Identifying acute illness phenotypes via deep temporal interpolation and clustering network on physiologic signatures.

Using clustering analysis for early vital signs, unique patient phenotypes with distinct pathophysiological signatures and clinical outcomes may be revealed and support early clinical decision-making. Phenotyping using early vital signs has proven challenging, as vital signs are typically sampled sporadically. We proposed a novel, deep temporal interpolation and clustering network to simultaneously extract latent representations from irregularly sampled vital signs and derive phenotypes. Four distinct clusters were identified. Phenotype A (18%) had the greatest prevalence of comorbid disease with increased prevalence of prolonged respiratory insufficiency, acute kidney injury, sepsis, and long-term (3-year) mortality. Phenotypes B (33%) and C (31%) had a diffuse pattern of mild organ dysfunction. Phenotype B's favorable short-term clinical outcomes were tempered by the second highest rate of long-term mortality. Phenotype C had favorable clinical outcomes. Phenotype D (17%) exhibited early and persistent hypotension, high incidence of early surgery, and substantial biomarker incidence of inflammation. Despite early and severe illness, phenotype D had the second lowest long-term mortality. After comparing the sequential organ failure assessment scores, the clustering results did not simply provide a recapitulation of previous acuity assessments. This tool may impact triage decisions and have significant implications for clinical decision-support under time constraints and uncertainty.

Mini-dose methotrexate combined with methylprednisolone for the initial treatment of acute GVHD: a multicentre, randomized trial.

BACKGROUND: There is an urgent unmet need for effective initial treatment for acute graft-versus-host disease (aGVHD) adding to the standard first-line therapy with corticosteroids after allogeneic haematopoietic stem cell transplantation (allo-HSCT). METHODS: We performed a multicentre, open-label, randomized, phase 3 study. Eligible patients (aged 15 years or older, had received allo-HSCT for a haematological malignancy, developed aGVHD, and received no previous therapies for aGVHD) were randomly assigned (1:1) to receive either 5 mg/m2 MTX on Days 1, 3, or 8 and then combined with corticosteroids or corticosteroids alone weekly. RESULTS: The primary endpoint was the overall response rate (ORR) on Day 10. A total of 157 patients were randomly assigned to receive either MTX plus corticosteroids (n = 78; MTX group) or corticosteroids alone (n = 79; control group). The Day 10 ORR was 97% for the MTX group and 81% for the control group (p = .005). Among patients with mild aGVHD, the Day 10 ORR was 100% for the MTX group and 86% for the control group (p = .001). The 1-year estimated failure-free survival was 69% for the MTX group and 41% for the control group (p = .002). There were no differences in treatment-related adverse events between the two groups. CONCLUSIONS: In conclusion, mini-dose MTX combined with corticosteroids can significantly improve the ORR in patients with aGVHD and is well tolerated, although it did not achieve the prespecified 20% improvement with the addition of MTX. TRIAL REGISTRATION: The trial was registered with clinicaltrials.gov (NCT04960644).

SMS121, a new inhibitor of CD36, impairs fatty acid uptake and viability of acute myeloid leukemia.

Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults and the second most common among children. AML is characterized by aberrant proliferation of myeloid blasts in the bone marrow and impaired normal hematopoiesis. Despite the introduction of new drugs and allogeneic bone marrow transplantation, patients have poor overall survival rate with relapse as the major challenge, driving the demand for new therapeutic strategies. AML patients with high expression of the very long/long chain fatty acid transporter CD36 have poorer survival and very long chain fatty acid metabolism is critical for AML cell survival. Here we show that fatty acids are transferred from human primary adipocytes to AML cells upon co-culturing. A drug-like small molecule (SMS121) was identified by receptor-based virtual screening and experimentally demonstrated to target the lipid uptake protein CD36. SMS121 reduced the uptake of fatty acid into AML cells that could be reversed by addition of free fatty acids and caused decreased cell viability. The data presented here serves as a framework for the development of CD36 inhibitors to be used as future therapeutics against AML.

Leukemia circulation kinetics revealed through blood exchange method.

