and renal pathology. [ABSTRACT FROM AUTHOR]

Recently, bispecific antibodies (BsAbs) are evolving the landscape of cancer treatment and have significantly improved the outcomes of relapsed or refractory cancer patients. As increasing BsAbs entered clinical practice, specific toxicities have emerged, and renal side-effects have been described. However, there are a lack of studies analyzing the nephrotoxicity in the anti-cancer BsAbs recipients systematically. In this review, we demonstrate the etiologies, mechanisms, other risk factors and treatment options of kidney injury in the BsAbs recipients to provide a more comprehensive insight into the nephrotoxicity post-BsAbs therapy. Significantly, due to the limited clinical trial data on each subject, we mainly conclude the related etiologies, mechanisms, and risk factors of nephrotoxicity that occur in T-cell-engaging BsAbs recipients. Nephrotoxicity associated with non-T-cell BsAbs may be associated with adverse nephrotoxicity of related monoclonal antibodies to two specific antigens. The aim of this paper is to provide nephrologists and oncologists with theoretical knowledge to provide better medical management for recipients who receive BsAbs, especially T-cell-engaging BsAbs treatment. [ABSTRACT FROM AUTHOR]

Introduction: Tumor lysis syndrome (TLS) occurs frequently during induction therapy for acute lymphoblastic leukemia (ALL). Patients are categorized into intermediate- or high-risk based on the lactate dehydrogenase (LDH) value and white blood cell (WBC) count, according to an expert panel, although no effort has been made to analyze TLS in ALL and its potential consequences. Methods: We retrospectively analyzed TLS, variables associated with its occurrence, and its impact on overall survival (OS) and mortality during induction in a cohort of ALL patients in their first induction regimen. Results: A total of 138 patients were included, 52.9% were male and the median age at diagnosis was 34 years. Most of them were treated with hyper-CVAD (39.1%) or a modified CALGB 10403 regimen (37.7%). TLS was identified in 42 patients (30.4%), and half of them fulfilled criteria for clinical TLS (C-TLS). Median OS was the lowest in C-TLS patients. An LDH 3 times greater than its upper laboratory normal (ULN) value and a WBC count equal to or greater than 50×109/L were associated with TLS development, and being male, hyperuricemia and an LDH 3 times greater than its ULN value were associated with C-TLS development. C-TLS and acute kidney injury were associated with excess mortality during induction. Conclusion: TLS was identified in almost one-third of ALL patients during induction therapy. Different thresholds for LDH value and WBC count as well as other variables could identify patients at risk of developing this complication, which is associated with shorter OS. C-TLS confers a higher risk for mortality during induction. [ABSTRACT FROM AUTHOR]

Innovations in oncology have expanded treatment eligibility, leading to a rise in cancer patients requiring critical care. This necessitates that all critical care clinicians possess a fundamental knowledge of prevalent oncological conditions and identify emergent scenarios requiring immediate action. This article will explore key oncological complications and their management approaches. [ABSTRACT FROM AUTHOR]

Serum magnesium levels exceeding 0.9 mmol/L are associated with increased survival rates in patients with CKD. This retrospective study aimed to identify risk factors for cardio-cerebrovascular events among patients receiving continuous ambulatory peritoneal dialysis (CAPD) and to examine their correlations with serum magnesium levels. Sociodemographic data, clinical physiological and biochemical indexes, and cardio-cerebrovascular event data were collected from 189 patients undergoing CAPD. Risk factors associated with cardio-cerebrovascular events were identified by univariate binary logistic regression analysis. Correlations between the risk factors and serum magnesium levels were determined by correlation analysis. Univariate regression analysis identified age, C-reactive protein (CRP), red cell volume distribution width standard deviation, red cell volume distribution width corpuscular volume, serum albumin, serum potassium, serum sodium, serum chlorine, serum magnesium, and serum uric acid as risk factors for cardio-cerebrovascular events. Among them, serum magnesium ≤0.8 mmol/L had the highest odds ratio (3.996). Multivariate regression analysis revealed that serum magnesium was an independent risk factor, while serum UA (<440 μmol/L) was an independent protective factor for cardio-cerebrovascular events. The incidence of cardio-cerebrovascular events differed significantly among patients with different grades of serum magnesium (χ2 = 12.023, p = 0.002), with the highest incidence observed in patients with a serum magnesium concentration <0.8 mmol/L. High serum magnesium levels were correlated with high levels of serum albumin (r = 0.399, p < 0.001), serum potassium (r = 0.423, p < 0.001), and serum uric acid (r = 0.411, p < 0.001), and low levels of CRP (r = −0.279, p < 0.001). In conclusion, low serum magnesium may predict cardio-cerebrovascular events in patients receiving CAPD. [ABSTRACT FROM AUTHOR]

Yoona Choi,1,2,&ast; Bo Kyung Kim,3,4,&ast; Jung-Hyun Won,2,5 Jae Won Yoo,6 Wona Choi,7 Surin Jung,7 Jae Yoon Kim,7,8 In Young Choi,7 Nack-Gyun Chung,6 Jae Wook Lee,6 Jung Yoon Choi,3,4 Hyoung Jin Kang,3,4,9 Howard Lee1,2,5,10,11 1Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea; 2Center for Convergence Approaches in Drug Development, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea; 3Department of Pediatrics, Seoul National University Hospital, Seoul, Republic of Korea; 4Seoul National University Cancer Research Institute, Seoul, Republic of Korea; 5Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea; 6Department of Pediatrics, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul, Republic of Korea; 7Department of Medical Informatics, College of Medicine, the Catholic University of Korea, Seoul, Republic of Korea; 8Department of Biomedicine & Health Sciences, the Catholic University of Korea, Seoul, Republic of Korea; 9Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea; 10Advanced Institutes of Convergence Technology, Suwon, Republic of Korea; 11Department of Clinical Pharmacology and Therapeutics, Seoul National University Hospital, Seoul, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Howard Lee, Department of Clinical Pharmacology and Therapeutics, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea, Email howardlee@snu.ac.kr Hyoung Jin Kang, Department of Pediatrics, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea, Email kanghj@snu.ac.krBackground: Rapid reduction of leukemic cells in the bone marrow during remission induction chemotherapy (RIC) can lead to significant complications such as tumor lysis syndrome (TLS). We investigated whether prephase steroid treatment before RIC could decrease TLS incidence and improve overall survival in pediatric patients with acute lymphoblastic leukemia (ALL).Methods: Data were extracted from the Common Data Model databases in two tertiary-care hospitals in Seoul, South Korea. Patients were classified into the treated or untreated group if they had received RIC with prephase steroid treatment ≥ 7 days before RIC in 2012– 2021 or not, respectively. Stabilized Inverse Probability of Treatment Weighting (sIPTW) was applied to ensure compatibility between the treated and untreated groups. The incidence of TLS within 14 days of starting RIC, overall survival (OS), and the incidence of adverse events of special interest were the primary endpoints. Multiple sensitivity analyses were performed.Results: Baseline characteristics were effectively balanced between the treated (n=308.4) and untreated (n=246.6) groups after sIPTW. Prephase steroid treatment was associated with a significant 88% reduction in the risk of TLS (OR 0.12, 95% CI: 0.03– 0.41). OS was numerically greater in the treated group than in the untreated group although the difference was not statistically significant (HR 0.64, 95% CI 0.25– 1.64). The treated group experienced significantly elevated risks for hyperbilirubinemia and hyperglycemia. The reduction in TLS risk by prephase steroid treatment was maintained in all of the sensitivity analyses.Conclusion: Prephase steroid treatment for ≥ 7 days before RIC in pediatric patients with ALL reduces the risk of TLS, while careful monitoring for toxicities is necessary. If adequately analyzed, real-world data can provide crucial effectiveness and safety information for proper management of pediatric patients with ALL, for whom prospective randomized studies may be difficult to perform for ethical and practical reasons.Keywords: pediatric acute lymphoblastic leukemia, tumor lysis syndrome, remission induction chemotherapy, prephase steroid treatment, common data model

