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Frontiers in Immunology 2024Acute myeloid leukemia (AML) is an aggressive heterogeneous disease characterized by several alterations of the immune system prompting disease progression and treatment...
characterization of acute myeloid leukemia patients undergoing hypomethylating agents and venetoclax regimen reveals a venetoclax-specific effect on non-suppressive regulatory T cells and PD-1TIM3 exhausted CD8 T cells.
Acute myeloid leukemia (AML) is an aggressive heterogeneous disease characterized by several alterations of the immune system prompting disease progression and treatment response. The therapies available for AML can affect lymphocyte function, limiting the efficacy of immunotherapy while hindering leukemia-specific immune reactions. Recently, the treatment based on Venetoclax (VEN), a specific B-cell lymphoma 2 (BCL-2) inhibitor, in combination with hypomethylating agents (HMAs) or low-dose cytarabine, has emerged as a promising clinical strategy in AML. To better understand the immunological effect of VEN treatment, we characterized the phenotype and immune checkpoint (IC) receptors' expression on CD4 and CD8 T cells from AML patients after the first and second cycle of HMA in combination with VEN. HMA and VEN treatment significantly increased the percentage of naïve CD8 T cells and TIM-3 CD4 and CD8 T cells and reduced cytokine-secreting non-suppressive T regulatory cells (Tregs). Of note, a comparison between AML patients treated with HMA only and HMA in combination with VEN revealed the specific contribution of VEN in modulating the immune cell repertoire. Indeed, the reduction of cytokine-secreting non-suppressive Tregs, the increased TIM-3 expression on CD8 T cells, and the reduced co-expression of PD-1 and TIM-3 on both CD4 and CD8 T cells are all VEN-specific. Collectively, our study shed light on immune modulation induced by VEN treatment, providing the rationale for a novel therapeutic combination of VEN and IC inhibitors in AML patients.
Topics: Humans; Leukemia, Myeloid, Acute; Sulfonamides; CD8-Positive T-Lymphocytes; Bridged Bicyclo Compounds, Heterocyclic; Hepatitis A Virus Cellular Receptor 2; Programmed Cell Death 1 Receptor; Middle Aged; Aged; T-Lymphocytes, Regulatory; Female; Male; Antineoplastic Combined Chemotherapy Protocols; Adult; Aged, 80 and over
PubMed: 38812504
DOI: 10.3389/fimmu.2024.1386517 -
Eastern Mediterranean Health Journal =... May 2024Although hepatitis B is vaccine-preventable, it remains a significant health problem. To the best of our knowledge, this is the first hepatitis B outbreak report from...
BACKGROUND
Although hepatitis B is vaccine-preventable, it remains a significant health problem. To the best of our knowledge, this is the first hepatitis B outbreak report from Türkiye.
AIMS
To investigate the cause of hepatitis B outbreak in a nursing home for the disabled and make recommendations for prevention.
METHODS
An outbreak of acute hepatitis B was declared in a nursing home for the disabled following the admission of 3 patients from the home in a hospital. Collaborative response was initiated with the Provincial Health Directorate through the Public Health Infectious Diseases Department. We began tracking the infection and monitoring active cases. Audits and controls were carried out to determine the source, establish protection and control measures, and prevent further transmission.
RESULTS
Six of the 65 nursing home residents were diagnosed with acute hepatitis B. Four of them had diabetes and their blood glucose levels were monitored for at least 12 months. Two of the patients had received dental treatment in the last 6 months. The frequency of both variables, which may be an indication of the transmission route, was statistically significantly greater in the acute hepatitis B group. All the patients who could be sequenced were identified as genotype D. While 3 patients recovered fully, 2 were diagnosed with chronic hepatitis B and one died due to fulminant hepatitis.
CONCLUSION
Standard routine immunization should be implemented as a preventive measure for acute hepatitis B. Frequent supervision and training on hygiene practices and safety precautions should be conducted for care staff working in collective residential facilities.
Topics: Humans; Disease Outbreaks; Nursing Homes; Male; Female; Hepatitis B; Aged; Middle Aged; Disabled Persons; Adult; Acute Disease; Aged, 80 and over
PubMed: 38808405
DOI: 10.26719/2024.30.4.292 -
Cureus Apr 2024Acute hepatitis can result from a wide variety of noninfectious causes that include, but are not limited to, drugs (drug-induced hepatitis), alcohol (alcoholic...
