Elevated Lactate Dehydrogenase Research Articles

APPLICATION OF THE INTERNATIONAL NEUROBLASTOMA RISK GROUP STAGING SYSTEM 2009 (INRGSS 2009) IN DIAGNOSIS AND PROGNOSIS OF CHILDHOOD NEUROBLASTOMA

Background: Neuroblastoma is the most common extracranial solid tumor of childhood. INRGSS 2009 divides patients into stages L1, L2, M, Ms, from which, in combination with histopathology, molecular biology, each patient will be divided into risk groups from which to guide prognosis and suitable treatment. Objectives: Describe the clinical and laboratory features of neuroblastoma in children; distribution of pediatric neuroblastoma stages according to the INRGSS 2009 classification and its value in predicting survival outcomes. Methods: This was a cross-sectional study combined with retrospective and prospective. Patients were diagnosed with neuroblastoma and classified according to INRGSS 2009 at the Pediatric Center, Hue Central Hospital. Results: The age at the time of diagnosis ranged from 1 day old to 9 years old, with a mean of 35.4 ± 25.5 months. Regarding primary tumor, 73.5% of cases were found in the abdomen, the mediastinum region (22.4%), an undetermined region (4.1%). Systemic symptoms, local symptoms and symptoms caused by metastasis were frequently reported. At the time of diagnosis, 73.5% of the patients had distant metastases (stage M or MS). The EFS of the whole group at 12 and 24 months old were 86.3 % and 64.7% respectively. The OS was 77.9% at 24 months old. Most of these patients had a progressive disease: 6.1% were in stage L1; 20.4% were in stage L2; 69.4% were in stage M; and 4.1% were in stage MS. Estimated mean of event-free survival for L1 was 38.7 ± 3.5 months, L2 was 40.5 ± 4.2 months and M was 28.0 ± 2.5 months (p < 0.05). Conclusions: Most neuroblastoma tumors are abdominal and have distant metastases. LDH and ferritin elevations are prevalent. Neuroblastoma outcomes can be predicted using the INRGSS 2009 classification.

Abstract PO1-18-07: Phase I trial of combination pembrolizumab and ruxolitinib in metastatic triple negative breast cancer

Abstract BACKGROUND: The amplification of genes PDL-1, PDL-2, and JAK2 on chromosome 9p24, known as the PDJ amplicon, has been identified in 15% of triple negative breast cancer (TNBC) and is associated with tumor infiltrating lymphocytes and elevated JAK2 mRNA, suggesting a coordinated inflammatory response in TNBC. Adding pembrolizumab to chemotherapy in KEYNOTE trials 355 and 522 has validated the use of PD-1 blockade in TNBC and redefined the standard of care. Despite preclinical data suggesting a role for targeting the IL- 6/JAK2/STAT3 pathway, the JAK1/JAK2 inhibitor ruxolitinib has not shown efficacy as a single Agent in breast cancer. This is the first phase I clinical trial evaluating the combination of pembrolizumab and ruxolitinib in the treatment of metastatic TNBC. METHODS: We conducted a phase I clinical trial with accrual from 2018 to 2023 at Mayo Clinic Arizona. Patients (n=12) received 200 mg of IV pembrolizumab per cycle (every 3 weeks) with 3+3 dose escalation of oral ruxolitinib twice a day (dose level 0: 10 mg PO BID, level 1: 15 mg PO BID, level 2: 20 mg PO BID). The primary endpoint was to determine the maximum tolerated dose (MTD) of ruxolitinib and secondary endpoints were treatment safety and efficacy. Clinical response was assessed by computed tomography of the chest, abdomen, and pelvis every 3 cycles. PD-L1 expression in tumor was measured by immunohistochemistry (IHC). The effect of the combined therapies on T and B cell populations were assessed by flow cytometry and antibody profiling of 695 tumor antigens and 8 viral antigens by nucleic acid protein programmable array. RESULTS: Twelve female patients with chemotherapy refractory metastatic TNBC were treated on study. All received 200 mg IV pembrolizumab every cycle. Due to rapid disease progression of three patients early after treatment initiation, eligibility was restricted to prohibit patients with extensive pulmonary disease or elevated LDH. Those patients were excluded from efficacy or correlative analysis. The most common toxicities were transaminitis (n=12), anemia/leukopenia (n=12), and fatigue (n=9). The majority of adverse events were grade 1 and occurred at dose level 2. There were 5 adverse events grade 3 or higher: respiratory or thoracic complications (n=3), hypertension (n=1), and abdominal pain (n=1), but MTD was not established. The median number of cycles was 4 for each dose level (range n=2.0-9.0) and the median time to progression was 3 months (range n=1.4-6.3). No patient had tumor response by RECIST v1.1 criteria and there was no association of disease stability with PD-L1 tumor expression by IHC. Circulating antibodies to tumor antigens remained stable, and viral-specific antibodies mildly decreased by month 2 in all patients at dose levels 0 and 1. Of the 7 patients reactive to TRIM21 autoantibodies, 2 patients had a transient increase at 2 months. CONCLUSIONS: The combination of pembrolizumab with ruxolitinib was well tolerated at all dose levels, and the number but not the severity of adverse events increased with higher ruxolitinib dose. Two of six patients in dose level 0 and 1 had stable disease for six months on treatment, suggesting that the lower dose levels of ruxolitinib (i.e. 10 mg PO BID) may have more activity in combination with pembrolizumab. Citation Format: Anelia Kassi, Jacqueline Carmona, Sarah M. Green, Heidi Kosiorek, Michael T. Barrett, Barbara A. Pockaj, Donald Northfelt, Karen S. Anderson. Phase I trial of combination pembrolizumab and ruxolitinib in metastatic triple negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-18-07.

