Elevated Lactate Dehydrogenase Research Articles

Increased serum level of IL-6 predicts poor prognosis in anti-MDA5-positive dermatomyositis with rapidly progressive interstitial lung disease

BackgroudAnti-melanoma differentiation-associated protein 5 antibody-positive dermatomyositis (anti-MDA5-positvie DM) is a subtype of dermatomyositis with a poor prognosis, characterized by rapidly progressive interstitial lung disease (RP-ILD). The study aims to investigate the significance of serum cytokines profiles and peripheral lymphocytes in predicting prognoses of anti-MDA5-positvie DM with RP-ILD. Furthermore, it seeks to analyze longitudinal data of lymphocytes during hospitalization to identify distinct trajectories and cluster patients accordingly.MethodsA total of 168 patients with anti-MDA5-positive DM were enrolled in this retrospective study from two cohorts. Univariate and multivariate Cox regression analyses were conducted to determine the predictors of 6-month all-cause mortality and RP-ILD. Group-based trajectory modeling (GBTM) was employed to model the trajectories of longitudinal peripheral lymphocytes.ResultsIn the multivariate Cox regression analysis, IL-6 ≥ 13.41pg/mL, lymphocytes < 0.5 × 109 /L, lymphocytes from 0.5 to 1.0 × 109 /L, older age, and elevated LDH were identified as independent predictors of 6-month all-cause mortality. Furthermore, IL-6 ≥ 13.41pg/mL, lymphocytes < 0.5 × 109 /L, and lymphocytes from 0.5 to 1.0 × 109 /L were found to be independent predictors of RP-ILD. Additionally, three trajectory groups of lymphocytes within the first week after admission were established based on GBTM. These groups included: Group 1, with low-level of lymphocytes that declined; Group 2, with medium-level of lymphocytes that slightly rose; and Group 3, with high-level of lymphocytes that rose. Notably, group 1 showed the highest mortality (90.7%) and all experiencing RP-ILD. Increased expression of IL-6 in lung tissues was observed in two cases with RP-ILD compared to two cases without RP-ILD. We also found the increased infiltration of CD4 + and CD8 + T cells, particularly CD8 + T cells, in lung tissues from patients with RP-ILD.ConclusionsOur study demonstrated that increased level of serum IL-6 (≥ 13.41pg/mL) and severe lymphopenia were promising predictors of 6-month all-cause mortality and the occurrence of RP-ILD in anti-MDA5-positive DM patients. Furthermore, tracking distinct trajectories of lymphocytes during hospitalization can be utilized to cluster patients.

Investigating the Relationship Between Demographic and Laboratory Factors with the Incidence of PTE in COVID-19

Background: In 2019, after the first case was discovered in Wuhan, China, the COVID-19 virus began to spread rapidly across the world, leading the WHO to declare the disease a public health emergency. Objectives: Thromboembolism refers to the formation of a clot in a vein, which then travels through the vascular system, potentially blocking blood flow in another location. Methods: This retrospective cohort study aimed to investigate the risk factors for pulmonary embolism in COVID-19 patients hospitalized at Firoozabadi Hospital from May to the end of December 2020. After extracting the required information, the data was entered into SPSS version 26 software for analysis. Results: In total, data from 283 COVID-19 patients admitted to Firouzabadi Hospital in Tehran in 2020 were collected. The average age of the patients was 58.8 ± 15.9 years. Among the 283 patients, 162 (57.6%) were male, 79 patients (27.9%) had pulmonary embolism, 102 patients (36%) were smokers, and 107 patients (37.8%) had a history of hypertension. A significant relationship was observed between the occurrence of pulmonary embolism and elevated levels of, white blood cells (WBC) (P = 0.0001), lactate dehydrogenase (LDH) (P = 0.0001), D-dimer (P = 0.0001), polymorphonuclear neutrophils (PMN) (P = 0.020), lymphocytes (P = 0.013), alkaline phosphatase (Alk.P) (P = 0.025), alanine aminotransferase (ALT) (P = 0.019), and aspartate aminotransferase (AST) (P = 0.017). Conclusions: Based on the results of this study, the incidence of pulmonary embolism in hospitalized COVID-19 patients who underwent CT angiography due to clinical suspicion of thrombosis was 27.9%. Additionally, factors such as smoking, a previous history of pulmonary thromboembolism, high WBC, elevated liver function tests (LFT), and elevated LDH levels were identified as risk factors for the occurrence of pulmonary embolism in these patients.

