Elevated Lactic Acid Dehydrogenase Research Articles

Circulating microRNAs as potential biomarkers of physical activity in geriatric patients with HCV

BackgroundCirculating microRNAs have been implicated in a diverse array of biological and pathological phenomena. Their potential utility as noninvasive biomarkers for screening and diagnosing various diseases has been proposed.ObjectiveThis study aimed to explore the potential role of the miRNAs miR-122 and miR-486 as molecular biomarkers in the pathogenesis of hepatitis C virus (HCV) infection. Thus, miR-122 and miR-486 were detected in the serum of HCV patients and healthy controls. Moreover, the potential correlations of miR-122 and miR-486 with viral complications, such as physical activity, pain, muscle fatigue, and HCV infection, were identified.MethodsA total of 150 subjects aged 30 to 66 years were included in this study. The patients were classified as patients with chronic hepatitis C virus (CHC) (n = 110) or healthy controls (n = 40). Real-time polymerase chain reaction (PCR) analyses were performed to determine miR-122 and miR-486 expression. Physical activity (PA), pain score, HCV genotyping, viral overload, aspartate transaminase (AST), alanine transaminase (ALT), lactic acid dehydrogenase (LDH), creatine kinase (CK), and antioxidant status were also estimated by using prevalidated questionnaires, PCR, and spectrophotometric analyses.ResultsCompared with those in normal controls, significant increases in the serum levels of miR-122 and miR-486 were reported in patients with CHC. In physically active CHC patients, there was a significant correlation between the expression of miRNAs and increased alanine transaminase (ALT), aspartate transaminase (AST), fibrosis scores, and inflammation activity, but no association was reported for hepatitis C virus (HCV) RNA or viral load. Additionally, significant decreases in LDH, CK, GSSG, and pain scores and increases in TAC, GSH, and the GSH/GSSG ratio were reported. Moreover, the expression of miR-122 and miR-486 was positively correlated with changes in body mass index (BMI) and liver fibrosis stage, as well as negatively correlated with sex, PA, TAC, GSH, GSSG, and the GSH/GSSG ratio.ConclusionMiR-122 and miR-486 expression levels were strongly correlated with physical activity, pain perception, and muscle fatigue biomarkers in HCV-infected patients. These miRNA levels were associated with elevated AST, ALT, fibrosis scores, LDH, CK, and antioxidant status, thus suggesting their potential as biomarkers for disease severity and oxidative stress. However, no correlation was observed with viral load or HCV-RNA expression, thus implying that these miRNAs may impact disease progression and symptoms through host factors, rather than directly affecting viral replication. In summary, the results demonstrated that molecular studies of miR-22 and miR-468 and their associations with PA, pain, adiposity, sex differences, and muscle fatigue, as well as routine biomarkers, could be useful as prognostic nanoninvasive biomarkers, thus providing novel therapeutic targets for CHC infection.

Analysis of Fungal and Bacterial Co-Infections in Mortality Cases among Hospitalized Patients with COVID-19 in Taipei, Taiwan.

Fungal or bacterial co-infections in patients with H1N1 influenza have already been reported in many studies. However, information on the risk factors, complications, and prognosis of mortality cases with coronavirus disease 2019 (COVID-19) are limited. We aimed to assess 36 mortality cases of 178 hospitalized patients among 339 patients confirmed to have had SARS-CoV-2 infections in a medical center in the Wenshan District of Taipei, Taiwan, between January 2020 and September 2021. Of these 36 mortality cases, 20 (60%) were men, 28 (77.7%) were aged >65 years, and the median age was 76 (54–99) years. Comorbidities such as hypertension, coronary artery disease, and chronic kidney disease were more likely to be found in the group with length of stay (LOS) > 7 d. In addition, the laboratory data indicating elevated creatinine-phosphate-kinase (CPK) (p < 0.001) and lactic acid dehydrogenase (LDH) (p = 0.05), and low albumin (p < 0.01) levels were significantly related to poor prognosis and mortality. The respiratory pathogens of early co-infections (LOS < 7 d) in the rapid progression to death group (n = 7 patients) were two bacteria (22.2%) and seven Candida species (77.8.7%). In contrast, pathogens of late co-infections (LOS > 7 d) (n = 27 patients) were 20 bacterial (54.1%), 16 Candida (43.2%), and only 1 Aspergillus (2.7%) species. In conclusion, the risk factors related to COVID-19 mortality in the Wenshan District of Taipei, Taiwan, were old age, comorbidities, and abnormal biomarkers such as low albumin level and elevated CPK and LDH levels. Bacterial co-infections are more common with Gram-negative pathogens. However, fungal co-infections are relatively more common with Candida spp. than Aspergillus in mortality cases of COVID-19.