Hemoglobin, Ferritin, and Lactate Dehydrogenase as Predictive Markers for Neonatal Sepsis

(1) Background: This study evaluates the predictive effectiveness of biomarkers in diagnosing newborn sepsis. (2) Methods: This was a case–control study conducted on neonates hospitalized at the Clinical Hospital “Louis Turcanu”, Timisoara, Romania, from October 2018 to July 2023. Using a vacutainer collection device, venous blood was collected at admission for complete blood tests, including ferritin, hemoglobin, LDH, and blood culture analysis. Neonates were divided into two groups: sepsis-positive and sepsis-negative. The outcome of interest was a diagnosis of sepsis. (3) Results: Data from 86 neonates, 51 of whom had been confirmed to have sepsis, were analyzed. This study found no significant difference in gestational age, infant weight, fetal growth restriction, or APGAR score between neonates with and without sepsis. However, there was a higher incidence of sepsis among neonates delivered via cesarean section. Neonatal patients with sepsis showed significantly higher levels of neonatal serum ferritin and LDH compared to those without sepsis. Ferritin and LDH biomarkers demonstrated excellent discriminatory capabilities in diagnosing neonatal sepsis. Logistic regression analysis revealed a significant association between elevated ferritin and LDH levels and the likelihood of neonatal sepsis, while anemia did not show a significant association. (4) Conclusions: LDH and ferritin concentrations are found to be predictive biomarkers for neonatal sepsis, indicating a potential role in detecting susceptible neonates and implementing prompt interventions to improve patient outcomes.

Treatment patterns, clinical outcomes and gene mutation characteristics of hepatitis B virus-associated mantle cell lymphoma.

Mantle cell lymphoma (MCL) is an uncommon and incurable B-cell lymphoma subtype that has an aggressive course. Hepatitis B virus (HBV) infection has been associated with an increased risk for B-cell lymphomas, and is characterized by distinct clinical and genetic features. Here, we showed that 9.5% of MCL Chinese patients were hepatitis B surface antigen positive (HBsAg+). Compared to HBsAg-negative (HBsAg-) patients, HBsAg+ MCL patients had a greater incidence of elevated lactate dehydrogenase (LDH), but no difference was observed in the other clinical characteristics, including sex, age, ECOG ps, Ann Arbor stage, MIPI, extranodal involvement and Ki-67. The HD-AraC (high-dose cytarabine) regimen was the main first-line induction regimen for younger HBsAg+ patients, and cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) were used for elderly patients. HBsAg seropositivity was associated with a significantly shorter PFS than HBsAg seronegativity when patients were treated with rituximab or CHOP-based regimens. Compared with CHOP, the HD-AraC regimen was associated with longer PFS in HBsAg+ patients. Treatment with a Bruton tyrosine kinase inhibitor (BTKi) alone can also cause HBV reactivation. Among the 74 patients who underwent targeted deep sequencing (TDS), the nonsynonymous mutation load of HBsAg+ MCL patients was greater than that of HBsAg- MCL patients. HDAC1, TRAF5, FGFR4, SMAD2, JAK3, SMC1A, ZAP70, BLM, CDK12, PLCG2, SMO, TP63, NF1, PTPR, EPHA2, RPTOR and FIP1L1 were significantly enriched in HBsAg+ MCL patients.