COMPREENDENDO A INTERSEÇÃO ENTRE HIV/AIDS E PNEUMONIA: UMA ANÁLISE ABRANGENTE DA LITERATURA

INTRODUCTION: The relationship between HIV/AIDS and pneumonia is complex and multifaceted. Individuals infected with HIV have a significantly higher risk of developing pneumonia, caused by both bacterial and viral agents, due to immune suppression from the virus. OBJECTIVE: To identify in the literature the relationship between HIV/AIDS and pneumonia in the context of nursing care. MATERIALS AND METHODS: This is an integrative literature review conducted in the MEDLINE, LILACS, and BDENF databases, using the descriptors: “HIV seropositivity,” “Pneumonia,” and “nursing care.” The descriptors were combined using the boolean operator AND, covering the period from 2018 to 2024. RESULTS: The study found that HIV-positive patients tend to experience a subacute progression of Pneumocystis jirovecii pneumonia (PCP), while immunocompromised patients without HIV face rapid progression, with a higher risk of respiratory failure and mortality. CT scans showed ground-glass opacities and elevated lactate dehydrogenase levels. Non-HIV patients had longer treatment delays and higher hospitalization and mortality rates. Lymphopenia, steroid use, and pneumothorax were associated with 60-day mortality. The incidence of bacterial pneumonia in people living with HIV decreased, linked to improved CD4 counts. Children with HIV showed higher mortality from coronavirus-related pneumonia. CONCLUSIONS: Future research should expand epidemiological surveillance, explore new therapies, and investigate co-infections in at-risk groups, particularly children. Additionally, strengthening public health policies and promoting prevention education are essential to improve clinical outcomes in vulnerable populations.

Risk factors for in-hospital mortality in older patients with acute respiratory distress syndrome due to COVID-19: a retrospective cohort study

BackgroundAdvancing age is associated with an increase in mortality among patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). This study aimed to determine risk factors for in-hospital mortality in patients over 60 years old with COVID-19-related ARDS (C-ARDS).MethodsThis was an observational, analytical, retrospective study conducted on a cohort that included all patients aged 60 years or older diagnosed with COVID-ARDSwho were admitted to a high-complexity hospital in Bogotá, Colombia, between March 2020 and July 2021.ResultsA total of 1563 patients were included in the analysis, with a median age of 73 years (interquartile range [IQR]: 67–80) and 811 deaths (51.8%). Independent risk factors for in-hospital mortality were identified as follows: patients aged 71–80 [OR 1.87 (95% CI 1.33–2.64)], age > 80 [OR 8.74 (95% CI 5.34–14.31)], lactate dehydrogenase (LDH) [OR 1.009 (95% CI 1.003–1.0015)], severe C-ARDS [OR 2.16 (95% CI 1.50–3.11)], use of invasive mechanical ventilation (IMV) [OR 12.94 (95% CI 9.52–17.60)], and use of steroids [OR 1.49 (95% CI 1.09–2.03)]. In patients over 80 years of age (n = 388), the primary risk factor associated with in-hospital mortality was the use of IMV (n = 76) [OR 6.26 (95% CI 2.67–14.69)], resulting in an in-hospital mortality rate of 89.4% (n = 68) when this therapy was implemented.ConclusionsThe primary risk factors for in-hospital mortality in patients older than 60 years were age, the use of IMV, the severity of C-ARDS, use of steroids and elevated LDH values. Among patients older than 80 years, the main risk factor for in-hospital mortality was the use of IMV. In cases of C-ARDS in older patients, the decision to initiate IMV should always be individualized; therefore, the use of alternative oxygen delivery systems as the first-line approach can be considered.

Different antinuclear antibody subgroups of anti-melanoma differentiation-associated gene 5-positive dermatomyositis had variability in clinical presentation: a multicentre retrospective cohort study

