Search

Background: There is limited research on what, when and how outcomes should be measured in psychological therapy trials in acute mental health inpatient wards. Objectives: This study aimed to consider what outcomes service users think are important to measure. Methods: This qualitative study explored the views of 14 participants, who had an inpatient admission within the last year, on outcomes of psychological therapies using semistructured interviews. Data were analysed using thematic analysis from a critical realist perspective with both inductive and deductive coding. Results: The 126 outcomes that were important to participants were mapped onto an established taxonomy of outcomes across different health areas and the socioecological framework to consider the wider context and help summarise the outcomes. Most of the outcomes were mapped to the intrapersonal and interpersonal level. In addition to the outcome mapping, three themes were constructed from the qualitative data: (1) I am not a problem I am a person, (2) Feeling cared for and loved, (3) What does getting better look like. Conclusions: Our results highlight the need for patient‐reported outcomes which are cocreated with service users, disseminating research and training on preventing dehumanising experiences, enhancing psychological safety and therapeutic relationships and improving access to psychological therapy. Patient or Public Contribution: The wider People with Personal Experience Involvement Committee at the University of Bath were consulted which included a focus group during the early planning stages. We also collaborated with a person with personal experience, at every stage of the research. This included developing our research question and aims, protocol, participant documents (e.g., information and debrief forms), advertisement and recruitment strategy, interview topic guide, the codes, the final themes and quotes and reviewing the manuscript. People with lived experience of being admitted to an acute mental health inpatient ward participated in our study. [ABSTRACT FROM AUTHOR]

We sought to characterize outcomes in patients undergoing pulmonary thromboendarterectomy electively versus after acute presentation. This is a retrospective analysis of patients who underwent pulmonary thromboendarterectomy from October 2015 to April 2022. Patients were divided into 2 groups depending on elective surgery or surgery during the same hospitalization as their presentation. In total, 69 patients were included: 45 in the hospitalized group and 24 in the elective group. Patients in the hospitalized group were less likely to have chronic lung disease, history of pulmonary embolism and hypertension, be on anticoagulation and medication for pulmonary hypertension, and present with >1 month of respiratory symptoms. They were more likely to have worse preoperative right ventricular function. Among other demographics, risk factors for venous thromboembolism were similar between both groups. Thirteen patients in the hospitalized group required preoperative extracorporeal membrane oxygenation. There was no difference in disease classification and operative, cardiopulmonary bypass, and hypothermic circulatory arrest durations between both groups. Postoperative complications were similar between both groups, except for greater frequency of deep vein thrombosis in the hospitalized group (26.7% vs 4.2%, P =.03). In-hospital and intensive care unit length of stay were similar between both groups. Overall, in-hospital mortality was 4.3% and was similar between both groups; P =.28. Our series shows that pulmonary thromboendarterectomy can be safely performed in patients presenting acutely, with comparable postoperative complications and in-hospital mortality to an elective setting. Such patients present with worse right ventricular function, sometimes requiring temporary mechanical support. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Postoperative acute liver failure, a complication following spine surgery, can cause delayed emergence from total intravenous anesthesia. Here, we report a case of acute severe postoperative liver failure following posterior spinal correction and fusion in a patient with congenital scoliosis. Case Report: A girl's congenital scoliosis worsened, and posterior spinal correction and fusion was scheduled. General anesthesia was induced with sevoflurane, fentanyl, target-controlled-infusion with propofol, and rocuronium. General anesthesia was maintained using target-controlled-infusion with propofol and remifentanil. The operation was completed with no remarkable complications. The operative time was 516 min and the anesthesia time was 641 min in the prone position. Emergence from anesthesia was poor, and it took 68 min to remove the tracheal tube after discontinuation of the anesthetic agents. The patient was drowsy and was transferred to her room in a general ward without reporting any pain, nausea, or dyspnea. On postoperative day 1, the results of laboratory investigations were suggestive of acute liver failure; contrast-enhanced computed tomography revealed a poorly enhanced area in the umbilical portion of the left liver lobe portal vein, indicating ischemic liver damage. Although no additional treatment was administered for acute liver failure, the patient recovered over time, and laboratory values normalized. No other postoperative complications were observed, and the patient was discharged on postoperative day 21. Conclusions: Delayed emergence from general anesthesia may be due to acute liver failure following posterior spinal correction and fusion. There are several possible causes of postoperative liver failure, including anesthetics, prone position, and spinal surgery. [ABSTRACT FROM AUTHOR]