Clinical Characteristics, Prognostic Factors and Outcomes of Paediatric Patients with Haemophagocytic Lymphohistiocytosis

Objective: Haemophagocytic lymphohistiocytosis (HLH) is a multi-system autoimmune disorder. The objective of this study was to find out the clinical characteristics and prognosis of paediatric patients with Haemophagocytic Lymphohistiocytosis. Study Design and setting: Cross sectional study conducted at Pak Emirates Military Hospital, Rawalpindi from July 2021 to June 2023.   Methodology: Children with diagnosis of HLH were assessed by including patients who were aged = 13 years during hospitalization. All the patients who had not been diagnosed by using the HLH-2004 criteria were disqualified. Relevant findings were noted by evaluating records pertinent to physical examination, radiology and laboratory markers. Prognosis was assessed by determining the underlying clinical aetiology and whether patient-related factors modulated the overall life expectancy.   Results: A total of 32 patient records were evaluated. Mean age at diagnosis was 44.3 ± 39.1 months (Range: 1-132 months) with majority being males [n=23 (71.9%)]. The common clinical characteristics included fever [n=29 (90.6%)], lymphadenopathy [n=27 (84.4%)], splenomegaly [n=23 (71.9%)] and hepatomegaly [n=23 (71.9%)]. Serum ferritin, bilirubin, ALT, AST, and LDH were also raised. All patients were followed for a mean period of 12 months and 18 (56.3%) children failed to survive. Negative prognostic indicators included severe anaemia (p=0.001), neutropenia (p=0.007), thrombocytopenia (p=0.033), and hyperferritinemia (p<0.001). Elevation of liver enzymes (ALT: p<0.001; AST: p=0.031), serum bilirubin (p=0.037), and LDH (p<0.001) also indicated worse disease prognosis.   Conclusion: HLH in childhood is a potentially life-threatening disease and carries a significant association with deranged liver function

P022 Unmasking the storm: hemophagocytic lymphohistiocytosis in systemic lupus erythematosus - a case series

Abstract Background/Aims Hemophagocytic lymphohistiocytosis (HLH), a critical illness of uncontrolled immunological activity and hyperinflammation, manifests as primary/familial or secondary form. Secondary HLH can be of multi-faceted etiology including infections, cancer, autoimmune and immunodeficiencies. HLH in context of systemic lupus erythematosus (SLE) is a rare entity and mirrors the clinical picture of SLE flare, adding to the diagnostic dilemma. Methods Our objective is to consider HLH as a key differential in unidentified autoimmune diseases. We present a trio of cases of undiagnosed SLE manifesting as HLH. Results A 13-year-old male presented with fever, rash, oral ulcers, and jaundice for a month with passage of dark coloured urine for last seven days. On examination, he had generalized lymphadenopathy, erythematous maculopapular rashes, palpable purpura, non-scarring alopecia, and hepatosplenomegaly. The labs revealed pancytopenia (Hb 9.8g/dL, WBC 2000/mm3, Platelets 23000/mm3), deranged creatinine (1.6mg/dL), transaminitis and hyperbilirubinemia, hyper-ferritinemia (2420µg/dL), hypertriglyceridemia (280mg/dL), hypofibrinogenemia (142mg/dL), and nephrotic range proteinuria (3.7g/24h). Diagnosis of SLE was confirmed by high titres of antinuclear antibody (ANA) and anti-double stranded DNA (dsDNA) and anti-Smith positivity. Renal biopsy showed class II lupus nephritis and acute tubular necrosis. Bone marrow biopsy revealed hemophagocytosis and the diagnosis of SLE complicated by HLH was made. A 16-year-old girl presented with fever and headache for three weeks, worsening over last ten days with irritable behaviour for one day, and respiratory distress that necessitated endotracheal intubation. The presence of pancytopenia (9.1/1940/41000), transamintis, hyper-ferritinemia (4040µg/dL), hypertriglyceridemia (250mg/dL), and low fibrinogen (133mg/dL) in laboratory evaluation raised a compelling suspicion of HLH confirmed by hemophagocytosis on marrow biopsy. Cerebrospinal fluid analysis was unremarkable, however MRI detected features of vasculitis with vasculitic infarcts. Direct Coomb’s test was positive. Autoimmune profiling unveiled positive results for ANA, anti-dsDNA, and anti-Smith antibodies consistent with SLE. A 21-year-old female presented with fever and arthralgias for two months. Investigations were suggestive of pancytopenia (7/1050/36000), raised ESR (126mm/hr) and CRP (54 mg/dL), elevated ferritin (4320 µg/dL), lactate dehydrogenase (1068U/L) and triglycerides (439mg/dL). The marrow biopsy was negative for hemophagocytosis while her soluble interleukin - 2 receptor levels were elevated (2740 U/ml). ANA and dsDNA were positive in significant titres, complement levels were low and Coombs test was positive, thereby confirming the primary diagnosis of SLE. All patients received methylprednisolone pulse along with cyclophosphamide in case 1 and IVIG in case 2 and 3, resulting in remarkable improvement. Conclusion With a prevalence of 0.9-4.6%, HLH secondary to SLE is an uncommon entity. The diagnosis of HLH related to SLE is challenging since the symptoms overlap, however findings of hyperferritinemia, hypofibrinogenemia, and hypertriglyceridemia favour HLH over SLE. Once HLH is proven, immunological testing for SLE is warranted to prevent diagnostic delay. Early treatment is needed to combat such a fulminant life-threatening illness. Disclosure R. Mishra: None. A. Rohatgi: None. S. Anuradha: None. N. Kumar: None. S. Singhla: None. S.T. Mathews: None. S. Kumar: None. P. Gautam: None.

