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Antitumor virotherapy stimulates the antitumor immune response during tumor cell lysis induced by oncolytic viruses (OVs). OV can be modified to express additional transgenes that enhance their therapeutic potential. In this study, we armed the spontaneously oncolytic Schwarz strain of measles viruses (MVs) with the gene encoding the cancer/testis antigen NY-ESO-1 to obtain MVny. We compared MV and MVny oncolytic activity and ability to induce NY-ESO-1 expression in six human melanoma cell lines. After MVny infection, we measured the capacity of melanoma cells to present NY-ESO-1 peptides to CD4 + and CD8 + T cell clones specific for this antigen. We assessed the ability of MVny to induce NY-ESO-1 expression and presentation in monocyte-derived dendritic cells (DCs). Our results show that MVny and MV oncolytic activity are similar with a faster cell lysis induced by MVny. We also observed that melanoma cell lines and DC expressed the NY-ESO-1 protein after MVny infection. In addition, MVny-infected melanoma cells and DCs were able to stimulate NY-ESO-1-specific CD4 + and CD8 + T cells. Finally, MVny was able to induce DC maturation. Altogether, these results show that MVny could be an interesting candidate to stimulate NY-ESO-1-specific T cells in melanoma patients with NY-ESO-1-expressing tumor cells. [ABSTRACT FROM AUTHOR]

Although calcineurin inhibitors (CNIs) have a well-established role in the prevention of graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT), their use can be limited by significant toxicities, which may result in premature treatment discontinuation. The optimal management of patients with CNI intolerance is unknown. The objective of this study was to determine the effectiveness of corticosteroids as GVHD prophylaxis for patients with CNI intolerance. This retrospective single-center study included consecutive adult patients with hematologic malignancies who underwent myeloablative peripheral blood allogeneic HCT with anti-thymocyte globulin, CNI, and methotrexate GVHD prophylaxis in Alberta, Canada. Multivariable competing-risks regression was used to compare cumulative incidences of GVHD, relapse, and non-relapse mortality between recipients of corticosteroid versus continuous CNI prophylaxis, and multivariable Cox proportional hazards regression was applied to compare overall survival, relapse-free survival (RFS) and moderate-to-severe chronic GVHD and RFS. Among 509 allogeneic HCT recipients, 58 (11%) patients developed CNI intolerance and were switched to corticosteroid prophylaxis at median 28 days (range 1-53) after HCT. Compared with patients who received continuous CNI prophylaxis, recipients of corticosteroid prophylaxis had significantly greater cumulative incidences of grade 2-4 acute GVHD (subhazard ratio [SHR] 1.74, 95% confidence interval [CI] 1.08–2.80, P = 0.024), grade 3–4 acute GVHD (SHR 3.22, 95% CI 1.55–6.72, P = 0.002), and GVHD-related non-relapse mortality (SHR 3.07, 95% CI 1.54–6.12, P = 0.001). There were no significant differences in moderate-to-severe chronic GVHD (SHR 0.84, 95% CI 0.43–1.63, P = 0.60) or relapse (SHR 0.92, 95% CI 0.53–1.62, P = 0.78), but corticosteroid prophylaxis was associated with significantly inferior overall survival (hazard ratio [HR] 1.77, 95% CI 1.20–2.61, P = 0.004), RFS (HR 1.54, 95% CI 1.06–2.25, P = 0.024), and chronic GVHD and RFS (HR 1.46, 95% CI 1.04–2.05, P = 0.029). Allogeneic HCT recipients with CNI intolerance are at increased risks of acute GVHD and poor outcomes despite institution of corticosteroid prophylaxis following premature CNI discontinuation. Alternative GVHD prophylaxis strategies are needed for this high-risk population. [ABSTRACT FROM AUTHOR]

Introduction: Azacitidine is a useful drug for myelodysplastic syndromes and acute myeloid leukemia. In clinical trials, hematologic toxicity and infection have been observed as adverse events (AEs) of this drug. However, information on the time to onset of high risk AEs and subsequent outcomes, as well as differences in the frequency of AEs due to the route of administration is lacking. In this study, we investigated azacitidine-induced AEs comprehensively using the Japanese Adverse Event Reporting Database (JADER) published by the Pharmaceuticals and Medical Devices Agency, with disproportionate analysis of AE incidence trends, time to onset, and subsequent outcomes. In addition, we analyzed the differences in AEs by route of administration and the number of days until the occurrence of AEs and generated hypotheses. Methods: The study used JADER data reported from April 2004 to June 2022. Risk estimation was conducted using reported odds ratio. A signal was detected when the lower limit of the 95% confidence interval of the calculated ROR was ≥1. Results: A total of 34 signals were detected as AEs due to azacitidine. Among them, 15 were hematologic toxicities and 10 were infections, which demonstrated a particularly high rate of death. Signals of AEs such as tumor lysis syndrome (TLS) and cardiac failure, which have been described in case reports, were also detected, and the rate of death after onset was high. In addition, more AEs generally occurred within the first month of treatment. Conclusion: The results of this study suggest that more attention should be paid to cardiac failure, hematologic toxicity, infection, and TLS. Because many patients in clinical trials have discontinued treatment due to serious AEs before the therapeutic effect became apparent, appropriate supportive care, dose reduction, and drug withdrawal are important for the continuation of treatment. [ABSTRACT FROM AUTHOR]

High serum uric acid levels have been associated with psoriasis as well as cardiovascular diseases and metabolic syndrome. The aim of this study was to evaluate the effect of biologic agent treatment on serum uric acid levels in patients with psoriasis. Between April 2019 and September 2022, serum uric acid levels were retrospectively evaluated in patients with psoriasis before and 3 months after biologic agent treatment. This study included 224 patients, 100 females and 124 males, who were treated with TNF-α, IL-17, IL-12/23, and IL-23 inhibitors. Uric acid levels were significantly higher in men compared to women (p < 0.001), higher in overweight and obese patients compared to those with normal weight (p = 0.004), and higher in patients with severe versus mild psoriasis (p = 0.028). The mean serum uric acid level decreased significantly from 5.89 ± 1.53 mg/dL to 5.41 ± 1.39 mg/dL in all patients 3 months after biological agent treatment (p < 0.001). A statistically significant decrease in serum uric acid levels was detected in patients treated with adalimumab (p < 0.001), infliximab (p = 0.002), ixekizumab (p = 0.001), secukinumab (p = 0.012), and ustekinumab (p < 0.001). Since high serum uric acid levels have been associated with increased risk for cardiovascular diseases and metabolic syndrome, treatment of psoriasis with adalimumab, infliximab, ixekizumab, secukinumab, and ustekinumab may have a positive impact on cardiometabolic comorbidities. [ABSTRACT FROM AUTHOR]

Solid organ transplantation from the same donor is an established procedure for end-stage organ failure that developed after a previous hematopoietic stem cell transplantation (HSCT); however, it is rarely done in patients transplanted with unmanipulated haplo-HSCT. There are no pediatric reports regarding the long-term performance of organ transplantation after haplo-HSCT with post-transplant cyclophosphamide (PTCY). A juvenile myelomonocytic leukemia patient, who underwent unmanipulated haplo-HSCT with PTCY from her mother at the age of 3 years, developed chronic liver graft versus host disease (GvHD) which was refractory to specific GvHD treatment. Liver transplantation (LT) from her mother (the donor of her haplo-HSCT) was decided as the next line of treatment. LT was performed on day 540 post-HSCT, and the donor's left lateral segment was appropriately removed and attached to the recipient. The symptoms of GvHD completely regressed in a month. The patient died on day 121 after LT, because of a possible hepato-pulmonary syndrome. Organ failure can develop after allo-HSCT secondary to GvHD and therefore performing HSCT from a haplodonor may be superior to a matched unrelated donor in terms of subsequent organ transplantation for organ failure. [ABSTRACT FROM AUTHOR]