Tumor immune microenvironment (TIME) consists of intra-tumor immunological components and plays a significant role in tumor initiation, progression, metastasis, and response to therapy. Chimeric antigen receptor (CAR)-T cell immunotherapy has revolutionized the cancer treatment paradigm. Although CAR-T cell immunotherapy has emerged as a successful treatment for hematologic malignancies, it remains a conundrum for solid tumors. The heterogeneity of TIME is responsible for poor outcomes in CAR-T cell immunotherapy against solid tumors. The advancement of highly sophisticated technology enhances our exploration in TIME from a multi-omics perspective. In the era of machine learning, multi-omics studies could reveal the characteristics of TIME and its immune resistance mechanism. Therefore, the clinical efficacy of CAR-T cell immunotherapy in solid tumors could be further improved with strategies that target unfavorable conditions in TIME. Herein, this review seeks to investigate the factors influencing TIME formation and propose strategies for improving the effectiveness of CAR-T cell immunotherapy through a multi-omics perspective, with the ultimate goal of developing personalized therapeutic approaches. [ABSTRACT FROM AUTHOR]

Recent years have seen a marked increase in research on chimeric antigen receptor T (CAR-T) cells, with specific relevance to the treatment of hematological malignancies. Here, the structural principles, iterative processes, and target selection of CAR-T cells for therapeutic applications are described in detail, as well as the challenges faced in the treatment of solid tumors and hematological malignancies. These challenges include insufficient infiltration of cells, off-target effects, cytokine release syndrome, and tumor lysis syndrome. In addition, directions in the iterative development of CAR-T cell therapy are discussed, including modifications of CAR-T cell structures, improvements in specificity using multi-targets and novel targets, the use of Boolean logic gates to minimize off-target effects and control toxicity, and the adoption of additional protection mechanisms to improve the durability of CAR-T cell treatment. This review provides ideas and strategies for the development of CAR-T cell therapy through an in-depth exploration of the underlying mechanisms of action of CART cells and their potential for innovative modification. [ABSTRACT FROM AUTHOR]

Background/Objectives: Acute pancreatitis (AP) is characterized by pancreatic gland inflammation, and its clinical course ranges from mild to severe. Predicting the severity of AP early and reliably is important. In this study, we investigate the potential use of the Controlling Nutritional Status (CONUT) score as a prognostic marker in acute pancreatitis. Methods: We examined 336 patients who had been hospitalized with an AP diagnosis in the internal medicine clinic. The patients included in the study were followed up for 5 years. The study analyzed the specific variables of age, gender, and AP etiology as recorded biochemical parameters for all study participants and calculated the effects of age, sex, Bedside Index of Severity in AP (BISAP), the revised Atlanta classification, and the CONUT score on mortality. Results: When compared with surviving patients, non-surviving patients had higher scores for BISAP, CONUT, and the Atlanta Classification (p ˂ 0.001). In the non-surviving group, hemoglobin, lymphocyte, and albumin levels were significantly lower and creatinine, uric acid, and procalcitonin levels were significantly higher compared to the surviving group (p ˂ 0.001, 0.003, ˂0.001, ˂0.001, 0.005, ˂0.001, respectively). The multivariate analysis showed a significant association of mortality with age, CONUT, and BISAP scores (p ˂ 0.003, 0.001, 0.012 respectively). The CONUT score was separated into two groups based on the median value. The predicted survival time in the group with a CONUT score > 2 (53.8 months) was significantly lower than in the group with a CONUT score ≤ 2 (63.8 months). The cumulative incidence of all-cause mortality was significantly higher in the patients with higher CONUT scores. Conclusions: This study has assigned the CONUT score as an independent risk factor for mortality in AP. [ABSTRACT FROM AUTHOR]

BACKGROUND: Tumor lysis syndrome (TLS) is an oncological emergency associated with hematological malignancies or highly proliferative solid tumors, commonly after chemotherapy. It is rarely associated with transient abnormal myelopoiesis. OBSERVATION: We report a rare case of a neonate with transient abnormal myelopoiesis and tumor lysis syndrome, complicated with concomitant heart failure due to an underlying atrioventricular septal defect. Hyperhydration was contraindicated due to heart failure. The patient was managed conservatively with full recovery. CONCLUSION: Tumor lysis syndrome should be suspected in neonates with transient abnormal myelopoiesis with electrolyte abnormalities. Treatment options should be considered carefully for their risks and benefits. [ABSTRACT FROM AUTHOR]

