-
International Journal of Molecular... May 2024The kidney injury molecule (KIM)-1 is shed from proximal tubular cells in acute kidney injury (AKI), relaying tubular epithelial proliferation. Additionally, KIM-1...
The kidney injury molecule (KIM)-1 is shed from proximal tubular cells in acute kidney injury (AKI), relaying tubular epithelial proliferation. Additionally, KIM-1 portends complex immunoregulation and is elevated after exposure to lipopolysaccharides. It thus may represent a biomarker in critical illness, sepsis, and sepsis-associated AKI (SA-AKI). To characterise and compare KIM-1 in these settings, we analysed KIM-1 serum concentrations in 192 critically ill patients admitted to the intensive care unit. Irrespective of kidney dysfunction, KIM-1 serum levels were significantly higher in patients with sepsis compared with other critical illnesses (191.6 vs. 132.2 pg/mL, = 0.019) and were highest in patients with urogenital sepsis, followed by liver failure. Furthermore, KIM-1 levels were significantly elevated in critically ill patients who developed AKI within 48 h (273.3 vs. 125.8 pg/mL, = 0.026) or later received renal replacement therapy (RRT) (299.7 vs. 146.3 pg/mL, < 0.001). KIM-1 correlated with markers of renal function, inflammatory parameters, hematopoietic function, and cholangiocellular injury. Among subcomponents of the SOFA score, KIM-1 was elevated in patients with hyperbilirubinaemia (>2 mg/dL, < 0.001) and thrombocytopenia (<150/nL, = 0.018). In univariate and multivariate regression analyses, KIM-1 predicted sepsis, the need for RRT, and multi-organ dysfunction (MOD, SOFA > 12 and APACHE II ≥ 20) on the day of admission, adjusting for relevant comorbidities, bilirubin, and platelet count. Additionally, KIM-1 in multivariate regression was able to predict sepsis in patients without prior (CKD) or present (AKI) kidney injury. Our study suggests that next to its established role as a biomarker in kidney dysfunction, KIM-1 is associated with sepsis, biliary injury, and critical illness severity. It thus may offer aid for risk stratification in these patients.
Topics: Humans; Hepatitis A Virus Cellular Receptor 1; Sepsis; Male; Female; Middle Aged; Critical Illness; Aged; Acute Kidney Injury; Biomarkers; Severity of Illness Index; Multiple Organ Failure; Intensive Care Units; Adult
PubMed: 38892009
DOI: 10.3390/ijms25115819 -
Italian Journal of Food Safety May 2024In this study, two Mediterranean coastal lagoons (Lesina and Varano) of southern Italy, located in the north of the Apulia region, were investigated for the presence of...
In this study, two Mediterranean coastal lagoons (Lesina and Varano) of southern Italy, located in the north of the Apulia region, were investigated for the presence of Shiga toxin (STEC) and potentially enteropathogenic species in parallel with norovirus (NoV), hepatitis A virus (HAV), hepatitis E virus (HEV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to evaluate the presence of potentially pathogenic bacteria and viruses in the water and sediments of these ecosystems. From March 2022 to February 2023, a total of 98 samples were collected: 49 water samples and 49 sediment samples. STEC strains were isolated in three samples (3.1%), of which one (2%) was water ( and positive) and two (4.1%) were sediment (both positive) samples. spp. were detected in twenty samples (20.4%), of which nine were water (18.4%) and eleven were sediment (22.4%) samples. The species detected included , , and . NoV was detected in 25 (25.5%) samples, while none of the water or sediment samples were positive for HAV, HEV, and SARS-CoV-2. The results of this study provide an overview of the presence of potentially pathogenic microorganisms in areas influenced by anthropogenic pressure. Monitoring the circulation of these pathogens could be useful to evaluate the water flowing into the lagoons, in particular discharge waters (, urban, agricultural, and livestock runoff), considering the presence of fish and shellfish farms in these sites.
PubMed: 38887590
DOI: 10.4081/ijfs.2024.12218 -
Hepatology Research : the Official... Jun 2024With the widespread use of immune checkpoint inhibitors (ICIs), liver injury (ICI-induced liver injury) as an immune-related adverse event has become a major concern in...