IntroductionThis study aimed to investigate the association between ANA and clinical characteristics as well as prognosis in a cohort of patients with anti-MDA5+ DM.Material and methodsWe conducted a systematic retrospective study of medical records from Nanjing Medical University myositis associated interstitial lung disease (ILD) contort.ResultsA total of 246 patients with anti-MDA5+ DM were enrolled in this study, with 28.5% males and 71.5% females. The median age was 53.0 years, the median disease duration was 2 months, and the median follow-up period was 12.0 months. ANA positivity rate at baseline was 52.4% in anti-MDA5+ DM patients. The ANA-positive group showed significantly higher positivity rates of anti-Ro52 antibodies (72.9% vs 54.7%, p=0.003) and anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies (9.3% vs 2.6%, p=0.033) compared to the ANA-negative group, but lower ALT levels [39.0 (21.5, 79.3) vs 51.3 (36.5, 95.8), p=0.006].In a subgroup analysis of the ANA-positive group, MDA5+++ patients had a higher incidence of RPILD compared to the MDA5+ group (P=0.028). In the ANA negative subgroup analysis, MDA5+++ patients had a higher mortality rate and worse prognosis compared to the MDA5+ group (P=0.026). Multivariate COX regression analysis showed that elevated LDH levels and the presence of rapidly progressive interstitial lung disease (RPILD) were associated with poor prognosis in ANA-negative anti-MDA5+ DM patients [hazard ratios of 1.002 (95% CI 1.001, 1.003, P = 0.020) and 13.694 (95% CI 15.032, 37.267, P &lt; 0.001), respectively].ConclusionsANA is frequently found in patients with anti-MDA5+ DM. High titres of anti-MDA5 antibodies are associated with mortality and RPILD.

Combined PD-1 and CTLA-4 Blockade in an International Cohort of Patients with Acral Lentiginous Melanoma.

Combination immune checkpoint blockade targeting PD-1 and CTLA-4 leads to high response rates and improved survival in advanced cutaneous melanoma (CM). Less is known about the efficacy of this combination in acral lentiginous melanoma (ALM). To determine the efficacy of combination immune checkpoint blockade targeting PD-1 and CTLA-4 in a real-world, diverse population of ALM. This multi-institutional retrospective study analyzed patients with histologically confirmed ALM treated with the combination of PD-1 and CTLA-4 inhibitors between 2010-2022. The primary objective of the study was objective response rate (ORR) per RECIST criteria. The secondary objectives were progression-free survival (PFS) and overall survival (OS). In total, 109 patients with advanced ALM treated with combined PD-1 and CTLA-4 blockade in any line of treatment were included. The majority of patients had stage IV disease (n=81, 74.2%). The ORR for the entire cohort was 18.3% (95% CI 11.6-26.9%), with 9 (8.3%) complete responses (CR) and 11 (10.1%) partial responses (PR). An additional 22 patients (20.2%) had stable disease (SD), and the disease control rate (DCR) was 38.5%. The median PFS was 4.2 months [95% CI 3.25-5.62], while the median OS was 17 months [95% CI 12.4%-23.1%]. A total of 95 patients (87.2%) had a treatment-related adverse event, with 40.4% (n=44/109) experiencing at least one grade 3 or 4 toxicity. Elevated LDH (p=.04), 2+ lines of prior therapy (p=.03), and Asian race/ethnicity (p=.04) were associated with worse OS, while Hispanic/Latino race/ethnicity was associated with better OS (p=.02). Combination of PD-1 and CTLA-4 blockade is less effective for ALM, as compared to CM, despite similar toxicity. Asian patients, in particular, appear to derive lower benefit from this regimen. Novel treatment approaches are needed for this rare melanoma subtype.

Evaluation of Ki-67 expression and large cell content as prognostic markers in MZL: a multicenter cohort study

Marginal zone lymphoma (MZL) can have varied presentations and pathologic features, including high Ki-67 expression ( > 20%) as well as increased numbers of large B cells (LC). However, there are limited data available demonstrating the prognostic significance of these variables in patients with MZL. In this multi-institutional retrospective cohort study of patients with MZL treated at 10 centers, we evaluated the association between the presence of Ki-67 expression and increased LCs on survival and risk of histologic transformation (HT). A total of 785 patients were included (60% with extranodal MZL, 20% with nodal MZL, and 20% with splenic MZL). Among the 440 patients with Ki-67 staining, 22% had high Ki-67 (Ki-67 >20%). The median progression-free survival (PFS) for patients with high Ki-67 was 5.4 years compared to 7.0 years for patients with low Ki-67 (HR = 1.45, 95%CI = 1.03–2.05). Ki-67 > 20% strongly correlated with high LDH level. The risk of HT was higher in patients with increased Ki-67 than those without (5-year risk, 9.8% vs 3.87%, p = 0.01). Twelve percent of patients had LC reported on biopsy with 6% having >10% LC. The presence of LC was associated with high Ki-67 (p < 0.001), but not associated with shorter PFS or overall survival (OS). The cumulative risk for HT was higher in patients with LC compared to those without LC (5-year risk, 9.4% vs 2.9%, p = 0.04). Receipt of anthracycline-based therapy did not impact PFS or OS in either group. Ki-67 staining >20% was a prognostic factor for worse survival and strongly correlated with elevated LDH. Novel therapies should be investigated for their potential ability to overcome the high-risk features in MZL. Our data reinforce the importance of obtaining biopsies at relapse or progression, particularly in patients with baseline high Ki-67 and increased LCs, given their increased risk for HT.

