Рembrolizumab as second line therapy for hepatocellular patient

The optimal hepatocellular cancer (HCC) therapy remains a challenge. Due to checkpoint inhibitors patients with intolerance to the targeted therapy and or those with the impaired liver function can get an appropriate drug therapy. This clinical observation illustrates the long-term effect of pembrolizumab as the 2-line therapy in a patient diagnosed with. Sorafenib in standard doses as first line therapy led to severe toxicity and necessitated the withdrawal of therapy. Although subsequently the doses were reduced and concomitant medications used, sorafenib therapy was discontinued due to pronounced side effects typical of kinase inhibitors. From August 2017 to September 2019, as a part of a clinical study, the patient received 35 courses of immunotherapy with pembrolizumab 200 mg i.v. every 3 weeks, with satisfactory tolerance. The best response - partial tumor regression – was achieved at 84 weeks of therapy and continues to this day. Favorable toxicity profile makes checkpoints inhibitors a good treatment option in patients with impaired liver function (Child-Pugh 7–8 points) or with intolerable toxicity of kinase inhibitors.

Macrophage Activation Syndrome secondary to Systemic Juvenile Idiopathic Arthritis: A Case Report

Macrophage activation syndrome is a rare but a life threatening condition commonly associated with Systemic Juvenile Idiopathic Arthritis. Its clinical presentation includes fever, hepatosplenomegaly, hypertriglyceridemia, hypofibrinogenemia, hyperferritinemia and impaired liver enzymes. The symptoms are alarming yet non-specific and often lead to a delayed diagnosis. A 12 year male presented with a history of intermittent fever and was started on antibiotics but failed to respond after several days of hospital stay. After a series of investigations to rule out multiple diagnoses he was diagnosed as a case of Macrophage Activation Syndrome secondary to Systemic onset Juvenile Arthritis and was treated with steroids.

COVID-19 Patients Symptoms: Gastrointestinal Presentations, Comorbidities and Outcome in a Canadian Hospital setting

Background: The Coronavirus disease 2019 (COVID-19) pandemic has had a significant global impact and Canada has seen significant morbidity and mortality nationwide. While public health interventions and provincially regulated health insurance coverage have been credited with minimizing transmission rates in Canada relative to neighboring countries, disease presentation has been presumed to be the same. Aim: We sought to determine factors associated with differences in gastrointestinal outcomes in COVID-19 patients at a Canadian hospital. Methods: We collected data from 192 hospital records of COVID-19 patients across seven Hamilton Health Sciences hospitals, a network of academic health centers located in Hamilton, Ontario serving one of the largest metropolitan areas in Canada. Statistical and correlative analysis of symptoms, comorbidities, and mortality were performed. Results: There were 192 patients. The mean age was 57.6 years (SD=21.0). For patients who died (n=27, 14%), mean age was 79.2 years old (SD=10.6) versus 54 years for survivors (SD=20.1). There was a higher mortality among patients with older age (p=0.000), long hospital stay (p=0.004), male patients (p=0.032), and patients in nursing homes (p=0.000). Patients with dyspnea (p=0.028) and hypertension (p=0.004) were more likely to have a poor outcome. Laboratory test values that were significant in determining outcomes were an elevated INR (p=0.007) and elevated creatinine (p=0.000). Cough and hypertension were the most common symptom and comorbidity, respectively. Diarrhea was the most prevalent (14.5%) gastrointestinal symptom. Impaired liver function was related to negative outcome (LR 5.6; p=0.018). Conclusion: In a Canadian cohort, elevated liver enzymes, prolonged INR and elevated creatinine were associated with poor prognosis. Hypertension was also linked to a higher likelihood of negative outcome.