Leukemias and their bone marrow microenvironments undergo dynamic changes over the course of disease. However, little is known about the circulation kinetics of leukemia cells, nor the impact of specific factors on the clearance of circulating leukemia cells (CLCs) from the blood. To gain a basic understanding of CLC dynamics over the course of disease progression and therapeutic response, we apply a blood exchange method to mouse models of acute leukemia. We find that CLCs circulate in the blood for 1-2 orders of magnitude longer than solid tumor circulating tumor cells. We further observe that: (i) leukemia presence in the marrow can limit the clearance of CLCs in a model of acute lymphocytic leukemia (ALL), and (ii) CLCs in a model of relapsed acute myeloid leukemia (AML) can clear faster than their untreated counterparts. Our approach can also directly quantify the impact of microenvironmental factors on CLC clearance properties. For example, data from two leukemia models suggest that E-selectin, a vascular adhesion molecule, alters CLC clearance. Our research highlights that clearance rates of CLCs can vary in response to tumor and treatment status and provides a strategy for identifying basic processes and factors that govern the kinetics of circulating cells.

Graft failure after allogeneic hematopoietic stem cell transplantation in pediatric patients with acute leukemia: autologous reconstitution or second transplant?

BACKGROUND: Graft failure (GF) is a rare but serious complication after allogeneic hematopoietic stem cell transplantation (HSCT). Prevention of graft failure remains the most advisable approach as there is no clear recommendation for the best strategies for reversing this complication. Administration of growth factor, additional hematopoietic progenitor boost, or a salvage HSCT are current modalities recommended for the treatment of GF. Autologous recovery without evidence of disease relapse occurs rarely in patients with GF, and in the absence of autologous recovery, further salvage transplantation following a second conditioning regimen is a potential treatment option that offers the best chances of long-term disease-free survival. The preconditioning regimens of second HSCT have a significant impact on engraftment and outcome, however, currently there is no consensus on optimal conditioning regimen for second HSCT in patients who have developed GF. Furthermore, a second transplant from a different donor or the same donor is still a matter of debate. OBSERVATIONS: We present our experience in managing pediatric patients with acute leukemia who encountered graft failure following stem cell transplantation. CONCLUSIONS AND RELEVANCE: Although a second transplantation is almost the only salvage method, we illustrate that some pediatric patients with acute leukemia who experience graft failure after an allogeneic stem cell transplant using Myeloablative conditioning (MAC) regimen may achieve long-term disease-free survival through autologous hematopoiesis recovery.

The Use of Diets in the Diagnosis and Treatment of Common Gastrointestinal Diseases in Dogs and Cats.

The nutritional health of dogs and cats is important to pet owners around the world. Nutrition is inextricably linked to the health of the gastrointestinal system and vice versa. Gastrointestinal signs, such as vomiting, diarrhea, anorexia, or weight loss, are one of the most common reasons that dog and cat owners make non-routine appointments with veterinarians. Those patients are evaluated systematically to identify and/or rule out the causes of the symptoms. Some causes of chronic diarrhea are within the gastrointestinal tract while others are secondary to pathogenic factors outside the digestive system. Some useful biomarkers of chronic intestinal disease (enteropathy) exist in serum and feces. After determination that the clinical signs are due to primary gastrointestinal disease and that there is no parasitism, specific diets are used for at least two weeks. There are several types of diets for pets with chronic enteropathies. There are limited ingredient diets and hydrolyzed protein diets with reduced levels of allergens. There are also highly digestible and fiber-enhanced diets. Some diets contain probiotics and/or prebiotics. If symptoms do not improve and the patient is stable, a diet from a different class may be tried. For chronic enteropathies, the prognosis is generally good for symptom resolution or at least improvement. However, if interventions with novel diets do not ameliorate the symptoms of chronic enteropathy, then antibiotic, anti-inflammatory, or immunosuppressant therapy or further, more invasive diagnostics such as taking an intestinal biopsy, may be indicated. Pancreatitis is a common gastrointestinal disease in dogs and cats and patients may present with mild to severe disease. Many patients with mild to moderate disease can be successfully treated with early supportive care, including feeding a low-fat diet. A novel pharmaceutical, fuzapladib (Panoquell-CA1) looks very promising for treating more severe forms of acute pancreatitis in dogs. Maintenance on a low-fat diet may prevent pancreatitis in at-risk dogs. Future advances in medicine will allow pet owners and veterinarians to use dietary management to maximize the health of their dogs and cats.

The road to refractory graft-versus-host disease is paved with good intentions.