Elucidation of the Possible Molecular Mechanism for the Anti-Apoptotic Effect of Terpene-Rich Extract of Amomum subulatum and Coriandrum sativum against Rodent Model of Cardiotoxicity

Background: Spices, including Amomum subulatum and Coriander sativum, are not only popular for improving food flavour but are also accepted worldwide for their health benefits in various disorders. Objective: This study aimed to elucidate the possible mechanism for the anti-apoptotic effect of terpene-rich extract of Amomum subulatum and Coriandrum sativum against the rodent model of cardiotoxicity. Methods: Effects of standardized terpenoids-rich aqueous methanolic extract of two commonly used spices, viz. Amomum subulatum Roxb. and Coriandrum sativum Linn., were investigated on doxorubicin-induced apoptotic changes and cardiotoxicity in Wistar rats with the aim of in-vestigating the mechanism. Prior to the in vivo experiment, the extracts were subjected to quan-titative estimation of possible bioactive markers of the terpenes by employing a newly devel-oped, optimized, and validated GC-MS method along with TLC profiling. Results: Cardiotoxicity was evident from elevated creatinine kinase (CK-MB), lactate dehydro-genase (LDH), and malondialdehyde (MDA) levels in the toxic control group after treatment with doxorubicin (2.5mg/kg i.p. given twice a week for three weeks). Caspase-3, Tumor necrosis factor-α (TNF-α), and Interleukin-6 (IL-6) were also induced in animals treated with doxorubi-cin. Treatment with Amomum subulatum and Coriandrum sativum at the doses of 100 and 200mg/kg exhibited significant (P&lt;0.001) reversal of CK-MB, LDH, MDA, Caspase-3, TNF-α, and IL-6 levels. This protective effect was further supported by the results of DNA gel electro-phoresis and histopathological observations. Conclusion: This study supports the cardioprotective role of selected spices against doxorubicin-induced cardiotoxicity through the anti-apoptotic mechanism.

Exploring the Frequency and Risk Factors of Hyperprogressive Disease in Patients with Advanced Melanoma Treated with Immune Checkpoint Inhibitors.

Hyperprogressive disease (HPD) is described as the unexpected rapid growth of a tumour accompanied by a decline in performance status. While immune checkpoint inhibitors (ICIs) have improved outcomes in advanced melanoma, HPD remains a significant challenge in a subset of patients. Although HPD has been extensively studied in various solid tumours, research specifically focusing on advanced melanoma remains limited. We analysed 158 advanced melanoma patients, with 66.5% (n = 105) receiving anti-PD-1 and 33.5% (n = 53) receiving nivolumab plus ipilimumab. The median overall survival was 4.9 months for patients with HPD compared to 8.9 months for those with progressive disease without HPD (p = 0.014). Factors associated with HPD included liver metastasis (p = 0.002), three or more metastatic sites (p < 0.001), elevated lactate dehydrogenase levels (p = 0.004), and Eastern cooperative oncology group performance status ≥2 (p = 0.023). Multivariate analysis identified the Royal Marsden Hospital score (HR 3.675, 95% CI: 1.166-11.580, p = 0.026) as an independent risk factor for HPD, with the MDA-ICI score also trending towards significance (HR 4.466, 95% CI: 0.947-21.061, p = 0.059). This study provides valuable insights into the frequency and factors associated with HPD in advanced melanoma patients treated with ICIs, highlighting the relevance of clinical markers and scoring systems in predicting HPD risk.

Real-world safety profile of zanubrutinib: a disproportionality analysis based on the FAERS database

ObjectiveZanubrutinib is a second-generation Bruton’s tyrosine kinase inhibitor that has been approved for the treatment of several B cell malignancies. The aim of this study was to evaluate adverse events...

Successful management of megaoesophagus associated with hypothyroidism in a dog: A case report

A seven-year-old male Dachshund was presented with a history of chronic regurgitation and weight loss for two months. On clinical examination, dry and rough hair coat with alopecia on nose bridge and rat tail appearance were observed. Elevated rectal temperature and increased respiratory rate were noticed. Auscultation of lung field revealed mild crackles. Leucocytosis and mild anaemia were evident on complete blood count. Hypercholesterolaemia, hypertriglyceridaemia and elevation of Lactate dehydrogenase (LDH) and Alkaline phosphatase (ALP) were observed in serum biochemistry. The total T4 (TT4) value was low and canine-specific thyroid stimulating hormone (cTSH) was elevated. Megaoesophagus was confirmed by plain radiography. Barium contrast radiograph revealed generalised dilatation with pooling of barium in the oesophagus. The animal was treated with levothyroxine sodium at 0.02 mg/kg BW PO BID and bethanechol at 10 mg PO TID. Supportive therapy included antibiotics, antacids and antiemetics. Elevated feeding was advised. The animal had no episodes of regurgitation even after one month Keywords: Megaoesophagus, hypothyroidism, bethanechol, elevated feeding

The Inhibition of Reactive Oxygen Species Modulator 1 Attenuates Sevoflurane-Induced Neural Injury via Reducing Apoptosis and Oxidative Stress.