Simple Summary: The recent growing interest in intermittent fasting (IF) is attributed to its preclinical benefits in various aspects of cancer management. Novel agents, namely, venetoclax and Bruton tyrosine kinase inhibitors (BTKIs), are widely used in the frontline setting of chronic lymphocytic leukemia (CLL). However, tumor lysis syndrome (TLS) and gastrointestinal bleeding (GIB) are particularly concerning for patients. This narrative review aimed to pioneer the exploration of the potential implications of IF for CLL patients receiving novel agents, focusing on GIB and TLS risks. In fluid-restricted IF, there is a higher risk of TLS with venetoclax due to dehydration, while in fluid-liberal IF, its absorption can be reduced. Moreover, during fasting conditions, the levels of gastric acid increase along with the risk of GIB in patients receiving BTKis. In the context of IF in CLL, further research is warranted to establish the safety of IF in CLL patients on novel agents. Intermittent fasting (IF) has recently gained popularity due to its emerging benefits in reducing weight and improving metabolic health. Concurrently, novel agents (NAs) like venetoclax and Bruton tyrosine kinase inhibitors (BTKIs) have revolutionized the treatment of chronic lymphocytic leukemia (CLL). Unfortunately, it is unclear whether the associated risks of tumor lysis syndrome (TLS) and gastrointestinal bleeding (GIB) are increased in IF practitioners receiving NAs. This review explored the literature available on the permissibility of IF in CLL patients undergoing treatment with first-line NAs (FLNAs). Literature was scoped to identify IF patterns and the available data on TLS and GIB risks associated with food and fluid intake in CLL patients receiving FLNAs. Although current evidence is insufficient to recommend IF in this population, it may be possible for patients on venetoclax to conservatively practice fluid-liberal IF, provided that adequate hydration and the consistent administration of food are achieved. In contrast, considering the significant risk of TLS and the pharmacokinetics of venetoclax, patients should be discouraged from practicing fluid-restricted IF, especially during the ramp-up phase. Moreover, patients on BTKIs ought to refrain from IF due to the possible risk of GIB until further data are available. Further research is needed to provide conclusive recommendations. [ABSTRACT FROM AUTHOR]

Simple Summary: Targeted agents, such as Bruton's Tyrosine Kinase inhibitors and BCL-2 inhibitors, have transformed the treatment landscape for Chronic Lymphocytic Leukemia (CLL). While these therapies offer a more precise approach compared to traditional chemotherapy, they also bring a spectrum of adverse events that can impact patient health and treatment efficacy. This review aims to provide a comprehensive overview of the management strategies for these AEs, encompassing cardiac complications, Tumor Lysis Syndrome, bleeding risks, and other organ-specific challenges. Our goal is to equip healthcare professionals with the knowledge to effectively manage these adverse events, enhancing patient safety and optimizing therapeutic outcomes. The insights from this review will contribute to better clinical decision-making and patient care in CLL treatment, highlighting the significance of personalized management in the era of targeted therapy. The treatment landscape for CLL has undergone a profound transformation with the advent of targeted agents (TAs) like Bruton's Tyrosine Kinase inhibitors (BTKis) and BCL-2 inhibitors (BCL-2is). These agents target crucial cellular pathways in CLL, offering superior efficacy over traditional chemo-immunotherapy, which has led to improved progression-free and overall survival rates. This advancement promises enhanced disease control and potentially normal life expectancy for many patients. However, the journey is not without challenges, as these TAs are associated with a range of adverse events (AEs) that can impact treatment efficacy and patient quality of life. This review focuses on detailing the various AEs related to TA management in CLL, evaluating their frequency and clinical impact. The aim is to present a comprehensive guide to the effective management of these AEs, ensuring optimal tolerability and efficacy of TAs. By reviewing the existing literature and consolidating findings, we provide insights into AE management, which is crucial for maximizing patient outcomes in CLL therapy. [ABSTRACT FROM AUTHOR]

Hematological malignancies may require rapid-onset treatment because of their short doubling time, notably observed in acute leukemias and specific high-grade lymphomas. Furthermore, in targeted onco-hematological scenarios, chemotherapy is deemed necessary as an emergency measure when facing short-term, life-threatening complications associated with highly chemosensitive hematological malignancies. The risks inherent in the disease itself, or in the initiation of treatment, may then require admission to the intensive care unit (ICU) to optimize monitoring and initial management protocols. Hyperleukocytosis and leukostasis in acute leukemias, tumor lysis syndrome, and disseminated intravascular coagulation are the most frequent onco-hematological complications requiring the implementation of emergency chemotherapy in the ICU. Chemotherapy must also be started urgently in secondary hemophagocytic lymphohistiocytosis. Tumor-induced microangiopathic hemolytic anemia and plasma hyperviscosity due to malignant monoclonal gammopathy represent infrequent yet substantial indications for emergency chemotherapy. In all cases, the administration of emergency chemotherapy in the ICU requires close collaboration between intensivists and hematology specialists. In this review, we provide valuable insights that aid in the identification and treatment of patients requiring emergency chemotherapy in the ICU, offering diagnostic tools and guidance for their overall initial management. [ABSTRACT FROM AUTHOR]

Venetoclax is active in both frontline and relapsed/refractory settings for the treatment of chronic lymphocytic leukemia (CLL). Although the prevalence and severity of tumor lysis syndrome (TLS) are well characterized in clinical trials, laboratory and clinical TLS remain relatively unexplored in real-world clinical practice. In this prospective, real-world observational study, we aimed to determine the incidence and outcomes of TLS in patients with CLL receiving venetoclax outside a clinical trial. The study (VeRVe) was conducted in centers in Austria, Germany, and Switzerland. Two hundred and thirty-nine patients were treated according to local label with at least one dose of venetoclax. Patient demographics, baseline characteristics, and blood chemistry at baseline were documented, and descriptive statistical analyses were conducted. Seventy eight patients (33%) were treated with venetoclax monotherapy, 101 (42%) with venetoclax in combination with rituximab and 60 (25%) with venetoclax in combination with obinutuzumab. In all cases, the TLS risk mitigation strategy adhered to the ramp-up protocol. Median age was 73 years and 66% of patients were male. The majority of patients (75%) had relapsed/refractory CLL, 63/192 (32.8%) patients tested had a del(17p) and 93/134 (69.4%) patients tested had unmutated immunoglobulin heavy chain variable region gene (IGHV). Clinical TLS occurred in 5 patients (2.1%) and laboratory TLS occurred in 15 patients (6.3%). Ten patients received specific treatment, of which 6 were hospitalized. There were no deaths due to a TLS event and venetoclax was well-tolerated. Of the 5 clinical TLS events reported, none were fatal or resulted in renal failure (NCT03342144, registered on Nov 10, 2017). [ABSTRACT FROM AUTHOR]

T cell-redirecting bispecific antibodies are specifically designed to bind to tumor-associated antigens, thereby engaging with CD3 on the T cell receptor. This linkage between tumor cells and T cells actively triggers T cell activation and initiates targeted killing of the identified tumor cells. These antibodies have emerged as one of the most promising avenues within tumor immunotherapy. However, despite success in treating hematological malignancies, significant advancements in solid tumors have yet to be explored. In this review, we aim to address the critical challenges associated with T cell-redirecting bispecific antibodies and explore novel strategies to overcome these obstacles, with the ultimate goal of expanding the application of this therapy to include solid tumors. This review summarizes the developments of T cell-redirecting bispecific antibodies, with a focus on therapy-associated key toxicities, challenges and future perspectives. [Display omitted] [ABSTRACT FROM AUTHOR]