A bone marrow test was performed with aspirate samples sent to the flow cytometry, molecular hematology, and cytogenetics laboratories. At the end of induction chemotherapy, a repeat bone marrow showed no residual leukemic blasts, and a flow cytometry-based minimal residual disease (MRD) was reported by the hematopathologist to be 0.15% (positive MRD taken as >=0.01%). Hematological malignancies, namely, leukemias and lymphomas comprise the major part of clinical practice for most centers that manage children with cancer. A child with severe musculoskeletal pains due to leukemia may be misdiagnosed as juvenile rheumatoid arthritis, and an astute hematopathologist can call the clinician after seeing the blood smear to prompt a bone marrow test before starting steroid therapy. [Extracted from the article]

Background and Objective: Although tumor lysis syndrome was reported with obinutuzumab and rituximab, the association with CD20 monoclonal antibodies for chronic lymphocytic leukemia is unclear. Methods: A disproportionality analysis was conducted to investigate the link between CD20 monoclonal antibodies and tumor lysis syndrome by accounting for known confounders and comparing with other anticancer drugs, using data from the US Food and Drug Administration Adverse Event Reporting System. Reporting odds ratios and the information component were calculated as disproportionality measures. A stepwise sensitivity analysis was conducted to test the robustness of disproportionality signals. Bradford Hill criteria were adopted to globally assess the potential causal relationship. Results: From 2004 to 2022, 197, 368, 41, and 14 tumor lysis syndrome reports were detected for obinutuzumab, rituximab, ofatumumab, and alemtuzumab (CD52 monoclonal antibody), respectively. Disproportionality signals were found for the above four monoclonal antibodies when compared with other anticancer drugs. Sensitivity analyses confirmed robust disproportionality signals for obinutuzumab, rituximab, and ofatumumab. The median onset time was 4.5, 1.5, and 2.5 days for rituximab, obinutuzumab, and ofatumumab, respectively. A potential causal relationship was fulfilled by assessing Bradford Hill criteria. Conclusions: This pharmacovigilance study on the FDA Adverse Event Reporting System detected a plausible association between CD20 monoclonal antibodies (but not CD52) and tumor lysis syndrome by assessing the adapted Bradford Hill criteria. Urgent clarification of drug- and patient-related risk factors is needed through large comparative population-based studies. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of malignancies, especially hematological tumors, but toxicities have tempered its success. The main impediments to the development of CAR-T cell therapies are the following: cytokine release syndrome (CRS), immune-effector-cell-associated neurotoxicity syndrome (ICANS), tumor lysis syndrome (TLS), and on-target/off-tumor toxicity (OTOT). This review summarizes these side effects' underlying mechanisms and manifestations over time. It provides potential prevention and treatment according to the consensus grading, stressing the significance of establishing strategies that anticipate, reduce, and navigate the beginning of these side effects. It is essential to fully comprehend the mechanisms underlying these toxicities to create efficient treatment and preventive approaches. [ABSTRACT FROM AUTHOR]

Effect of high-cutoff hemodialysis vs conventional hemodialysis on hemodialysis independence among patients with myeloma cast nephropathy: a randomized clinical trial. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/GMMG-HD4 trial. Patients with MM are susceptible to AKI and it is most commonly due to hypovolemia, hypercalcemia or myeloma-specific kidney diseases such as light chain cast nephropathy. Multiple myeloma (MM) is an incurable malignant condition of proliferative plasma cells that has deleterious effects on the skeletal, renal and hematological systems. [Extracted from the article]

Background: Acute myeloid leukemia (AML) has been considered an oncologic emergency that requires initiation of chemotherapy immediately after diagnosis. With the introduction of novel targeted therapies, there is a potential benefit associated with delaying definitive treatment for identification of actionable therapeutic targets. Unfortunately, cytogenetic/molecular testing can take >7 days to return, and there is not a consensus regarding the prognostic impact of time from diagnosis to treatment (TDT) in AML. Methods: A literature review and meta‐analysis of studies done to date that evaluate TDT was conducted. Studies that reported baseline characteristics, TDT, and outcomes for patients with AML were selected. Outcomes included overall survival (OS), complete remission (CR), and mortality. Studies that measured CR rates within each TDT range and data to calculate odds ratios were included in the meta‐analysis. The remaining outcomes were synthesized descriptively for literature review. Results: Thirteen studies were identified, which comprised a total of 14,946 patients. Median TDT values were between 1 and 8 days. Several studies found a significant association between prolonged TDT and older age and lower proliferation burden. Four of 11 studies did not detect a significant relationship between TDT and OS. No studies found a significant association between TDT and early death. Six of eight studies did not find a significant association between TDT and CR rate. The meta‐analysis found a significant association between prolonged TDT and decreased achievement of CR (p <.05). Conclusions: Results were highly variable but suggest it may be feasible to pursue cytogenetic/molecular testing in patients who are clinically stable, particularly in those aged 60 years and older. This systematic review and meta‐analysis examines the impact of time from diagnosis to treatment (TDT) on clinical outcomes in patients with newly diagnosed acute myeloid leukemia. The data suggest that it may be feasible to wait for the results of cytogenetic and molecular testing in patients who are clinically stable, particularly in those aged 60 years and older, who seem to be less susceptible to the effects of prolonged TDT. [ABSTRACT FROM AUTHOR]

Purpose: The Internet is a ubiquitous source of medical information, and natural language processors are gaining popularity as alternatives to traditional search engines. However, suitability of their generated content for patients is not well understood. We aimed to evaluate the appropriateness and readability of natural language processor-generated responses to urology-related medical inquiries. Materials and Methods: Eighteen patient questions were developed based on Google Trends and were used as inputs in ChatGPT. Three categories were assessed: oncologic, benign, and emergency. Questions in each category were either treatment or sign/symptom-related questions. Three native English-speaking Board-Certified urologists independently assessed appropriateness of ChatGPT outputs for patient counseling using accuracy, comprehensiveness, and clarity as proxies for appropriateness. Readability was assessed using the Flesch Reading Ease and Flesh-Kincaid Reading Grade Level formulas. Additional measures were created based on validated tools and assessed by 3 independent reviewers. Results: Fourteen of 18 (77.8%) responses were deemed appropriate, with clarity having the most 4 and 5 scores (P [ .01). There was no significant difference in appropriateness of the responses between treatments and symptoms or between different categories of conditions. The most common reason from urologists for low scores was responses lacking information dsometimes vital information. The mean (SD) Flesch Reading Ease score was 35.5 (SD[10.2) and the mean Flesh-Kincaid Reading Grade Level score was 13.5 (1.74). Additional quality assessment scores showed no significant differences between different categories of conditions. Conclusions: Despite impressive capabilities, natural language processors have limitations as sources of medical information. Refinement is crucial before adoption for this purpose. [ABSTRACT FROM AUTHOR]

Hyperuricemia (HUA) is a common chronic metabolic disease that can cause renal failure and even death in severe cases. Berberine (BBR) is an isoquinoline alkaloid derived from Phellodendri Cortex with strong antioxidant, anti-inflammatory, and anti-apoptotic properties. The purpose of this study was to investigate the protective effects of berberine (BBR) against uric acid (UA)-induced HK-2 cells and unravel their regulatory potential mechanisms. The CCK8 assay was carried out to detect cell viability. The expression levels of inflammatory factors interleukin-1β (IL-1β) and interleukin-18 (IL-18) and Lactate dehydrogenase (LDH) were measured using Enzyme-linked immunosorbent assays (ELISA). The expression of the apoptosis-related protein (cleaved-Caspase3, cleaved-Caspase9, BAX, BCL-2) was detected by western blot. The effects of BBR on the activities of the NOD-like receptor family pyrin domain containing 3 (NLRP3) and the expression of the downstream genes were determined by RT-PCR and western blot in HK-2 cells. From the data, BBR significantly reversed the up-regulation of inflammatory factors (IL-1β, IL-18) and LDH. Furthermore, BBR down-regulated protein expression of pro-apoptotic proteins BAX, cleaved caspase3 (cl-Caspase3), cleaved caspase9 (cl-Caspase9), and enhanced the expression of antiapoptotic protein BCL-2. Simultaneously, BBR inhibited the activated NLPR3 and reduced the mRNA levels of NLRP3, Caspase1, IL-18, and IL-1β. Also, BBR attenuated the expression of NLRP3 pathway-related proteins (NLRP3, ASC, Caspase1, cleaved-Caspase1, IL-18, IL-1β, and GSDMD). Furthermore, specific NLRP3-siRNA efficiently blocked UA-induced the level of inflammatory factors (IL-1β, IL-18) and LDH and further inhibited activated NLRP3 pathway. Collectively, our results suggested that BBR can alleviate cell injury induced by UA. The underlying unctionary mechanism may be through the NLRP3 signaling pathway. [ABSTRACT FROM AUTHOR]

