Elevated Lactate Dehydrogenase Research Articles

Pumpkin seed oil lessens the colchicine-induced altered sex male hormone balance, testicular oxidative status, sperm abnormalities, and collagen deposition in male rats via Caspase3/Desmin/PCNA modulation

This study examined the efficiency of pumpkin seed oil (PSO) to rescue the colchicine (CHC)-induced adverse impacts on sperm characteristics, male sex hormones, testicular architecture, oxidative status, DNA content, collagen deposition, and immune expression of desmin and PCNA. Male Sprague Dawley rats were divided into four experimental groups (n = 10 each): control (distilled water), CHC (0.6 mg/kg b.wt), PSO (4 mL/kg b.wt), and CHC + PSO. After 60 days of dosing, CHC significantly reduced sperm motility (19%), sperm concentration (38%), estradiol (52%), testosterone (37%), luteinizing hormone (54%), and follicle-stimulating hormone (29%) compared to the control. Yet, the testicular tissues of CHC-administered rats exhibited elevated abnormal sperms (156%), malondialdehyde (354%), lactate dehydrogenase (73%), Caspase-3 (66%), and 8-hydroxyguanosine (65%) but lower reduced glutathione (74%), catalase (73%), and superoxide dismutase (78%) compared to the control group. Moreover, CHC induced testicular degeneration, distorted seminiferous tubules, apoptotic cells, exfoliated spermatogenic cells, reduced DNA content, decreased PCNA and desmin immune-expression, and increased collagen deposition. PSO effectively reversed the CHC-induced alterations in sperm quality and testicular function and architecture, likely through its antioxidant, antifibrotic, anti-apoptotic, and DNA-protective properties. These results suggest that PSO may be a beneficial intervention for long-term CHC users and may protect against CHC-induced male reproductive toxicity.

Effectiveness of fractionated rituximab in preventing tumor lysis syndrome in aggressive B-cell lymphoma: Insights from real-life clinical practice.

Tumor lysis syndrome (TLS) is a potentially life-threatening condition resulting from the rapid destruction of malignant cells, leading to electrolyte imbalances and severe complications, such as acute kidney injury, arrhythmias, and seizures. TLS can be managed through hyperhydration, urate-lowering treatments, and a steroid prophase strategy. This study aims to explore the impact of fractionated rituximab, an anti-CD20 antibody, on the occurrence and severity of TLS during the initial cycle in patients with aggressive B-cell non-Hodgkin lymphoma (B-NHL). Data was retrospectively collected from 94 of 186 patients. Among the 94 patients included in the analysis, the median age was 70. Histologies were diffuse large B-cell lymphoma (75%), Burkitt lymphoma (13%) and high-grade B-cell lymphoma (8%). The majority were at an advanced stage (93%) with a high IPI score (75%). Most patients received anthracycline-containing regimens (72%) and prophylactic allopurinol (83%) and/or rasburicase (26%). Steroid prophase was administered to 82% of patients. The study identified one clinical TLS case and six laboratory TLS cases. Significant TLS factors included BL histology, elevated baseline LDH (⟩500 U/l), and rasburicase usage. Infusion reactions were rare (3%). Median progression-free survival was 2.6 years, and 2-year overall survival was 33%, irrespective of TLS occurrence. In this real-life study, clinical TLS occurrence was low (1%). TLS appeared more frequent in BL but did not impact overall survival. Fractionated initial rituximab dosing in addition to preventive strategies is a feasible approach in preventing clinical TLS, warranting further prospective investigation.

Prognostic impact of concordant and discordant bone marrow involvement on diffuse large B-cell lymphoma.