End-of-Life Care for Older Adults with Aggressive Non-Hodgkin Lymphoma.

Background: Aggressive non-Hodgkin lymphoma (NHL) commonly affects older adults and is often treated with intensive therapies. Receipt of intensive therapies and absence of a clear transition between the curative and palliative phases of treatment yield prognostic uncertainty and risk for poor end-of-life (EOL) outcomes. However, data regarding the EOL outcomes of this population are lacking. Methods: We conducted a retrospective analysis of adults ≥65 years with aggressive NHL treated with systemic therapy at Massachusetts General Hospital from April 2000 to July 2020 who subsequently died. We abstracted patient and clinical characteristics and EOL outcomes from the medical record. Using multivariable logistic regression, we examined factors associated with hospitalization within 30 days of death and hospice utilization. Results: Among 91 patients (median age = 75 years; 37.4% female), 70.3% (64/91) were hospitalized, 34.1% (31/91) received systemic therapy, and 23.3% (21/90) had an intensive care unit admission within 30 days of death. The rates of palliative care consultation and hospice utilization were 47.7% (42/88) and 39.8% (35/88), respectively. More than half of patients (51.6%, 47/91) died in a hospital or health care facility. In multivariable analysis, elevated lactic acid dehydrogenase was associated with risk of hospitalization within 30 days of death (odds ratio [OR] 3.61, p = 0.014). Palliative care consultation (OR 4.45, p = 0.005) was associated with a greater likelihood of hospice utilization, whereas hypoalbuminemia (OR 0.29, p = 0.026) was associated with a lower likelihood of hospice utilization. Conclusions: Older adults with aggressive NHL often experience high health care utilization and infrequently utilize hospice care at the EOL. Our findings underscore the need for interventions to optimize the quality of EOL care for this population.

Small cells indifferentiated hepatoblasotma in childhood : a rare aggressive malignancy

A new born of two months years old was admitted for abdominal mass which the echography confirmed the hepatic origin. The biological analysis showed an elevated Lactic Acid Dehydrogenase (LDH) serum level, but no elevated alpha fetoprotein neither catecholamins nor other marquers. The abdominal scan confirmed hepatic mass at the expense of two segments. The fine needle scan guided biopsy was done and revealed a neoplastic proliferation of cells, histologically slightly larger than lymphocytes and measure (7-8 um) in size. They are round to oval with scant cytoplasm, relatively fine nuclear chromatin, inconspicuous nucleoli and only minimal mitotic activity. They grow in a diffuse pattern but usually form clusters either intimately inter-mixed with other epithelial cell types or forming nests in an almost ‘organoid’ pattern (A). Immunohistochemically, small cells showed positivity for pancytokeratin (B) as well as vimentin (D). They did not express alpha-fetoprotein (AFP) (C). Thus, the final diagnosis been retained : small cell undifferentiated hepatoblastomas (SCUD-HB) is associated with an aggressive biological course and poor survival. The negative prognostic impact is conferred even by small areas in an otherwise large tumor. Rarely, particularly in infants, the entire hepatoblastoma is composed of small undifferentiated cells ; such tumors account for approximately 5% of all hepatoblastomas. SCUD-HB is associated with low or normal serum AFP levels. SCUD-HB retain expression of INI1 but a small subset present morphological rhabdoid features, including loss of nuclear expression of INI1. Transition between the two types has been described.

Potential therapeutic effect of Moroccan propolis in hyperglycemia, dyslipidemia, and hepatorenal dysfunction in diabetic rats.

Objective(s):The effect of propolis collected in Morocco on blood glucose, lipid profile, liver enzymes, and kidney function was investigated in control and diabetic rats. Materials and Methods:Antioxidant activity of propolis was evaluated with the use of DPPH, 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS•+), ferric reducing power and total antioxidant activity assay. To study its effect in streptozotocin (STZ)-induced diabetes, the rats were divided into eight groups; four control and four diabetics. The animals received distilled water, glibenclamide, or propolis extract, 50 mg/kg/BW) or 100 mg/kg/b.wt, daily for 15 days. Blood glucose, triglyceride, lactic acid dehydrogenase, liver enzymes, creatinine, blood urea, lipid profile, and body weight were measured on day 15 after commencement of the treatment. Results:Propolis has a strong antioxidant activity and high total flavonoids and polyphenols content. Glibenclamide and propolis have no significant effect on lipid parameters, and renal and hepatic function in non-diabetic rats. However, propolis or glibenclamide caused a significant lowering of blood glucose after a single administration and at day 15 after daily administration in diabetic rats (P<0.05). Both interventions significantly lowered lactic acid dehydrogenase, increased body weight, and ameliorated dyslipidemia and abnormal liver and kidney function caused by diabetes. The effect of propolis was dose-dependent and in a high dose it was more potent than glibenclamide. Conclusion:Propolis exhibited strong antihyperglycemic, antihyperlipidemic, and hepato-renal protective effects in diabetes, and significantly lowered the elevated lactic acid dehydrogenase. The study demonstrated for the first-time the effect of Moroccan propolis in diabetes and it will pave the way for clinical investigations.