Guidelines recommend rasburicase for high-risk patients to prevent tumor lysis syndrome (TLS). However, little information is available on the incidence and outcome of TLS in AML patients. We analyzed 145 patients with AML who underwent induction therapy before the approval of rasburicase to evaluate the incidence of TLS and the necessity of rasburicase as prophylaxis. Three patients had already developed clinical TLS (CTLS) at diagnosis of AML, and another three developed CTLS after the initiation of chemotherapy. In patients without TLS at diagnosis of AML, the risk for developing TLS was classified as high in 44 patients, intermediate in 41 and low in 57, according to the current guidelines. Allopurinol alone was administered to prevent hyperuricemia in all patients. All three patients who developed CTLS after diagnosis of AML were at high risk of TLS, and had elevated serum creatinine levels and a WBC count greater than 200,000 per microliter at diagnosis of AML. Allopurinol may be insufficient to prevent TLS in high-risk patients with renal dysfunction at diagnosis of AML, especially those with a high tumor burden and a WBC count of 200,000 or more, which indicates that prophylactic administration of rasburicase should be considered. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinical efficacy of Niaoduqing Granule combined with Febusta in the treatment of renal damage in patients with hyperuricemia (HUA). Methods Eighty-two HUA patients with renal damage in our hospital from March 2020 to March 2022 were divided into observation group (n = 41) and control group (n = 41). The control group was treated with Febusta, while observation group with Niaoduqing granule and Febusta. Two groups were treated for 12 weeks. Blood uric acid, renal function, Cys C and β2-MG level change and adverse reactions in the two groups were compared. Results The total effective rate in the observation group was higher than in the control group (P < 0.05). After treatment, the level of serum uric acid, BUN, Scr, 24h Upro, Cys C and β2-MG decreased in the two groups (P < 0.05), with more significant results in the observation group (P < 0.05). No obvious adverse reactions were observed in the two groups. Conclusion Niaoduqing Granule combined with Febusta has good effect in treating HUA patients with renal impairment. It reduces the level of blood uric acid, Cys C and β2-MG, which protect the renal function of patients [ABSTRACT FROM AUTHOR]

This document provides a list of references to studies and articles related to CAR-T cell therapy for various types of lymphoma and multiple myeloma. The studies mentioned discuss the outcomes, safety, and efficacy of CAR-T cell therapies such as lisocabtagene maraleucel, axicabtagene ciloleucel, brexucabtagene autoleucel, ciltacabtagene autoleucel, and idecabtagene vicleucel. The document also includes references to studies that discuss the potential risk of secondary malignancies and other long-term effects associated with CAR-T cell therapy. [Extracted from the article]

PURPOSE: Decision about the optimal timing of a treatment procedure in patients with hematologic neoplasms is critical, especially for cellular therapies (most including allogeneic hematopoietic stem-cell transplantation [HSCT]). In the absence of evidence from randomized trials, real-world observational data become beneficial to study the effect of the treatment timing. In this study, a framework to estimate the expected outcome after an intervention in a time-to-event scenario is developed, with the aim of optimizing the timing in a personalized manner. METHODS: Retrospective real-world data are leveraged to emulate a target trial for treatment timing using multistate modeling and microsimulation. This case study focuses on myelodysplastic syndromes, serving as a prototype for rare cancers characterized by a heterogeneous clinical course and complex genomic background. A cohort of 7,118 patients treated according to conventional available treatments/evidence across Europe and United States is analyzed. The primary clinical objective is to determine the ideal timing for HSCT, the only curative option for these patients. RESULTS: This analysis enabled us to identify the most appropriate time frames for HSCT on the basis of each patient's unique profile, defined by a combination relevant patients' characteristics. CONCLUSION: The developed methodology offers a structured framework to address a relevant clinical issue in the field of hematology. It makes several valuable contributions: (1) novel insights into how to develop decision models to identify the most favorable HSCT timing, (2) evidence to inform clinical decisions in a real-world context, and (3) the incorporation of complex information into decision making. This framework can be applied to provide medical insights for clinical issues that cannot be adequately addressed through randomized clinical trials. How to personalize the timing of stem-cell transplantation for hematologic neoplasms with multistate decision models. [ABSTRACT FROM AUTHOR]

Tumor lysis syndrome (TLS) is an oncological emergency characterized by metabolic and electrolyte imbalances associated with the rapid destruction of tumor cells. It is commonly recognized when cytotoxic treatment for hematological malignancies is initiated. Spontaneous TLS with solid tumors like rhabdomyosarcoma (RMS) is exceedingly rare. It has been noted that the highest incidence of this tumor occurs in individuals under the age of 20 years, with an incidence rate of 4.4 cases per 1 million. Here, we present the case of a 22-year-old male who presented with spontaneous clinical TLS. A computed tomography (CT) scan revealed a large pelvic mass, diffuse lymphadenopathy, and infiltration of the ocular muscles. Subsequently, a biopsy was conducted, and the histopathological results indicated alveolar rhabdomyosarcoma. Our literature review revealed five cases of spontaneous TLS caused by RMS, with our patient being the only adult among all published cases. [ABSTRACT FROM AUTHOR]

Venetoclax is a first-in-class B-cell lymphoma-2 (BCL-2) inhibitor approved as continuous monotherapy and in combination with rituximab as fixed-treatment duration for relapsed and refractory chronic lymphocytic leukemia (R/R CLL). DEVOTE was a 24-week, multicenter observational study (NCT03310190) evaluating the safety, healthcare resource utilization (HCRU) and health-related quality of life (HRQoL) of patients initiating venetoclax for R/R CLL in Canada. Overall, 89 patients received 1 dose of venetoclax; 80% had prior exposure (42% resistant) to ibrutinib. Biochemical tumor lysis syndrome (TLS) occurred in five patients. We observed differences in hospitalization across Canadian provinces including in patients at low risk for TLS with no clear impact on TLS incidence. Additionally, a rapid and sustained improvement in several domains of HRQoL was observed during venetoclax initiation. Early adoption of venetoclax was mainly for R/R CLL patients with few treatment options; nonetheless, acceptable toxicity and a positive impact on HRQoL were observed. [ABSTRACT FROM AUTHOR]