Acute hepatitis can result from a wide variety of noninfectious causes that include, but are not limited to, drugs (drug-induced hepatitis), alcohol (alcoholic hepatitis), immunologic (autoimmune hepatitis, primary biliary cholangitis), or as a result of indirect insult secondary to biliary tract dysfunction (cholestatic hepatitis), pregnancy-related liver dysfunction, shock, or metastatic disease. In clinical settings, these causes are not uncommon to overlap with each other or are masked by obviously visible causes in medical history. We reported our scenario of a patient who has a heavy history of alcohol use and presented with alcohol withdrawal symptoms and a marked elevation of liver enzymes. Interestingly, further investigations suggested Wilson's disease could be an underlying culprit of acute hepatitis in this patient. This case again emphasized that Wilson's disease can be masked under multiple causes and various scenarios, which alerts clinicians that a broad approach should be made for every case of acute hepatitis.
PubMed: 38803772
DOI: 10.7759/cureus.59025 -
Yonago Acta Medica May 2024Patients taking multiple drugs and various health foods often develop acute hepatitis. We hypothesized that the interaction between health foods and drug metabolism was...
BACKGROUND
Patients taking multiple drugs and various health foods often develop acute hepatitis. We hypothesized that the interaction between health foods and drug metabolism was the cause of severe liver injury in these patients. Therefore, we studied changes in the activity of the drug-metabolizing enzyme, cytochrome P450 (CYP), using slimming health food extracts and elucidated the molecular mechanism of liver injury onset through hepatotoxicity evaluation.
METHODS
For cytotoxicity testing, health food extract samples were added to HepG2 cells derived from hepatic parenchymal cells and culture medium, and cell viability was calculated 48 h after culture. To evaluate CYP3A4 induction, 3-1-10 cells constructed with a reporter linked to CYP3A4 gene were used, and reporter activity was measured 48 h after culture.
RESULTS
In the chronological order of the slimming health food intake history of the patient, niacinamide and extracts strongly inhibited HepG2 cell viability. In contrast, dietary supplements A and extract strongly induced CYP3A4 reporter activity.
UNLABELLED
To confirm CYP3A4 induction in humans, humanized CYP3A/pregnane X receptor (PXR) mice were treated with forskolin. CYP3A4 mRNA expression levels were elevated 3.9 times compared to that of the control group ( < 0.05).
CONCLUSION
extract showed the strongest transcriptional activation of CYP3A4 gene. In a mouse model of human-type drug metabolism, forskolin induced CYP3A4 transcription. Thus, we concluded that CYP3A4 induction by is one of the causes of crucial hepatocellular injury, which is a type of liver injury caused by the active metabolite of acetaminophen produced by CYP3A4.
PubMed: 38803590
DOI: 10.33160/yam.2024.05.004 -
Turkish Journal of Haematology :... May 2024The survival rates of children with acute lymphoblastic leukemia (ALL) have improved over the years, but infections remain a significant cause of morbidity and...
OBJECTIVE
The survival rates of children with acute lymphoblastic leukemia (ALL) have improved over the years, but infections remain a significant cause of morbidity and mortality. Chemotherapy has a range of harmful side effects including the loss of protective antibodies against vaccine-preventable diseases. The objective of this study was to evaluate the serological status of pediatric ALL cases before and after the intensive chemotherapy.
MATERIALS AND METHODS
Children treated and followed up for ALL at Dokuz Eylül University were included in this retrospective cross-sectional study. Antibody levels against hepatitis A, hepatitis B, and rubella were routinely assessed both at the time of diagnosis and six months after completion of chemotherapy. However, measles, mumps, and varicella antibody levels were evaluated just six months after the treatment.
RESULTS
Seventy-eight children who completed chemotherapy for ALL were recruited. All participants had nonprotective antibody levels for at least one of the diseases. The highest seropositivity rate was found for hepatitis A (55.1%) and the lowest for measles (17.9%) after chemotherapy. Overall, 50.7%, 30.6%, and 45.7% of the patients significantly lost their humoral immunity against hepatitis B, hepatitis A, and rubella, respectively. Patients in the higher-risk group for ALL had a lower seropositivity rate than the other risk group patients. There were statistically significant relations between the protective antibody rates of hepatitis A and varicella and the age of the patients. Except for the hepatitis A vaccination, pre-chemotherapy vaccination did not affect post-chemotherapy serology. On the other hand, all children with a history of varicella before the diagnosis showed immunity after chemotherapy.
CONCLUSION
All patients, including those previously fully vaccinated, are at great risk of infection due to the decrease in protective antibody levels after chemotherapy. There is a need for routine post-chemotherapy serologic testing and re-vaccination based on the results obtained.
PubMed: 38801016
DOI: 10.4274/tjh.galenos.2024.2024.0150 -
Clinical Case Reports Jun 2024This case emphasizes the significance of COVID-19 in pediatric patients presenting with unusual hepatic manifestations, urging clinicians to broaden their diagnostic...