Background: Anodal transcranial direct current stimulation (tDCS) is a beneficial adjunctive tool in stroke rehabilitation. However, only a few studies have investigated its effects on acute stroke and recruited only individuals with mild motor deficits. This study investigated the effect of five consecutive sessions of anodal tDCS and conventional physical therapy on brain activity and motor outcomes in individuals with acute stroke, with low and high motor impairments. Methods: Thirty participants were recruited and randomly allocated to either the anodal or sham tDCS group. Five consecutive sessions of tDCS (1.5 mA anodal or sham tDCS for 20 min) were administered, followed by conventional physical therapy. Electroencephalography (EEG), Fugl-Meyer Motor Assessment (FMA), and Wolf Motor Function Test (WMFT) were performed at pre-, post-intervention (day 5), and 1-month follow-up. Sub-analyses were performed on participants with low and high motor impairments. The relationship between EEG power and changes in motor functions was assessed. Results: Linear regression showed a significant positive correlation between beta bands and the FMA score in the anodal group. Elevated high frequency bands (alpha and beta) were observed at post-intervention and follow-up in all areas of both hemispheres in the anodal group, while only in the posterior area of the non-lesioned hemisphere in the sham group; however, such elevation induced by tDCS was not greater than sham. Lower limb function assessed by FMA was improved in the anodal group compared with the sham group at post-intervention and follow-up only in those with low motor impairment. For the upper limb outcomes, no difference between groups was found. Conclusions: Five consecutive days of anodal tDCS and physical therapy in acute stroke did not result in a superior improvement of beta bands that commonly related to stroke recovery over sham, but improved lower extremity functions with a post-effect at 1-month follow-up in low motor impairment participants. The increase of beta bands in the lesioned brain in the anodal group was associated with improvement in lower limb function. Trial registration: NCT04578080, date of first registration 10/01/2020. [ABSTRACT FROM AUTHOR]

Acute chylous peritonitis is an uncommon medical condition that can occur suddenly, resulting in the buildup of chylous fluid in the peritoneal cavity. It is considered idiopathic because the exact cause is often unknown. The symptoms of acute chylous idiopathic peritonitis can mimic other abdominal emergencies, making it challenging to diagnose and manage, requiring a multidisciplinary approach. We present a case report of acute idiopathic chylous peritonitis miming acute abdomen, how was successfully treated with surgery, and provide a comprehensive review of the available literature on this topic. Chylous peritonitis is a rare condition whose clinical presentation mimics an acute abdomen. It is necessary to undertake careful exploration. An emergent laparotomy is indicated to treat the peritonitis and search for and treat the underlying cause. [ABSTRACT FROM AUTHOR]

Post-stroke language recovery remains one of the main unresolved topics in the field of aphasia. In recent years, there have been efforts to identify specific factors that could potentially lead to improved language recovery. However, the exact relationship between the recovery of particular language functions and possible predictors, such as demographic or lesion variables, is yet to be fully understood. In the present study, we attempted to investigate such relationships in 42 patients with aphasia after left hemisphere stroke, focusing on three language domains: auditory comprehension, naming and speech fluency. Structural imaging data were also obtained for the identification of the lesion sites. According to our findings, patients demonstrated an overall improvement in all three language domains, while no demographic factor significantly contributed to aphasia recovery. Interestingly, specific lesion loci seemed to have a differential effect on language performance, depending on the time of testing (i.e., acute/subacute vs. chronic phase). We argue that this variability concerning lesion–deficit associations reflects the dynamic nature of aphasia and further discuss possible explanations in the framework of neuroplastic changes during aphasia recovery. [ABSTRACT FROM AUTHOR]