Sevoflurane causes neural injury by promoting apoptosis and oxidative stress. Reactive oxygen species modulator 1 (ROMO1) regulates apoptosis and oxidative stress, while its role in sevoflurane-induced neural injury remains unclear. This study intended to investigate the effect of ROMO1 knockdown on viability, apoptosis, and oxidative stress in sevoflurane-treated HT22 cells and its downstream pathway. HT22 cells were untreated (blank control), or treated with 1%, 2%, and 4% sevoflurane, respectively. Moreover, HT22 cells were transfected with siROMO1 small interfering RNA (siROMO1) or negative control siRNA (siNC) and then stimulated with 4% sevoflurane for further assays. Sevoflurane dose-dependently decreased cell viability and increased apoptosis rate versus blank control in HT22 cells. Sevoflurane elevated reactive oxygen species (ROS) fluorescence intensity, malondialdehyde (MDA), and lactate dehydrogenase (LDH) release, while reducing superoxide dismutase (SOD) activity in a dose-dependent manner versus blank control in HT22 cells. It also dose-dependently increased the relative mRNA and protein expressions of ROMO1 versus blank treatment in HT22 cells. Moreover, siROMO1 plus 4% sevoflurane increased cell viability, while decreasing apoptosis rate, ROS fluorescence intensity, MDA, and LDH release versus siNC plus 4% sevoflurane in HT22 cells. siROMO1 plus 4% sevoflurane elevated the phosphorylation of protein kinase B (AKT) versus siNC plus 4% sevoflurane in HT22 cells. ROMO1 inhibition reverses sevoflurane-induced neural injury by reducing apoptosis and oxidative stress in HT22 cells. The results indicate that ROMO1 may be a potential target for the management of sevoflurane-induced neural injury.

Cardiac Angiosarcoma with Unusual Cytologic Features Causing Cardiac Tamponade in a Young Adult Patient

Abstract Introduction/Objective Cardiac angiosarcoma is a rare endothelial malignancy with poor prognosis, frequent metastasis, and short median survival of only a few months. The disease has a wide age spectrum and can occur in young adult patients. The cytological diagnosis of cardiac angiosarcomas is challenging as cases are rare and its cytology is not extensively described or reported in literature. Here, we describe a rare case of cardiac angiosarcoma with unusual cytologic features. Methods/Case Report Our patient is a 30 year old male presenting with three days of worsening dyspnea and palpitations and was discovered on ultrasound to have large pericardial effusion compressing the right ventricle and causing cardiac tamponade. CT/MRI imaging revealed a 4.5 x 4.3 x 2.6 cm mass inside the right ventricle with extra- cardiac invasion through the pericardium and into the anterior mediastinum. Pericardiocentesis yielded 1.5 liters of hemorrhagic, brown, pericardial fluid with elevated LDH and protein levels. Cytology of the pericardial fluid revealed numerous tumor cells occurring singly or in monolayered, acinar clusters or cohesive spheres containing amorphous, eosinophilic cores made of collagen as evidenced on trichrome stain. The tumor cells possessed hyperchromatic, irregular, variably sized nuclei, prominent nucleoli, and cytoplasmic vacuoles. The tumor cells were positive for vimentin, CD31, and CD34, and showed high Ki67 proliferation index &amp;gt; 50%. A catheter-mediated biopsy of the right ventricular mass revealed spindled and epithelioid tumor cells strongly positive for CD31, CD34, and vimentin, focally positive for Factor VIII and AE1/AE3, and showing high Ki67 proliferation index of roughly 50%. The cytological, histological, and immunohistochemical findings were most consistent with cardiac angiosarcoma as the diagnosis. The patient eventually developed worsening chronic left chest pain and expired from cardiac arrest six months after his diagnosis. Results (if a Case Study enter NA) NA Conclusion We report a rare case of cardiac angiosarcoma with unusual cytologic features, manifesting as acinar clusters and cohesive spheres with collagenous cores that are not typical of malignant endothelial neoplasms. Currently there are no effective, standardized therapies that can significantly prolong survival for this malignancy, and treatment is often palliative. The cytological diagnosis of cardiac angiosarcoma is challenging given the rarity of this disease and the paucity of literature describing its cytology.