Refractory acute graft-versus-host disease (GVHD) occurs when the immune injury exceeds the capacity of injured tissues to regenerate and repair. While glucocorticoids have been used for decades to treat GVHD, Arnhold, Chang, and colleagues in this issue of the JCI question whether this approach can in fact be counterproductive. Using in vivo experimental models of GVHD and in vitro intestinal organoids, the study authors show that glucocorticoid exposure directly impeded small intestinal epithelial proliferation and survival, thus preventing the resolution of injury. These findings suggest that future treatment approaches for acute GVHD should include measures to reduce immune reactivity as well as interventions to actively promote tissue resilience.

Complementary and alternative medicines and liver disease.

Complementary and alternative medicines (CAM) include conventional medical treatments. Patients worldwide use CAM at alarming rates; thus, reports of CAM-related DILI have been on the rise. The clinical presentations include asymptomatic liver test abnormalities, acute hepatitis with or without jaundice, acute cholestatic liver disease (bland or with hepatitis), acute liver failure, severe hepatitis with features of portal hypertension, and acute decompensation of known or unknown cirrhosis that can lead to acute-on-chronic liver failure. Acute hepatitis with or without necrosis, hepatocellular and canalicular cholestasis, herb-induced or CAM-triggered autoimmune hepatitis, granulomatous hepatitis, severe steatohepatitis, and vanishing bile duct syndrome are common liver biopsy findings in CAM-DILI. The presence of preexisting liver disease predicts severe liver injury, risk of progression to liver failure, and decreased transplant-free survival in patients with CAM-DILI. This review discusses global epidemiology and trends in CAM-DILI, clinical presentation, assessment and outcomes, commonly emerging threats in the context of hepatotoxic herbs, pragmatic assessment of "liver beneficial" herbs and health care myths, patient communication, regulatory framework, and future directions on research in CAM.

Acute calcific periarthritis in a proximal interphalangeal joint of the hand after acute trauma: a rare case.

Acute calcific periarthritis (ACP) in the interphalangeal joints of the hand is rare, with less than 100 cases reported. A rare case of ACP in a proximal interphalangeal (PIP) joint of the hand, in a young black woman, after acute trauma, is presented. She experienced severe pain and limited range of motion, and was medicated with an oral corticoid, which was followed by a rapid resolution of the symptoms. At six months, there were no signs of clinical or radiographic recurrence. Recognition of ACP allows for avoiding unnecessary treatments. In this case, treatment with corticoids might have played a role in a faster recovery.

La periartritis calcificada aguda (PCA) en las articulaciones interfalángicas de la mano es rara, con menos de 100 casos reportados. Se presenta un caso raro de PCA en una articulación interfalángica proximal (IFP) de la mano, en una mujer joven de raza negra, después de un traumatismo agudo. Experimentó dolor intenso y rango de movimiento limitado, y fue medicada con un corticoide oral, lo que fue seguido por una rápida resolución de los síntomas. A los seis meses no hubo signos de recurrencia clínica ni radiológica. El reconocimiento de PCA permite evitar tratamientos innecesarios. En este caso, el tratamiento con corticoides podría haber contribuido a una recuperación más rápida.

Retrospective analysis of the incidence of appendiceal neoplasm and malignancy in patients treated for suspected acute appendicitis.

BACKGROUND: Nonoperative management of uncomplicated appendicitis is currently being promoted as treatment option, albeit 0.7-2.5% of appendectomies performed due to suspected acute appendicitis show histologically malignant findings. The purpose of this study was to investigate the incidence of neoplasm and malignancy of the appendix in patients presenting with suspected acute appendicitis in real world setting. METHODS: This is a retrospective single-centre investigation of 457 patients undergoing appendectomy between the years 2017-2020. The patients' demographics, symptoms and diagnosis, intraoperative findings, and histopathological results were analysed. RESULTS: In 3.7% (n = 17) histological analysis revealed neoplasms or malignancies. Median age was 48 years (20-90 years), without sex predominance. Leukocytes (11.3 ± 3.7 G/l) and C-reactive protein (54.2 ± 69.0 mg/l) were elevated. Histological analysis revealed low-grade mucinous appendiceal neoplasia (n = 3), sessile serrated adenoma of the appendix (n = 3), neuroendocrine tumours (n = 7), appendiceal adenocarcinoma of intestinal type (n = 3), and goblet cell carcinoma (n = 1). Additional treatment varied between no treatment or follow-up due to early tumour stage (n = 4), follow-up care (n = 3), additional surgical treatment (n = 8), or best supportive care (n = 2). CONCLUSIONS: Preoperative diagnosis of appendiceal tumours is difficult. Nonoperative management of patients with acute, uncomplicated appendicitis potentially prevents the correct diagnosis of malignant appendiceal pathologies. Therefore, close follow-up or surgical removal of the appendix is mandatory.