Background: India accounts for 13.3% of global disability-adjusted life years (DALYs) lost due to stroke with a relatively younger age of onset compared to the Western population. In India's public healthcare system, many stroke patients seek care at tertiary-level government-funded medical colleges where an optimal level of stroke care is expected. However, there are no studies from India that have assessed the quality of stroke care, including infrastructure, imaging facilities, or the availability of stroke care units in medical colleges. Aim: This study aimed to understand the existing protocols and management of acute stroke care across 22 medical colleges in India, as part of the baseline assessment of the ongoing IMPETUS stroke study. Methods: A semi-structured quantitative pre-tested questionnaire, developed based on review of literature and expert discussion, was mailed to 22 participating sites of the IMPETUS stroke study. The questionnaire assessed comprehensively all components of stroke care, including human resources, emergency system, in-hospital care, and secondary prevention. A descriptive analysis of their status was undertaken. Results: In the emergency services, limited stroke helpline numbers, 3/22 (14%); prenotification system, 5/22 (23%); and stroke-trained physicians were available, 6/22 (27%). One-third of hospitals did not have on-call neurologists. Although non-contrast computed tomography (NCCT) was always available, 39% of hospitals were not doing computed tomography (CT) angiography and 13/22 (59%) were not doing magnetic resonance imaging (MRI) after routine working hours. Intravenous thrombolysis was being done in 20/22 (91%) hospitals, but 36% of hospitals did not provide it free of cost. Endovascular therapy was available only in 6/22 (27%) hospitals. The study highlighted the scarcity of multidisciplinary stroke teams, 8/22 (36%), and stroke units, 7/22 (32%). Lifesaving surgeries like hematoma evacuation, 11/22 (50%), and decompressive craniectomy, 9/22 (41%), were performed in limited numbers. The availability of occupational therapists, speech therapists, and cognitive rehabilitation was minimal. Conclusion: This study highlighted the current status of acute stroke management in publicly funded tertiary care hospitals. Lack of prenotification, limited number of stroke-trained physicians and neurosurgeons, relatively lesser provision of free thrombolytic agents, limited stroke units, and lack of rehabilitation services are areas needing urgent attention by policymakers and creation of sustainable education models for uniform stroke care by medical professionals across the country. [ABSTRACT FROM AUTHOR]

Stroke is the second leading cause of death and a major cause of disability worldwide. Stroke severity scales serve as reliable means to track a patient's neurological deficit, predict outcome, and guide treatment decisions in clinical practice. The National Institute of Health Stroke Scale (NIHSS) was introduced over 30 years ago, marking a significant milestone in the field of stroke. Over the years, there have been notable advancements in acute stroke care. Despite several modifications made to NIHSS, none has yet succeeded in effectively capturing all the complex effects of a stroke. This review focuses on the pitfalls of NIHSS and emphasizes the need for a quick and comprehensive clinical and upgraded version of the stroke severity rating scale. [ABSTRACT FROM AUTHOR]

Background The use of myocardial reperfusion—mainly via angioplasty—has increased in our region to over 95%. We wondered whether old and very old patients have benefited from this development. Methods Setting: Greater Paris Area (Ile-de-France). Data Regional registry, prospective, including since 2003, data from 39 mobile intensive care units performing prehospital treatment of patients with ST segment elevation myocardial infarction (STEMI) (<24 h). Parameters Demographic, decision to perform reperfusion and outcome (in-hospital mortality). Primary endpoint Reperfusion decision rate by decade over age 70. Secondary endpoint Outcome. Results We analysed the prehospital management of 27,294 patients. There were 21,311 (78%) men and 5,919 (22%) women with a median age of 61 (52–73 years). Among these patients, 8,138 (30%) were > 70 years, 3,784 (14%) > 80 years and 672 (2%) > 90 years. The reperfusion decision rate was 94%. It decreased significantly with age: 93, 90 and 76% in patients in their seventh, eighth and ninth decade, respectively. The reperfusion decision rate increased significantly over time. It increased in all age groups, especially the higher ones. Mortality was 6%. It increased significantly with age: 8, 16 and 25% in patients in their seventh, eighth and ninth decade, respectively. It significantly decreased over time in all age groups. The odds ratio of the impact of reperfusion decision on mortality reached 0.42 (0.26–0.68) in patients over 90 years. Conclusion the increase in the reperfusion decision rate was the greatest in the oldest patients. It reduced mortality even in patients over 90 years of age. [ABSTRACT FROM AUTHOR]