Pneumocystis Jirovecii Pneumonia in Renal Transplant Recipients: A National Center Experience

BackgroundPneumocystis jirovecii pneumonia (PCP) represents an important cause of morbidity and mortality in kidney transplant recipients. In recent years an increasing number of PCP outbreaks have been reported worldwide. Patients and MethodsWe performed a retrospective study including the demographic, clinical, laboratory, and therapeutic parameters of all renal transplant recipients with PCP in Slovenia during the period from January 1, 2006, to December 31, 2011. ResultsAt the end of the 2011, 13/601 (2.2%) kidney transplant recipients followed in our center experienced PCP. The median time from transplantation to development of disease was 17 months (range, 3–148). Three recipients had PCP during the first year after transplantation because of early trimethoprim and sulfamethoxazole (TMP-SMX) discontinuation; in 3, it was related to acute graft rejection treatment; and in 6, to cytomegalovirus (CMV) infection. Pneumocystis jirovecii was microbiologically confirmed in 10 recipients. In 10 of 13 patients serum concentrations of lactic acid dehydrogenase (LDH) were increased. In addition, serum concentrations of beta-d-glucan was determined in 9 cases was elevated in each one. ConclusionThe incidence of PCP was low, most probably owing to prolonged (12 months) TMP-SMX prophylaxis. Premature TMP-SMX discontinuation in the first year after transplantation, treatment of graft rejection and CMV infection seemed to be risk factors for PCP. Elevated serum beta-d-glucan concentration was a better noninvasive indicator of P jirovecii infection than elevated serum LDH concentration. In cases with no microbiological conformation, beta-d-glucan and LDH concentrations were helpful to establish the diagnosis of PCP for early treatment.

Predictive Factors for the Development of Brain Metastasis in Advanced Unresectable Metastatic Melanoma

Melanoma that metastasizes to distant sites is associated with a grave prognosis. The objectives of the study were (1) to identify predictive factors for the development of brain metastases from the time of diagnosis of stage III/IV disease, (2) to identify predictive factors for the development of central nervous system (CNS) metastases from the time of diagnosis of primary melanoma, and (3) to assess whether the incidence of brain metastasis is more frequent in patients who had no tumor response to systemic therapy for stage III/IV disease compared with those who had partial or complete response. We collected and retrospectively analyzed information of 740 patients with advanced metastatic melanoma treated at MD Anderson Cancer Center over 15 years. Three hundred and twenty-nine patients had CNS metastases. The characteristics of these patients in terms of median age, sex, primary site, Breslow thickness, stage at first visit, baseline serum parameters, and response to systemic therapy were compared with those of patients who did not develop CNS metastasis. Cox proportional hazards models were used to analyze the cause-specific hazard function for CNS metastasis and deaths without CNS metastasis. We identified that M-stage [stage M1b vs. stage III or M1a, hazard ratio (HR)=2.64; stage M1c vs. stage III or M1a, HR=2.13, P<0.0001] and lactic acid dehydrogenase (LDH) (elevated vs. normal LDH, HR=1.51, P<0.001) at diagnosis of unresectable stage III/IV disease can independently predict the risk of developing CNS metastasis from the time of diagnosis of stage III/IV disease. Older age (HR=1.01, P=0.076), chemoresistance (stable disease+progressive disease vs. complete response+partial response HR=2.91, P<0.0001), low level of albumin (vs. normal HR=2.87, P<0.0001), elevated LDH (vs. normal HR=1.55, P=0.0004), and M-stage (M1c disease vs. stage III or M1a HR=1.89, P<0.0001) can independently predict shorter time to death without CNS metastasis from the diagnosis of stage III/IV disease. The location (head and neck vs. limbs HR=1.56, P=0.028; trunk and abdomen vs. limbs HR=1.45, P=0.029; unknown site vs. limbs HR=8.43, P=0.036) and pathology [Clark level (CL)=3 and/or BR2 to 4 mm vs. CL≤2 and/or BR<2 mm HR=1.60, P=0.037; CL>3 and/or BR> 4 mm vs. CL≤2 and/or BR<2 mm HR=2.03, P=0.001) of the primary melanoma can independently predict CNS metastasis-free interval from the time of diagnosis of primaries. Age (HR=1.012, P=0.034) and pathology of the primary melanoma (CL>3 and/or BR>4 mm vs. CL≤2 and/or BR<2 mm HR=1.54, P=0.024) can independently predict time to death without CNS metastasis from primaries. We identified the predictive factors associated with the development of CNS metastasis in patients with unresectable metastatic melanoma.