With the widespread use of immune checkpoint inhibitors (ICIs), liver injury (ICI-induced liver injury) as an immune-related adverse event has become a major concern in clinical practice. Because severe cases of liver injury require administration of corticosteroids, a comprehensive evaluation is crucial, including clinical course, blood and imaging tests, and if necessary, pathological examination through liver biopsy. As with liver injury induced by other drugs, classification of injury type by R-value is useful in deciding treatment strategies for ICI-induced liver injury. Histologically, the most representative feature is an acute hepatitis-like hepatocellular injury, characterized by diffuse lobular inflammation accompanied by CD8-positive T lymphocytes. Another condition that can cause liver injury during ICI treatment is cholangitis accompanied by non-obstructive bile duct dilatation and bile duct wall thickening. Many cases of ICI-induced cholangitis are classified as non-hepatocellular injury type, and they have been reported to respond poorly to corticosteroids. It is essential that gastroenterologists/hepatologists and doctors in various departments work in cooperation to develop a system that achieves early diagnosis and appropriate treatment of ICI-induced liver injury.
PubMed: 38884591
DOI: 10.1111/hepr.14078 -
American Journal of Translational... 2024Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in the world. Hepatitis E infection is commonly widespread by the fecal oral routes and...
OBJECTIVE
Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in the world. Hepatitis E infection is commonly widespread by the fecal oral routes and contaminated water. This study was designed to explore the prevalence and risk factors of hepatitis E infection in pregnant women of the Multan district, Pakistan.
METHODS
The study comprised of a total of 500 enrolled patients, among which, 105 pregnant females with hepatitis E infection fulfilled the criteria for anti-HEV antibodies. Pregnant women without significant complications and without hepatitis E infection were excluded from this study. Hepatic profile, complete blood count, coagulation markers, and standard protocol were also assessed for fetal maternal hemorrhage.
RESULTS
Our results showed that 105 patients (66.66%, CI 95%) had HEV infection with mean age 25±5 years. Serum bilirubin levels were increased in 74 patients (70.47%), aspartate transaminase was elevated > 200 IU/L in 71 patients (67.61%), alanine transaminase was above the 100 IU/L in 65 patients (245 IU/L), and low platelet counts were found in 45 patients (42.85%). Moreover, fetal distress cases were 9 (10.84%) and maternal distress cases were about 11 (13.25%). Fetal mortality cases were 39 (37.14%), and maternal mortality cases were about 22 (20.95%) due to hepatic comma, intravascular coagulation, and hepatic failure.
CONCLUSION
It was concluded that the prevalence of Hepatitis E during pregnancy is associated with high risk factors of unhygienic practices, blood transfusion, and noncompliance with universal infection control techniques. Maternal fatalities and fetal consequences were exacerbated by HEV infection.
PubMed: 38883386
DOI: 10.62347/SLWM5449 -
Cureus May 2024Adult-onset Still's disease (AOSD) is a rare multisystem inflammatory disorder. A 71-year-old lady who was on treatment for AOSD presented with clinical evidence of...
Adult-onset Still's disease (AOSD) is a rare multisystem inflammatory disorder. A 71-year-old lady who was on treatment for AOSD presented with clinical evidence of heart failure and was subsequently found to have impaired renal and hepatic function. Following extensive workup including a liver biopsy, the cause of liver dysfunction was determined to be congestive hepatopathy, while renal dysfunction was presumed to stem from the low output state. The etiology of myocardial dysfunction, driving liver and kidney injury, was considered to be myocarditis from AOSD or global myocardial dysfunction from a systemic inflammatory state. Management involved pulse-dose glucocorticoids followed by taper and anakinra for AOSD, alongside goal-directed medical therapy for cardiac failure. At follow-up after a month, hepatic and renal function had fully recovered, whereas cardiac function remained compromised, evidenced by persistently depressed ejection fraction and global hypokinesia on a repeat echocardiogram. This report delineates a systematic approach to multiorgan dysfunction in a patient with a rare condition such as AOSD and reviews the reported causes of hepatic and cardiac involvement in AOSD.
PubMed: 38883113
DOI: 10.7759/cureus.60400 -
The Journal of the Association of... Apr 2024Hemophagocytic lymphohistiocytosis (HLH) is an aggressive hematological disorder caused by uncontrolled activation of cytotoxic T-cells (CTL), natural killer (NK) cells,...
Hemophagocytic lymphohistiocytosis (HLH) is an aggressive hematological disorder caused by uncontrolled activation of cytotoxic T-cells (CTL), natural killer (NK) cells, and macrophages leading to hyperinflammation and cytokine storm. The clinical course is characterized by high-grade fever, cytopenia, and multiorgan dysfunction. HLH is classified as either primary/familial or secondary, the latter being most often triggered by infections, malignancies, and autoimmune disorders. Viral infections are commonly known to cause HLH with Epstein-Barr virus (EBV), cytomegalovirus (CMV), influenza virus, adenovirus, and parvovirus being most often implicated. Hepatitis E virus (HEV) has infrequently been reported to cause HLH with less than five cases being reported in the literature. We report a case of a young man who presented with hepatitis E-associated HLH.