In diffuse large B-cell lymphoma (DLBCL), bone marrow (BM) involvement includes two types that are concordant involvement and discordant involvement. It has been reported that concordant BM involvement has a worse prognosis than discordant involvement in previous studies. However, the prognostic effects of concordant or discordant BM involvement on DLBCL still need further research. In this work, DLBCL cases with BM involvement were collected and analyzed to better reflect the prognostic implications of concordant and discordant BM involvement. We reviewed the cases with newly diagnosed DLBCL and BM involvement from April 2018 to April 2022 in Northern Jiangsu People's Hospital. Overall survival (OS) and progression-free survival (PFS) were accessed by the Kaplan-Meier method and compared between groups by the log-rank test. A multivariate regression analysis based on Cox proportional hazard model was used to test the independent effect of each variable on survival. In total, 32 patients were included and 15 (46.9%) patients had concordant BM involvement and 17 (53.1%) patients had discordant BM involvement. Compared with the discordant group, the concordant group tended to be older and had elevated lactate dehydrogenase level. The outcome of patients with concordant BM involvement was worse than the discordant subset, including OS (P=0.04) and PFS (P=0.03). Furthermore, the discordant BM involvement was excluded to acquire a BM-adjusted International Prognostic Index (IPI) score. The significance of BM-adjusted IPI scores to predict OS was improved greatly compared with the previous IPI scores (P=0.053 vs. P=0.16). Multivariate analysis showed that the BM-adjusted IPI was an independent predictor for OS [hazard ratio =3.406; 95% confidence interval (CI): 1.145-10.127; P=0.03]. These results highlight the requirement for identifying BM infiltration type accurately and then adjusting the IPI score by excluding discordant BM involvement since concordant involvement can partly predict a poor prognosis of DLBCL with BM involvement other than discordant involvement.

WITHDRAWN: Shenmai Injection Exerts the Cardioprotective Effects by Modulating Autophagy-apoptosis via Beclin-1

Background and aimDespite the excellent efficacy of anthracyclines, their clinical application is subject to cardiotoxicity. Studies have shown that Shenmai Injection(SMI) alleviated anthracycline-induced myocardial injury, however, the exact mechanism has not been clarified. Experimental procedureEach intervention was explored by detecting the viability of cardiomyocytes, LDH leakage rate, and CK levels. Finally, the effects of each intervention on autophagy-apoptosis and Beclin-1 were observed by using mCherry-EGFP-LC3B double fluorescence method, Annexin V/propidium iodide (PI), and protein immunoblotting method to explain the mechanism of Shenmai Injection. Key resultsThe viability of H9c2 cells in the model group decreased, accompanied by elevated LDH leakage rate and CK levels after doxorubicin intervention (P<0.01 or P<0.05). In contrast, SMI reversed above situation (P<0.01 or P<0.05). Besides, autophagy and apoptosis up-regulated in the model group (P<0.01), accompanied by upregulated Beclin-1, LC3-II, LC3-II/LC3-I, apoptosis effector proteins Cleaved-Caspase-9, Cleaved-Caspase-9/Caspase-9, Cleaved-Caspase-3, Cleaved-Caspase-3/Caspase-3 expressions and the downregulation of p62 protein, anti-apoptotic protein Bcl2 expressions (P<0.01 or P<0.05). Nonetheless, autophagy and apoptosis were decreased with the help of SMI (P<0.01 or P<0.05). ConclusionSMI alleviated autophagy and apoptosis of damaged cardiomyocytes by regulating Beclin-1.

Real-world results of first-line immunotherapy or targeted therapy for metastatic melanoma in Finland: a cohort study.

Aim: First-line (1L) immunotherapy has yielded superior overall survival (OS) in metastatic melanoma (MM) but some patients are ineligible for immunotherapy or need rapid response with 1L targeted therapy (TT).Materials & methods: Retrospective cohort study of real-world patients treated with 1L immunotherapy (144 BRAF wild type, 85 BRAF-mutated) or 1L TT (143 BRAF-mutated) for MM in Finland during 2014-2021.Results: Baseline brain metastases, liver metastases and elevated LDH were less common, 2-year OS rates were higher (60.3-63.5% vs. 33.8%) and more patients were alive without the next-line treatment (38.0-43.8% vs. 23.3%) in patients with 1L immunotherapy.Conclusion: Real-world patients with 1L immunotherapy for MM had favorable baseline characteristics and better treatment outcomes than observed in patients with 1L TT.

Southwest Oncology Group S0826: A phase 2 trial of SCH 727965 (NSC 727135, dinaciclib) in patients with stage IV melanoma.