Objective: To compare the clinical efficacy of febuxostat combined with a low‐purine diet versus allopurinol combined with a low‐purine diet in the treatment of gout. Method s : In this prospective controlled trial, 98 gout patients admitted to our hospital from February 2021 to December 2022 were enrolled as study subjects. Patients were randomly assigned to the study group (febuxostat combined with a low‐purine diet) and the control group (allopurinol combined with a low‐purine diet), with 49 patients in each group. The therapeutic effect was evaluated based on joint function and serum uric acid levels after treatment, and classified into three levels: markedly effective, effective, and ineffective. The levels of inflammatory factors, including tumor necrosis factor‐a (TNF‐a), cytokine interleukin‐1beta (IL‐1β), and interleukin (IL)‐18 (IL‐18), were collected. The Numeric Rating Scale (NRS) was used to assess the degree of pain in patients. Clinical indicators before and 6 months after treatment were compared between the two groups. Results: There was no statistically significant difference in age and gender between the two groups. After 6 months of treatment, the effective rate in the study group (48 cases, 97.96%) was higher than that in the control group (42 cases, 85.71%), with a statistically significant difference (p =.027). At the same time, the study group had significantly lower levels of serum uric acid (162.39 μmol/L ± 17.23 μmol/L vs. S198.32 μmol/L ± 18.34 μmol/L, p <.001), creatinine (87.39 mmol/L ± 9.76 mmol/L vs. 92.18 mmol/L ± 9.27 mmol/L, p =.014), total cholesterol (3.65 mmol/L ± 0.65 mmol/L vs. 4.76 mmol/L ± 0.73 mmol/L, p <.001), and triglycerides (1.76 mmol/L ± 0.32 mmol/L vs. 2.28 mmol/L ± 0.41 mmol/L, p <.001) compared to the control group, with statistically significant differences (p <.05). After treatment, the levels of inflammatory factors and degree of pain in the study group were significantly lower than those in the control group (all p <.05). During the treatment process, the incidence of adverse reactions in the study group (2 cases, 4.08%) was lower than that in the control group (9 cases, 18.37%), with a statistically significant difference (p =.025). Conclusion: Febuxostat combined with a low‐purine diet can reduce inflammatory factors and alleviate the degree of pain in gout patients, significantly improving their clinical symptoms. [ABSTRACT FROM AUTHOR]

Introduction: Obesity is a risk factor for the development of diabetes, and these two are directly implicated in an individual's risk of developing Non Alcoholic Fatty Liver Disease (NAFLD), which is a major factor in Metabolic Syndrome (MS). NAFLD and Type 2 Diabetes Mellitus (T2DM) are known to frequently coexist and act synergistically to elevate the risk of hepatic as well as extrahepatic complications. Aim: To determine the levels of renal profile, electrolytes, Glycosylated Haemoglobin (HbA1c), and Body Mass Index (BMI) in T2DM patients with and without NAFLD, as well as in control subjects, and to assess the correlation of BMI and HbA1c with renal profile and electrolytes in T2DM patients with and without NAFLD. Materials and Methods: This case-control study was conducted in the Department of Biochemistry and the Diabetes Speciality Clinic in the Department of General Medicine at MGM Medical College and Hospital, Navi Mumbai, Maharashtra, India, from December 2021 to March 2023. The study included a total of 90 subjects divided into three groups (30 in each): Group 1-Control, Group 2-T2DM with NAFLD, and Group 3-T2DM without NAFLD. Aseptic blood collection was performed, and Renal Function Test (RFT), electrolytes, and HbA1c levels were analysed. Group comparisons were done using unpaired t-tests, and correlation analysis was conducted using Pearson's correlation with Statiistical Package for Social Sciences (SPSS) software version 25.0. Results: The authors found that 57% of the total enrolled population were female, while the remaining 43% were male, with a mean age of (49.03±5.09) years. Mean levels of HbA1c (9.55±1.78, 8.61±1.42%), BMI (28.84±4.19, 23.51±2.09) kg/m², Urea (31.62±6.28, 33.02±5.11) mg/dL, Creatinine (1.29±0.18, 1.36±0.10) mg/dL, and Uric acid (6.74±1.19, 6.01±0.83) mg/dL were found to be significantly higher in Group 2 and Group 3, respectively, compared to controls. A positive significant correlation of BMI with uric acid, HbA1c with urea, creatinine, and uric acid in Group 2 and 3 was observed. However, no derangement was observed concerning electrolytes in any group. Conclusion: The correlation of urea, creatinine, and uric acid with HbA1c provides the authors with information on impaired renal function in diabetic as well as NAFLD participants. Hyperuricaemia in these individuals can aggravate the risk of T2DM and NAFLD, leading to its progression in Non Alcoholic Steatohepatitis (NASH), respectively. [ABSTRACT FROM AUTHOR]

The exact prognostic role of cardiovascular (CV) risk factors in patients with BCR::ABL1 negative chronic myeloproliferative neoplasms (MPNs) remains unknown as it is often masked by other MPN-related features that bear strong prognostic impact on thrombotic risk. Therefore, current MPN treatment is not primarily guided by presence of CV risk factors. Treatment of CV risk factors in MPN patients usually mirrors that from the general population, despite the fact that CV risk factors in MPNs have their own specificities. Moreover, the optimal target levels for different metabolic deflections in MPNs (i.e., low-density lipoprotein, serum uric acid, or glycated hemoglobin levels) have not been defined. In the current review, we separately discuss the most important aspects of every individual CV risk factor (arterial hypertension, hyperlipidemia, chronic kidney disease, smoking, diabetes mellitus, hyperuricemia, and obesity and cachexia) in MPNs, summarize recent advances in the field, and propose future directions and research areas which may be needed to appropriately manage CV risk factors in MPNs. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) caused more deaths in 2017 than breast cancer, prostate, and brain cancers combined. This is primarily due to their aggressive metastatic nature, leading to more fatal rates of cancer patients. Despite this condition, there are no clinically approved drugs that can target metastasis. The NSCLC with EGFR T790M-overexpressing HER2 shows the resistance to osimertinib and trastuzumab starting 10--18 months after the therapy, and thus prospects are grim to these patients. To target the recalcitrant ERBB2 driver oncogene, we developed two engineered destabilizing 3'UTR ERBB2 constructs that degrade the endogenous ERBB2 transcript and proteins by overwriting the encoded endogenous ERBB2 mRNA with the destabilizing message. When iron oxide nanocages (IO nanocages) were used as vehicles to deliver them to tumors and whole tissues in mice bearing tumors, it was well tolerated and safe and caused no genome rearrangement whereas they were integrated into genome deserts (non-coding regions). We achieved significant reduction of the primary tumor volume with desARE3'UTRERBB2-30, achieving 50% complete tumor lysis and inhibiting 60%--80% of liver metastasis, hepatomegaly, and 90% of lung metastasis, through ERBB2 downregulation. These constructs were distributed robustly into tumors, livers, lungs, kidneys, and spleen and mildly in the brain and not in the heart. They caused no abnormality in both short- and long-term administrations as well as in healthy mice. In summary, we accomplished significant breakthrough for the therapeutics of intractable lung cancer patients whose cancers become resistant and metastasize. [ABSTRACT FROM AUTHOR]