Acute hyperuricemia most commonly occurs in patients who experience tumor-lysis syndrome. Hyperuricemia along with other electrolyte abnormalities like hyperkalemia, hypocalcemia, and hyperphosphatemia leads to acute kidney injury (AKI) due to acute uric acid nephropathy which is associated with significant morbidity. High risk patients are thus closely monitored for signs of these laboratory abnormalities. Extreme exercise, rhabdomyolysis, and seizures are rare causes of acute hyperuricemia. Serum uric acid level is not routinely monitored as a part of postictal labs. We report an unusual case of AKI in a young male and no associated rhabdomyolysis who was found to have acute uric acid nephropathy. Timely administration of Rasburicase prevented the need for dialysis in this patient and led to complete renal recovery. This case illustrates the importance of doing a urine microscopy and checking uric acid level in patients who develop unexplainable AKI, as timely management helps improve outcome. [ABSTRACT FROM AUTHOR]

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Introduction. Prephase treatment (PP) is recommended in diffuse large B-cell lymphomas (DLBCL) to decrease therapy-related toxicities and to avoid tumour lysis syndrome. Data in the real world are limited, and no study has evaluated the impact on overall survival. We aimed to evaluate overall survival (OS), progression-free survival (PFS), and grade III-IV toxicities during the first cycle according to PP. Methods and Materials. All DLBCL diagnosed between 2014 and 2017 and aged between 18 and 80 years were identified by the Poitou-Charentes General Cancer Registry (France). PP was defined as any treatment prior to first-line, excluding anthracycline and/or Rituximab. We performed propensity score matching (PSM) to control characteristics at diagnosis, reduce bias, and approximate a randomized trial. Results. Three hundred and forty patients received first-line treatment in 17 hospital centers: 126 (37%) with prephase and 214 (63%) without prephase (NPP). After PSM, 97 patients remained in each group without significant difference in characteristics at diagnosis; matched PP patients had a 2-year OS of 71% (vs. 77%, P = 0.32), a 2-year PFS of 61% (vs. 74%, P = 0.12), and 26% grade III-IV toxicities (vs. 27%, P = 0.75). No tumour lysis syndrome was reported. PP nonsignificantly decreases grade III-IV toxicities for patients with high tumour load (P = 0.82) or elderly patients (P = 0.81). Conclusion. PP treatment does not affect survival nor does it reduce therapy-related toxicities even for patients with high tumour load or elderly patients. Further studies are needed to evaluate the efficacy and safety of PP. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnea–hypopnea syndrome is the most common form of SRBDs. Recurrent hypoxia, which accompanies OSAHS, increases the degradation of ATP, which in turn increase uric acid concentration that can be used as a biomarker of tissue hypoxia in OSAHS. There is still debate about whether OSAHS is an independent contributor to pulmonary arterial hypertension. Aim of the work: This study aimed to correlate serum uric acid levels and PAH in OSAHS patients. Methods: We enrolled 100 patients diagnosed with OSAHS using polysomnography. Patients were divided into three severity groups: mild OSA (5 ≤ AHI < 15), moderate OSA (15 ≤ AHI < 30), and severe (30 ≤ AHI < 60). Serum uric acid was measured the morning after polysomnography. All patients underwent standard echocardiograms, and pulmonary artery systolic pressure calculation was done. Results: Among our studied patients (66% males, 34% females), the mean age was 53.04 ± 8.45 years. Six percent, 38%, and 56% were diagnosed as mild, moderate, and severe OSAHS, respectively. The mean AHI was 31.93 ± 11.78 event. Pulmonary HTN was detected in 78% of patients. Those with elevated uric acid levels represented 92.3% of patients versus 9.1% of patients without pulmonary HTN, p < 0.001. The level of serum uric acid positively correlated with pulmonary HTN level. Conclusion: Pulmonary arterial pressure correlated positively with serum uric acid level. Both serum uric acid level and PAP positively correlated with the severity of OSA. Further confirmation with right heart catheterization is essential. Trial registration: NCT05967754, on July 22, 2023 — retrospectively registered. [ABSTRACT FROM AUTHOR]

This document provides information on a small-molecule inhibitor called BMF-219, which has shown promise in inhibiting cancer cell signaling. It introduces a Phase I study called COVALENT-101, which aims to evaluate the safety and efficacy of BMF-219 in patients with various types of leukemia and lymphoma. The study found that intermittent dosing of duvelisib was effective in controlling the disease and had manageable side effects. Another study explored the impact of comorbidities on treatment outcomes in chronic lymphocytic leukemia (CLL) patients, finding that comorbidities were associated with poorer response and survival. The document also discusses the potential benefits of combining CAR T cell therapy with bispecific antibodies (BsAb) in CLL and other B-cell non-Hodgkin lymphomas (B-NHL), as well as the use of PI3Kδ inhibitors to improve T cell function in CLL patients. These studies provide valuable insights into treatment options and prognostic factors for CLL patients. [Extracted from the article]

Uric acid is the final product of purine metabolism and is converted to allantoin in most mammals via the uricase enzyme. The accumulation of loss of function mutations in the uricase gene rendered hominoids (apes and humans) to have higher urate concentrations compared to other mammals. The loss of human uricase activity may have allowed humans to survive environmental stressors, evolution bottlenecks, and life-threatening pathogens. While high urate levels may contribute to developing gout and cardiometabolic disorders such as hypertension and insulin resistance, low urate levels may increase the risk for neurodegenerative diseases. The double-edged sword effect of uric acid has resurrected a growing interest in urate's antioxidant role and the uricase enzyme's role in modulating the risk of obesity. Characterizing both the effect of uric acid levels and the uricase enzyme in different animal models may provide new insights into the potential therapeutic benefits of uric acid and novel uricase-based therapy. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukemia (CLL), is a hematologic malignancy characterized by the uncontrolled proliferation of mature B lymphocytes. CLL is the most prevalent leukemia in Western countries. Its presentation can range from asymptomatic with the incidental finding of absolute lymphocytosis on a routine blood test, to symptomatic disease requiring immediate intervention. Prognosis of the disease is defined by the presence or absence of specific mutations such as TP53, chromosomal abnormalities such as del(17p), a type of IGHV mutational status, and elevation of B2M and LDH. Treatment of CLL in the United States and Europe has evolved over the recent years thanks to the development of targeted therapies. The standard of care has shifted from traditional chemoimmunotherapy approaches to targeted therapies including Bruton tyrosine kinase inhibitors (BTKis) and BCL2 inhibitors, administered either as monotherapy or in combination with CD20 monoclonal antibodies. Several clinical trials have also recently evaluated combinations of BTKi and venetoclax and showed the combination to be well tolerated and able to induce deep remissions. Targeted therapies have a good safety profile overall; however, they also have unique toxicities that are important to recognize. Diarrhea, fatigue, arthralgia, infections, cytopenias, bleeding, and cardiovascular toxicities (including atrial fibrillation, ventricular arrhythmias, and hypertension) are the adverse events (AEs) commonly associated with BTKis. Initiation of therapy with venetoclax requires close monitoring because of the risk for tumor lysis syndrome associated with this agent, particularly in patients with a high disease burden. Development of newer target therapies is ongoing and the therapeutic landscape in CLL is expanding rapidly. [ABSTRACT FROM AUTHOR]