P024 Dermatomyositis, a blurred clinical picture

Abstract Background/Aims We present a case of MDA5 dermatomyositis(DM) in a 25-year-old male, initially presenting with seronegative inflammatory polyarthritis affecting the hands. No classic features of DM were noted and CK was normal. Sulfasalazine was started and subsequently stopped after an ALT rise. Lung-function performed prior to planned methotrexate was abnormal. A CT neck, thorax and abdomen showed unusual pulmonary appearances with focal basal ground glass opacities with reverse halo, without widespread interstitial lung disease(ILD). A bronchoscopy excluded atypical infection. He then developed scaly lesions over the extensor PIPJs, periungual lesions, periorbital swelling and sicca symptoms. CK remained normal, extended myositis screening was negative. LDH and troponins were elevated. A skin biopsy of the hand rash was consistent with dermatomyositis. Methods Muscle pain persisted and an MRI proximal muscles showed muscle oedema and inflammation. A muscle biopsy was requested but not performed as he developed an olecranon bursa with staphylococcal aureus infection. The bursa broke down, required wash-outs, antibiotics and was left to heal by secondary intention. A repeat myositis screen was positive for MDA5 antibody. Immunosuppression was delayed because of concerns that prednisolone, Mycophenolate mofetil(MMF) or Rituximab would cause further wound breakdown and increased risk of infection. The patient was monitored with serial lung-function but didn’t develop ILD. Dermatology confirmed there was active dermatomyositis in the wound edges. The wound only finally healed with additional IVIG therapy. The patient is now established on Rituximab, having been unable to tolerate MMF. Results This case highlights that continued reassessment of the evolving clinical picture is vital to reach the correct diagnosis, and that one should not be reassured by a normal CK. Instead the ALT rise (along with mild elevations of LDH and troponin) was likely reflecting muscle inflammation, not liver inflammation secondary to Sulfasalazine. The repeatedly infected olecranon bursa and large open wound raised concerns about immunosuppressive agents. However, the lack of healing was due to active DM and escalation of treatment was required rather than treatment delay. IVIG was given with excellent and rapid effect. This is licensed for refractory skin involvement in DM, to be considered when infection concern is high. Conclusion The pulmonary involvement with reverse halo sign was felt by the MDT to be nonspecific initially, with a wide differential. In the clinical context, this was reflecting an atypical presentation of MDA5 positive ILD. This antibody can be associated with rapidly progressive ILD and death in approximately one third of cases. Had our patient shown evidence of significant pulmonary progression, high dose immunosuppression would have been commenced despite potential infection risk. Not all patients testing positive for MDA5 develop rapidly progressive ILD but clinical suspicion should be high with frequent serial monitoring of lung function and radiology. Disclosure L. Maltas: None. J. Vila: None. A. Ray: None.

Tumor lysis syndrome following letrozole for locally advanced breast cancer: a case report

BackgroundLetrozole, 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 presentationAn 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.ConclusionsAlthough 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.

OA14 Subcutaneous panniculitis-like T-cell lymphoma: a mimic of lupus erythematous panniculitis