Cell cycle inhibition is an established therapeutic approach for some cancers. A multicenter, single-arm, phase 2 trial (ClinicalTrials.gov identifier NCT00937937) of the cyclin-dependent kinase inhibitor SCH 727965 (NSC 747135; dinaciclib) was conducted in patients with metastatic melanoma to determine its clinical activity. Patients with metastatic melanoma of cutaneous or mucosal origin were eligible if they had zero to one previous treatments, a Zubrod performance status of 0-1, and adequate organ function. SCH 727965 50 mg/m2 was given intravenously every 3 weeks until progression. Co-primary end points were 1-year overall survival (OS) and 6-month progression-free survival (PFS). Seventy-two patients were enrolled from July 1, 2009, to November 1, 2010, at 24 institutions. Sixty-eight percent of patients had M1c disease, and 43% had elevated lactate dehydrogenase levels. Twenty-eight patients (39%) experienced grade 4 adverse events, including 20 cases of neutropenia. Sixty-seven patients were evaluable for response. There was a response in zero of 67 patients (95% confidence interval [CI], 0%-5%), and stable disease was observed in 21%. The estimated median PFS was 1.4 months (95% CI, 1.4-1.5 months), and the 6-month PFS rate was 6% (2%-13%). The median OS was 8.2 months (95% CI, 5.5-10.5 months), and the 1-year OS rate was 38% (95% CI, 26%-49%). This multicenter, US National Cancer Institute Cancer Therapy Evaluation Program-sponsored trial of SCH 727965 was conducted at a time when the current generation of effective therapies for melanoma were not available. Although the null hypothesis of 1-year OS was rejected, the minimal PFS impact and substantive toxicity indicated that this regimen lacks justification for further investigation as a single agent.

DA-R-EPOCH May Mitigate the Adverse Prognostic Implication of the Diagnosis-to-Treatment Interval (DTI) in Large B-Cell Lymphomas

BackgroundShort diagnosis-to-treatment interval (DTI) is associated with high-risk disease and poor survival in diffuse large B-cell lymphoma (DLBCL). There is a paucity of literature on DTI and survival in DLBCL treated with first-line DA-R-EPOCH. We hypothesized that rapid initiation of DA-R-EPOCH in aggressive and high-risk DLBCL mitigates the adverse prognostic implication of short DTI. Patients and MethodsWe retrospectively examined the association of DTI, categorically (short DTI ≤ 14 and long > 14 days) and continuously, with clinical features and survival outcomes in DLBCL treated with first-line DA-R-EPOCH at our institution. ResultsA total 190 patients were analyzed, 21% with high-grade DLBCL subtypes, 56% IPI ≥ 3, and median DTI of 13 days. The short DTI cohort contained more patients with IPI ≥ 3, bulky disease, and elevated LDH. When analyzed categorically and continuously, DTI was not associated with significant differences in PFS or OS. There was significant multivariable interaction between bulky disease, DTI, and PFS (P = .033), with improved PFS in patients with bulky disease in the short DTI cohort. ConclusionWe found that negative prognostic implications of DTI are mitigated in DLBCL patients treated with first-line DA-R-EPOCH, suggesting that urgent initiation of DA-R-EPOCH in high-risk DLBCL, including bulky disease, may improve survival. Our study's shorter DTI compared with DTIs reported in prospective DLBCL trials highlights DTI as a marker of external validity in clinical trial results. Future trials should implement protocols encouraging shorter, realistic DTIs to avoid selection bias against high-risk patients who are unable to delay treatment.

Interstitial Lung Disease in Primary Sjögren's Syndrome: Risk factors for occurrence and radiographic progression.

The aim of this study is to investigate the characteristics of Primary Sjögren's syndrome (pSS)- interstitial lung disease (ILD) patients and compare them to those of pSS patients without ILD in the tertiary pSS-ILD cohort to evaluate potential risk factors for ILD occurrence and disease progression. Patients followed up who met the 2016 American College of Rheumatology-European League Against Rheumatism classification criteria for pSS were retrospectively analyzed. The patients were grouped as those with ILD and those without ILD according to medical records. High-resolution computed tomography (HRCT)/ thorax CT (TCT) results of all ILD patients were evaluated. Data on demographics, comorbidities, clinical characteristics and laboratory findings were collected. A total of 378 pSS patients, including 60 with ILD and 318 without ILD were detected to have at least one obtainable HRCT/TCT and were included in the study. In the cohort of pSS patients with at least one HRCT or TCT, the frequency of ILD was 15.8%. In the ILD group, the most common HRCT pattern was NSIP, and the most common findings were ground glass opacities, traction bronchiectasis, and honeycombing. Logistic regression analysis showed that male gender (OR:2.90), being diagnosed with pSS over the age of 50(OR:4,24), smoking history (OR:2.38), elevated LDH(OR:3.27), elevated ESR(OR:2.51) and lymphopenia (OR:5.12) were related with development of ILD while being diagnosed with ILD after the age of 60 (OR:8.5) was related with radiographic progression. The study results provided a large spectrum view for pSS-ILD and pointed out several risk factors for ILD occurrence and radiographic progression.