Acute diverticulitis with extraluminal air: is conservative treatment sufficient? A single-center retrospective study.

BACKGROUND: Acute diverticulitis with extraluminal air constitutes a heterogeneous condition whose management is controversial. The aims of this study are to report the failure rate of conservative treatment for diverticulitis with extraluminal air and to report risk factors of conservative treatment failure. METHODS: A retrospective study was performed from an institutional review board-approved database of patients admitted with acute diverticulitis with extraluminal air from 2015 to 2021 at a tertiary referral center. All patients managed for acute diverticulitis with covered perforation (without intraabdominal abscess) were included. The primary endpoint was failure of medical treatment, defined as a need for unplanned surgery or percutaneous drainage within 30 days after admission. RESULTS: Ninety-three patients (61% male, mean age 57 ± 17 years) were retrospectively included. Ten patients had failure of conservative treatment (11%). These patients were significantly older than 50 years (n = 9/10, 90% versus n = 47/83, 57%, p = 0.007), associated with cardiovascular disease (n = 6/10, 60% versus n = 10/83, 12%, p = 0.002), American Society of Anesthesiologists (ASA) score of 3-4 (n = 4/7, 57% versus 6/33, 18%, p = 0.05), under anticoagulant and antiplatelet (n = 6/10, 60% versus n = 11/83, 13%, p = 0.04) and steroid or immunosuppressive therapy (n = 3/10, 30% versus 5/83, 6%, p = 0.04), and with distant pneumoperitoneum location (n = 7/10, 70% versus n = 14/83, 17%, p = 0.001) compared with those with successful conservative treatment. On multivariate analysis, only distant pneumoperitoneum was an independent risk factor of failure (odds ratio (OR) 6.5, 95% confidence interval (CI) [2-21], p = 0.002). CONCLUSIONS: Conservative treatment with antibiotics for acute diverticulitis with extraluminal air is safe with a success rate of 89%. Patients with distant pneumoperitoneum should be carefully monitored.

ALKBH5 suppresses autophagic flux via N6-methyladenosine demethylation of ZKSCAN3 mRNA in acute pancreatitis.

BACKGROUND: Increasing evidence has demonstrated that N6-methyladenosine (m6A) RNA modification plays an essential role in a wide range of pathological conditions. Impaired autophagy is a critical hallmark of acute pancreatitis (AP). AIM: To explore the role of the m6A modification of ZKSCAN3 in the regulation of autophagy in AP. METHODS: The AP mouse cell model was established by cerulein-treated mouse pancreatic acinar cells (MPC-83), and the results were confirmed by the levels of amylase and inflammatory factors. Autophagy activity was evaluated by specific identification of the autophagy-related microstructure and the expression of autophagy-related genes. ZKSCAN3 and ALKBH5 were knocked down to study the function in AP. A m6A RNA binding protein immunoprecipitation assay was used to study how the m6A modification of ZKSCAN3 mRNA is regulated by ALKBH. RESULTS: The increased expression of amylase and inflammatory factors in the supernatant and the accumulation of autophagic vacuoles verified that the AP mouse cell model was established. The downregulation of LAMP2 and upregulation of LC3-II/I and SQSTM1 demonstrated that autophagy was impaired in AP. The expression of ZKSCAN3 was upregulated in AP. Inhibition of ZKSCAN3 increased the expression of LAMP2 and decreased the expression of the inflammatory factors, LC3-II/I and SQSTM1. Furthermore, ALKBH5 was upregulated in AP. Knockdown of ALKBH5 downregulated ZKSCAN3 expression and restored decreased autophagic flux in AP. Notably, the bioinformatic analysis revealed 23 potential m6A modification sites on ZKSCAN3 mRNA. The m6A modification of ZKSCAN3 mRNA was significantly decreased in AP. Knockdown of ALKBH5 increased the modification of ZKSCAN3 mRNA, which confirmed that ALKBH5 upregulated ZKSCAN3 expression in a m6A-dependent manner. CONCLUSION: ALKBH5 inhibits autophagic flux through m6A demethylation of ZKSCAN3 mRNA in AP, thereby aggravating the severity of the disease.