Deficient activity of von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura in the setting of adult-onset Still's disease

Deficient activity of von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura in the setting of adult-onset Still's disease

Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP)

Ninety patients with progressive recurrent lymphoma were treated with a combination of cisplatin 100 mg/m2 intravenously (IV) by continuous infusion over 24 hours, followed by cytosine arabinoside in two pulses each at a dose of 2 g/m2 given 12 hours apart. Dexamethasone, 40 mg orally or IV, was given on days 1 through 4. Vigorous hydration was reinforced by routine use of mannitol. Treatments were repeated at 3- to 4-week intervals for six to ten courses. Most patients had not achieved complete remission (CR) with prior therapies, which included Adriamycin (all patients) and methotrexate and VP-16 (58 patients). Median patient age was 55 years. Intermediate-grade lymphoma was the most frequent pathologic diagnosis. Seven patients died within two weeks of therapy; of the remaining 83 patients, 28 (34%) or 31% if all patients are considered, achieved CR, and 22 (26.5%) achieved partial remission (PR). Response was evident after the first two cycles of chemotherapy and appeared to be independent of the histopathologic type of lymphoma. To date, only eight of the complete responders have relapsed at a median follow-up of 11 months. The overall 2-year survival in 25%. Further analysis showed that patients with low tumor burden and normal lactic acid dehydrogenase (LDH) had a high CR response rate (67%) and a survival rate of 61% at 2 years. In contrast, patients with both high tumor burden and elevated serum LDH levels had a negligible CR rate, and only 5% are surviving at 1 year. Patients with either high tumor burden with normal LDH or low tumor burden with elevated LDH had an intermediate survival. Myelosuppression-related infection was the most frequent serious complication of this regimen (31%) and the cause of death of ten patients. Acute lysis syndrome was also observed in five patients with high tumor burden and was the cause of death in three of these patients. DHAP has proven to be an effective non-crossresistant regimen for patients with relapsing or refractory lymphoma, particularly for patients who have favorable prognostic characteristics.

Effective Salvage Therapy for Lymphoma With Cisplatin in Combination With High-Dose Ara-C and Dexamethasone (DHAP)

AbstractNinety patients with progressive recurrent lymphoma were treated with a combination of cisplatin 100 mg/m2 intravenously (IV) by continuous infusion over 24 hours, followed by cytosine arabinoside in two pulses each at a dose of 2 g/m2 given 12 hours apart. Dexamethasone, 40 mg orally or IV, was given on days 1 through 4. Vigorous hydration was reinforced by routine use of mannitol. Treatments were repeated at 3- to 4-week intervals for six to ten courses. Most patients had not achieved complete remission (CR) with prior therapies, which included Adria-mycin (all patients) and methotrexate and VP-16 (58 patients). Median patient age was 55 years. Intermediate-grade lymphoma was the most frequent pathologic diagnosis. Seven patients died within two weeks of therapy; of the remaining 83 patients, 28 (34%) or 31 % if all patients are considered, achieved CR, and 22 (26.5%) achieved partial remission (PR). Response was evident after the first two cycles of chemotherapy and appeared to be independent of the histopathologic type of lymphoma. To date, only eight of the complete responders have relapsed at a median follow-up of 11 months. The overall 2-year survival is 25%. Further analysis showed that patients with low tumor burden and normal lactic acid dehydrogenase (LDH) had a high CR response rate (67%) and a survival rate of 61 % at 2 years. In contrast, patients with both high tumor burden and elevated serum LDH levels had a negligible CR rate, and only 5% are surviving at 1 year. Patients with either high tumor burden with normal LDH or low tumor burden with elevated LDH had an intermediate survival. Myelosuppression-related infection was the most frequent serious complication of this regimen (31 %) and the cause of death of ten patients. Acute lysis syndrome was also observed in five patients with high tumor burden and was the cause of death in three of these patients. DHAP has proven to be an effective non-crossresistant regimen for patients with relapsing or refractory lymphoma, particularly for patients who have favorable prognostic characteristics.