Musculoskeletal Symptoms and Misdiagnoses in Children With Acute Myeloid Leukaemia: A Nationwide Cohort Study.

Childhood cancer often presents with non-specific signs and symptoms that might mimic non-malignant disorders including musculoskeletal diseases, potentially leading to rheumatic and orthopaedic misdiagnoses. We aimed to compare clinical presentation, diagnostic interval and survival in paediatric acute myeloid leukaemia (AML) with and without initial musculoskeletal symptoms. This nationwide retrospective, cohort study reviewed medical records of 144 children below 15 years diagnosed with AML in Denmark from 1996 to 2018. Musculoskeletal symptoms occurred in 29% (42/144) of children with AML and 8% (11/144) received an initial musculoskeletal misdiagnosis, being mainly non-specific and pain-related. The children with and without musculoskeletal symptoms did not differ markedly up to the diagnosis of AML and blood counts were affected equally in both groups. However, the children with prior musculoskeletal symptoms were more likely to have elevated levels of LDH and ferritin. Furthermore, they revealed a tendency towards a longer total interval (median 53 days vs. 32 days, p = 0.07), but the overall survival did not differ. AML should be considered as an underlying cause in children with unexplained musculoskeletal symptoms and abnormal blood counts. Concomitant elevation of LDH and ferritin should strengthen the suspicion.

Intravascular lymphoma: A diagnostic challenge for a treatable cause of rapidly progressive dementia

Intravascular large B-cell lymphoma (IVLBCL) is a rare hematological malignancy where its development in the intravascular environment is the main characteristic. Despite its ability to affect multiple organic systems, there is a tropism for the central nervous system, which may be related to several clinical syndromes, making this condition a great mimic and consequently a diagnostic challenge. Rapidly progressive dementia may be one of the presenting phenotypes of IVLBCL. This case report aims to highlight the main red flags, such as sustained elevation of lactate dehydrogenase, organomegaly and specific lesions with vasculitis-like bleeding, all that can be used as clinical clues to direct the differential diagnosis. In addition, it reinforces the role of early brain biopsy in this context, since IVLBCL is a treatable disease.

Coexpression of MYC and BCL2 oncoproteins in primary nodal versus primary extranodal diffuse large B-cell lymphoma

Objectives: Diffuse large B-cell lymphoma (DLBCL) is a morphologically and molecularly diversified disease with aggressive biological behavior. The double expression of MYC/BCL2 proteins portends a poorer prognosis. This study aims to evaluate the frequency, describe the clinicopathological features of the double-expressor phenotype of DLBCL in primary nodal (PN) versus primary extranodal (PEN) sites, and investigate their associations. Materials and Methods: A total of 48 patients with the double-expressor phenotype of lymphoma (DEPL) in a tertiary care hospital were included over three years. Clinicopathological parameters and associations were investigated based on the primary site. Statistical Analysis: Data were documented and analyzed using appropriate statistical tests. Results: The incidence of DEPL in our study was 28.7%. The median age of all DEPL patients was 56 years, with a predominance of men (69%). DEPL cases were further subcategorized as PN-DEPL (n = 33) and PEN-DEPL (n=15). Males were affected almost equally in both groups. More PN-DEPL patients exhibited B symptoms (82%), elevated lactate dehydrogenase (LDH) levels (73%), III/IV stage disease (71%), and maximum revised international prognostic index (R-IPI) score (64%) compared to PEN-DEPL patients. On the other hand, bone marrow (BM) involvement (87%), activated B-cell-type phenotype (80%), pathologic stage I/II (67%), and Ki67 index &gt;90% (93%) were more common in PEN-DEPL patients. Conclusions: Significant differences were observed between PN-DEPL and PEN-DEPL in terms of B symptoms, LDH levels, stage at presentation, BM involvement, pathological subtype, Ki67 index, and R-IPI score. This study provides an estimate of the burden of this aggressive entity and encourages further prognostic studies and therapeutic trials.