Abstract Background/Aims Lupus erythematosus panniculitis (LEP) is a rare variant of cutaneous lupus erythematosus characterised by tender, erythematous subcutaneous nodules or plaques on the face, trunk and proximal extremities. Without treatment, profound lipoatrophy frequently occurs, which often has a devastating psychosocial impact. Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare form of cutaneous T-cell lymphoma, which may appear in a similar manner. SPTCL initially preferentially infiltrates the subcutaneous adipose tissue and symptoms vary widely depending on the stage of the disease. Early-stage disease presents as painless self-resolving subcutaneous nodules on limbs and trunk. Methods We present the case of a young woman who presented with progressively developing, widespread painful cutaneous lesions, pyrexia of unknown origin and general malaise for one month. She had a history of hurthle cell neoplasm and a strong family history of malignancy. Initial examination revealed 1-2 cm firm, skin-coloured subcutaneous nodules over her lower back, chest and thigh, with groin and axillary lymphadenopathy. Further lesions progressively developed over a three-month period, with lesions turning increasingly erythematous and with associated ulceration. Of note, a significant periorbital lesion appeared, associated with an ipsilateral facial palsy. Results Initial bloods revealed an elevated LDH with cholestatic liver function tests. PET-CT imaging showed an enlarged axillary node with extensive pathology throughout the subcutaneous fat of unknown aetiology. Due to the family history, underlying haematological malignancy and atypical Sweet’s were considered for this unusual presentation. Seropositivity for anti-Ro and ENA, alongside raised angiotensin converting enzyme, broadened the differentials to include LEP, mixed atypical connective tissue disease and cutaneous sarcoid. Notably, complement, myositis panel and creatine kinase were normal. Lupus vulgaris was considered due to high local prevalence and excluded with T-SPOT testing. Histopathological analysis of lesional skin from the upper arm found predominantly subcutaneous infiltrates of atypical lymphoid cells with irregular hyperchromatic nuclei and rimming of individual fat cells. T-cell clonality analysis detected clonal T-cell receptor beta (V-J and D-J) gene rearrangements consistent with SPTCL. Her orbital and cutaneous lesions responded well to six cycles of CHOEP (cyclophosphamide, hydroxydaunorubicin, oncovin, etoposide, prednisone) and the patient returned to functional baseline. Conclusion This case demonstrates the diagnostic difficulties when managing a patient with relapsing remitting panniculitis. Whilst the initial presentation of SPTCL here was classical, with widespread multifocal subcutaneous nodules, the appearance of facial symptoms in SPTCL is rare. Diagnostic uncertainty is frequent in both LEP and SPTCL due to the initial non-specific cutaneous presentation. This case emphasises the importance of clinicopathological correlation for accurate diagnosis. Interestingly, up to 20% of SPTCL patients have concomitant autoimmune diseases, and there is evidence suggesting a potential association between LEP and subcutaneous SPTCL beyond chance, leading some researchers to propose that these two entities exist along a spectrum. Disclosure D. Li: None. L. Spencer: None.

Serum chemistry profiling and prognostication in systemic mastocytosis: a registry-based study of the ECNM and GREM

AbstractCertain laboratory abnormalities correlate with subvariants of systemic mastocytosis (SM) and are often prognostically relevant. To assess the diagnostic and prognostic value of individual serum chemistry parameters in SM, 2607 patients enrolled within the European Competence Network on Mastocytosis, and 575 patients enrolled within the German Registry on Eosinophils and Mast Cells were analyzed. For screening and diagnosis of SM, tryptase was identified as the most specific serum parameter. For differentiation between indolent and advanced SM (AdvSM), the following serum parameters were most relevant: tryptase, alkaline phosphatase, β2-microglobulin, lactate dehydrogenase (LDH), albumin, vitamin B12, and C-reactive protein (P < .001). With regard to subvariants of AdvSM, an elevated LDH of ≥260 U/L was associated with multilineage expansion (leukocytosis, r = 0.37, P < .001; monocytosis, r = 0.26, P < .001) and the presence of an associated myeloid neoplasm (P < .001), whereas tryptase levels were highest in mast cell leukemia (MCL) vs non-MCL (308 vs 146 μg/L, P = .003). Based on multivariable analysis, the hazard-risk weighted assignment of 1 point to LDH (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.1-4.0; P = .018) and 1.5 points each to β2-microglobulin (HR, 2.7; 95% CI, 1.4-5.4; P = .004) and albumin (HR, 3.3; 95% CI, 1.7-6.5; P = .001) delineated a highly predictive 3-tier risk classification system (0 points, 8.1 years vs 1 point, 2.5 years; ≥1.5 points, 1.7 years; P < .001). Moreover, serum chemistry parameters enabled further stratification of patients classified as having an International Prognostic Scoring System for Mastocytosis–AdvSM1/2 risk score (P = .027). In conclusion, serum chemistry profiling is a crucial tool in the clinical practice supporting diagnosis and prognostication of SM and its subvariants.