Molecular testing in a patient with multiple alloantibodies and warm autoimmune hemolytic anemia: A case study

Abstract Introduction/Objective We present a case of RBC alloimmunization and warm autoimmune hemolytic anemia (WAIHA) in a patient with a recent RBC transfusion. Serological testing followed by molecular testing revealed a rare D+ C- E- partial c+ partial e+ VS+ V+ hrS+ hrB+vw/- predicted phenotype. Methods/Case Report A 75-year-old black male with secondary myelofibrosis presented with a sudden onset of chest pain, dyspnea and weakness during an RBC transfusion. The patient was subsequently admitted for further workup. Labs showed low hemoglobin, low haptoglobin, elevated LDH and a positive direct antiglobulin (DAT) test. The patient was started on intravenous immunoglobulin and steroids for suspected WAIHA. On immunohematology serologic testing, blood typed as B-positive and polyspecific DAT positive with anti-IgG positive and anti-C3 negative. Serum plasma studies showed probable warm autoimmune hemolytic anemia and allo anti-S, -E, and -C by previous history. Eluate studies showed panagglutinin and antibody with D-like specificity. Immucor PreciseTypeTM Human Erythrocyte Antigen (HEA) Molecular BeadChip test predicted a partial e antigen and potential hrB-. Genotyping for RHD variants was performed and revealed RHD*01 (homozygous or hemizygous). Targeted genomic testing did not detect variants associated with common partial or weak RhD antigens. Based on this testing, the patient was not predicted to be at risk of allo-anti-D. An RHCE genotype for C, c, E and e variants including hrB and hrS showed RHCE*ce48C,733G/RHCE*ce733G with predicated phenotype of D+ C- E- partial c+ partial e+ VS+ V+ hrS+ hrB+vw/-. Based on the RHCE testing, the patient was predicted to be at risk for allo-anti-c, -e, -f (ce) and possibly anti-hrB. Results (if a Case Study enter NA) NA Conclusion In this case, serologic testing alone did not reveal a precise diagnosis. Molecular testing aided in the diagnosis of WAIHA and will help guide future transfusions. Pathologists must consider molecular testing when faced with a challenging serologic diagnosis.

Clinical characteristics and survival outcomes of patients with primary central nervous system lymphoma treated with high-dose methotrexate-based polychemotherapy and consolidation therapies

Given the rarity of primary central nervous system lymphoma (PCNSL), evaluations of different high-dose methotrexate-(HD-MTX)-based treatment regimens is sparse. This retrospective, multicenter study evaluates clinical characteristics and outcomes (progression-free, overall and disease-specific survival) after five HD-MTX-based polychemotherapeutic regimens and two consolidation therapies. 346 patients with histologically confirmed PCNSL, treated with ≥ 1 cycle HD-MTX-based strategies (≥3g/m2/cycle) were included. The regimens included MATRIX (HD-MTX, HD-AraC, thiotepa, and rituximab), (R)MBVP±HD-AraC (HD-MTX, teniposide/etoposide, carmustine, prednisolone, ± HD-AraC, ± rituximab), (R)MP (HD-MTX, procarbazine, ± rituximab), and a combination of HD-MTX and HD-AraC. The overall response rate after induction was 69 %, 28 % complete remission and progressive disease was observed in 100 (29 %) patients. 126 (36 %) patients received consolidation, including high-dose-BCNU-thiotepa with autologous stem cell transplantation (HD-BCNU-TT/ASCT, n = 59 (17 %)) or whole brain radiotherapy (WBRT, n = 67 (19 %)). Clinical characteristics associated with adverse mortality risk by multivariable prognostication contained age > 60 years (HR 1.61, p = 0.011), elevated LDH (HR 1.75, p = 0.004) and WHO status ≥ 2 (HR 1.56, p = 0.010). Independently, induction regimens containing HD-AraC demonstrated survival benefit compared to induction regimens without HD-AraC (HR 0.59, p = 0.002). Without preference for HD-BCNU-TT/ASCT or WBRT, a favorable effect of consolidation (HR 0.44 and HR 0.42, p < 0.001) was confirmed, also with consolidation as time-dependent variable. Competing risk analysis showed similar low incidence of lymphoma-unrelated deaths in consolidated and unconsolidated patients. This study confirms that age, elevated LDH and WHO status increase the mortality risk. HD-AraC containing treatment regimens and consolidation with HD-BCU-TT/ASCT or WBRT were associated with superior survival, including a favorable low incidence of lymphoma-unrelated deaths.

