Leptospirosis is a neglected bacterial disease caused by leptospiral infection that carries a substantial mortality risk in severe cases. Research has shown that acute, chronic, and asymptomatic leptospiral infections are closely linked to acute and chronic kidney disease (CKD) and renal fibrosis. Leptospires affect renal function by infiltrating kidney cells via the renal tubules and interstitium and surviving in the kidney by circumventing the immune system. The most well-known pathogenic molecular mechanism of renal tubular damage caused by leptospiral infection is the direct binding of the bacterial outer membrane protein LipL32 to toll-like receptor-2 expressed in renal tubular epithelial cells (TECs) to induce intracellular inflammatory signaling pathways. These pathways include the production of tumor necrosis factor (TNF)-α and nuclear factor kappa activation, resulting in acute and chronic leptospirosis-related kidney injury. Few studies have investigated the relationship between acute and chronic renal diseases and leptospirosis and further evidence is necessary. In this review, we intend to discuss the roles of acute kidney injury (AKI) to/on CKD in leptospirosis. This study reviews the molecular pathways underlying the pathogenesis of leptospirosis kidney disease, which will assist in concentrating on potential future research directions.

The burden of mental illness is profound and growing. Each year, almost one in three adults in the non-institutionalized community has a diagnosable mental or addictive disorder, and this figure climbs to approximately 40% among emergency departments patients. We described the principal cardiovascular acute disease and their emotional and behavioral consequences where psychological intervention could improve the care pathway and clinical outcome. Peer-reviewed articles from Medline, Psycinfo, Web of Science, Scopus, and Cochrane library, about psychological and psychopathological sequelae in cardiovascular acute disease were searched. The psychological and psychopathological sequelae associated to stroke include emotional and behavioral changes and cognitive impairment. Fear, symptoms of depression, anxiety or specific post-traumatic symptoms like intrusions, hyper-arousal and/or cognitive avoidance are common in people suffering of cardiovascular acute disease treated at emergency departments. In emergency departments, health personnel must recognize psychological and psychopathological sequelae in cardiovascular acute disease in order to develop effective interventions for these patients. Identify factors that are associated with both psychological distress and physical distress and promote interventions aimed at reducing psychological distress and improving psychological health empowerment is an important element to consider in order to offer the best care to vulnerable population as that suffering of cardiovascular acute disease.

Diabetic kidney disease (DKD) is a common complication of type 1 and 2 diabetes and often presents during adolescence and young adulthood. Given the growing incidence of both type 1 and type 2 diabetes in children and adolescents, DKD represents a significant public health problem. Acute kidney injury (AKI) in youth with diabetes is strongly associated with risk of DKD development. This review will summarize the epidemiology and pathophysiology of AKI in children with diabetes, the relationship between AKI and DKD, and the potential therapeutic interventions. Finally, we will appraise the impact of the recent COVID-19 infection pandemic on AKI in children with diabetes.

Despite overwhelming evidence of the clinical and financial benefit of urgent cholecystectomy, there is variable enthusiasm and uptake across the UK. In 2014, following the First National Emergency Laparotomy Audit Organisational Report, we implemented a specialist-led urgent surgery service, whereby all patients with gallstone-related pathologies were admitted under the direct care of specialist upper gastrointestinal surgeons. We have analysed 5 years of data to investigate the results of this service model.

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Diabetic ketoacidosis (DKA) and hyperglycaemia without ketoacidosis are common acute complications of diabetes. Their association with acute kidney injury (AKI) and diabetic kidney disease (DKD) was studied.

Acute gut graft-versus-host disease (aGVHD) is a leading threat to the survival of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Abnormal gut microbiota is correlated with poor prognosis in allo-HSCT recipients. A disrupted intestinal microenvironment exacerbates dysbiosis in GVHD patients. We hypothesized that maintaining the integrity of the intestinal barrier may protect gut microbiota and attenuate aGVHD. This hypothesis was tested in a murine aGVHD model and an in vitro intestinal epithelial culture. Millipore cytokine array was utilized to determine the expression of proinflammatory cytokines in the serum. The 16S rRNA sequencing was used to determine the abundance and diversity of gut microbiota. Combining Xuebijing injection (XBJ) with a reduced dose of cyclosporine A (CsA) is superior to CsA alone in improving the survival of aGVHD mice and delayed aGVHD progression. This regimen also reduced interleukin 6 (IL-6) and IL-12 levels in the peripheral blood. 16S rRNA analysis revealed the combination treatment protected gut microbiota in aGVHD mice by reversing the dysbiosis at the phylum, genus, and species level. It inhibited enterococcal expansion, a hallmark of GVHD progression. It inhibited enterococcal expansion, a hallmark of GVHD progression. Furthermore, Escherichia coli expansion was inhibited by this regimen. Pathology analysis revealed that the combination treatment improved the integrity of the intestinal tissue of aGVHD mice. It also reduced the intestinal permeability in aGVHD mice. Besides, XBJ ameliorated doxorubicin-induced intestinal epithelial death in CCK-8 assay. Overall, combining XBJ with CsA protected the intestinal microenvironment to prevent aGVHD. Our findings suggested that protecting the intestinal microenvironment could be a novel strategy to manage aGVHD. Combining XBJ with CsA may reduce the side effects of current aGVHD prevention regimens and improve the quality of life of allo-HSCT recipients.