Thrombotic Microangiopathy in Solid Organ Transplantation

Thrombotic Microangiopathy (TMA) is a syndrome characterized by microangiopathic hemolytic anemia (MAHA) and thrombocytopenia. The presence of schistocytes on peripheral smear, a negative Coombs test, elevated lactate dehydrogenase, increased reticulocyte count and low haptoglobin are often the clues for MAHA. The microvascular process often targets vasculature in kidneys, brain, gastrointestinal system, heart, and skin. A timely diagnosis and treatment are often crucial to prevent severe end organ damage and death. TMA is classified into primary and secondary forms. Primary TMA includes TTP and complement mediated or atypical hemolytic uremic syndrome (aHUS), often related to a mutation or deficiency and clinically expressed in the setting of a precipitant condition. Secondary TMA is a manifestation of underlying disorder and can occur in clinical scenarios associated with autoimmune disease, malignancy, infections, SOT (Solid Organ Transplant), pregnancy, HSCT (Hematopoietic Stem Cell Transplantation), medications, or methylmalonic acidemia. Transplant associated TMA (TA-TMA) can be complement mediated or aHUS and could be related to the ischemic reperfusion injury, induction regimen, calcineurin inhibitor (CNI) use, mammalian target of rapamycin (MTOR) inhibitor use, or could be infection related. Cost, access, and turnaround time are often the limitations for certain TTP and complement specific testing. Treatment should not be delayed while waiting for such tests. Treatment must be individualized based on the underlying cause of TMA. Terminal complement blockade utilizing monoclonal antibodies directed against C5 complement is the treatment for complement mediated TMA. C5 inhibitors have also been used successfully in treatment of secondary HUS cases where, unlike aHUS, defects in complement cannot be demonstrated. Such treatment has demonstrated improvement in renal function, MAHA and platelet counts.

Outcome and feasibility of radiotherapy bridging in large B-cell lymphoma patients receiving CD19 CAR T in the UK.

Radiotherapy (RT) has potential synergistic effects with chimeric antigen receptor (CAR) T but is not widely used as bridging therapy due to logistical challenges and lack of standardised protocols. We analysed RT bridging in a multicentre national cohort of large B-cell lymphoma patients approved for 3L axicabtagene ciloleucel or tisagenlecleucel across 12 UK centres. Of 763 approved patients, 722 were leukapheresed, 717 had data available on bridging therapy. 169/717 (24%) received RT bridging, 129 as single modality and 40 as combined modality treatment (CMT). Of 169 patients, 65.7% had advanced stage, 36.9% bulky disease, 86.5% elevated LDH, 41.7% international prognostic index (IPI) ≥3 and 15.2% double/triple hit at the time of approval. Use of RT bridging varied from 11% to 32% between centres and increased over time. Vein-to-vein time and infusion rate did not differ between bridging modalities. RT-bridged patients had favourable outcomes with 1-year progression-free survival (PFS) of 56% for single modality and 47% for CMT (1-year PFS 43% for systemic bridging). This is the largest cohort of LBCL patients receiving RT bridging prior to CAR T reported to date. Our results show that RT bridging can be safely and effectively used even in advanced stage and high-risk disease, with low dropout rates and excellent outcomes.

Evaluating the Prognostic Variables for Overall Survival in Patients with Metastatic Renal Cell Carcinoma: A Meta-Analysis Of 29,366 Patients

Background: Scoring systems are a method of risk assessment used to stratify patients with metastatic renal cell carcinoma (mRCC) and guide systemic therapy. The variables are weighed equally when calculating total score. However, the difference of even 1 positive predictor can change one's risk category and therapy. Objective: To compare the relative strength of association between predictive variables and overall survival (OS) in mRCC. Methods: A search of Medical Literature Analysis and Retrieval System Online (MEDLINE) and Embase was conducted. Clinical studies, retrospective and prospective, were included if the association of at least 1 predictor and OS in patients with mRCC receiving first-line systemic therapy was evaluated. Meta-analysis was performed to generate pooled hazard ratios (HRs) and 95% CIs for OS for predictors with ≥ 5 included studies. Sensitivity analysis identified outlier heterogeneity and publication bias. Results: Sixty-six studies containing 29,366 patients were included. Meta-analysis indicated lung metastases, bone metastases, thrombocytosis, time to systemic therapy &lt; 1 year, liver metastases, hypercalcemia, anemia, elevated neutrophil-lymphocyte ratio, multiple metastatic sites, neutrophilia, poor Eastern Cooperative Oncology Group (ECOG) status, no previous nephrectomy, elevated lactate dehydrogenase, Fuhrman grade 3 or 4, central nervous system metastases, elevated C-reactive protein, and Karnofsky Performance Status &lt; 80% were associated with significantly worse OS. The HRs varied from 1.34 to 2.76, representing heterogeneity in predictive strength. The effects of study heterogeneity and publication bias were minimal to moderate across all predictors. Conclusions: Based on the differences in pooled HRs, prognostic strength between the variables is likely not equivalent. Restructuring scoring models, through inclusion of other variables and usage of relative weighting, should be considered to improve accuracy of risk stratification.

[Correlation Analysis of Peripheral Blood B Cell Count with Clinical Features and Prognosis in Patients Newly Diagnosed with Diffuse Large B-Cell Lymphoma].