COVID-19 Severity among Cancer-COVID Patients with Different Types of Cancer: A Case Series of Five Patients

Background: People with malignancy are under increased threat in the current COVID-19 pandemic. It is crucial to study the severity of COVID-19 in different cancer type as the microenvironments are different. Besides, the effect on specific organs should be studied to understand the long-term consequences of both the diseases and its treatment. Methods: In our retrospective case series, we are presenting degree of severity in 5 cancer-COVID patients based on their clinical characteristics. All the patients were RT-PCR confirmed COVID-19 patients with malignancy. The demographic and clinical data of the patients were retrieved from the hospital database.Results: The cancers include; stomach (1), bladder (2), glioma (3), lungs (4) and hard palate cancer (5). Patient-4 and 5 were receiving chemotherapy when they got infected and had highly dysregulated liver function and higher CT severity score (19/25) compared to the nonrecipients. In patient-2 inflammatory and other haematological parameters we highly dysregulated suggesting a possible bottle neck of older age. Interestingly in the patient-3 the COVID-19 markers like lymphocyte, neutrophil and platelet levels were close to or within the normal limits unlike other patients. Conclusions: All the patents included in our report died during hospitalization. The patients receiving chemotherapy had possible impaired liver function and died early compared to the nonrecipients. The characteristic COVID-19 markers like lymphopenia, neutrophilia and thrombocytopenia did not occur in the glioma patient. The effect of cancer-COVID and its treatment on specific organs like the liver and kidney need to be studied during treatment and follow-up.

Hyperlactatemia and lactate acidosis in the practice of pediatricians

Assessment of blood lactate / lactic acid levels by a General pediatrician is sometimes difficult. Lactate is a product of cellular metabolism of glucose, fatty acids, and some interchangeable amino acids. The norm of lactate in the blood is not defined by international standards, so it depends on the methodology and reagents used in the laboratory. The level of lactate in the blood is the result of an equilibrium between the processes of its formation and utilization. The leading causes of increased blood lactate are anaerobic muscle activity (heavy exercise, seizures), impaired liver and kidney function, lung and heart diseases (respiratory failure, circulatory failure), diabetes, sepsis, regional tissue circulatory disorders (burns and injuries), shocks, some severe abnormalities in the condition of newborns, mitochondrial diseases, and medications. Lactatacidosis is a rare dangerous complication caused by certain pathological conditions (diseases or syndromes), which can end in death. Identification of the cause of lactic acidosis and differential diagnosis of its type is a crucial factor for choosing a treatment strategy. Lactatacidotic coma in diabetes mellitus is a rare, but possible complication, that requires intensive complex treatment in intensive care units. The pediatrician should be able to assess the level of lactate in the blood, analyze the possible causes of hyperlactatemia, and know the algorithm of actions in the development of lactate acidosis.

The Correlation of Transaminase Enzymes on the Prognosis of Covid-19 Patients in the ICU Infection Center Dr. Wahidin Sudirohusodo General Hospital Makassar

Corona Virus Disease 2019 (COVID-19) is an infectious disease that has been designated as a worldwide pandemic. Symptoms of Covid-19 are not only respiratory symptoms but also extrapulmonary symptoms, including the discovery of impaired liver function in the form of increased transaminase enzymes. Therefore, this study was conducted to see the correlation of transaminase enzymes with the prognosis of COVID-19 patients treated in the Intensive Care Unit (ICU) Dr. Wahidin Sudirohusodo Hospital. The study was conducted on June to August 2021. The cross-sectional analytical research method used retrospective medical record data for the period from July to December 2020 with a sample of 137 patients with COVID-19 confirmed. From the results of the Pearson test, patients with increased SGOT were associated with a mortality prognosis (p=0.000, p<0.05) with a correlation coefficient (r) of -0.383 and an increase in SGPT were associated with a mortality prognosis (p=0.013, p<0.05) with a correlation coefficient (r) of -0.211. From the results of the Kruskal Wallis test, there were differences in prognosis in patients with increased SGOT and SGPT grades 1,2,3, and 4 (p = 0.000 and p = 0.028). There is a correlation between the increased transaminase enzymes with the prognosis of the patient's mortality. Patients with severe elevated SGOT and SGPT enzymes had a greater prognosis of mortality than those with mild enzyme elevations. Extrapulmonary symptoms of stroke were associated with increased SGOT and myocardial infarction symptoms, and nephropathy was associated with increased SGOT and SGPT. Comorbid coronary artery disease and hepatitis were associated with increased SGOT and SGPT.