Recent advancements in genetic engineering have made it possible to modify Natural Killer (NK) cells to enhance their ability to fight against various cancers, including solid tumors. This comprehensive overview discusses the current status of genetically engineered chimeric antigen receptor NK-cell therapies and their potential for treating solid tumors. We explore the inherent characteristics of NK cells and their role in immune regulation and tumor surveillance. Moreover, we examine the strategies used to genetically engineer NK cells in terms of efficacy, safety profile, and potential clinical applications. Our investigation suggests CAR-NK cells can effectively target and regress nonhematological malignancies, demonstrating enhanced antitumor efficacy. This implies excellent promise for treating tumors using genetically modified NK cells. Notably, NK cells exhibit low graft versus host disease (GvHD) potential and rarely induce significant toxicities, making them an ideal platform for CAR engineering. The adoptive transfer of allogeneic NK cells into patients further emphasizes the versatility of NK cells for various applications. We also address challenges and limitations associated with the clinical translation of genetically engineered NKcell therapies, such as off-target effects, immune escape mechanisms, and manufacturing scalability. We provide strategies to overcome these obstacles through combination therapies and delivery optimization. Overall, we believe this review contributes to advancing NK-cell-based immunotherapy as a promising approach for cancer treatment by elucidating the underlying mechanisms, evaluating preclinical and clinical evidence, and addressing remaining challenges. [ABSTRACT FROM AUTHOR]

Venetoclax, a highly selective BCL‐2 inhibitor, combined with hypomethylating agents (HMAs) azacitidine or decitabine, is approved for the treatment of newly diagnosed acute myeloid leukemia (ND AML) in patients who are ineligible to receive intensive chemotherapy. Previous clinical studies initiated venetoclax plus HMA in an inpatient setting owing to concerns of tumor lysis syndrome (TLS). This study (NCT03941964) evaluated the efficacy and safety of venetoclax plus HMA in a United States community–based outpatient setting in patients with ND AML (N = 60) who were treatment naïve for AML, ineligible to receive intensive chemotherapy, had no evidence of spontaneous TLS at screening, and were deemed as appropriate candidates for outpatient initiation of venetoclax plus HMA by the investigator. Patients received venetoclax in combination with azacitidine (75 mg/m2) or decitabine (20 mg/m2) for up to 6 cycles during the study. With a median time on study of 18.3 weeks, the best response rate of composite complete remission was 66.7%, and the overall post‐baseline red blood cell (RBC) and platelet transfusion independence rate was 55.0%, consistent with results of studies in which treatment was initiated in an inpatient setting. Key adverse events included nausea, anemia, thrombocytopenia, neutropenia, and white blood cell count decrease of any grade (≥50% of patients). The observed safety profile was generally consistent with that of venetoclax plus HMA observed in inpatient AML studies. With close monitoring, 2 cases of TLS were identified, appropriately managed, and the patients were able to continue study treatment. Clinical Trials Registration: This study is registered at ClinicalTrials.gov. The registration identification number is NCT03941964. [ABSTRACT FROM AUTHOR]

Tumor lysis syndrome (TLS) is a life-threatening hemato-oncological emergency in which the patient presents with severe metabolic derangements that include hyperuricemia, hyperphosphatemia, hyperkalemia, and hypocalcemia. However, very rarely, a highly aggressive neoplasm such as acute lymphoblastic leukemia (ALL) or Burkitt lymphoma can present with spontaneous TLS. Preventive actions can reduce its prevalence and severity. Here, we present a male patient who was admitted to the intensive care unit with unspecific symptoms and hidden malignancy. On further evaluation, the patient had hyperphosphatemia, hyperuricemia, a large mediastinal mass, pericardial effusion, and left-sided massive pleural effusion and was also found to be in spontaneous TLS. On further evaluation, the patient was diagnosed with acute T-cell lymphoblastic leukemia. [ABSTRACT FROM AUTHOR]

This editorial discusses the use of Pentixather, a radiopharmaceutical labeled with gallium-68, in the treatment of hematological disorders such as multiple myeloma and lymphomas. The studies reviewed showed that Pentixather radioligand therapy (RLT) was effective and tolerable in heavily pretreated patients, with neutropenia and infections being the most common adverse effects. However, further research and validation through multicenter studies are needed to fully understand the potential of Pentixather RLT in these conditions. Clinical trials are currently underway to investigate the efficacy of different radioligands in managing lymphomatous central nervous system involvement and multiple myeloma. [Extracted from the article]

Background: Letrozole, an aromatase inhibitor, is used to treat breast cancer in postmenopausal women. Tumor lysis syndrome (TLS) is a complication that can trigger multiple organ failure caused by the release of intracellular nucleic acids, phosphate, and potassium into the blood due to rapid tumor cell disintegration induced by drug therapy. TLS is uncommon in solid tumors and occurs primarily in patients receiving chemotherapy. Herein, we report a rare occurrence of TLS that developed in a patient with locally advanced breast cancer following treatment with letrozole. Case presentation: An 80-year-old woman with increased bleeding from a fist-sized left-sided breast mass presented to our hospital. Histological examination led to a diagnosis of invasive ductal carcinoma of the luminal type. The patient refused chemotherapy and was administered hormonal therapy with letrozole. Seven days after letrozole initiation, she complained of anorexia and diarrhea. Blood test results revealed elevated blood urea nitrogen (BUN) and creatinine (Cr) levels, and she was admitted to our hospital for intravenous infusions. On the second day after admission, marked elevations of LDH, BUN, Cr, potassium, calcium, and uric acid levels were observed. Furthermore, metabolic acidosis and prolonged coagulation capacity were observed. We suspected TLS and discontinued letrozole, and the patient was treated with hydration, febuxostat, and maintenance hemodialysis. On the third day after admission, her respiratory status worsened because of acute respiratory distress syndrome associated with hypercytokinemia, and she was intubated. On the fourth day after admission, her general condition did not improve, and she died. Conclusions: Although TLS typically occurs after chemotherapy initiation, the findings from the present case confirm that this syndrome can also occur after hormonal therapy initiation and should be treated with caution. [ABSTRACT FROM AUTHOR]