To evaluate the time to discontinuation (TTD) and baseline characteristics among patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) treated with first-line (1L) venetoclax + obinutuzumab (VO) in the United States. A nationwide electronic health record-derived database was used to select adults with CLL/SLL initiating a 1L venetoclax-based regimen between April 11, 2016–July 31, 2020. Study measures included TTD (defined as >120-day treatment gap or switching therapy) and baseline characteristics by discontinuation status. A total of 113 patients receiving 1L VO on/before July 31, 2020 were eligible for analysis (mean age: 65.9 years; 31.9% women). During the first 60 days post-treatment initiation, 3.5% had tumor lysis syndrome (TLS). The proportion of patients using corticosteroids, anti-hyperuricemics, and anti-emetics was higher during the first 60 days post-treatment initiation (100.0%, 78.8%, and 52.2%, respectively) than the period from day 61 onward (67.0%, 45.5%, and 33.9%, respectively). Mean (median) duration of active treatment was 11.6 (12.1) months; 16.8% discontinued treatment before completing 12 cycles, 68.1% completed ≥12 cycles (among which 29.9% completed ≥15 cycles), and 15.0% who did not discontinue treatment were censored before completing 12 cycles. Kaplan-Meier analysis showed that median TTD was 13.8 months. Relative to those completing ≥12 cycles, patients discontinuing treatment before completing the prescribed 12 cycles were older (70.4 vs. 65.1 years) and had poorer renal function (36.8% vs. 13.0% with creatinine clearance <60 mL/min). A small proportion of CLL/SLL patients who were older and had poorer baseline renal function discontinued 1L VO prior to completing 12 treatment cycles. Additionally, treatment utilization, including medications related to TLS mitigation and management, was more intense during the initiation phase of VO. Further research with longer follow-up to assess long-term outcomes of VO treatment after early discontinuation is warranted. [ABSTRACT FROM AUTHOR]

Background: Efficacy and safety of mogamulizumab, a monoclonal antibody directed against C‐C chemokine receptor 4, were demonstrated in a previous multinational clinical trial conducted in patients with previously treated cutaneous T‐cell lymphoma (CTCL): Sézary syndrome (SS) or Mycosis Fungoides (MF). Objectives: The real‐world French OMEGA study aimed to describe effectiveness and tolerability of mogamulizumab in adult patients with CTCL, overall and according to the disease (SS or MF). Methods: In this retrospective study, patients treated with mogamulizumab for SS or MF were included from 14 French expert centres. The overall response rate (ORR) under treatment was described (primary criterion), as well as treatment use and safety data. Results: The 122 analysed patients (69 SS, 53 MF) were aged 66.6 ± 12.1 years at mogamulizumab initiation, and their median disease duration was 2.5 years (IQR: 1.3–5.6). Prior to treatment start, they received a median of three systemic CTCL therapies (2–5). Overall, 77.8% of patients suffered from advanced disease (Stage IIB–IVB), with frequent blood (B1/B2) involvement (67.5%). Over the treatment period (median: 4.6 months, 2.1–7.2), 96.7% of patients received all the planned mogamulizumab infusions. Among the 109 patients evaluable for effectiveness, ORR was 58.7% (95% CI [48.9–68.1]) overall, 69.5% [56.1–80.8] in SS and 46.0% [31.8–60.7] in MF. Compartmental response in the blood was observed in 81.8% [69.1–90.9] of SS patients. Skin responses were observed in 57.0% [47.0–66.5] of patients overall, 66.7% [52.9–78.6] in SS and 46.0% [31.8–60.7] in MF. The most common serious adverse drug reactions were rash (8.1% of patients) and infusion‐related reactions (2.4%) which led to treatment discontinuation in 7.3% and 0.8% of patients, respectively. One patient with SS died from mogamulizumab‐related tumour lysis syndrome. Conclusions: This large French study confirmed the effectiveness and tolerability of mogamulizumab in SS and MF patients in routine medical practice. [ABSTRACT FROM AUTHOR]

Introduction: Venetoclax is utilized with low-dose cytarabine or a hypomethylating agent for the treatment of acute myeloid leukemia. Clinical trials report a risk of tumor lysis syndrome and the package insert recommends a venetoclax dose ramp-up at the initiation. The purpose of this study was to evaluate the risk of tumor lysis syndrome in a large population of patients with acute myeloid leukemia outside of a clinical trial and evaluate the incidence of hospital-acquired complications during inpatient ramp-up. Methods: We performed a retrospective study of adult patients with acute myeloid leukemia receiving venetoclax with a hypomethylating agent or low-dose cytarabine. The primary outcome was the incidence of tumor lysis syndrome. Secondary outcomes included risk factors for tumor lysis syndrome, length of admission, and incidence of hospital-acquired complications. Results: One hundred thirteen patients were included. Although all patients were given some form of prophylaxis, the incidence of tumor lysis syndrome was 8.8%. All were laboratory tumor lysis syndrome; one with hyperuricemia, nine with hypocalcemia, and ten with hyperphosphatemia. Six patients received sevelamer. Tumor lysis syndrome was resolved in all cases. No clinical tumor lysis syndrome occurred. Hepatic dysfunction, tumor lysis syndrome high-risk stratification, higher baseline white blood cell count, and lactate dehydrogenase levels were more common in the tumor lysis syndrome group. Hospital-acquired complications reached 13% in those directly admitted for dose ramp-up. Conclusions: Tumor lysis syndrome was uncommon and manifested as minor lab abnormalities. White blood cell count continues to be an indicator of risk for tumor lysis syndrome. Those who present with an elevated white blood cell or are otherwise at high risk for tumor lysis syndrome should be admitted for ramp-up. Otherwise, initiation and monitoring of venetoclax are feasible in the outpatient setting. [ABSTRACT FROM AUTHOR]

Background The nephrotoxicity of bortezomib, a proteasome inhibitor, has not yet been elucidated, although tumor lysis syndrome (TLS) associated with multiple myeloma (MM) has been reported to increase after introduction of the drug. This study compared the incidence and risk factors for acute kidney injury (AKI) and TLS in patients with MM after bortezomib-based chemotherapy to investigate drug-related nephrotoxicity. Methods From 2006 to 2017, 276 patients who underwent a first cycle of bortezomib-based chemotherapy for MM were identified in a single tertiary hospital. Laboratory TLS was defined according to the Cairo-Bishop definition. Development of AKI was assessed by AKI Network criteria within 7 days of the first chemotherapy. Results The median (interquartile range) age was 65 (56–72) years, and baseline estimated glomerular filtration rate (eGFR) was 61.3 (34.1–89.1) mL/min/1.73 m2. The incidences of AKI and laboratory TLS were 17% (n  = 47) and 13% (n  = 36), respectively. Ten (3.6%) subjects met both AKI and TLS criteria. Multivariate analyses showed that lower eGFR category [30–59, odds ratio (OR) 3.005 (95% confidence interval 1.163–7.976); 15–29, OR 4.225 (1.183–15.000); <15, OR 16.154 (3.831–70.920) vs ≥60, P  < .001], lower serum albumin level [per 1 increase, OR 0.479 (0.256–0.871), P  = .018], renal amyloidosis [OR 13.039 (4.108–44.041), P  < .001] and use of acyclovir during bortezomib treatment [OR 3.689 (1.133–14.469), P  = .042] were predictors of AKI. MM stages and β-2-microglobulin were not associated with increased risk of AKI. Regarding laboratory TLS, MM stage and β-2-microglobulin were higher in those with TLS than in others. In multivariate analyses, β-2-microglobulin level [OR 1.204 (1.005–1.461), P  = .038] and absence of high-risk chromosome abnormalities [OR 0.143 (0.022–0.588), P  = .016] were associated with higher risk of TLS. Conclusions Development of AKI was often observed in the absence of TLS in patients with MM after treatment with bortezomib. In addition, the risk factors for AKI and TLS varied widely. These findings indicate the potential nephrotoxicity of bortezomib irrespective of TLS in patients with decreased kidney function. [ABSTRACT FROM AUTHOR]