Serum Nostrin-A risk factor of death, kidney replacement therapy and acute kidney disease in acute kidney injury.

BACKGROUND: The prediction of Acute Kidney Injury (AKI)-related outcomes remains challenging. Persistent kidney excretory dysfunction for longer than 7 days has been defined as Acute Kidney Disease (AKD). In this study, we prospectively quantified serum Nostrin, an essential regulator of endothelial NO metabolism, in hospitalized patients with AKI. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In-hospital subjects with AKI of various etiology were identified through the in-hospital AKI alert system of the Brandenburg University Hospital. Serum Nostrin, and serum NGAL and KIM-1 were measured within a maximum of 48 hours from the timepoint of initial diagnosis of AKI. The following endpoints were defined: in-hospital death, need of kidney replacement therapy (KRT), recovery of kidney function (ROKF) until discharge. RESULTS: AKI patients had significantly higher serum Nostrin levels compared to Controls. The level of serum Nostrin increased significantly with the severity of AKI. Within the group of AKI patients (n = 150) the in-hospital mortality was 16.7%, KRT was performed in 39.3%, no ROKF occurred in 28%. Patients who required KRT had significantly higher levels of serum Nostrin compared to patients who did not require KRT. Significantly higher levels of serum Nostrin were also detected in AKI patients without ROKF compared to patients with ROKF. In addition, low serum Nostrin levels at the timepoint of AKI diagnosis were predictive of in-hospital survival. For comparison, the serum concentrations of NGAL and KIM-1 were determined in parallel to the Nostrin concentrations and the results confirm the prognostic properties of serum Nostrin in AKI. CONCLUSIONS: The current study suggests serum Nostrin as novel biomarker of AKI-associated mortality, KRT and Acute Kidney Disease.

Incidence, risk factors, and outcomes of the transition of HIPEC-induced acute kidney injury to acute kidney disease: a retrospective study.

BACKGROUND: Acute kidney injury (AKI) is recognized as a common complication following cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Characterized by prolonged renal function impairment, acute kidney disease (AKD) is associated with a higher risk of chronic kidney disease (CKD) and mortality. METHODS: From January 2018 to December 2021, 158 patients undergoing CRS-HIPEC were retrospectively reviewed. Patients were separated into non-AKI, AKI, and AKD cohorts. Laboratory parameters and perioperative features were gathered to evaluate risk factors for both HIPEC-induced AKI and AKD, with the 90-day prognosis of AKD patients. RESULTS: AKI developed in 21.5% of patients undergoing CRS-HIPEC, while 13.3% progressed to AKD. The multivariate analysis identified that ascites, GRAN%, estimated glomerular filtration rate (eGFR), and intraoperative (IO) hypotension duration were associated with the development of HIPEC-induced AKI. Higher uric acid, lessened eGFR, and prolonged IO hypotension duration were more predominant in patients proceeding with AKD. The AKD cohort presented a higher risk of 30 days of in-hospital mortality (14.3%) and CKD progression (42.8%). CONCLUSIONS: Our study reveals a high incidence of AKI and AKI-to-AKD transition. Early identification of risk factors for HIPEC-induced AKD would assist clinicians in taking measures to mitigate the incidence.

The integration of single-cell and bulk RNA-seq atlas reveals ERS-mediated acinar cell damage in acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a clinically common acute abdominal disease, whose pathogenesis remains unclear. The severe patients usually have multiple complications and lack specific drugs, leading to a high mortality and poor outcome. Acinar cells are recognized as the initial site of AP. However, there are no precise single-cell transcriptomic profiles to decipher the landscape of acinar cells during AP, which are the missing pieces of jigsaw we aimed to complete in this study. METHODS: A single-cell sequencing dataset was used to identify the cell types in pancreas of AP mice and to depict the transcriptomic maps in acinar cells. The pathways' activities were evaluated by gene sets enrichment analysis (GSEA) and single-cell gene sets variation analysis (GSVA). Pseudotime analysis was performed to describe the development trajectories of acinar cells. We also constructed the protein-protein interaction (PPI) network and identified the hub genes. Another independent single-cell sequencing dataset of pancreas samples from AP mice and a bulk RNA sequencing dataset of peripheral blood samples from AP patients were also analyzed. RESULTS: In this study, we identified genetic markers of each cell type in the pancreas of AP mice based on single-cell sequencing datasets and analyzed the transcription changes in acinar cells. We found that acinar cells featured acinar-ductal metaplasia (ADM), as well as increased endocytosis and vesicle transport activity during AP. Notably, the endoplasmic reticulum stress (ERS) and ER-associated degradation (ERAD) pathways activated by accumulation of unfolded/misfolded proteins in acinar cells could be pivotal for the development of AP. CONCLUSION: We deciphered the distinct roadmap of acinar cells in the early stage of AP at single-cell level. ERS and ERAD pathways are crucially important for acinar homeostasis and the pathogenesis of AP.