Background/Objectives: Serum uric acid is an established cardiovascular risk factor. Higher serum uric acid levels are associated with overweight and obesity. We assessed whether non-interventional weight changes affect serum uric acid levels. Methods: We performed a retrospective analysis of 19,193 participants referred to annual medical screening. Body mass index (BMI) and serum uric acid were measured annually. Subjects were divided into five groups according to changes in BMI between visits: large reduction (reduction of more than 5% in BMI), moderate reduction (reduction of more than 2.5% and 5% or less in BMI), unchanged (up to 2.5% change in BMI), moderate increase (increase of more than 2.5% and 5% or less in BMI), and large increase (increase of more than 5% in BMI). The primary outcome was serum uric acid level changes between visits. Results: A decrease in serum uric acid levels was evident as BMI decreased and an increase in serum uric acid levels was associated with an increase in BMI. The proportion of patients whose serum uric acid levels were increased by at least 10% between visits increased with the relative increase in BMI, while the proportion of patients whose serum uric acid levels were reduced by at least 10% decreased with the relative decrease in BMI. Conclusions: Non-interventional weight changes, even modest, are associated with significant alterations in serum uric acid levels. Our findings may aid in better risk stratification and the primary prevention of cardiovascular morbidity and mortality. [ABSTRACT FROM AUTHOR]

Introduction: Sorafenib is currently the first-line treatment for patients with advanced hepatocellular carcinoma (HCC). Nevertheless, sorafenib resistance remains a huge challenge in the clinic. Therefore, it is urgent to elucidate the mechanisms underlying sorafenib resistance for developing novel treatment strategies for advanced HCC. In this study, we aimed to investigate the role and mechanisms of interleukin-22 (IL-22) in sorafenib resistance in HCC. Methods: The in vitro experiments using HCC cell lines and in vivo studies with a nude mouse model were used. Calcium staining, chromatin immunoprecipitation, lactate dehydrogenase release and luciferase reporter assays were employed to explore the expression and roles of IL-22, STAT3 and CD155 in sorafenib resistance. Results: Our clinical results demonstrated a significant correlation between elevated IL-22 expression and poor prognosis in HCC. Analysis of transcriptomic data from the phase-3 STORM-trial (BIOSTORM) suggested that STAT3 signaling activation and natural killer (NK) cell infiltration may associate sorafenib responses. STAT3 signaling could be activated by IL-22 administration in HCC cells, and then enhanced sorafenib resistance in HCC cells by promoting cell proliferation and reducing apoptosis in vitro and in vivo. Further, we found IL- 22/STAT3 axis can transcriptionally upregulate CD155 expression in HCC cells, which could significantly reduce NK cell-mediated HCC cell lysis in a coculture system. Conclusions: Collectively, IL-22 could contribute to sorafenib resistance in HCC by activating STAT3/CD155 signaling axis to decrease the sensitivities of tumor cells to sorafenib-mediated direct cytotoxicity and NK cell-mediated lysis. These findings deepen the understanding of how sorafenib resistance develops in HCC in terms of IL-22/STAT3 signaling pathway, and provide potential targets to overcome sorafenib resistance in patients with advanced HCC. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a poor prognosis. Current treatment options are limited and often ineffective. CAR T cell therapy has shown success in treating hematologic malignancies, and there is growing interest in its potential application in solid tumors, including GBM. However, current CAR T therapy lacks clinical efficacy against GBM due to tumor-related resistance mechanisms and CAR T cell deficiencies. Therefore, there is a need to improve CAR T cell therapy efficacy in GBM. Methods: We conducted large-scale CRISPR interference (CRISPRi) screens in GBM cell line U87 MG cells co-cultured with B7-H3 targeting CAR T cells to identify genetic modifiers that can enhance CAR T cell-mediated tumor killing. Flow cytometry-based tumor killing assay and CAR T cell activation assay were performed to validate screening hits. Bioinformatic analyses on bulk and single-cell RNA sequencing data and the TCGA database were employed to elucidate the mechanism underlying enhanced CAR T efficacy upon knocking down the selected screening hits in U87 MG cells. Results: We established B7-H3 as a targetable antigen for CAR T therapy in GBM. Through large-scale CRISPRi screening, we discovered genetic modifiers in GBM cells, including ARPC4, PI4KA, ATP6V1A, UBA1, and NDUFV1, that regulated the efficacy of CAR T cell-mediated tumor killing. Furthermore, we discovered that TNFSF15 was upregulated in both ARPC4 and NDUFV1 knockdown GBM cells and revealed an immunostimulatory role of TNFSF15 in modulating tumor-CAR T interaction to enhance CAR T cell efficacy. Conclusions: Our study highlights the power of CRISPR-based genetic screening in investigating tumor-CAR T interaction and identifies potential druggable targets in tumor cells that confer resistance to CAR T cell killing. Furthermore, we devised targeted strategies that synergize with CAR T therapy against GBM. These findings shed light on the development of novel combinatorial strategies for effective immunotherapy of GBM and other solid tumors. [ABSTRACT FROM AUTHOR]

Spontaneous occurrence of Tumor Lysis Syndrome (TLS) is very rare. Only 3 pediatric case reports were reported in literature. All 3 patients presented with therapy-sensitive disease. Unfortunately, only one patient survived. It is preventable in 100% of patients, but TLS is a hard nut to crack. We present three distinct cases of spontaneous tumor lysis syndrome within the pediatric population, each associated with different types of tumors. A 3-year-old boy with mediastinal germ cell tumor of stage III, had hyperuricemia and hyperphosphatemia on presentation, tumor lysis syndrome improved but later died with sepsis, another patient of 4-year-old girl with precursor B cell acute lymphoblastic lymphoma had hyperkalemia, hyperuricemia and hyperphosphatemia on presentation and third patient was 6-year-old boy with abdominal Burkitt lymphoma stage III presented with hyperkalemia, hyperuricemia, hyperphosphatemia and Acute Kidney Injury (AKI) before initiation of chemotherapy. Later both these patients improved and survived. Spontaneous tumor lysis syndrome has high mortality, so it is of utmost importance to diagnose it timely. Swift and effective responses to spontaneous TLS can significantly reduce the risk of mortality linked to this critical emergency condition. [ABSTRACT FROM AUTHOR]