Background: Tumor lysis syndrome (TLS) and its most serious complication, acute kidney injury (AKI) are one of the emergency conditions in onco-hematology. It is difficult to predict the degree of kidney involvement. Therefore, we studied children with leukemia and lymphoma treated in four Hungarian tertiary centers (inpatient university clinics) retrospectively (2006–2016) from a nephrological aspect. Method: Data of 31 pediatric patients were obtained from electronic- and paper-based medical records. Physical status, laboratory test results, treatments, and outcomes were assessed. Patients were analyzed according to both "traditional" TLS groupings, as laboratory TLS or clinical TLS, and nephrological aspect based on pRIFLE classification, as mild or severe AKI. Results: Significant differences were found between the changes in parameters of phosphate homeostasis and urea levels in both classifications. Compared to age-specific normal phosphate ranges, before the development of TLS, hypophosphatemia was common (19/31 cases), while in the post-TLS period, hyperphosphatemia was observed (26/31 cases) most frequently. The rate of daily change in serum phosphate level was significant in the nephrological subgroups, but peaks of serum phosphate level show only a moderate increase. The calculated cut-off value of daily serum phosphate level increased before AKI was 0.32 mmol/L per ROC analysis for severe TLS–AKI. The 24-h urinalysis data of eight patients revealed transiently increased phosphate excretion only in those patients with TLS in whom serum phosphate was elevated in parallel. Conclusion: Daily serum phosphate level increase can serve as a prognostic factor for the severity of pediatric TLS, as well as predict the severity of kidney involvement. [ABSTRACT FROM AUTHOR]

Keywords: CAR-T cell therapy; Viral infections; Immunotherapy; Chimeric antigen receptors; Viral antigens EN CAR-T cell therapy Viral infections Immunotherapy Chimeric antigen receptors Viral antigens 1839 1842 4 08/02/23 20230901 NES 230901 Dear Editor, The emergence of chimeric antigen receptor T (CAR-T) cell therapy has ushered in a new era of optimism in the realm of viral infection treatment. Balancing challenges and opportunities: an exploration of CAR-T cell therapy in viral infecti... While CAR-T cell therapy exhibits promising potential for treating viral infections, several substantial challenges still exist. Originally designed for cancer therapy [[1]], CAR-T cell therapy employs the genetic modification of a patient's T cells to express chimeric antigen receptors (CARs) that precisely identify and potentially target viral antigens, thereby eradicating cells infected with the virus. [Extracted from the article]

Background: Sacrococcygeal teratomas (SCTs) are the most common congenital neoplasm and often require resection soon after birth. There are rare reports of cardiac arrest during surgery due to manipulation of the tumor triggering secondary necrosis and hyperkalemia. Case presentation: This case describes a very preterm infant with a SCT who develops spontaneous preoperative tumor lysis syndrome (TLS). The medical team utilized rasburicase and the patient underwent total gross resection at 40 h of life. Conclusions: We emphasize the importance of the early recognition and management of tumor lysis syndrome in SCT with rasburicase, aggressive management of hyperkalemia and consideration of early resection of SCTs even in the case of a very premature infant. [ABSTRACT FROM AUTHOR]

Introduction: Tumor lysis syndrome (TLS) is often diagnosed in children with hematological malignancies and can be life threatening due to metabolic disturbances. Continuous renal replacement therapy (CKRT) can reverse these disturbances relatively quickly when conventional medical management fails. Our objective was to investigate the benefit of CKRT in the management of TLS in children admitted to the intensive care unit with hematologic malignancies. In addition, we sought to assess risk factors for acute kidney injury (AKI) in the setting of TLS. Methods: Retrospective review of all children admitted to the intensive care unit with TLS who received CKRT from January 2012 to August 2022. Results: Among 222 children hospitalized with TLS from January 2012 to August 2022, 20 (9%) underwent CKRT to manage TLS in the intensive care unit. The patients' median age was 13 years (range 3-17 y), and most were males (18/20). Tcell acute lymphoblastic leukemia was the most common diagnosis (n=10), followed by acute myeloid leukemia (n=4), Burkitt lymphoma (n=4), and B-cell acute lymphoblastic leukemia (n=2). Five patients required mechanical ventilation, and 2 required vasopressors. The most common indication for CKRT was hyperphosphatemia, followed by, hyperuricemia, and hyperkalemia. All metabolic abnormalities corrected within 12 h of initiation of CKRT. CKRT courses were brief, with a median duration of 2 days (range 1-7 days). Having higher serum phosphorus levels 12 h preceding CKRT was significantly associated with severe acute kidney injury (AKI). The median phosphorus level was 6.4 mg/dL in children with no/mild AKI and 10.5 mg/dL in children with severe AKI (p=0.0375). Serum uric acid levels before CKRT were not associated with AKI. All children survived to hospital discharge, and the one-year survival rate was 90%. Conclusion: CKRT is safe in children with hematologic malignancies with severe TLS and reverses metabolic derangements within 6-12 h. Most patients had AKI at the initiation of CKRT but did not require long-term kidney replacement therapy. Hyperphosphatemia before initiation of CKRT is associated with higher risk of AKI. [ABSTRACT FROM AUTHOR]

Uricase (or Urate oxidase), a key enzyme involved in purine metabolism, is commonly used in treating conditions such as gout, hyperuricemia, and tumor lysis syndrome. In this study, a uricase-producing strain (named CSAJ-16) was isolated from the soil sample of Cangshan Mountain, Yunnan Province, China. This strain was identified as Arthrobacter sp. CSAJ-16. Based on the gene sequence alignment, the uricase gene (named aruox) of Arthrobacter sp. CSAJ-16 was amplified and heterologously expressed. The recombinant uricase (ArUOX) was about 32 kDa. The optimal pH and temperature of ArUOX were pH 7 and 20°C, respectively. The ArUOX remained above 50% relative activity after incubation at 37°C for 100 min or at pH 6.0–8.6 for 24 h. Moreover, metal ions such as K+, Mg2+, Ca2+, Ba2+ and Pb2+ can significantly enhance the activity of ArUOX (> 200%). These enzymatic properties indicate that ArUOX has potential applications in pharmaceutical enzymes and uric acid detection kits. [ABSTRACT FROM AUTHOR]

Background: The Warburg effect is a rare condition in tumor biology, illustrated by significant lactate production in the presence of oxygen. The Warburg effect is associated with very poor prognosis in patients with malignancy. Case presentation: We report a 76-year-old Caucasian woman with double-expressor diffuse large B cell lymphoma who presented with severe lactic acidosis and extreme hypoglycemia with normal mentation. Her lactic acidosis was initially controlled with a bicarbonate infusion, and the patient was started promptly on steroids, followed by chemotherapy, but her clinical course was complicated by tumor lysis syndrome, acute renal failure requiring hemodialysis, and progressive liver failure. She manifested a temporary clinical response to chemotherapy but eventually died of complications. Conclusions: This case demonstrates the importance of prompt recognition of the Warburg effect, aggressive supportive measures, and early initiation of chemotherapy. Future studies are needed to characterize the role of hemodialysis in this setting. [ABSTRACT FROM AUTHOR]