The objective of this study was to evaluate the clinical disease, humoral response and viral distribution of recent Porcine rubulavirus (PorPV) isolates in experimentally infected pigs. Four, 6-piglet (5-days old) groups were employed (G1-84, G2-93, G3-147, and G4-T). Three viral strains were used for the experimental infection: the reference strain LPMV-1984 (Michoacán 1984) and two other strains isolated in 2013, one in Queretaro (Qro/93/2013) and the other in Michoacán (Mich/147/2013). Each strain was genetically characterized by amplification and sequencing of the gene encoding hemagglutinin-neuroamidase (HN). The inoculation was performed through the oronasal and ocular routes, at a dose of 1×106TCID50/ml. Subsequently, the signs were evaluated daily and necropsies were performed on 3 different days post infection (dpi). We recorded all micro- and macroscopic lesions. Organs from the nervous, lymphatic, and respiratory system were analyzed by quantifying the viral RNA load and the presence of the infectious virus. The presence of the viral antigen in organs was evidenced through immunohistochemistry. Seroconversion was evaluated through the use of a hemagglutination inhibition test. In the characterization of gene HN, only three substitutions were identified in strain Mich/147/2013, two in strain LPMV/1984 (fourth passage) and one in strain Qro/93/2013, with respect to reference strain LPMV-84, these changes had not been identified as virulence factors in previously reported strains. Neurological alterations associated with the infection were found in all three experimental groups starting from 3dpi. Groups G1-84 and G3-147 presented the most exacerbated nervous signs. Group G2-93 only presented milder signs including slight motor incoordination, and an increased rectal temperature starting from day 5 post infection (PI). The main histopathological findings were the presence of a mononuclear inflammatory infiltrate (lymphocytic/monocytic) surrounding the ventricles in the brain and focal interstitial pneumonitis with distention of the alveolar sacs in the lungs. PorPV and RNA distribution were identified in the organs of the nervous, lymphatic, and respiratory systems of the piglets analyzed at different times (days 5, 10, and 15 PI). The viral antigen was detected in the brain and lungs in most of the assessed groups. Seroconversion was evident in groups G1-84 and G2-93. Groups G1-84 and G3-147 were the most clinically affected by the experimental infection. Both strains were isolated in the state of Michoacán. The virulence of the new isolates maintains similar characteristics to those reported more than 30 years ago.

Despite advances in allogeneic hematopoietic cell transplantation, acute graft-versus-host disease (aGVHD) remains its leading complication, yet with heterogeneous outcomes. Here, we analyzed aGVHD phenotypes and clinical classifications in depth in large, multicenter cohorts involving 3019 patients and addressed prevailing gaps by developing data-driven models. We compared, tested and verified these along with all conventional classifications in independent cohorts and found that data-driven grading outperformed conventional grading in Akaike information criterion and concordance index metrics. Data-driven classifications refined aGVHD assessment with up to 12 severity grades, which were associated with distinct nonrelapse mortality (NRM) and confirmed the key role of intestinal aGVHD. We developed an online calculator for physicians to implement principal component-derived grading (PC1). These results provide substantial insight into the evaluation of aGVHD phenotypes and multiorgan involvement, which relegates the exclusive reporting of overall aGVHD severity grades in transplant registries and clinical trials. Data-driven aGVHD grading provides an expandable platform to refine classification and transplant risk assessment.

Interstitial lung disease (ILD) is frequently associated with collagen diseases. The prognosis of acute-onset diffuse ILD (AoDILD) occurring in collagen disease patients is very poor. Here, we investigated serum biomarker profiles of AoDILD to find markers predicting outcome in patients with collagen diseases.