Prognostic significance of serum lactic acid dehydrogenase in Ewing's tumor of bone.

Pretreatment serum lactic acid dehydrogenase (LDH) levels were examined in 82 patients with Ewing's tumor of bone (23 metastatic and 59 localized). The percentage of patients with increased serum LDH levels was significantly higher in the metastatic group than in the group of patients with localized disease (87 vs. 45%). After treatment with combined therapy, in this latter group the recurrence rate was significantly higher in patients with elevated serum LDH levels at admission than in those with normal serum LDH levels (50 vs. 9%). Of the 16 patients with localized disease who relapsed, 13 (81%) had elevated serum LDH levels at the time of recurrence. These results indicate that in Ewing's tumor serum LDH levels may serve as useful prognostic markers and could be valuable in monitoring the effectiveness of combined therapy.

Hepatic cell integrity in hypodynamic states.

Changes in liver integrity were studied in isolated perfused cat livers during simulated shock conditions (i.e., combined hypoxia, acidosis, and ischemia) or under the influence of each hypodynamic state separately. The combined hypodynamic stimuli depressed carbon clearance 51% and significantly elevated lactic acid dehydrogenase (LDH) and cathepsin D activities in the perfusate. The perfused liver was more seriously affected by hypoxia than by acidosis or ischemia alone. Reticuloendothelial clearance was depressed 20% and 25% in acidosis and hypoxia, respectively. Hypoxia also induced a 3-fold increase in cathepsin D and a 13-fold increase in LDH activities in the perfusate. After 150 min of hypoxia or ischemia, free cathepsin D in liver tissue increased significantly. The impairment of liver cell integrity (i.e., of Kupffer and parenchymal cells) occurred between 60 and 90 min during simulated shock conditions, indicating that the liver is stable for 60 min when it is exposed to hypoperfusion. The perfused liver is sensitive to local stimuli that predominate in circulatory shock, particularly hypoxia. These stimuli promote the release of lysosomal and cytoplasmic enzymes as well as depress phagocytosis by the reticuloendothelial system, phenomena that exacerbate the shock state.

Elevated Lactic Acid Dehydrogenase in Aqueous Humor in An Eye Without Retinoblastoma

A 14-month-old boy had a microphthalmic left eye. An anterior chamber paracentesis was performed six days after examination under anesthesia. Lactic acid dehydrogenase (LDH) level in the aqueous humor was 1,158 mu and was 202 mu in the serum. The aqueous humor/serum LDH ratio was 5.73. This eye was eventually enucleated and found to have retinal dysplasia and diffuse hemorrhagic necrosis. There was no eividence of retinoblastoma. The elevated LDH level in aqueous humor was probably secondary to the ocular tissue necrosis and hemorrhage. This false-positive result emphasizes the limitation of using the aqueous humor/serum LDH ratio to distinguish eyes with retinoblastoma from those without retinoblastoma.

Rheumatoid Pleuritis with Effusion

SUMMARY 1.Rheumatoid pleuritis with effusion may occur in the course of rheumatoid disease without radiographic evidence of lung involvement. 2.Unusual characteristics of the pleural fluid in rheumatoid disease have been discussed with particular reference to low glucose level, cosinophilia, and elevated lactic acid dehydrogenase level. 3.Needle biopsy of the parietal pleura is strongly recommended for confirming the suspected diagnosis of rheumatoid pleuritis and for ruling out other causes of pleural effusion. Repeat biopsies are indicated when the initial attempt is nondiagnostic. 4.The occurrence of rheumatoid pleural effusion has no prognostic significance for the subsequent course of arthritis. 5.Specific treatment for rheumatoid pleural effusion is not presently available nor indicated except thoracentesis for comfort.

Pulmonary Rheumatoid Nodule With Cavitation and Chronic Lipid Effusion

Unusual findings were noted in a case of nodular rheumatoid pulmonary disease with roentgenographic evidence of cavitation. Biopsy specimen of the cavitated nodule was identical microscopically to the patient's typical subcutaneous rheumatoid nodule. Of further interest was the associated pleural effusion with low glucose concentration, high total lipid content, and extremely high lactic acid dehydrogenase level. To the best of the author's knowledge, chronic lipid effusion and elevated lactic acid dehydrogenase have not been previously reported in association with rheumatoid disease of the lung. The diagnostician must consider rheumatoid disease in the differential diagnosis of cavitary pulmonary lesions in the patient with associated rheumatoid disease. Adequate biopsy and microscopic confirmation of the process are still required for definite diagnosis.