Type B lactic acidosis is an uncommon medical emergency in which acid production overwhelms hepatic clearance. This specific etiology of lactic acidosis occurs without organ hypoperfusion and has been most commonly described in patients with hematologic malignancies but also in patients with solid tumors. The mechanism by which cancer cells switch their glucose metabolism toward increasingly anaerobic glycolytic phenotypes has been described as the "Warburg effect." Without treating the underlying malignancy, the prognosis for patients diagnosed with malignancy-related type B lactic acidosis is extremely poor. Here, we present a case of a 66-year-old male who was diagnosed with type B lactic acidosis secondary to mantle cell lymphoma. Bicarbonate drip was started to correct the lactic acidosis. The patient was also immediately treated with rituximab chemotherapy combined with rasburicase to avoid the hyperuricemia associated with tumor lysis syndrome. He responded to the early treatment and was discharged with normal renal function. Type B lactic acidosis secondary to hematologic malignancy is important to recognize. In order to successfully treat this syndrome, early diagnosis and simultaneous treatment of the imbalance of lactic acid levels and the underlying malignancy are necessary. [ABSTRACT FROM AUTHOR]

Background/aim: In terms of breast cancer risk, there is no consensus on the effect of uric acid (UA) levels. The aim of our study was to clarify the link between UA and breast cancer risk in a prospective case–control study and to find the UA threshold point. Methods: We designed a case–control study with 1050 females (525 newly diagnosed breast cancer patients and 525 controls). We measured the UA levels at baseline and confirmed the incidence of breast cancer through postoperative pathology. We used binary logistic regression to study the association between breast cancer and UA. In addition, we performed restricted cubic splines to evaluate the potential nonlinear links between UA and breast cancer risk. We used threshold effect analysis to identify the UA cut-off point. Results: After adjusting for multiple confounding factors, we found that compared with the referential level (3.5–4.4 mg/dl), the odds ratio (OR) of breast cancer was 1.946 (95% CI 1.140–3.321) (P < 0.05) in the lowest UA level and 2.245 (95% CI 0.946–5.326) (P > 0.05) in the highest level. Using the restricted cubic bar diagram, we disclosed a J-shaped association between UA and breast cancer risk (P-nonlinear < 0.05) after adjusting for all confounders. In our study, 3.6 mg/dl was found to be the UA threshold which acted as the optimal turning point of the curve. The OR for breast cancer was 0.170 (95% CI 0.056–0.512) to the left and 1.283 (95% CI 1.074–1.532) to the right of 3.6 mg/dl UA (P for log likelihood ratio test < 0.05). Conclusion: We found a J-shaped association between UA and breast cancer risk. Controlling the UA level around the threshold point of 3.6 mg/dl provides a novel insight into breast cancer prevention. [ABSTRACT FROM AUTHOR]

Introduction. It is now known that cancer is a major public health problem; on the other hand, it is less known, or rather, often underestimated, that a significant percentage of cancer patients will experience a cancer-related emergency. These conditions, depending on the severity, may require treatment in intensive care or in the emergency departments. In addition, it is not uncommon for a tumor pathology to manifest itself directly, in the first instance, with a related emergency. The emergency unit proves to be a fundamental and central unit in the management of cancer patients. Many cancer cases are diagnosed in the first instance as a result of symptoms that lead the patient's admittance into the emergency room. Materials and Methods. This narrative review aims to analyze the impact of acute oncological cases in the emergency setting and the role of the emergency physician in their management. A search was conducted over the period January 1981–April 2023 using the main scientific platforms, including PubMed, Scopus, Medline, Embase and Google scholar, and 156 papers were analyzed. Results. To probe into the main oncological emergencies and their management in increasingly overcrowded emergency departments, we analyzed the following acute pathologies: neurological emergencies, metabolic and endocrinological emergencies, vascular emergencies, malignant effusions, neutropenic fever and anemia. Discussion/Conclusions. Our analysis found that a redefinition of the emergency department connected with the treatment of oncology patients is necessary, considering not only the treatment of the oncological disease in the strict sense, but also the comorbidities, the oncological emergencies and the palliative care setting. The need to redesign an emergency department that is able to manage acute oncological cases and end of life appears clear, especially when this turns out to be related to severe effects that cannot be managed at home with integrated home care. In conclusion, a redefinition of the paradigm appears mandatory, such as the integration between the various specialists belonging to oncological medicine and the emergency department. Therefore, our work aims to provide what can be a handbook to detect, diagnose and treat oncological emergencies, hoping for patient management in a multidisciplinary perspective, which could also lead to the regular presence of an oncologist in the emergency room. [ABSTRACT FROM AUTHOR]

The bone marrow niche maintains hematopoietic stem cell (HSC) homeostasis and declines in function in the physiologically aging population and in patients with hematological malignancies. A fundamental question is now whether and how HSCs are able to renew or repair their niche. Here, we show that disabling HSCs based on disrupting autophagy accelerated niche aging in mice, whereas transplantation of young, but not aged or impaired, donor HSCs normalized niche cell populations and restored niche factors in host mice carrying an artificially harassed niche and in physiologically aged host mice, as well as in leukemia patients. Mechanistically, HSCs, identified using a donor lineage fluorescence‐tracing system, transdifferentiate in an autophagy‐dependent manner into functional niche cells in the host that include mesenchymal stromal cells and endothelial cells, previously regarded as "nonhematopoietic" sources. Our findings thus identify young donor HSCs as a primary parental source of the niche, thereby suggesting a clinical solution to revitalizing aged or damaged bone marrow hematopoietic niche. [ABSTRACT FROM AUTHOR]

Background: Acute myocardial infarction is life threatening condition. Prompt action is essential as it has very high mortality in hospital and long-term mortality and morbidity. Recent studies which states the association between killip class and uric acid level. So our goal is to find out the any quantal relationship between killip class and serum uric acid in acute myocardial infarction in our population. This study aims to determine the serum uric acid levels in patients with acute myocardial infraction and to corelate the levels of uric acid with the severity of myocardial infraction. Material and Methods: 100 Patients more than 18 years of age who were diagnosed as a case of ST elevation myocardial infarction were included. The subjects were diagnosed with history, physical examination, electrocardiographic changes and biochemical markers. Results: The results in our study shows that Serum Uric acid levels are significantly higher in Killip Class 3 & 4 that is correlated similarly to ECHO cardiographic findings (moderate and severe LV dysfunction). Conclusion: The study results show that elevated Uric acid level had an objective correlation with ECHO cardio graphic evaluation of LV dysfunction. Combination of Serum Uric acid and Killip's class after STEMI is a good predictor of mortality and severity of heart failure. [ABSTRACT FROM AUTHOR]

No systematic synthesis of all cases of spontaneous tumor lysis syndrome (STLS) in adult patients with solid tumors is available to date. Herein, we aim to recognize specific STLS characteristics and parameters related to a worse prognosis. We conducted a systematic search for randomized controlled trials, cohorts, case-control studies, and case reports. The primary endpoints were death and the need for renal replacement therapy (RRT) due to STLS. We estimated crude odds ratios (ORs) with 95% confidence intervals (95%CI) via univariate binary logistic regression. We included one cohort of 9 patients and 66 case reports of 71 patients [lung cancer 15(21.1%)]. Regarding the case reports, most patients [61(87.1%)] had metastatic disease [liver 46(75.4%)], developed acute kidney injury [59(83.1%)], needed RRT [25(37.3%)], and died due to STLS [36(55.4%)]. Metastatic disease, especially in the liver [p = 0.035; OR (95%CI): 9.88 (1.09, 89.29)] or lungs [p = 0.024; 14.00 (1.37, 142.89)], was significantly associated with STLS-related death compared to no metastasis. Cases resulting in death had a significantly higher probability of receiving rasburicase monotherapy than receiving no urate-lowering agents [p = 0.034; 5.33 (1.09, 26.61)], or the allopurinol-rasburicase combination [p = 0.023; 7.47 (1.40, 39.84)]. Patients receiving allopurinol were less likely to need RRT compared to those not receiving it or those receiving rasburicase. In conclusion, current anecdotal evidence demonstrated that metastatic disease, especially in the liver and lungs, may be associated with STLS-related death compared to no metastatic status. Careful surveillance of high-risk cases within larger studies is essential to identify markers predicting morbidity or mortality. [ABSTRACT FROM AUTHOR]