Purpose: In this study, we investigated the clinical profile, survival at discharge, and proportion of children with acute liver failure (ALF) meeting the criteria for, yet surviving without, liver transplantation (LT). Methods: Medical case records of children aged >28 days to =15 years over a period of 7 years, identified from pediatric admission and discharge registers, were screened. Children satisfying the criteria for ALF were included in this study. Results: A total of 71 records meeting the pediatric ALF (PALF) criteria were included. The survival rate at discharge was 61% (n=44). A considerable proportion of children satisfied the King's College Criteria (KCC) (56.3%) and the European Association for the Study of the Liver (EASL) criteria (7%) for LT at admission. Nonetheless, the survival rate in the absence of LT was 42.5% in children who satisfied the KCC and 20% in those who met the EASL criteria. Infection (29.5%) and paracetamol overdose (19.7%) were the major identifiable causes of PALF. Hepatitis A was the most common infection identified. No significant predictors of poor outcomes were identified in multivariable analysis. Conclusion: Our study highlights the changing survival rates and the clinical and etiological profiles of patients with PALF. In areas with poor access to LT services, survival in these children could be improved through early referral to centers with adequate intensive care facilities. Preventing ALF and referring patients to LT services are paramount to reducing mortality. [ABSTRACT FROM AUTHOR]

Acute biliary pancreatitis (ABP) poses significant challenges in determining the optimal timing and approach for cholecystectomy, particularly in mild, moderately severe, and severe forms. This article reviews the existing literature on cholecystectomy timing and its impact on outcomes in ABP. A systematic literature search yielded 41 relevant articles from PubMed and Scopus databases. In mild ABP, early cholecystectomy within 72 hours of onset is increasingly favoured due to reduced technical difficulty and lower risk of recurrent pancreatitis. Conversely, delayed cholecystectomy, although traditionally practiced, may lead to higher recurrence rates and prolonged hospital stays. For moderate severe ABP, evidence remains limited, but early cholecystectomy appears to decrease hospital stay without increasing perioperative complications. In severe ABP, consensus suggests delaying cholecystectomy until peripancreatic collections resolve, typically 6 to 10 weeks post-onset, to minimize surgical morbidity. The role of endoscopic retrograde cholangiopancreatography (ERCP) alongside cholecystectomy remains contentious, with guidelines recommending its use in specific scenarios such as cholangitis or biliary obstruction. However, routine ERCP in mild ABP lacks robust evidence and may increase complications. Challenges persist regarding the management of residual choledocholithiasis post-ABP, highlighting the need for improved diagnostic criteria and management protocols. Overall, this review underscores the evolving landscape of cholecystectomy timing in ABP and provides insights into current best practices and areas for future research. [ABSTRACT FROM AUTHOR]

Background Phenotypic classification is a method of grouping patients with similar phenotypes. Aim We aimed to use phenotype classification based on a clustering process for risk stratification of patients with non-valvular atrial fibrillation (AF) and second, to assess the benefit of the Atrial Fibrillation Better Care (ABC) pathway. Methods Patients with AF were prospectively enrolled from 27 hospitals in Thailand from 2014 to 2017, and followed up every 6 months for 3 years. Cluster analysis was performed from 46 variables using the hierarchical clustering using the Ward minimum variance method. Outcomes were a composite of all-cause death, ischemic stroke/systemic embolism, acute myocardial infarction and heart failure. Results A total of 3405 patients were enrolled (mean age 67.8 ± 11.3 years, 58.2% male). During the mean follow-up of 31.8 ± 8.7 months. Three clusters were identified: Cluster 1 had the highest risk followed by Cluster 3 and Cluster 2 with a hazard ratio (HR) and 95% confidence interval (CI) of composite outcomes of 2.78 (2.25, 3.43), P  < 0.001 for Cluster 1 and 1.99 (1.63, 2.42), P  < 0.001 for Cluster 3 compared with Cluster 2. Management according to the ABC pathway was associated with reductions in adverse clinical outcomes especially those who belonged to Clusters 1 and 3 with HR and 95%CI of the composite outcome of 0.54 (0.40, 073), P  < 0.001 for Cluster 1 and 0.49 (0.38, 0.63), P  < 0.001 for Cluster 3. Conclusion Phenotypic classification helps in risk stratification and prognostication. Compliance with the ABC pathway was associated with improved clinical outcomes. [ABSTRACT FROM AUTHOR]