Impact of COVID-19 on acute appendicitis presentation, management and pathology findings in adult and paediatric populations.

BACKGROUND: We investigated the impact of the COVID-19 pandemic on trends of presentation, management and pathology findings in patients who underwent an appendicectomy for suspected acute appendicitis. METHOD: The retrospective study reviewed patients (n = 939 adults and n = 329 children) who had an appendicectomy performed for suspected acute appendicitis and histopathology assessment in the Belfast Health and Social Care Trust, Northern Ireland. Pre-COVID-19 (March 2019 to February 2020) and COVID-19 Year 1 (March 2020 to February 2021) data were compared. Chi-squared tests were applied to compare timeframes. RESULTS: 513 adult appendicectomies were performed in the immediate year pre-COVID-19, compared to 426 in COVID-19 Year 1, representing a 17% reduction. No such reduction was seen within the paediatric population, likely related to a change in regional paediatric referral criteria during the pandemic. When comparing COVID-19 Year 1 with pre-pandemic, fewer patients presented with <24 hours of symptoms (45% v 53%, p = 0.005), and there was greater use of pre-operative computed tomography imaging in adults (63.2% v 48.7%, p<0.001). Fewer adult and paediatric cases of simple acute appendicitis and non-diagnostic specimens, with relative increased proportions of perforated acute appendicitis, were observed in COVID-19 Year 1 compared with pre-pandemic. No absolute increase in perforated acute appendicitis cases was observed in adults. CONCLUSION: Year 1 of the COVID-19 pandemic was associated with delayed presentation of acute appendicitis in adults and children. In adults, an overall reduction in appendicectomy operations, increased use of pre-operative diagnostic imaging, and fewer specimens showing simple acute appendicitis or non-diagnostic features, collectively support appropriate restriction of surgery for those patients with a more certain acute appendicitis diagnosis.

Diagnostic and prognostic value of plasma miR-106a-5p levels in patients with acute heart failure.

BACKGROUND: It is essential to find reliable biomarkers for early diagnosis and prognosis of acute heart failure (AHF) for its mitigation. Currently, increasing attention is paid to the role of microRNAs (miRNAs/miRs) as diagnostic or prognostic markers for cardiovascular diseases. Since plasma miR-106a-5p has been observed to be downregulated in AHF, its value in the diagnosis and prognostic assessment of AHF deserves further exploration. Accordingly, this study analyzed the diagnostic and prognostic value of plasma miR-106a-5p in AHF patients. METHODS: Prospectively, this study included 127 AHF patients who met the 2021 European Society of Cardiology Guidelines and 127 control individuals. Plasma miR-106a-5p levels were determined with RT-qPCR. Spearman correlation analysis was performed to evaluate the correlation of plasma miR-106a-5p levels with NT-proBNP and hs-CRP levels in AHF patients. All AHF patients were followed up for 1 year and allocated into poor and good prognosis groups, and plasma miR-106a-5p levels were compared. The diagnostic and prognostic value of plasma miR-106a-5p for AHF was assessed with a receiver-operating characteristic curve. RESULTS: Plasma miR-106a-5p was lowly expressed in AHF patients versus controls (0.53 ± 0.26 vs. 1.09 ± 0.46) and showed significant negative correlations with NT-proBNP and hs-CRP levels. Plasma miR-106a-5p level < 0.655 could assist in AHF diagnosis. Plasma miR-106a-5p levels were markedly lower in poor-prognosis AHF patients than in good-prognosis patients. Plasma miR-106a-5p level < 0.544 could assist in predicting poor prognosis in AHF patients. CONCLUSION: Plasma miR-106a-5p is downregulated in AHF patients and could assist in diagnosis and poor prognosis prediction of AHF.

A retrospective multicentre clinical study on management of isolated splenic vein thrombosis: risks and benefits of anticoagulation.