Introduction: Our study investigated leukapheresis's effect on delayed induction therapy outcomes in patients with acute leukemia presenting with symptomatic hyperleukocytosis. Methods: This retrospective cohort study included 30 adult patients diagnosed with acute leukemia who underwent leukapheresis for leukostasis. The patients were divided into the first 24 h and >24 h groups, according to the time from diagnosis to induction therapy (TDT). Results: There was no significant difference between the TDT groups regarding complete remission (CR), 4‐week mortality, and overall survival (OS) at a median follow‐up of 409 days. Tumor lysis syndrome, disseminated intravascular coagulation, and hemoglobin levels were significant in early mortality. In univariate analysis, age, hemoglobin levels, patients' eligibility for intensive chemotherapy, and achieving CR were critical factors for OS. Conclusion: The study findings suggest that waiting for the clinical and laboratory results may be a safe and reasonable approach before assigning patients the best treatment option with leukapheresis. [ABSTRACT FROM AUTHOR]

Background: In patients undergoing percutaneous coronary intervention (PCI), contrast-induced acute kidney injury (CIAKI) is a frequent complication, especially in diabetics, and is connected with severe mortality and morbidity in the short and long term. Therefore, we aimed to develop a CIAKI predictive model for diabetic patients. Methods: 3514 patients with diabetes from four hospitals were separated into three cohorts: training, internal validation, and external validation. We developed six machine learning (ML) algorithms models: random forest (RF), gradient-boosted decision trees (GBDT), logistic regression (LR), least absolute shrinkage and selection operator with LR, extreme gradient boosting trees (XGBT), and support vector machine (SVM). The area under the receiver operating characteristic curve (AUC) of ML models was compared to the prior score model, and developed a brief CIAKI prediction model for diabetes (BCPMD). We also validated BCPMD model on the prospective cohort of 172 patients from one of the hospitals. To explain the prediction model, the shapley additive explanations (SHAP) approach was used. Results: In the six ML models, XGBT performed best in the cohort of internal (AUC: 0.816 (95% CI 0.777–0.853)) and external validation (AUC: 0.816 (95% CI 0.770–0.861)), and we determined the top 15 important predictors in XGBT model as BCPMD model variables. The features of BCPMD included acute coronary syndromes (ACS), urine protein level, diuretics, left ventricular ejection fraction (LVEF) (%), hemoglobin (g/L), congestive heart failure (CHF), stable Angina, uric acid (umol/L), preoperative diastolic blood pressure (DBP) (mmHg), contrast volumes (mL), albumin (g/L), baseline creatinine (umol/L), vessels of coronary artery disease, glucose (mmol/L) and diabetes history (yrs). Then, we validated BCPMD in the cohort of internal validation (AUC: 0.819 (95% CI 0.783–0.855)), the cohort of external validation (AUC: 0.805 (95% CI 0.755–0.850)) and the cohort of prospective validation (AUC: 0.801 (95% CI 0.688–0.887)). SHAP was constructed to provide personalized interpretation for each patient. Our model also has been developed into an online web risk calculator. MissForest was used to handle the missing values of the calculator. Conclusion: We developed a novel risk calculator for CIAKI in diabetes based on the ML model, which can help clinicians achieve real-time prediction and explainable clinical decisions. [ABSTRACT FROM AUTHOR]

We introduce a new model that captures the cellular evolution of patients with chronic lymphocytic leukemia who are receiving chemotherapy. As chemotherapy can induce allergic reactions and tumor lysis syndrome, we took into account the process of desensitization and the number of dead leukemic cells in the body. The mathematical model uses delayed-differential equations. Qualitative properties of the solutions are proved, including partial stability with respect to some variables and to the invariant set of positive initial data. Numerical simulations are also used to complete the description of the interplay between the immune system's function, the chemotherapeutic activity and the allergic reactions caused by the therapy. [ABSTRACT FROM AUTHOR]

Background: Impaired sensitivity to thyroid hormones is a newly proposed clinical entity associated with hyperuricemia in the subclinical hypothyroid population. However, it is unknown whether the association exists in the euthyroid population. This study aimed to explore the association of impaired sensitivity to thyroid hormones (assessed by the thyroid feedback quantile-based index [TFQI], parametric thyroid feedback quantile-based index [PTFQI], thyrotrophic thyroxine resistance index [TT4RI] and thyroid-stimulating hormone index [TSHI]) with hyperuricemia and quantify the mediating effect of body mass index BMI in the euthyroid population. Methods: This cross-sectional study enrolled Chinese adults aged ≥ 20 years who participated in the Beijing Health Management Cohort (2008–2019). Adjusted logistic regression models were used to explore the association between indices of sensitivity to thyroid hormones and hyperuricemia. Odds ratios [OR] and absolute risk differences [ARD] were calculated. Mediation analyses were performed to estimate direct and indirect effects through BMI. Results: Of 30,857 participants, 19,031 (61.7%) were male; the mean (SD) age was 47.3 (13.3) years; and 6,515 (21.1%) had hyperuricemia. After adjusting for confounders, individuals in the highest group of thyroid hormone sensitivity indices were associated with an increased prevalence of hyperuricemia compared with the lowest group (TFQI: OR = 1.18, 95% CI 1.04–1.35; PTFQI: OR = 1.20, 95% CI 1.05–1.36; TT4RI: OR = 1.17, 95% CI 1.08–1.27; TSHI: OR = 1.12, 95% CI 1.04–1.21). BMI significantly mediated 32.35%, 32.29%, 39.63%, and 37.68% of the associations of TFQI, PTFQI, TT4RI and TSHI with hyperuricemia, respectively. Conclusions: Our research revealed that BMI mediated the association between impaired sensitivity to thyroid hormones and hyperuricemia in the euthyroid population. These findings could provide useful evidence for understanding the interaction between impaired sensitivity to thyroid hormone and hyperuricemia in euthyroid individuals and suggest the clinical implications of weight control in terms of impaired thyroid hormones sensitivity. Keypoints: Quetions To what extent is impaired sensitivity to thyroid hormones associated with hyperuricemia through body mass index (BMI) in the euthyroid population? Findings In this cross-sectional study of 30,857 euthyroid adults, impaired sensitivity to thyroid hormones was independently associated with an increased prevalence of hyperuricemia. BMI mediated 32.3–39.6% of the association between impaired sensitivity to thyroid hormones and hyperuricemia. Meaning This study revealed that BMI mediated the association between impaired sensitivity to thyroid hormones and hyperuricemia in the euthyroid population, suggesting the potential clinical benefit of weight control in maintaining metabolic health among individuals with impaired thyroid hormones sensitivity. [ABSTRACT FROM AUTHOR]

Summary: This retrospective, observational study evaluated patterns of inpatient versus outpatient tumour lysis syndrome (TLS) monitoring during venetoclax ramp‐up in 170 patients with chronic lymphocytic leukaemia. The primary outcome was clinical/biochemical TLS. Two clinical and four biochemical TLS occurred (4.1%). Five of the six events occurred in high‐risk patients, four occurred at 20 mg dose and three at the 6‐h time‐point. Inpatient versus outpatient TLS rates within the high‐risk subgroup were 15% and 8%. Risk category was the only predictor of TLS events in multivariate analysis. Outpatient escalation did not associate with clinically meaningful TLS events, suggesting outpatient escalation has manageable associated TLS risks, including in high‐risk cohorts. These observations require confirmation in larger studies. [ABSTRACT FROM AUTHOR]