The role of the Comprehend, Cope and Connect model in embedding a psychotherapeutic approach throughout a team, and making such an approach available to those with severe mental health problems, is outlined. The model is explained: its starting point in felt sense; its distributed model of the self, and its co-produced, trauma informed formulation that leads to new ways of coping with the internal state, which can be supported by a wider team. The way in which this makes a psychotherapeutic approach, with emphasis on the power of relationship, available to acute psychiatric and other services providing for those with severe mental health problems, is outlined. The inclusion of spirituality and its applicability to diverse populations is also covered, along with its, so far limited, research base. [ABSTRACT FROM AUTHOR]

Background: Noncontrast CT (NCCT) is used to evaluate for intracerebral hemorrhage (ICH) and ischemia in acute ischemic stroke (AIS). Large vessel occlusions (LVOs) are a major cause of AIS, but challenging to detect on NCCT. Aims: The purpose of this study is to evaluate an AI software called RAPID NCCT Stroke (RAPID, iSchemaView, Menlo Park, CA) for ICH and LVO detection compared to expert readers. Methods: In this IRB approved retrospective, multicenter study, stand-alone performance of the software was assessed based on the consensus of 3 neuroradiologists and sensitivity and specificity were determined. The platform's performance was then compared to interpretation by readers comprised of eight general radiologists (GR) and three neuroradiologists (NR) in detecting ICH and hyperdense vessel sign (HVS) indicating LVO. Results: A total of 244 cases were included. Of the 244, 115 were LVOs and 26 were ICHs. One hundred three cases did not have LVO nor ICH. Stand-alone performance of the software demonstrated sensitivities and specificities of 96.2 and 99.5% for ICH and 63.5 and 95.1% for LVO detection. Compared to all 11 readers and eight GR readers only respectively, the software demonstrated superiority, achieving significantly higher sensitivities (63.5% versus 43.6%, p < 0.0001 and 63.5% versus 40.9%, p = 0.001). Conclusion: The RAPID NCCT Stroke platform demonstrates superior performance to radiologists for detecting LVO from a NCCT. Use of this software platform could lead to earlier LVO detection and expedited transfer of these patients to a thrombectomy capable center. [ABSTRACT FROM AUTHOR]

Background: Acute hepatic porphyria (AHP) is a family of rare genetic diseases, including acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and delta-aminolevulinic acid dehydratase-deficient porphyria. The objective of this retrospective cohort study was to provide information on the clinical features of AHP in Japan—including acute attacks, chronic symptoms, and long-term complications. Methods: Patients with AHP between April 2008 and June 2020 were selected from Japan's Medical Data Vision claims database. Patients with AHP were matched 1:10, by sex and age, to patients without AHP. The outcomes were evaluated overall, for patients age ≥ 55 years, and for the matched population. Results: A total of 391 patients with AHP were included from the Japanese Medical Data Vision database. During the observation period (April 2008–June 2020), 18.2% (71/391) of patients experienced 1 acute attack and 10.5% (41/391) experienced ≥ 2 attacks. Chronic symptoms with rates ~ 10% or higher in the AHP population compared with the matched population included neurotic, stress-related, and somatoform disorders (21.7% vs. 6.7% [15.0% difference]); sleep disorders (23.0% vs. 9.9% [13.1% difference]); other and unspecified abdominal pain (13.6% vs. 3.7% [9.9% difference]); and nausea and vomiting, excluding chemotherapy-induced emesis (17.9% vs. 8.1% [9.8% difference]). Long-term complications with higher incidence rates in the AHP population compared with the matched population included fibrosis and cirrhosis of liver (15.9% vs. 3.0% [12.9% difference]), polyneuropathies and other disorders of the peripheral nervous system (20.5% vs. 7.9% [12.6% difference]), liver cancer (16.9% vs. 4.7% [12.2% difference]), renal failure (16.4% vs. 4.3% [12.1% difference]), and hypertension (26.1% vs. 18.8% [7.3% difference]). Among AHP patients age ≥ 55 years, the most common long-term complications were hypertension, kidney failure, and liver cancer. Conclusions: In Japan, patients with AHP experience a high clinical burden in terms of acute attacks, chronic symptoms, and long-term complications. The clinical burden related to chronic symptoms and long-term complications was substantially higher in Japanese patients with AHP compared with a matched population without AHP. Recognizing these signs and symptoms of AHP may aid physicians in making an earlier diagnosis, which may help patients avoid attack triggers, implement disease management, and reduce lifetime disease burden. [ABSTRACT FROM AUTHOR]