INTRODUCTION: Isolated splenic vein thrombosis (iSVT) is a common complication of pancreatic disease. Whilst patients remain asymptomatic, there is a risk of sinistral portal hypertension and subsequent bleeding from gastric varices if recanalisation does not occur. There is wide variation of iSVT treatment, even within single centres. We report outcomes of iSVT from tertiary referral hepatobiliary and pancreatic (HPB) units including the impact of anticoagulation on recanalisation rates and subsequent variceal bleeding risk. METHODS: A retrospective cohort study including all patients diagnosed with iSVT on contrast-enhanced CT scan abdomen and pelvis between 2011 and 2019 from two institutions. Patients with both SVT and portal vein thrombosis at diagnosis and isolated splenic vein thrombosis secondary to malignancy were excluded. The outcomes of anticoagulation, recanalisation rates, risk of bleeding and progression to portal vein thrombosis were examined using CT scan abdomen and pelvis with contrast. RESULTS: Ninety-eight patients with iSVT were included, of which 39 patients received anticoagulation (40%). The most common cause of iSVT was acute pancreatitis n = 88 (90%). The recanalisation rate in the anticoagulation group was 46% vs 15% in patients receiving no anticoagulation (p = 0.0008, OR = 4.7, 95% CI 1.775 to 11.72). Upper abdominal vascular collaterals (demonstrated on CT scan angiography) were significantly less amongst patients who received anticoagulation treatment (p = 0.03, OR = 0.4, 95% CI 0.1736 to 0.9288). The overall rate of upper GI variceal-related bleeding was 3% (n = 3/98) and it was independent of anticoagulation treatment. Two of the patients received therapeutic anticoagulation. CONCLUSION: The current data supports that therapeutic anticoagulation is associated with a statistically significant increase in recanalisation rates of the splenic vein, with a subsequent reduction in radiological left-sided portal hypertension. However, all patients had a very low risk of variceal bleeding regardless of anticoagulation. The findings from this retrospective study should merit further investigation in large-scale randomised clinical trials.

Deep learning assists in acute leukemia detection and cell classification via flow cytometry using the acute leukemia orientation tube.

This study aimed to evaluate the sensitivity of AI in screening acute leukemia and its capability to classify either physiological or pathological cells. Utilizing an acute leukemia orientation tube (ALOT), one of the protocols of Euroflow, flow cytometry efficiently identifies various forms of acute leukemia. However, the analysis of flow cytometry can be time-consuming work. This retrospective study included 241 patients who underwent flow cytometry examination using ALOT between 2017 and 2022. The collected flow cytometry data were used to train an artificial intelligence using deep learning. The trained AI demonstrated a 94.6% sensitivity in detecting acute myeloid leukemia (AML) patients and a 98.2% sensitivity for B-lymphoblastic leukemia (B-ALL) patients. The sensitivities of physiological cells were at least 80%, with variable performance for pathological cells. In conclusion, the AI, trained with ResNet-50 and EverFlow, shows promising results in identifying patients with AML and B-ALL, as well as classifying physiological cells.

Hybrid noncovered open stents in repair of DeBakey type 1 acute aortic dissections.

OBJECTIVES: The indications for use, evidence base and experience with the novel noncovered open hybrid surgical stents for acute type A aortic dissection repair for concurrent stabilization of the 'downstream' aorta remains limited. We review the evidence base and the development of these stents. METHODS: Data were collected from Pubmed/Medline literature search to develop and review the evidence base for safety and efficacy of non-covered surgical stents. Existing guidelines for use and developments were reviewed. RESULTS: A single randomized control trial and 4 single-centre studies were included in the review with a total worldwide experience of 241 patients. The deployment was easy and did not add significantly to the primary operation. The mortality and new stroke ranged from 6.3-18.7%. Safe and complete deployment was accomplished in 92-100%. There was no device-related reintervention. There was a significant improvement in malperfusion in over 90% of the cases with varying degrees of remodelling (60-90%) of the downstream aorta. CONCLUSIONS: Open noncovered stent grafts represent a major technical advancement as an adjunct procedure for acute dissection repairs, e.g. hemiarch repair. It has potential for wider use by non-aortic surgeons due to simplicity of technique. Limited safety and efficacy data confirm the device to be safe, feasible and reproducible with potential for wider adoption. However, long-term trial and registry data are required before recommendations for standard use outside of high-volume experienced aortic centres.