Medical professionals, particularly in regions with a high burden of human immunodeficiency virus (HIV), should be alert to the hematological complications of HIV, which may include cytopenias, malignancy, and coagulation disturbances. Patients may present with these conditions as the first manifestation of HIV infection. Hematological abnormalities are often multifactorial with opportunistic infections, drugs, malignancy, and HIV infection itself contributing to the clinical presentation, and the diagnosis should consider all these factors. Life-threatening hematological complications requiring urgent diagnosis and management include thrombotic thrombocytopenic purpura, superior mediastinal syndrome, spinal cord compression, and tumor lysis syndrome due to aggressive lymphoma. Antiretroviral therapy is the therapeutic backbone, including for patients with advanced HIV, in addition to specific therapy for the complication. This article reviews the impact of HIV on the hematological system and provides a clinical and diagnostic approach, including the role of a bone marrow biopsy, focusing on perspectives from sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Objectives: Hyperkalemia is a common electrolyte disturbance encountered in hospitalized older patients secondary to age-related physiological changes in the kidneys, multiple comorbidities, and the burden of multiple medication usage. Metabolic acidosis, rhabdomyolysis, and tumor lysis syndrome cause the shift of potassium into the extracellular space. This contributes to hyperkalemia. This study aims to determine the outcomes in patients with hyperkalemia admitted to a tertiary care center and to list the factors contributing to the development of hyperkalemia in these patients. Methods: This was a prospective observational study conducted among older inpatients (≥60 years of age) admitted to the geriatric and medical wards in a tertiary care hospital. The patients with hyperkalemia were followed up till discharge or death. Results: Among the 225 study participants who presented with hyperkalemia, the mortality rate was found to be 22.2%. In the multivariate analysis, older people aged more than 70 years (P = 0.007) and those who were male had a significantly higher mortality (P = 0.009). The use of angiotensin-converting enzyme inhibitors (ACEIs) (P = 0.049) and beta-blockers (P = 0.02) was significantly associated with the development of hyperkalemia. Conclusions: ACEIs and beta-blockers increased the risk of developing hyperkalemia in the study population. Hyperkalemia was found to be associated with an increase in mortality, especially in the very old (>70 years) and in males. [ABSTRACT FROM AUTHOR]

ObjectiveTo investigate the potential association between tumor lysis syndrome (TLS) and drugs for the treatment of malignant melanoma (MM).MethodsReports of TLS recorded in the FDA Adverse Event Reporting System (FAERS) (January 2004–2023q3) were identified. Demographic and clinical characteristics were described, and disproportionality signals were assessed through the Reporting Odds Ratio (ROR) and Information Component (IC). The latency of TLS with anticancer drugs was described based on parametric models. Subgroup analysis was conducted to explore the differences of TLS signals in different age and sex.ResultsWe found 5 (1.49%), 59 (17.61%), 79 (23.58%), 19 (5.67%), 13 (3.88%), 13 (3.88%), 33 (9.85%), 49 (14.63%), 16 (4.78%) TLS reports with pembrolizumab, nivolumab, ipilimumab, dabrafenib, vemurafenib, dacarbazine, “encorafenib and binimetinib”, “nivolumab and ipilimumab”, “dabrafenib and trametinib”, respectively. The combination of encorafenib and binimetinib showed the strongest signal of TLS (IC025 = 3.98). The median days of latency of TLS with combination of encorafenib and binimetinib is 2 days, which was much shorter than nivolumab (22.0 days) and ipilimumab (21.5 days). TLS cases associated with drugs for MM were predominantly recorded in females and aged 25–65 years. After excluding confounding factors such as pre-existing diseases and co-treated drugs, the disproportionate signal of TLS with “encorafenib and binimetinib” remained strong.ConclusionsStronger disproportionate signal of TLS was detected in MM patients using the combination of encorafenib and binimetinib than other drugs. Further research is needed to investigate the underlying mechanisms and identify patient-related predisposing factors to support safe prescribing of the combination of encorafenib and binimetinib.

This article discusses a case of melanosis and isolated follicular vitiligo in a man with metastatic melanoma who was treated with immune checkpoint inhibitors. Melanosis is characterized by hyperpigmentation of the skin and mucous membranes and is often associated with metastatic melanoma. Follicular vitiligo is a rare subtype of vitiligo that primarily affects the hair follicles. The patient experienced melanodermia, melanuria, and poliosis as side effects of the treatment. The article highlights the importance of recognizing these cutaneous manifestations during immunotherapy for melanoma. [Extracted from the article]

The article explores the potential relationship between uric acid and the progression of polycystic kidney disease (PKD). Previous research has shown that high levels of uric acid can worsen the outcomes of PKD, but the mechanism behind this is not fully understood. The article suggests that further research is needed to investigate the interplay between uric acid metabolism and other signaling mechanisms, as well as the role of specific genes and transporters. The study was supported by grants from the National Institutes of Health and the Ben J. Lipps Research Fellowship Program, and the authors declare no conflicts of interest. [Extracted from the article]

Abstract Objective The purpose of our study is to investigate the laboratory and clinical features of tumor lysis syndrome (TLS) and acute kidney injury (AKI) in childhood non-Hodgkin lymphomas (NHL) and to reveal their impact on long term kidney function in survivors. Methods Our single-center retrospective study included 107 patients (0-18 years old) with NHL who were admitted and treated at our hospital between 1998 and 2020. The relationship between TLS and age, gender, histopathological subgroup, tumor stage, lactate dehydrogenase (LDH) level at presentation, bone marrow and kidney involvement were assessed. The long-term renal functions of the patients were investigated. Results 80.3% of the patients were male with a median age of 9.8 years. The most common detected histopathological subgroup was Burkitt lymphoma. Hyperhydration with or without alkalinisation, and allopurinol were used in first-line treatment and prophylaxis of TLS. Laboratory TLS and clinical TLS was observed in 30.8% and 12.1% of patients, respectively. A significant correlation was found between young age, advanced stage, high LDH level at presentation, and TLS. AKI was observed in 12.1% of the patients. When the glomerular filtration rate values of the patients at the first and last admissions were compared after an average of 6.9 years, a mean decrease of 10 mL/min/1.73 m2 was found. It was not, however, found to be statistically significant. Conclusion Lower age, advanced stage, and high LDH level at presentation were found to be risk factors for TLS in our study. Long-term renal function loss was not observed in the survivors who received early and careful prophylaxis/treatment for TLS. The survivors are still being followed up.

PurposeThe phase II CAPTIVATE study investigated first-line treatment with ibrutinib plus venetoclax for chronic lymphocytic leukemia in two cohorts: minimal residual disease (MRD)-guided randomized treatment discontinuation (MRD cohort) and fixed duration (FD cohort). We report tumor debulking and tumor lysis syndrome (TLS) risk category reduction with three cycles of single-agent ibrutinib lead-in before initiation of venetoclax using pooled data from the MRD and FD cohorts.Patients and methodsIn both cohorts, patients initially received three cycles of ibrutinib 420 mg/day then 12 cycles of ibrutinib plus venetoclax (5-week ramp-up to 400 mg/day).ResultsIn the total population (N = 323), the following decreases from baseline to after ibrutinib lead-in were observed: percentage of patients with a lymph node diameter ≥5 cm decreased from 31% to 4%, with absolute lymphocyte count ≥25 × 109/L from 76% to 65%, with high tumor burden category for TLS risk from 23% to 2%, and with an indication for hospitalization (high TLS risk, or medium TLS risk and creatinine clearance