Diagnosis and treatment of hematological malignancies, a diverse category of tumors that begin in the blood and bone marrow, are extremely difficult. Our knowledge of these conditions has been revolutionized by the development of cytogenetics, the study of chromosomes and genetic abnormalities. A total of 180 patients with benign and malignant hematological malignancy had peripheral bone marrow or blood samples obtained using the standard Gbanding procedure. Fifty-one percent of patients had normal karyotypes. In addition, thirty individuals (15%) had a complicated karyotype whereas eightyfive percent (85%) had a normal one. Three-hundred and three percent of patients were diagnosed with Pre-B Acute Lymphoblastic Leukemia (Pre-B ALL), followed by twenty percent with Chronic Myelogenous Leukemia (CML), and fourteen percent with Acute Lymphocytic Leukemia. [ABSTRACT FROM AUTHOR]

Purpose: Patellar tendon ruptures (PTR) occur predominantly in middle-aged patients following indirect trauma. The aim of this study was to quantify the short-term results using a suture tape augmentation technique for the repair of PTR. Methods: All consecutive patients with acute (< 6 weeks) PTR who underwent suture tape augmentation between 03/2014 and 11/2019 at a single institution with a minimum follow-up of 12 months were retrospectively evaluated. Outcome measures included Visual Analog Scale (VAS) for pain, Tegner Activity Scale (TAS) and return to sport rates, Lysholm score, International Knee Documentation Committee subjective knee form (IKDC) as well as Knee Injury and Osteoarthritis Outcome Score (KOOS). Additionally, a standardized clinical examination and an isometric strength evaluation of knee extension and flexion were performed. It was hypothesized that high return to sport rates and good functional outcome would be observed and that the majority of patients would not present with a severe (> 20%) knee extension strength deficit when compared to the contralateral side. Results: A total of 7 patients (mean age 37.0 ± SD 13.5 years; 6 male/1 female) were available for final assessment at a median follow-up of 17.0 (25–75% IQR 16.0–77.0) months. Three injuries occurred during ball sports, two injuries occurred during winter sports, and one injury each occurred during a motorcycling and skateboarding accident. The average time between trauma and surgery was 4.7 ± 2.6 days. At follow-up, patients reported little pain (VAS: 0 [0–0.4]). Return to sport was possible for all patients 8.9 ± 4.0 months postoperatively at a high level (TAS: 7.0 [6.0–7.0]). Five patients (71.4%) returned to the preinjury level of play, and 2 (28.6%) did not return to the preinjury level of play. Patient-reported outcome measures were moderate to good (Lysholm score: 80.4 ± 14.5; IKDC: 84.2 ± 10.6; KOOS subscales: pain 95.6 ± 6.0, symptoms 81.1 [64.9–89.1], activities of daily living 98.5 [94.1–100], sport and recreation function 82.9 ± 14.1 and knee-related quality of life 75.9 ± 16.3). All patients were very satisfied (57.1%) or satisfied (42.9%) with the postoperative result. No postoperative complications were reported. Strength measurements revealed a severe knee extension deficit in 3 patients (42.9%), but no significant deficit of isometric knee extension or flexion strength in comparison with the contralateral side was observed overall (p > 0.05). Conclusion: Suture tape augmentation in acute PTR repair leads to good functional outcome without major complications. Although a severe knee extension strength deficit may occur in some patients postoperatively, an excellent return to sports rate and high patient satisfaction can be expected nonetheless. Level of evidence: Retrospective cohort study; III. [ABSTRACT FROM AUTHOR]