KEY CLINICAL MESSAGE
This case emphasizes the significance of COVID-19 in pediatric patients presenting with unusual hepatic manifestations, urging clinicians to broaden their diagnostic lens. The unexpected elevation of SARS-CoV-2 antibodies and the effective use of N-acetyl cysteine highlight the importance of adaptability in treatment strategies.
ABSTRACT
This case report presents a unique manifestation of severe hepatic involvement in a 4-year-old girl with thalassemia minor and COVID-19. Despite the absence of prominent respiratory symptoms, the patient exhibited jaundice, elevated liver enzymes, and coagulopathy. Initial suspicion of viral hepatitis was replaced by the discovery of significantly elevated SARS-CoV-2 antibodies. A multidisciplinary approach, including gastroenterology consultation and an extensive workup, was pivotal in ruling out alternative etiologies. Unconventional use of N-acetyl cysteine contributed to clinical improvement, highlighting the need for adaptable treatment strategies. This case underscores the importance of heightened awareness in recognizing atypical presentations of COVID-19 in pediatric patients, especially those with underlying health conditions. Further exploration into nuanced manifestations and treatment approaches is warranted for comprehensive clinical management.
PubMed: 38799536
DOI: 10.1002/ccr3.8955 -
Vaccines May 2024The aim of this study was to analyse the impact of the introduction of universal adolescent HBV vaccination on the incidence of acute hepatitis B virus (HBV) infections....
The aim of this study was to analyse the impact of the introduction of universal adolescent HBV vaccination on the incidence of acute hepatitis B virus (HBV) infections. Acute HBV cases reported to the Spanish National Epidemiological Surveillance Network between 2005 and 2021 were included. For regions starting adolescent vaccination in 1991-1993 and in 1994-1996, HBV incidence rates were compared by calculating the incidence rate ratio (IRR) and 95% confidence interval (CI). We also analysed the 2017 Spanish national seroprevalence survey data. The overall acute HBV incidence per 100,000 persons was 1.54 in 2005 and 0.64 in 2021 ( < 0.001). The incidence in 2014-2021 was lower for regions that started adolescent vaccination in 1991-1993 rather than in 1994-1996 (IRR 0.76; 95% CI 0.72-0.83; < 0.001). In the 20-29 age group, incidence in regions that started adolescent vaccination in 1991-1993 was also lower (IRR 0.87; 95% CI 0.77-0.98; = 0.02 in 2005-2013 and IRR 0.71; 95% CI 0.56-0·90; < 0.001 in 2014-2021). Anti-HBc prevalence in the 35-39 age group was lower in the regions that started vaccination earlier, although the difference was not statistically significant ( = 0.09). Acute HBV incidence decreased more in the young adult population in regions that began adolescent vaccination earlier. Maintaining high universal vaccination coverage in the first year of life and in at-risk groups is necessary to achieve HBV elimination by 2030.
PubMed: 38793738
DOI: 10.3390/vaccines12050488 -
Viruses May 2024An increase in the number of cases of acute hepatitis of unknown origin (HUO) in children was observed in 2021. Adenovirus and adeno-associated virus 2 (AAV2) infections...
BACKGROUND AND AIMS
An increase in the number of cases of acute hepatitis of unknown origin (HUO) in children was observed in 2021. Adenovirus and adeno-associated virus 2 (AAV2) infections have been suggested as possible triggers. However, the potential etiology is still unclear. We aimed to characterize a cohort of children with HUO in Israel in view of the COVID-19 pandemic.
METHOD
Demographics, clinical data, and laboratory results on the children compatible with the CDC criteria for HUO were collected by the established registry of the Ministry of Health. Available specimens were sent to the Central Virology Laboratory.
RESULTS
A total of 39 children were included in the registry. A total of 20 were enrolled prospectively, in which human herpes virus 6 (HHV6) infection or reactivation was identified in 11/19, adenovirus was found in 4/19 of the cases, and AAV2 was detected in 2/16. Past COVID-19 exposure was recorded for 24/39 of the children. A total of 10 children underwent liver biopsy, and 8 were successfully treated with steroids and 2 underwent liver transplantation.
CONCLUSIONS
The COVID-19 pandemic and the related containment measures combined with reactivation or active infection with other viruses could have been a trigger for the HUO outbreak. In our cohort, HHV6 was the most abundant finding.
Topics: Humans; COVID-19; Child; Female; Male; Child, Preschool; Infant; Israel; SARS-CoV-2; Adolescent; Herpesvirus 6, Human; Disease Outbreaks; Prospective Studies; Acute Disease; Pandemics
PubMed: 38793689
DOI: 10.3390/v16050808 -
Viruses May 2024Hepatitis E virus (HEV) genotype 3 is the major cause of acute viral hepatitis in several European countries. It is acquired mainly by ingesting contaminated pork, but...