Splenic spread and hepatic encephalopathy in metastatic malignant melanoma.

An older adult patient was admitted with epigastric pain and vomiting and found to have an abdominal mass, increased cholestatic liver enzymes and markedly elevated serum lactate dehydrogenase (LDH). Imaging revealed extensive liver metastases of unknown primary but also an unusual splenic metastasis diagnosed by liver biopsy as malignant melanoma. The patient became lethargic and developed mental status changes associated with asterixis, abnormal EEG, and increased serum ammonia levels. All reversed with high-dose lactulose and had no alternative explanation other than an unusual hepatic encephalopathy secondary to portosystemic shunts bypassing the extensively metastatic liver.

Clinical features of pneumocystis pneumonia in non-human immunodeficiency virus-infected patients: A systemic review and meta-analysis

Objectives: Pneumocystis pneumonia (PCP) is an opportunistic disease that causes potentially fatal pneumonia in immunocompromised individuals. The clinical features of PCP without HIV remain incompletely understood. Methods: This study aimed to identify the clinical features of PCP without HIV in a systematic review following a meta-analysis. Results: 65 articles that included 10,133 PCP patients without HIV infection were enrolled. PCP occurred most commonly at age 59.2 years (95%CI: 57.7, 60.7) in a gender ratio of approximately 3 to 2 (males to females). Dyspnea, fever, cough, and sputum were nonspecific clinical findings in 73% (95%CI: 69, 79), 73% (95%CI: 65, 81), 56% (95%CI: 48%, 64%), and 32% (96%CI: 16, 48) of patients, respectively. Viral, bacterial, and fungal co-infection were observed in 28% (95%CI: 13, 44), 19% (95%CI: 13, 25), and 11% (95%CI: 6, 16) of patients, respectively. Laboratory data showed a trend of elevated WBC, LDH, CRP, β-D glucan, and KL-6. Ground glass opacity (GGO) was found in 87% (95%CI: 83, 91) of patients. In-hospital mortality was 41% (95%CI: 35, 46). Conclusions: PCP is a life-threatening disease in immune-compromised patients. Despite being a nonspecific clinical finding, GGO might offer a clue to diagnosing PCP in high-risk patients.

Clinical and laboratory analysis of a large imported typhoid fever outbreak in The Netherlands.

Typhoid fever is a rarely encountered disease in the Western world. In our study, patients with imported typhoid fever were characterized by a febrile illness with a relative bradycardia, headache and abdominal pain. Only a few patients presented with diarrhoea. An elevated CRP and lactate dehydrogenase (LD) were the most common laboratory abnormalities. Complications like focal abscesses occurred quite frequently.

Post-COVID Interstitial Lung Disease: How do We Deal with This New Entity?

In the postacute phase of coronavirus disease-2019 (COVID-19), survivors may have persistent symptoms, lung function abnormalities, and sequelae lesions on thoracic computed tomography (CT). This new entity has been defined as post-COVID interstitial lung disease (ILD) or residual disease. To evaluate the characteristics, risk factors and clinical significance of post-COVID ILD. Multicenter cross-sectional analysis of data from a randomized clinical study. In this study, patients with persistent respiratory symptoms 3 months after recovery from COVID-19 were evaluated by two pulmonologists and a radiologist. post-COVID ILD was defined as the presence of respiratory symptoms, hypoxemia, restrictive defect on lung function tests, and interstitial changes on follow-up high-resolution computed tomography (HRCT). At the three-month follow-up, 375 patients with post-COVID-19 syndrome were evaluated, and 262 patients were found to have post-COVID ILD. The most prevalent complaints were dyspnea (n = 238, 90.8%), exercise intolerance (n = 166, 63.4%), fatigue (n = 142, 54.2%), and cough (n = 136, 52%). The mean Medical Research Council dyspnea score was 2.1 ± 0.9, oxygen saturation was 92.2 ± 5.9%, and 6-minute walking distance was 360 ± 140 meters. The mean diffusing capacity of the lung for carbon monoxide was 58 ± 21, and the forced vital capacity was 70% ± 19%. Ground glass opacities and fibrotic bands were the most common findings on thoracic HRCT. Fibrosis-like lesions such as interlobular septal thickening and traction bronchiectasis were observed in 38.3% and 27.9% of the patients, respectively. No honeycomb cysts were observed. Active smoking [odds ratio (OR), 1.96; 95% confidence interval (CI), 1.44-2.67), intensive care unit admission during the acute phase (OR, 1.46; 95% CI, 1.1-1.95), need for high-flow nasal oxygen (OR, 1.55; 95% CI, 1.42-1.9) or non-invasive ventilation (OR, 1.31; 95% CI, 0.8-2.07), and elevated serum lactate dehydrogenase levels (OR, 1.23; 95% CI 1.18-1.28) were associated with the development of post-COVID ILD. At the 6-month follow-up, the respiratory symptoms and pulmonary functions had improved spontaneously without any specific treatment in 35 patients (13.4%). The radiological interstitial lesions had spontaneously regressed in 54 patients (20.6%). The co-existence of respiratory symptoms, radiological parenchymal lesions, and pulmonary functional abnormalities which suggest a restrictive ventilatory defect should be defined as post-COVID-19 ILD. However, the term “fibrosis” should be used carefully. Active smoking, severe COVID-19, and elevated lactate dehydrogenase level are the main risk factors of this condition. These post-COVID functional and radiological changes could disappear over time in 20% of the patients.