Background: Gestational Diabetes Mellitus (GDM) is a prevalent metabolic disorder during pregnancy, carrying significant health risks for both mothers and infants. Early detection and risk assessment are crucial for effective management. This study investigates the potential of first-trimester serum uric acid levels as an early predictor of GDM in pregnant women attending a tertiary care hospital in Uttar Pradesh, India. Material and Methods: A prospective cohort study was conducted, enrolling 500 pregnant women in their first trimester. Clinical data, including demographic information, medical history, and anthropometric measurements, were collected. Laboratory measurements of uric acid, fasting glucose, and insulin resistance indices were performed. Participants were followed throughout pregnancy, and GDM diagnosis was established using the standard oral glucose tolerance test (OGTT) during the second trimester. Statistical analysis included logistic regression, ROC curve analysis, and calculation of sensitivity, specificity, and predictive values. Results: Elevated first-trimester serum uric acid levels exhibited a significant association with GDM development. Participants with uric acid levels between 4.0 - 4.5 mg/dL had an odds ratio of 1.82 (95% CI: 1.51-2.21) compared to those with levels below 4.0 mg/dL, indicating increased GDM risk. Uric acid levels > 4.5 mg/dL showed a sensitivity of 85% but a specificity of 68%. Combining uric acid with traditional risk factors, such as maternal age and BMI, may enhance predictive accuracy. Conclusion: First-trimester serum uric acid levels are a potential early predictor of GDM. Elevated uric acid levels were associated with increased GDM risk, though specificity may benefit from a multi-factorial predictive model. This study underscores the clinical significance of uric acid in GDM risk assessment and highlights the potential for improved screening strategies. [ABSTRACT FROM AUTHOR]

Summary: There are a diverse range of haematological malignancies with varying clinical presentations and prognoses. Patients with haematological malignancy may require admission to critical care at the time of diagnosis or due to treatment related effects and complications. Although the prognosis for such patients requiring critical care has improved, there remain uncertainties in optimal clinical management. Identification of patients who will benefit from critical care admission is challenging and selective involvement of palliative care may help to reduce unnecessary and non‐beneficial treatments. While patients with haematological malignancy can present a challenge to critical care physicians, good outcomes can be achieved. In this narrative review, we provide a brief overview of relevant haematological malignancies for the critical care physician and a summary of recent treatment advances. Subsequently, we focus on critical care management for the patient with haematological malignancy including sepsis; acute respiratory failure; prevention and treatment of tumour lysis syndrome; thrombocytopaenia; and venous thromboembolism. We also discuss immunotherapeutic‐specific related complications and their management, including cytokine release syndrome and immune effector cell associated neurotoxicity syndrome associated with chimeric antigen receptor T‐cell therapy. While the management of haematological malignancies is highly specialised and increasingly centralised, acutely unwell patients often present to their local hospital with complications requiring critical care expertise. The aim of this review is to provide a contemporary overview of disease and management principles for non‐specialist critical care teams. [ABSTRACT FROM AUTHOR]

Background: Arteriovenous fistula dysfunction is a widely disputed subject in the scientific literature on end-stage kidney disease (ESKD). The main cause of mortality and morbidity in these patients is the non-maturation or dysfunction of the arteriovenous fistula. Despite the many complications, the native arteriovenous fistula remains the gold standard in the treatment of these patients requiring renal replacement. This study aims to discuss the predictive role of some systemic inflammatory biomarkers (NLR, PLR, SII, IL-6), intimal hyperplasia, and neoangiogenesis (characterized by intimal-media CD31-positive relative surface) in arteriovenous fistula maturation failure. Methods: The present study was designed as an observational, analytical, and prospective study which included patients diagnosed with ESKD with indications of radio-cephalic arteriovenous fistula (RCAVF). Demographic data, comorbidities, preoperative laboratory data and histological/digital morphometry analysis results were processed. The patients included were divided into two groups based on their AVF maturation status at 8 weeks: "Maturation" (Group 1) and "Failed Maturation" (Group 2). Results: There was no difference in the demographic data. In terms of comorbidities, the second group had a greater incidence of heart failure (p = 0.03), diabetes (p = 0.04), peripheral artery disease (p = 0.002), and obesity (p = 0.01). Additionally, regarding the laboratory findings, these patients had higher levels of serum uric acid (p = 0.0005), phosphates (p < 0.0001), and creatinine (p = 0.02), as well as lower levels of total calcium (p = 0.0002), monocytes (p = 0.008), and lymphocytes (p < 0.0001). Moreover, all inflammatory markers (p = 0.001; p < 0.0001; p = 0.006, and p = 0.03) and Ca-P product (p < 0.0001) had higher baseline values in Group 2. Upon immunohistochemical analysis, regarding the density of neoformed vessels, there was a higher incidence of CD31-positive surfaces (p = 0.006) and CD31-positive relative surfaces (p = 0.001); the NLR (r = 0.323; p = 0.03), PLR (r = 0.381; p = 0.04), SII (r = 0.376; p = 0.03), and IL-6 (r = 0.611; p < 0.001) are all significantly correlated with vascular density, as evidenced by CD31. Conclusions: Heart failure, peripheral artery disease, obesity, and diabetes, as well as the systemic inflammatory markers (NLR, PLR, SII, IL-6), intimal hyperplasia, and CD31-positive relative surfaces are predictors of arteriovenous fistula maturation failures. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to determine the levels of C-reactive protein and uric acid levels in preeclampsia pregnant and to determine severity by the association among CRP, uric acid concentration, BMI and blood pressure. Methods: A case control study was conducted in 30 diagnosed preeclamptic pregnancy, 30 normal pregnant women of comparable gestational age in 3rd trimester admitted in the dept. of obstetrics and gynaecology. Results: Maximum number of PE cases belongs to age group of 31-35 years (60%) and maximum number of control group belongs to age group of 21-25 years (40%). It was also observed that mean age in control group is 25.5±3.6 (years), whereas in study group 29.5±4.2 (Years). In study group, maximum number of patients have severe proteinuria i. e. >+++ (55%), and in control group maximum number of patients have proteinuria of (+) (58%) which is considered as physiologically normal. But, both study and control groups mild proteinuria (++) is observed in 40% and 38% patients respectively. There was a significant difference of proteinuria between study group and control group (p=0.001). The mean values of serum uric acid and CRP levels always remain higher in study group than that of control group. The mean values of both serum uric acid and CRP levels in study group were near to their respective upper limits of normal range. There was a strong positive correlation between serum uric acid and blood pressure (systolic and diastolic) with highly significant. A positive correlation is also observed between serum uric acid and serum CRP level. Conclusion: Serum uric acid and CRP may be feasible to be used as biomarkers for identifying women at risk of preeclampsia. The aetiology of preeclampsia is not well established but having more information about the condition will help in the monitoring and treatment of the pregnant to ensure her and her baby are well. [ABSTRACT FROM AUTHOR]

Although some tumor lysis syndrome (TLS) cases have been reported with patients with multiple myeloma (MM) taking monoclonal antibodies (mAbs), the association between TLS and mAbs remains mostly unknown. We aim to investigate the association between TLS and mAbs and describe clinical features. We conducted a disproportionality analysis to investigate the link between mAbs and TLS by excluding known confounders and compared with other anticancer drugs. The association between mAbs and TLS was evaluated using information component (IC). Drug–drug interaction signals were calculated based on the Ω shrinkage measure. Parametric distribution with the goodness‐of‐fit test was used for the reported time‐to‐onset analysis. From 2016 Q1, to 2022 Q4, a total of 274 TLS with mAbs were reported in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. There were 27% of patients with TLS with mAbs who died and 20.1% occurred a life‐threatening situation. Daratumumab, elotuzumab, and belantamab mafodotin presented a robust disproportionate signal of TLS after excluding known confounders (IC025 > 0). Daratumumab had the highest disproportionate signal of TLS among all anticancer drugs for MM. Reported time‐to‐onset analysis showed the median days for TLS with daratumumab, isatuximab, elotuzumab, and belantamab mafodotin were 1.5, 14.5, 5.5, and 5.5 days, respectively. The drug–drug interaction analysis showed the co‐administration of drugs known to increase urate, induce hyperkalemia, or hypocalcemia elevated the reporting frequency for TLS with mAbs (Ω025 > 0). Our postmarketing pharmacovigilance analysis detected the reporting association of TLS and mAbs in patients with MM. Additional studies with robust epidemiological study designs that can validate these findings are warranted. [ABSTRACT FROM AUTHOR]