Unilateral non-hemorrhagic adrenal infarction (NHAI) is a very uncommon cause of acute abdomen in pregnancy. Diagnosis is highly challenging due to its rarity, heterogeneity of clinical presentation, and inconclusiveness of the initial workup. Timely recognition is pivotal to ensuring optimal outcomes. Here we describe a case of spontaneous unilateral NHAI diagnosed in a singleton pregnant woman at 32 weeks' gestation at our centre and provide the findings of an extensive literature review on the topic. We identified 22 articles describing 31 NHAI cases in 30 obstetric patients: NHAI occurs more frequently on the right side and in the third trimester, and diagnosis is formulated more than 24 h after clinical presentation in 50% of cases; second-level imaging is always necessary to reach a definitive diagnosis and start appropriate treatment. A high degree of clinical suspicion is needed to promptly recognize NHAI in pregnancy, thus allowing appropriate multidisciplinary management and timely treatment initiation. Promotion of knowledge and awareness of NHAI as a potential cause of acute abdomen in pregnancy is mandatory to improve clinical practice and, ultimately, perinatal outcomes. [ABSTRACT FROM AUTHOR]

Background: Surgical intervention for acute corrosive injury is often required. It is associated with considerable morbidity and mortality. Sparce data is available on the types and timing of surgery after acute corrosive ingestion and complications associated with the same. Methods: This is a retrospective single‐center study from a tertiary care center in India. All patients who underwent surgical exploration after acute corrosive intake between January 2003 and June 2014 were enrolled in the study. Data on patients' presentation, their endoscopic findings, indications of surgery, type of surgery and post‐operative follow‐up was retrieved. Results: Out of 170 patients who presented with acute corrosive ingestion, 24 patients (14.11%) required emergency surgery. The mean interval between ingestion and surgery was 9.92 ± 9.03 days. Presence of peritonitis was the most common indication for surgery (n = 10; 41.7%) followed by mediastinitis (n = 7; 29.2%). A total of 17 resectional and 7 non‐resectional procedures were performed. Thirteen (54%) patients succumbed to their illness post‐operatively due to multi‐organ failure (n = 9), refractory shock (n = 3) or pulmonary thromboembolism (n = 1). Patients with early surgery (≤7 days) after corrosive ingestion had similar mortality compared to patients with late surgery (>7 days) (50% versus 67%; P = 0.30). Of the 11 surviving patients, eight patients (72%) underwent successful reconstructive surgery on follow‐up. Conclusions: Emergency surgery after corrosive ingestion carries high morbidity and mortality. However, after the initial stormy acute phase, majority of patients can undergo successful reconstructive surgery on follow‐up. [ABSTRACT FROM AUTHOR]

Objectives Two new classifications of myeloid neoplasms have recently been published: the International Consensus Classification (ICC) and the 5th edition of the World Health Organization classification (WHO5). We sought to examine the real-world impact of dueling classifications on patient diagnoses. Methods Our institutional pathology database was searched, and 237 specimens with a diagnosis of myeloid neoplasia were randomly selected. For each case, a classification based on the WHO5 and the ICC was assigned. The WHO5 and ICC diagnoses were compared to determine their degree of concordance. Results After applying the WHO5 and ICC diagnostic criteria, 134 (56.5%) cases were classified as concordant, 63 (26.6%) cases had terminological differences, 37 (15.6%) cases had minor diagnostic discrepancies, and 3 (1.3%) cases had major diagnostic discrepancies. Cases with minor diagnostic discrepancies included 25 cases of myelodysplastic syndrome (MDS), 10 cases of acute myeloid leukemia (AML), and 2 cases of myeloid precursor lesions. Cases with major diagnostic discrepancies included 2 cases that were diagnosed as MDS, not otherwise specified (NOS), according to the ICC but classified as AML with NPM1 alteration and AML with RBM15::MRTFA according to the WHO5 and 1 case that was characterized as chronic myelomonocytic leukemia according to the ICC and as AML with NPM1 alteration according to the WHO5. Conclusions This study confirms that a majority of cases are classified similarly using the 2 systems. Given the overall similarity of the systems, future harmonization of the classifications should be pursued to avoid confusion and multiple diagnoses. [ABSTRACT FROM AUTHOR]