Prognostic Role of Clinicopathological Characteristics and Serum Markers in Metastatic Melanoma Patients Treated with BRAF and MEK Inhibitors.

A total of 199 patients with advanced melanoma treated with BRAF + MEK inhibitors were included in our single-center retrospective study. We analyzed the risk of progression and death using multivariate Cox proportional hazard models. The predictive effect of prognostic factors on progression-free survival (PFS) was evaluated in ROC analysis. We found that primary tumor localization, Clark level, pT category, baseline M stage and baseline serum S100B are independent and significant prognostic factors for PFS. The discriminative power of the combination of these factors was excellent for predicting 18 month PFS (AUC 0.822 [95% CI 0.727; 0.916], p < 0.001). Primary tumor localization on the extremities, Clark level V, baseline M1c stage or M1d stage, and elevated baseline serum S100B and LDH levels were independently and significantly associated with unfavorable overall survival (OS). Baseline M stage and serum S100B appear to be independent prognostic factors for both PFS and OS in melanoma patients treated with BRAF + MEK inhibitors. We newly identified significant and independent prognostic effects of primary tumor localization and Clark level on survival that warrant further investigation.

A Prospective Study on Lactate Dehydrogenase Levels in Acute Intestinal Obstruction as a Marker of Bowel Gangrene.

Background Intestinal obstruction continues to be one of the most common causes of emergencies presenting to the surgical department. A thorough clinical examination along with relevant investigations continue to be best modality for timely management and prompt decision-making in such cases. Objectives The aim of this study was to identify patients of intestinal obstruction with elevated levels of serum lactate dehydrogenase (LDH) and correlate elevated LDH levels with bowel viability. Materials and methods The study comprised 46 cases of intestinal obstruction and their serum LDH values measured prior to surgical intervention/first day of admission. The intra-operative bowel viability was noted and compared with LDH values obtained, and their correlation was studied along with other variables of the patient. Results In our study, it was found that a serum LDH level of >800 IU/L signified an abnormal bowel with increased risk of bowel gangrene, as indicated by a sensitivity of 75% and a specificity of 94%. Gangrenous bowel was found to be more associated with causes such as superior mesenteric artery/vein thrombosis, volvulus, and habits such as alcoholism and tobacco consumption. Elevated LDH levels, however, do not correlate with the length of the affected gangrenous bowel, with the duration of presentation of symptoms, or as a predictor of mortality. Conclusion Serum LDH can be used as a good predictor of gangrenous bowel in cases of intestinal obstruction.

CLEC5A Promotes Neuronal Pyroptosis in Rat Spinal Cord Injury Models by Interacting with TREM1 and Elevating NLRC4 Expression.