To explore the correlation between peripheral blood B cell count and clinical features and prognosis of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). The relationship of peripheral blood B cell count with clinical features, laboratory indexes and prognosis in 67 patients with newly diagnosed DLBCL was retrospectively analyzed. Patients were divided into low B-cell count group (B cell＜0.1×109/L, n=34) and high B-cell count group (B cell≥0.1×109/L, n=33) according to the median B cell count values. Compared with the high B cell count group, the low B cell count group had a higher proportion of patients with Lugano stage III-IV, elevated LDH, elevated β2-MG and IPI score 3-5 and increased CRP (P =0.033, 0.000, 0.023, 0.001, 0.033). The peripheral CD3+ and CD4+ cell counts of patients in the low B cell count group were significantly lower than those in the high B cell count group (P =0.010, 0.017). After initial treatment, overall response rate (ORR) and complete remission (CR) rate in high B cell count group were significantly higher than those in low B cell count group (P =0.032, 0.013). The median follow-up time of patients was 23(2-77) months, progression-free survival (PFS) and overall survival (OS) of patients in the high B cell count group were significantly better than those in the low B cell count group (P =0.001, 0.002). Univariate analysis showed that pretreatment low B cell count in the peripheral blood was associated with shortened PFS and OS (HR=4.108, P =0.002; HR=8.218, P =0.006). Multivariate analysis showed that low B cell count was an independent prognostic factor for shortened PFS (HR=3.116, P =0.037). Decreased peripheral blood B cell count in newly diagnosed DLBCL patients is associated with high-risk clinical features and may affect the efficacy of immunochemotherapy, which is associated with poor clinical prognosis.

Elevated serum lactate dehydrogenase aids prediction of mortality in Pneumocystis jirovecii pneumonia without underlying human immunodeficiency virus infection – derivation of a clinical risk score

Pneumocystis jirovecii pneumonia (PCP) is associated with significant mortality amongst patients without underlying human immunodeficiency virus infection (HIV). We sought to develop a risk score to predict mortality in this population. We reviewed patients with a presumed or confirmed PCP and a negative HIV test from 2006-2023. We constructed a multivariable model to identify parameters independently associated with mortality and the adjusted odds ratios were converted to weights to derive a risk score. Subsequently, we compared the performance of our score to the CURB-65 score by means of area under receiver operating characteristic curve (AUC). In total, we examined 93 patients with PCP without HIV. Mortality was 31.2%. Risk factors for mortality included older age, male sex and high serum lactate dehydrogenase levels (LDH) and C-reactive protein levels. A risk score was derived comprising age>65 years (2 points), male sex (2 points) and LDH>770U/L (3 points). Our risk score (AUC 0.71, 95%CI 0.60-0.82) performed better than the CURB-65 score (AUC 0.53, 95%CI 0.41-0.66). A low-risk score of 0-1 had excellent negative predictive value for mortality (97.5%). In conclusion, a risk score comprising age, sex and LDH can predict mortality in PCP without underlying HIV and help with prognostication.

The Effect of Elevated Serum Lactate Dehydrogenase Level on Survival of Newly Diagnosed Acute Myeloid Leukemia (AML) Patients

The Effect of Elevated Serum Lactate Dehydrogenase Level on Survival of Newly Diagnosed Acute Myeloid Leukemia (AML) Patients

Blood Plasma as a Sampling Model during Drug-induced Thrombocytopenia: Effects of Antioxidants

OBJECTIVE Blood plasma, a complex biological mixture, plays a part in a variety of roles including clotting, defense, and transport, and reflects the overall status of blood components. Drug-induced thrombocytopenia (DIT) is characterized by abnormally low platelet count (below ~150,000 per μL) which can be caused by adverse effects of medications. This study aims to address a basic question, can plasma be employed as a sampling model to assess the oxidative stress (OS) changes and antioxidant status during DIT? The objective was to analyze the antioxidant status and OS in plasma during DIT, and to determine the effects of antioxidant supplementation such as Caripill™, L-Carnitine (LC), and vanillic acid (VA) during DIT. METHODS Male Wistar rats were used as animal models and grouped into control groups (n=5) and thrombocytopenia groups (n=5). Antioxidants were given to the thrombocytopenic and the control rats (50 mg/kg body weight) once a day for 7 days. Blood plasma from both groups was evaluated for total antioxidant capacity, antioxidant enzymes, markers of lipid peroxidation, protein oxidation, and OS. RESULTS The antioxidants significantly increased the total antioxidant capacity (CUPRAC) and ferric-reducing antioxidant power (FRAP) of the plasma and decreased the levels of conjugate dienes. Caripill™ also reduced lipid peroxidation, significantly elevated protein sulfhydryl and nitrite/nitrate levels, LC elevated lactate dehydrogenase levels, and VA increased superoxide dismutase activity and attenuated lipid peroxidation during DIT. CONCLUSIONS The antioxidants Caripill™, vanillic acid, and L-carnitine were demonstrated to be beneficial during DIT and to have prospects in alternate therapeutics. This study confirms that plasma can be utilized as a sampling model to study changes during OS situations.