The present study used microarray analysis to screen the plasma expression of microRNAs (miRNAs) in patients with acute Kawasaki disease (KD) and aimed to explore the pathogenesis of KD. Plasma was collected from children with acute KD (n=6) and from healthy control children (n=6). Total RNA was extracted and differential miRNA expression between the two groups was determined. Differentially expressed miRNAs were validated using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) in an independent cohort (n=8). Target genes of the differentially expressed miRNAs were predicted and analyzed for gene ontology term enrichment and Kyoto Encyclopedia of Genes and Genomes pathways. miRNA microarray analysis revealed that seven miRNAs (miRs) were significantly upregulated (hsa‑let‑7b‑5p, hsa‑miR‑223‑3p, hsa‑miR‑4485, hsa‑miR‑4644, hsa‑miR‑4800‑5p, hsa‑miR‑6510‑5p and hsa‑miR‑765) and three were significantly downregulated (hsa‑miR‑33b‑3p, hsa‑miR‑4443 and hsa‑miR‑4515) in acute KD compared with the healthy controls. hsa‑miR‑223‑3p expression levels detected by RT‑qPCR were consistent with the microarray results. A total of 62 target genes of hsa‑miR‑223‑3p were predicted. In total, 10 differentially expressed miRNAs were identified in acute KD, of which hsa‑miR‑223‑3p was verified by RT‑qPCR.

The success of allogeneic hematopoietic cell transplantation is limited by acute graft-versus-host disease (GvHD), a severe complication accompanied by high mortality rates. Yet, the molecular mechanisms initiating this disease remain poorly defined. In this study, we show that, after conditioning therapy, intestinal commensal bacteria and the damage-associated molecular pattern uric acid contribute to Nlrp3 inflammasome-mediated IL-1β production and that gastrointestinal decontamination and uric acid depletion reduced GvHD severity. Early blockade of IL-1β or genetic deficiency of the IL-1 receptor in dendritic cells (DCs) and T cells improved survival. The Nlrp3 inflammasome components Nlrp3 and Asc, which are required for pro-IL-1β cleavage, were critical for the full manifestation of GvHD. In transplanted mice, IL-1β originated from multiple intestinal cell compartments and exerted its effects on DCs and T cells, the latter being preferentially skewed toward Th17. Compatible with these mouse data, increased levels of active caspase-1 and IL-1β were found in circulating leukocytes and intestinal GvHD lesions of patients. Thus, the identification of a crucial role for the Nlrp3 inflammasome sheds new light on the pathogenesis of GvHD and opens a potential new avenue for the targeted therapy of this severe complication.

The criteria for the diagnosis of kidney disease outlined in the Kidney Disease: Improving Global Outcomes guidelines are based on a patient's current, historical, and baseline data. The diagnosis of acute kidney injury, chronic kidney disease, and acute-on-chronic kidney disease requires previous measurements of creatinine, back-calculation, and the interpretation of several laboratory values over a certain period. Diagnoses may be hindered by unclear definitions of the individual creatinine baseline and rough ranges of normal values that are set without adjusting for age, ethnicity, comorbidities, and treatment. The classification of correct diagnoses and sufficient staging improves coding, data quality, reimbursement, the choice of therapeutic approach, and a patient's outcome.

Allogeneic hematopoietic stem cell transplantation (HSCT) has been widely used for the treatment of hematologic malignant and non-malignant hematologic diseases and other diseases. However, acute graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic transplantation. Acute GVHD may occur in 30% of transplant recipients, which is a syndrome of erythematous skin eruption, cholestatic liver disease and intestinal dysfunction, resulting from the activation of donor T lymphocytes by host antigen-presenting cells, resulting in an immune-mediated inflammatory response. Recent scientific advances in the understanding of the pathogenesis involved in the development of acute GVHD and clinical investigation have provided more effective therapeutic strategies for acute GVHD. This review focuses on major scientific and clinical advances in the treatment of acute GVHD.

Sepsis commonly contributes to acute kidney injury (AKI); however, the frequency with which sepsis develops as a complication of AKI and the clinical consequences of this sepsis are unknown. This study examined the incidence of, and outcomes associated with, sepsis developing after AKI.

Acute pancreatitis is a severe systemic disease triggered by a sterile inflammation and initial local tissue damage of the pancreas. Immune cells infiltrating into the pancreas are main mediators of acute pancreatitis pathogenesis. In addition to their antimicrobial potency, macrolides possess anti-inflammatory and immunomodulatory properties which are routinely used in patients with chronic airway infections and might also beneficial in the treatment of acute lung injury. We here tested the hypothesis that the macrolide antibiotic azithromycin can improve the course of acute experimental pancreatitis via ameliorating the damage imposed by sterile inflammation, and could be used as a disease specific therapy. However, our data show that azithromycin does not have influence on caerulein induced acute pancreatitis in terms of reduction of organ damage, and disease severity. Furthermore Infiltration of immune cells into the pancreas or the lungs was not attenuated by azithromycin as compared to controls or ampicillin treated animals with acute experimental pancreatitis. We conclude that in the chosen model, azithromycin does not have any beneficial effects and that its immunomodulatory properties cannot be used to decrease disease severity in the model of caerulein-induced pancreatitis in mice.