Topics: Humans; Lymphohistiocytosis, Hemophagocytic; Male; Hepatitis E; Adult; Acute Disease
PubMed: 38881088
DOI: 10.59556/japi.72.0499 -
The Lancet. Infectious Diseases Jun 2024In 2020, WHO guidelines prioritised the use of a standard fully oral short treatment regimen (STR) consisting of bedaquiline, levofloxacin or moxifloxacin, ethionamide,...
BACKGROUND
In 2020, WHO guidelines prioritised the use of a standard fully oral short treatment regimen (STR) consisting of bedaquiline, levofloxacin or moxifloxacin, ethionamide, ethambutol, high-dose isoniazid, pyrazinamide, and clofazimine for the management of rifampicin-resistant tuberculosis. A high prevalence of resistance to constituent drugs precluded its widespread use by countries in the WHO European region. We evaluated three 9-month fully oral modified STRs (mSTRs) in which ethionamide, ethambutol, isoniazid, and pyrazinamide were replaced by linezolid, cycloserine, or delamanid (or a combination).
METHODS
This multicountry, prospective, single-arm, cohort study examined the effectiveness and safety of mSTRs for fluoroquinolone-susceptible, rifampicin-resistant pulmonary tuberculosis in 13 countries in the WHO European region during 2020-23. We enrolled adults and children of all ages with bacteriologically confirmed rifampicin-resistant, fluoroquinolone-susceptible pulmonary tuberculosis, and children (aged 0-18 years) with clinically diagnosed disease and a confirmed contact with rifampicin-resistant, fluoroquinolone-susceptible tuberculosis. Participants aged 6 years or older received one of two regimens: bedaquiline, linezolid, levofloxacin, clofazimine, and cycloserine; or bedaquiline, linezolid, levofloxacin, clofazimine, and delamanid. Children younger than 6 years received delamanid, linezolid, levofloxacin, and clofazimine. Participants were followed up for 12 months after successful treatment completion to detect recurrence and death. The primary outcome was the cumulative probability of not having an unsuccessful study outcome (defined as treatment failure, on-treatment loss to follow-up, death, or recurrence) before 22 months of study follow-up. The primary safety outcome was the incidence of each adverse event of interest (peripheral neuropathy, optic neuritis, myelosuppression, hepatitis, prolonged QT interval, hypokalaemia, and acute kidney injury) of grade 3 or higher severity during the treatment course.
FINDINGS
Between Aug 28, 2020 and May 26, 2021, 7272 patients were screened and 2636 were included in the treatment cohort. 1966 (74·6%) were male, 670 (25·4%) were female, and median age was 43 years (IQR 33-53). Treatment success was recorded for 2181 (82·7%) participants. The cumulative probability of not having an unsuccessful study outcome 22 months after treatment initiation was 79% (95% CI 78-81). Increasing age (adjusted hazard ratio 2·61 [95% CI 1·70-4·04] for people aged >64 years vs 35-44 years), HIV-positive status (1·53 [1·16-2·01]), presence of bilateral cavities (1·68 [1·29-2·19]), smoking history (1·34 [1·05-1·71]), baseline anaemia (1·46 [1·15-1·86]), unemployment (1·37 [1·04-1·80]), elevated baseline liver enzymes (1·40 [1·13-1·73]), and excessive alcohol use (1·47 [1·14-1·89]) were positively associated with unsuccessful study outcomes. In the safety cohort of 2813 participants who received at least one dose, 301 adverse events of interest were recorded in 252 (9·0%) participants with the most frequent being myelosuppression (139 [4·9%] participants, 157 [52·2%] events).
INTERPRETATION
The high treatment success and good safety results indicate considerable potential for the use of mSTRs in programmatic conditions, especially for individuals not eligible for the current WHO-recommended 6-month regimen and in settings with a need for alternative options.
FUNDING
The Global Fund to Fight AIDS, Tuberculosis and Malaria; United States Agency for International Development; Government of Germany; and WHO.
TRANSLATION
For the Russian translation of the abstract see Supplementary Materials section.
PubMed: 38880112
DOI: 10.1016/S1473-3099(24)00228-7 -
Acta Biochimica Et Biophysica Sinica Jun 2024Hepatitis E virus (HEV) is the major pathogen of viral hepatitis. Immunocompromised individuals infected by HEV are prone to chronic hepatitis and increase the risk of...