The effect of eccentric arm cycling on muscle damage and injury-related biomarkers.

There is a scarcity of information regarding the effect of upper-body eccentric exercise on biomarkers of muscle damage. This study sought to investigate the effect of eccentric arm cycling on muscle damage [exercise-induced muscle damage (EIMD)]. Ten subjects performed a 15 min eccentric arm cycling protocol (cadence 49 ± 7 rpm, power absorbed 248 ± 34 W). Maximal voluntary contraction (MVC) of the elbow flexors was evaluated at rest and at 5 min, 24 h, and 48 h post-exercise. In addition, blood samples were drawn at rest and thereafter at 30 min, 24 h, and 48 h intervals after exercise for quantification of creatine kinase (CK), myoglobin, lactate dehydrogenase (LDH) and endothelin (ET-1) concentrations. Delayed onset muscle soreness (DOMS) was assessed using a category ratio scale (0-10). Myoglobin was increased from baseline at 30 min post-exercise (+114%, 46.08 ± 22.17 µg/L, p = 0.018). Individual peak values were higher than baseline values for CK (+72.8%, 204 ± 138 U/L, p = 0.046) and LDH (+17%, 3.3 ± 0.88 nmole/min/mL, p = 0.017), but not for ET-1 (+9%, 1.4 ± 0.48 pg/mL, p = 0.45). DOMS was reported at 24 h (median 4) and 48 h (median 4) post-exercise and MVC of the elbow flexors were reduced from baseline (216 ± 44 N) at 5 min (-34%, 147 ± 61 N, p < 0.001), 24 h (-17%, 181 ± 56 N, p = 0.005) and 48 h (-9%, 191 ± 54 N, p = 0.003). Eccentric arm cycling incites EIMD with reduced MVC and elevation of myoglobin, CK and LDH.

Clinicopathological analysis of primary central nervous system lymphoma in patients with or without HIV infection

The clinicopathological features of HIV-related primary central nervous system lymphoma (PCNSL) and immunocompetent primary central nervous system lymphoma (IC-PCNSL) were found to be distinct. Thirty-seven patients with HIV-related PCNSL and thirty patients with IC-PCNSL were included in our study. Hematoxylin & eosin (HE) staining, immunohistochemical detection using CD10, MUM1, CD20, Bcl-2, Bcl-6, p53, C-MYC, Ki67, methyltransferase like factor 3 (METTL3) antibodies and Epstein–Barr encoding region (EBER) in situ hybridization were performed. All of the patients were classified as the diffuse large B-cell lymphoma (DLBCL) histological type. Patients with HIV-related PCNSL were younger and more likely to be male, with elevated lactate dehydrogenase (LDH) and low sugar content in cerebrospinal fluid (CSF) compared to patients with IC-PCNSL.The positive rates of METTL3, Bcl-2, p53 and EBER were significantly higher in HIV-related PCNSL patients than in IC-PCNSL patients. Furthermore, we also found that the expression of METTL3 was lower in germinal centre B-cell (GCB)-like DLBCL (n = 7) than in non-GCB like DLBCL (n = 30) in HIV-related PCNSL (P = 0.030); however, in IC-PCNSL patients, the expression of METTL3 was not significantly different between GCB-like DLBCL and non-GCB-like DLBCL (P = 0.670). Although the manifestations are similar in PCNSL patients with and without HIV, HIV-related PCNSL differs from IC-PCNSL in terms of pathological characteristics including METTL3, Bcl-2, p53 and EBER. We therefore suggest that the pathogenesis of HIV-related PCNSL and IC-PCNSL may differ according to host immune status.

Newcastle disease virus enhances the antitumor efficacy of Doxorubicin in a cervical cancer mouse model