(1) Background: Inflammatory bowel disease (IBD) induces a process of systemic inflammation, sharing common ground with acute coronary syndromes (ACS). Growing evidence points towards a possible association between IBD and an increased risk of ACS, yet the topic is still inconclusive. Therefore, we conducted a systematic review aiming to clarify these gaps in the evidence. (2) Methods: We conducted a systematic search on EMBASE, Cochrane Library, and PubMed, identifying observational studies published prior to November 2020. The diagnosis of IBD was confirmed via histopathology or codes. Full articles that fulfilled our criteria were included. Quality assessment was performed using the Newcastle-Ottawa scale (NOS). (3) Results: We included twenty observational studies with a total population of ~132 million subjects. Fifteen studies reported a significant association between ACS and IBD, while the remaining five studies reported no increase in ACS risk in IBD patients. (4) Conclusions: ACS risk in IBD patients is related to hospitalizations, acute active flares, periods of active disease, and complications, with a risk reduction during remission. Interestingly, a general increase in ACS risk was reported in younger IBD patients. The role of corticosteroids and oral contraceptive pills in increasing the ACS risk of IBD patients should be investigated.

The etiology of autoimmune hepatitis (AIH) is unknown, though hepatotropic viruses may be potential triggers. Hepatitis E virus (HEV) infection, an increasingly recognized cause of acute hepatitis, has been misdiagnosed as AIH due to the occurrence of autoantibodies during its acute phase. It has also been suggested that HEV infection may lead to or unmask AIH. The HEV seroprevalence has been ascertained in patients with AIH, but the prevalence of AIH-related autoantibodies in patients with HEV infection has not been systematically tested. We aimed to investigate whether acute HEV infection is associated with the presence of AIH-relevant autoantibodies, following the liver autoimmune serology guidelines of the International AIH Group. We tested 48 patients with acute HEV infection. Half of them had at least one autoantibody, 17% two autoantibodies. Anti-nuclear antibody (ANA) were detected in 16 (33%), anti-smooth muscle antibody (SMA) in 10 (21%), and anti-neutrophil cytoplasmic antibody (ANCA) in 7 (14.6%). Of note, two patients showed SMA with VG or VGT patterns and five had ANA with homogeneous appearance, both being typical of AIH type 1. Other AIH-specific autoantibodies were negative. Atypical anti-mitochondrial antibody, without evidence of primary biliary cholangitis, was positive in one patient, disappearing at follow-up. Follow-up (median 12 months) serum was available from seven autoantibody positive patients: two became negative, while five remained positive, although no patient developed AIH to date. In conclusion, autoantibodies are frequently present during acute HEV infection, indicating that HEV should always be excluded before diagnosing AIH. Importantly, a minority of patients with acute hepatitis E develops AIH-specific autoantibodies, and, though they did not progress to autoimmune liver disease in the short-term, they warrant long-term monitoring.

Kidney involvement in patients with coronavirus disease 2019 (COVID-19) is common, and can range from the presence of proteinuria and haematuria to acute kidney injury (AKI) requiring renal replacement therapy (RRT; also known as kidney replacement therapy). COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and serves as an independent risk factor for all-cause in-hospital death in patients with COVID-19. The pathophysiology and mechanisms of AKI in patients with COVID-19 have not been fully elucidated and seem to be multifactorial, in keeping with the pathophysiology of AKI in other patients who are critically ill. Little is known about the prevention and management of COVID-19 AKI. The emergence of regional 'surges' in COVID-19 cases can limit hospital resources, including dialysis availability and supplies; thus, careful daily assessment of available resources is needed. In this Consensus Statement, the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI based on current literature. We also make recommendations for areas of future research, which are aimed at improving understanding of the underlying processes and improving outcomes for patients with COVID-19 AKI.

Melbourne, Australia, witnessed a thunderstorm asthma outbreak on 21 November 2016, resulting in over 8,000 hospital admissions by 6 P.M. This is a typical acute disease event. Because the time to respond is short for acute disease events, an algorithm based on time between events has shown promise. Shorter the time between consecutive incidents of the disease, more likely the outbreak. Social media posts such as tweets can be used as input to the monitoring algorithm. However, due to the large volume of tweets, a large number of alerts may be produced. We refer to this problem as alert swamping.