INTRODUCTION
Hepatitis E virus (HEV) genotype 3 is the major cause of acute viral hepatitis in several European countries. It is acquired mainly by ingesting contaminated pork, but has also been reported to be transmitted through blood transfusion. Although most HEV infections, including those via blood products, are usually self-limiting, they may become chronic in immunocompromised persons. It is thus essential to identify HEV-infected blood donations to prevent transmission to vulnerable recipients.
AIMS
Prior to the decision whether to introduce HEV RNA screening for all Swiss blood donations, a 2-year nationwide prevalence study was conducted.
METHODS
All blood donations were screened in pools of 12-24 samples at five regional blood donation services, and HEV RNA-positive pools were subsequently resolved to the individual donation index donation (X). The viral load, HEV IgG and IgM serology, and HEV genotype were determined. Follow-up investigations were conducted on future control donations (X + 1) and previous archived donations of the donor (X - 1) where available.
RESULTS
Between October 2018 and September 2020, 541,349 blood donations were screened and 125 confirmed positive donations were identified (prevalence 1:4331 donations). At the time of blood donation, the HEV RNA-positive individuals were symptom-free. The median viral load was 554 IU/mL (range: 2.01-2,500,000 IU/mL). Men (88; 70%) were more frequently infected than women (37; 30%), as compared with the sex distribution in the Swiss donor population (57% male/43% female, < 0.01). Of the 106 genotyped cases (85%), all belonged to genotype 3. Two HEV sub-genotypes predominated; 3h3 (formerly 3s) and 3c. The remaining sub-genotypes are all known to circulate in Europe. Five 3ra genotypes were identified, this being a variant associated with rabbits. In total, 85 (68%) X donations were negative for HEV IgM and IgG. The remaining 40 (32%) were positive for HEV IgG and/or IgM, and consistent with an active infection. We found no markers of previous HEV in 87 of the 89 available and analyzed archive samples (X - 1). Two donors were HEV IgG-positive in the X - 1 donation suggesting insufficient immunity to prevent HEV reinfection. Time of collection of the 90 (72%) analyzed X + 1 donations varied between 2.9 and 101.9 weeks (median of 35 weeks) after X donation. As expected, none of those tested were positive for HEV RNA. Most donors (89; 99%) were positive for anti-HEV lgG/lgM (i.e., seroconversion). HEV lgM-positivity (23; 26%) indicates an often-long persistence of lgM antibodies post-HEV infection.
CONCLUSION
The data collected during the first year of the study provided the basis for the decision to establish mandatory HEV RNA universal screening of all Swiss blood donations in minipools, a vital step in providing safer blood for all recipients, especially those who are immunosuppressed.
Topics: Humans; Hepatitis E; Blood Donors; Switzerland; Hepatitis E virus; Male; Female; Adult; Prevalence; Middle Aged; RNA, Viral; Genotype; Hepatitis Antibodies; Immunoglobulin M; Young Adult; Immunoglobulin G; Viral Load; Aged; Adolescent
PubMed: 38793625
DOI: 10.3390/v16050744 -
Journal of Personalized Medicine May 2024Sepsis remains a major health challenge worldwide, characterized by a dysregulated host response to infection, leading to high mortality and morbidity in intensive care...
BACKGROUND
Sepsis remains a major health challenge worldwide, characterized by a dysregulated host response to infection, leading to high mortality and morbidity in intensive care units (ICUs). The Fibrosis 4 (FIB-4) index, originally developed to assess liver fibrosis in hepatitis C patients, has recently been explored for its potential prognostic value in sepsis patients.
METHOD
this study retrospectively analyzed 309 sepsis patients admitted to the Internal Medicine and An-aesthesia ICUs between 12 December 2021 and 15 December 2023 to investigate the relationship between FIB-4 levels, the Acute Physiology and Chronic Health Evaluation (APACHE), the Sequential Organ Failure Assessment (SOFA), and clinical outcomes.
RESULTS
This study found that higher FIB-4 measurements were statistically significantly associated with increased 28-day mortality, with a cut-off value of 4.9, providing a sensitivity of 54.92% and specificity of 74.25%. Logistic regression analysis indicated that elevated FIB-4 levels were a significant predictor of early mortality, suggesting that the FIB-4 index could serve as a valuable prognostic tool in assessing the severity and prognosis of sepsis patients.
CONCLUSIONS
by elucidating the potential role of the FIB-4 index in sepsis prognosis, this study contributes to the ongoing efforts to improve risk stratification and enhance patient care in sepsis management.
PubMed: 38793113
DOI: 10.3390/jpm14050531