Background and aimsCervical cancer (CC) is a common cancer among women, often treated with Doxorubicin (Doxo). Research is underway to explore the use of oncolytic virus (OV) therapy as a means to improve drug efficacy and enhance the immune system’s tumor-fighting capabilities. Hence, our study purposes to evaluate the therapeutic potential of Newcastle disease virus (NDV) in increasing the antitumor efficacy of Doxo in mouse models of CC.Methods and materialsTC1 cells were administered to C57BL/6 mice (Female) in a range of 6 to 8 weeks age (n = 40) to induce tumor growth. After tumor development, four treatment groups of mice were formed. Treatment were performed through NDV, Doxo, and a combination of both in three groups of treatment twice in a one-week intervention manner, while the control group treated with PBS. Following the last treatment, half of these mice were subjected to euthanize due to the immune-response assessment, and the other half were followed up till they died naturally in a certain period of time.ResultsMice that underwent the combined treatment showed significantly improved survival rates and slower tumor progression in comparison with the control group. This combined treatment substantially elevated nitric oxide (NO) and lactate dehydrogenase (LDH) levels in the splenocytes cultures of mice bearing cervical tumors. Furthermore, combination therapy resulted in a notable elevation in TNF-α, IL-12, and IFN-γ, secretion alongside a reduction in the release of TGF-β and IL-4 within the splenocytes in counter with the treatment of just NDV or Doxo.ConclusionAccording to the findings of this study, it seems that utilizing NDV can improve the effectiveness of Doxo in a mouse model of CC, suggesting it can serve as an adjunct therapy alongside chemotherapy.

Effects of four-week lasting aerobic treadmill training on hepatic injury biomarkers, oxidative stress parameters, metabolic enzymes activities and histological characteristics in liver tissue of hyperhomocysteinemic rats.

Disruptions in homocysteine (Hcy) metabolism may increase the liver's susceptibility to developing conditions such as alcoholic liver disease, viral hepatitis, hepatocellular carcinoma (HCC), and cirrhosis. The aim of this study was to examine effects of aerobic treadmill training on hepatic injury biomarkers in sera, oxidative stress parameters, the activity of metabolic enzymes, and histological characteristics in the liver tissue of rats with experimentally induced hyperhomocysteinemia. Male Wistar albino rats were divided into four groups (N = 10, per group): C-saline 0.2mL/day sc. 2×/day for 14days + saline 0.5mL ip.1×/day for 28days; H-homocysteine 0.45µmol/g b.w. 2×/day for 14days + saline 0.5mL ip.1×/day for 28days; CPA-saline 0.2mL/day sc. 2×/day for 14days + aerobic treadmill training for 28days; and HPA-homocysteine 0.45µmol/gb.w. 2×/day for 14days + aerobic treadmill training for 28days. The serum albumin concentration was decreased in both physically active (PA) groups compared to sedentary groups. Concentration of malondialdehyde in liver tissue homogenates was lower in both PA groups compared to the H group. The total lactate dehydrogenase and malate dehydrogenase activities were significantly elevated in the HPA group compared to the C and H groups. Activities of aminotransferases in sera samples, and activities of catalase and superoxide dismutase in liver tissue did not significantly differ between groups. No significant histological changes were found in liver tissue in groups. This study demonstrated that aerobic treadmill training can reduce lipid peroxidation in liver tissue under hyperhomocysteinemic conditions, providing a protective effect. However, hyperhomocysteinemia can alter energy metabolism during aerobic exercise, shifting it toward anaerobic pathways and leading to elevated lactate dehydrogenase activity in the liver. Given that conditions like hyperhomocysteinemia are associated with an increased risk of cardiovascular diseases and liver damage, understanding how exercise influences these dynamics could guide therapeutic approaches.

Biopolymers: Histopathologic Case Series of Patients with Permanent Synthetic Fillers Presenting Chronic Granulomatous Reaction and Hypercalcemia

Background: Biopolymers, which are diverse and permanent synthetic fillers, are nonbiocompatible allogeneic materials. Their implantation can result in clinical, radiological, and histopathological manifestations that contribute to our understanding of foreign-body-induced human adjuvant disease. Methods: We conducted a descriptive observational case series involving 20 patients who underwent open biopolymer removal surgery in the buttocks and lumbosacral regions using the Meticulous Approach Safer and Keeper technique, followed by gluteal reconstruction with autologous tissue. Histopathological analysis was performed. This study was conducted in Bogotá, Colombia, from 2020 to 2023. Results: Documented clinical records and histopathological analyses of the 20 patients revealed an inflammatory response that was initially considered healthy. Cytoplasmic vacuolization in reactive adipocytes was observed in all cases, meriting consideration in the differential diagnosis of liposarcoma and suggesting local aggressiveness. One patient showed a positive lymphocytic inflammatory response in the Alcian blue test. Hypercalcemia was present in 30% of the patients, elevated lactate dehydrogenase in 40%, and elevated parathyroid hormone levels in 15%. Conclusions: Surgeons should consider measuring lactate dehydrogenase, serum calcium, and parathyroid hormone levels to assess the severity and guide clinical practice. Secondary prevention through the open surgical removal of biopolymers is recommended.