Albendazole in malignant ascites: a case report and literature review on the successes and adverse effects of therapy

Malignant ascites places a significant burden on the healthcare system and has a profound effect on patient quality of life. Albendazole (ABZ) is an anti-helminthic agent that has shown to rapidly reduce malignant ascites with minimal side effects in pre-clinical trials. The following case study explores the effect of ABZ on ascitic volume in a patient with malignant ascites secondary to metastatic colorectal adenocarcinoma. The patient is a 54-year-old man who underwent an ultrasound guided ascitic drainage for worsening ascites secondary to hepatic metastases from sigmoid adenocarcinoma. He was commenced on ABZ based on literature demonstrating that ABZ decreases the volume of malignant ascites via the inhibition of vascular endothelial growth factor. Over the next week, the volume of ascitic fluid decreased significantly, however the patient developed neutropenia unresponsive to granulocyte colony stimulating factor likely in the context of impaired liver function. The efficacy of ABZ in this case study as well as in the literature demonstrates the promising potential for use in reducing malignant ascites. However, this case demonstrates the need for caution for use in patients with liver impairment due to changes to first pass metabolism leading to increased circulating drug toxicity and thus, adverse outcomes.

Human Menstrual Blood-derived Stem Cell Transplantation Suppresses Liver Injury in DDC-induced Chronic Cholestasis

Background: Cholestasis liver injury can lead to serious symptoms and prognoses in the clinic. Currently, an effective medical treatment is not available for cholestasis liver injury. Human menstrual blood-derived stem cells (MenSCs) have been considered an emerging treatment in various diseases. However, efficiency of MenSCs in cholestasis liver injury has been less investigated. Methods: C57/BL6 mice were fed with 3,5-diethoxycarbonyl-1,4- dihydroxychollidine (DDC) to induce chronic cholestasis liver injury model. DDC mice were injected with either phosphate buffer saline (PBS) or MenSCs at 2 and 4 weeks. Mice were sacrificed at 5 weeks. Serum and liver tissues were collected to test liver function and pathological changes. Proteomics and western blot were used to explore the related molecular mechanisms. Adeno-associated virus (AAV)9 infected mice were used for verifications of MenSC treatment target and related molecular mechanism. Results: We found that MenSCs could protect mice against DDC-induced cholestasis by improving impaired liver function and tissue damage. MenSCs markedly prolonged survival rate of mice, decreased the mice serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), direct bilirubin (DBIL) and total bilirubin (TBIL) levels as well as intrahepatic cholestasis, bile duct dilation and fibrosis. The results further indicated that MenSCs repaired DDC-induced tight junction (TJ) and bile transport function damage and inhibited COL1A1, α-SMA and TGF-β1 activation by upregulating liver β-catenin expression. MenSC transplantation could be an effective treatment method for cholestasis liver injury.

Diseases of the digestive organs and COVID-19

With a new coronavirus infection (COVID-19), gastroenterological symptoms are often detected, which is due to both the damage to the digestive organs by the SARS-CoV-2 coronavirus and the exacerbation of chronic diseases, as well as aggressive multicomponent therapy. The severity of gastroenterological manifestations, primarily impaired liver function, is associated with a more severe and complicated course of COVID-19 infection. Numerous mechanisms of damage to the digestive organs in COVID-19 have been identified: direct damage by the virus due to resuscitation and multicomponent therapy, impaired central and peripheral nervous regulation, immunothrombotic syndrome, virus persistence in the gastrointestinal tract, induction of autoimmune reactions by the virus, humoral disorders (changes in serotonin levels, bradykinin, activation of mast cells). Violation of the microbial-tissue complex of the intestine and the permeability of the intestinal barrier, induced by the SARS-CoV-2 virus, ensures the formation and progression of chronic systemic inflammation, cytokine aggression, insulin resistance, endothelial dysfunction, which affect the severity of the infection. Therapy for patients with COVID-19 should include therapeutic approaches aimed at correcting disorders of the intestinal microbiota, intestinal barrier permeability, and relief of gastroenterological manifestations (bibliography: 20 refs).