Pyroptosis, an inflammatory Programmed cell death, has recently been found to play an important role in spinal cord injury (SCI). C-type lectin domain family 5 member A (CLEC5A), triggering receptor expressed on myeloid cells 1 (TREM1), and NLR-family CARD-containing protein 4 (NLRC4) have been reported to be associated with neuronal pyroptosis, but few studies have clarified their functions and regulatory mechanisms in SCI. In this study, CLEC5A, TREM1, and NLRC4 were highly expressed in lidocaine-induced SCI rat models, and their knockdown alleviated lidocaine-induced SCI. The elevation of proptosis related indicators LDH, ASC, GSDMD-N, IL-18, caspase-1, and IL-1β levels in SCI rats was attenuated after silencing of CLEC5A, TREM1, or NLRC4. Lidocaine-induced the decrease in cell viability and the elevation in cell death were partly reversed after CLEC5A, TREM1, or NLRC4 silencing. Lidocaine-mediated effects on the levels of LDH, ASC, GSDMD-N, IL-18, caspase-1, and IL-1β in lidocaine-induced PC-12 cells were weakened by downregulating CLEC5A, TREM1, or NLRC4. CLEC5A could interact with TREM1 to mediate NLRC4 expression, thus accelerating neuronal pyroptosis, ultimately leading to SCI exacerbation. In conclusions, CLEC5A interacted with TREM1 to increase NLRC4 expression, thus promoting neuronal pyroptosis in rat SCI models, providing new insights into the role of neuronal pyroptosis in SCI.Significance statement Pyroptosis has been reported to be involved in SCI. Higher levels of CLEC5A, TREM1, and NLRC4 associated with neuronal pyroptosis. However, the role and regulatory mechanism of CLEC5A, TREM1, and NLRC4 in SCI were not clear. Here, high expression of CLEC5A, TREM1, and NLRC4 was observed in lidocaine-induced SCI rat models. CLEC5A could interact with TREM1 to enhance the expression of NLRC4, thus accelerating neuronal pyroptosis in rat SCI models. These findings identify CLEC5A, TREM1, and NLRC4 as potential therapeutic targets for SCI.

Unraveling the complexity: Case reports of drug-induced hemolytic anemia due to ceftriaxone

Abstract: Drug-induced hemolytic anemia (DIHA) is a rare but significant condition characterized by the premature destruction of red blood cells (RBCs) triggered by certain medications. Ceftriaxone, a commonly used antibiotic, has been linked to DIHA, presenting diagnostic challenges due to its diverse clinical manifestations. This study examines three cases of DIHA caused by ceftriaxone therapy at our center. The patients presented with symptoms such as fatigue, jaundice, and dark urine following ceftriaxone therapy. Laboratory tests indicated hemolytic anemia with decreased hemoglobin, elevated lactate dehydrogenase, and positive direct antiglobulin tests. Immunohematological workups confirmed ceftriaxone-induced antibodies targeting RBCs and guided management strategies, including discontinuation of ceftriaxone, supportive therapy, and corticosteroids. Timely diagnosis and collaboration between clinicians and laboratory specialists are crucial for optimal patient outcomes.

VCd versus VRd in Newly Diagnosed Multiple Myeloma: Matched Real-World Analysis from the Balkan Myeloma Study Group (BMSG)

BackgroundBortezomib, dexamethasone and cyclophosphamide (VCd) remains a popular regimen, due to its activity and low toxicity, while bortezomib, lenalidomide and dexamethasone (VRd) is widely used in US and Europe; both are combined with anti-CD38 monoclonal antibodies but VCd and VRd have not been compared directly in adequately powered prospective trials. AimWe compared the outcomes of 1216 patients treated with VCd (N = 690) or VRd (N = 526) in a real-world setting. ResultsPatients treated with VCd had more often severe renal dysfunction, ISS-3 disease, hypercalcemia, elevated LDH, anemia, thrombocytopenia, poor performance while VRd-treated were older and received less often autologous transplant but more frequently maintenance but the duration of induction was similar. VRd was associated with substantially higher overall response and CR/VGPR rates to induction(P < .001) and improved PFS and OS in univariate analysis, especially among patients with standard risk disease, without renal dysfunction and in the elderly; however, in multivariate analysis there was no significant difference in either PFS or OS. In patients strictly matched 1:1 for major prognostic variables (188 in each group, total N = 376), the superiority of VRd in terms of responses rates and depth of response was confirmed, but without significant PFS or OS difference. ConclusionVRd is a more active induction regimen than VCd, although use of maintenance with lenalidomide may dilute the PFS or OS benefit. VCd induction remains an option in special circumstances. With the implementation of monoclonal antibodies, VCd backbone can be considered for patients without access to or who do not tolerate VRd.