Hepatitis E virus (HEV) is the major pathogen of viral hepatitis. Immunocompromised individuals infected by HEV are prone to chronic hepatitis and increase the risk of hepato-cellular carcinoma (HCC). Inhibitor of growth family member 5 (ING5) is a tumor suppressor that is expressed at low levels in cancer tumors or cells. However, the underlying relationship between ING5 and HEV infection is unclear. In the present study, acute and chronic HEV animal models are used to explore the interaction between ING5 and HEV. Notably, the expression of ING5 is significantly increased in both the livers of acute HEV-infected BALB/c mice and chronic HEV-infected rhesus macaques. In addition, the relationship between HEV infection and ING5 expression is further identified in human hepatoma (HepG-2) cells. In conclusion, HEV infection strongly upregulates ING5 expression both and , which has significant implications for further understanding the pathogenic mechanism of HEV infection.
PubMed: 38877781
DOI: 10.3724/abbs.2024091 -
Science Immunology Jun 2024Nucleic acids are major structures detected by the innate immune system. Although intracellular single-stranded DNA (ssDNA) accumulates during pathogen infection or...
Nucleic acids are major structures detected by the innate immune system. Although intracellular single-stranded DNA (ssDNA) accumulates during pathogen infection or disease, it remains unclear whether and how intracellular ssDNA stimulates the innate immune system. Here, we report that intracellular ssDNA triggers cytokine expression and cell death in a CGT motif-dependent manner. We identified Schlafen 11 (SLFN11) as an ssDNA-activated RNase, which is essential for the innate immune responses induced by intracellular ssDNA and adeno-associated virus infection. We found that SLFN11 directly binds ssDNA containing CGT motifs through its carboxyl-terminal domain, translocates to the cytoplasm upon ssDNA recognition, and triggers innate immune responses through its amino-terminal ribonuclease activity that cleaves transfer RNA (tRNA). Mice deficient in Slfn9, a mouse homolog of SLFN11, exhibited resistance to CGT ssDNA-induced inflammation, acute hepatitis, and septic shock. This study identifies CGT ssDNA and SLFN11/9 as a class of immunostimulatory nucleic acids and pattern recognition receptors, respectively, and conceptually couples DNA immune sensing to controlled RNase activation and tRNA cleavage.
Topics: Animals; Female; Humans; Male; Mice; DNA, Single-Stranded; HEK293 Cells; Immunity, Innate; Mice, Inbred C57BL; Mice, Knockout; Nuclear Proteins; Ribonucleases
PubMed: 38875319
DOI: 10.1126/sciimmunol.adj5465 -
Journal of Zoo and Wildlife Medicine :... Jun 2024Rodents are typically viewed as asymptomatic reservoirs for leptospirosis infection, as clinical disease in rodents is rarely described. This report includes three...
Rodents are typically viewed as asymptomatic reservoirs for leptospirosis infection, as clinical disease in rodents is rarely described. This report includes three separate cases of leptospirosis in Patagonian maras () over a 3-yr period in multiple locations within a single zoo. All three cases presented with varying clinical signs including lethargy, conjunctival hyperemia, hyperbilirubinemia, and presumed renal azotemia. Infection with spp. was diagnosed antemortem by PCR on whole blood ( = 1, Case 1) or urine ( = 2, Cases 2 and 3). antibody titers measured by serum microagglutination testing ( = 3) were elevated or increased in all three animals over a 1-3-wk period for serovars Bratislava and Hardjo (Case 1) and Grippotyphosa (Case 2 and 3). Two of the three animals responded to treatment with penicillin and doxycycline and supportive care, whereas one animal did not respond to treatment. Postmortem findings in this individual included conjunctivitis, chemosis, dehydration, icterus, tricavitary serosanguinous effusions, necrotizing hepatitis, diffuse pulmonary congestion, and edema. Immunohistochemical examination identified scattered organisms within hepatocytes and renal tubular epithelial cells. A wild raccoon () at the institution tested positive by PCR on kidney tissue for the same spp. serovar and was the suspected source of infection. This case series highlights the clinical importance of leptospirosis as a differential for Patagonian maras presenting with lethargy, ocular signs, acute hepatic disease, and azotemia.
Topics: Animals; Leptospirosis; Male; Female; Animals, Zoo; Anti-Bacterial Agents; Leptospira; Rodent Diseases; Rodentia
PubMed: 38875208
DOI: 10.1638/2023-0042