Survival and treatment outcomes in patients with leptomeningeal disease from metastatic melanoma

Abstract Background Melanoma leptomeningeal disease (LMD) has poor prognosis. However, the management of patients with advanced melanoma has evolved with time, including those with LMD. We reviewed a large cohort of melanoma LMD patients to assess factors associated with survival. METHODS Retrospective clinical data was collected on patients diagnosed with LMD at MD Anderson Cancer Center from 2015-2020. Overall survival (OS) was determined from LMD diagnosis to date of death or last follow-up. The Kaplan-Meier method and log-rank test were used to estimate OS and to assess univariate group differences, respectively. Multivariable associations of survival with variables of interest were determined using Cox proportional hazards regression models. RESULTS 172 patients were identified. The median age at LMD diagnosis was 53 (range 20-79) years, and all patients had radiographic evidence of LMD on MRI of either brain or spine. 143 patients previously received systemic therapy (83%), with a median of two prior treatments (range 0-5). 81 patients (47%) had concurrent uncontrolled systemic disease and 80 patients (53%) had elevated serum LDH at the time of diagnosis. With a median follow-up of 4.0 months (range 0.1-65.3 months), median OS for all patients from LMD diagnosis was 4.9 months. Patients (n=45) who received intrathecal (IT) therapy or systemic immunotherapy for LMD had a median OS of 8.0 months and 10.2 months, respectively. On multivariable analysis, decreased performance status, positive CSF cytology, elevated LDH, and whole brain radiation were associated with worse OS. CONCLUSIONS Despite many advances in therapeutic options, the outcomes of melanoma patients with LMD remains poor. However, a subset of patients appears to derive benefit from LMD-directed treatment.

18F-FDG positron emission tomography-computed tomography and Richter transformation: A retrospective study with a cohort of 12 consecutive patients

Richter transformation (RT) refers to a transformational process of chronic lymphocytic leukemia (CLL) into a more aggressive form. CLL is considered an indolent lymphoma with no avidity to 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). RT transforms CLL into a diffuse large B-cell lymphoma, Hodgkin&amp;rsquo;s lymphoma, or prolymphocytic leukemia, and the lymphoid tissue becomes highly FDG avid. The main value of 18F-FDG PET/CT in CLL patients lies in its ability to exclude RT with high negative predictive value and identify sites of increased 18F-FDG uptake that is suitable for biopsy. In our retrospective analysis, we examined 12 patients suspected of RT, who were included in our study between November 2018 and December 2022. 18F-FDG PET/CT was considered for patients with enlarged lymph node, fever, and elevated lactate dehydrogenase levels. A cutoff standardized uptake value (SUVmax) = 5 was chosen empirically based on our institutional practice. Extranodal disease was suspected if abnormal 18F-FDG uptake was observed in the liver, spleen, bone marrow, or another organ. In this study, the specificity of 18F-FDG PET/CT was 44.5%, with positive and negative predictive values of 37.5% and 100%, respectively. Frequencies of cases with increased uptake of 18F-FDG in the &amp;ldquo;only nodal sites&amp;rdquo; and &amp;ldquo;nodal and extranodal sites,&amp;rdquo; relative to positive biopsies, were 20% and 66%, respectively.

A Comprehensive Review on Serum Lactate Dehydrogenase (LDH) and Uric Acid in Preeclampsia: Implications for Maternal Health and Disease Severity.

Preeclampsia, a hypertensive disorder unique to pregnancy, remains a significant cause of maternal and fetal morbidity and mortality worldwide. Serum lactate dehydrogenase (LDH) and uric acid have garnered attention as potential biomarkers in understanding preeclampsia's pathophysiology and clinical management. Elevated LDH and uric acid levels have been associated with disease severity and adverse outcomes, highlighting their potential utility in risk stratification and guiding management strategies. This comprehensive review explores the roles of LDH and uric acid in preeclampsia, summarizing current evidence regarding their diagnostic, prognostic, and therapeutic implications. Future research directions are also discussed, including understanding and validation studies. Integrating LDH and uric acid measurements into routine clinical practice may facilitate early detection and intervention, ultimately improving outcomes for preeclamptic pregnancies. This review underscores the importance of serum biomarkers in enhancing our understanding and managing preeclampsia, aiming to optimize maternal and fetal health.