Objectives C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are commonly used inflammatory markers. C-reactive protein is more sensitive and specific for monitoring acute inflammation. However, it is commonly co-ordered with ESR despite recommendations against this. Our objective was to reduce unnecessary ESR orders and ESR/CRP co-ordering rates across a large safety net health system. Methods This was a quality improvement project that used a quasi-experimental pre- and postintervention interrupted time-series regression analysis. Patients with a positive COVID-19 test were excluded. We designed a nonintrusive, normative nudge within the ESR order that recommended against co-ordering ESR and CRP. In addition, a best practice advisory triggered when ESR and CRP were simultaneously ordered. The outcome measures were ESR order rates per 1000 patient days in the inpatient setting and per 1000 patient encounters in the outpatient setting, as well as ESR/CRP co-ordering rates. Results Inpatient ESR orders decreased from 12.02 preintervention to 5.61 per 1000 patient days (–53.3%, P <.001). Outpatient ESR orders decreased from 6.09 to 4.07 per 1000 patient encounters (–33.2%, P <.001). Relative co-ordering rates decreased by 50%. Conclusions This electronic health record initiative successfully reduced ESR testing across 11 hospitals and 70 ambulatory centers in a safety net setting. [ABSTRACT FROM AUTHOR]

This position paper provides an overview of the assessment and management of both acute and chronic graft‐versus‐host disease (GvHD). There is a focus on the use of ruxolitinib, a selective inhibitor of Janus kinase (JAK)1 and JAK2, for the treatment of corticosteroid‐refractory and corticosteroid‐dependent GvHD. [ABSTRACT FROM AUTHOR]

Introduction: Acute upper gastrointestinal bleeding is a common cause of emergency department admissions. The standard approach for the diagnosis and treatment of acute upper gastrointestinal bleeding (AUGIB) involves an endoscopy of the upper gastrointestinal tract. While daytime emergency endoscopy has been well studied, there is limited evidence regarding its effectiveness during the nighttime. Patients and Methods: We conducted a retrospective cohort study at a single center, analyzing adult patients with AUGIB referred for emergency endoscopy outside of regular hospital hours. Patients treated with endoscopic hemostatic methods were categorized into day-hours and night-hours groups based on the timing of the gastroscopy. The primary clinical endpoint was 120-day all-cause mortality, with secondary endpoints including hemostasis and recurrence. Results: In the population of 752 enrolled patients with acute upper gastrointestinal bleeding symptoms, 592 had a gastroscopy during the day hours between 8.00 a.m. and 10.00 p.m., while 160 had procedures performed at night between 10:00 p.m. and 8:00 a.m. In the day-hours group, the median time from symptom onset to endoscopy was 10 h (IQR 6–15), compared to 6 h (IQR 4–16) in the night-hours group. The gastroscopy duration (time to reach hemostasis during endoscopy) was significantly shorter during the night hours (p < 0.001). In both groups, endoscopic intervention after the sixth hour from symptom onset yielded improved outcomes, while treatment before the fifth hour resulted in poorer outcomes. Although the night-hours group had higher 120-day all-cause mortality, the difference was not statistically significant. Conclusions: Our findings indicate that emergency therapeutic gastroscopy for acute upper gastrointestinal bleeding is similarly effective during both day and night hours, particularly when performed after the sixth hour from symptom onset. [ABSTRACT FROM AUTHOR]

Older patients are typically underrepresented in clinical trials despite representing a major proportion of the patient population. We aim to describe the feasibility of performing body composition measures, physical function measures, and patient-reported questionnaires within the first 24 hours of admission in a large sample of older acutely admitted medical patients. In addition, we aim to characterize patients with missing measurements. Secondary analyses of cross-sectional data from a cohort study. A total of 1071 acutely admitted patients aged ≥65 years from the acute medical ward at Bispebjerg Hospital, were enrolled within the first 24 hours of hospitalization. Body composition was investigated using direct segmental multifrequency bioelectrical impedance analyses (DSM-BIA) and physical function was assessed using hand grip strength (HGS) and the 30-second sit-to-stand test (STS). The orientation-memory-concentration test (OMC) was used to evaluate the prevalence of cognitive impairments within 24 hours of hospitalization, and the OMC in conjunction with the Strength, Assistance walking, Rise from a chair, Climb stairs, and Falls questionnaire (SARC-F) was used to assess the feasibility of patient-reported outcomes (PROs). Mean age was 78.8 ± 7.8 years (53.0% female). HGS was performed in 96.2% of the enrolled patients, whereas the PRO, 30-second STS, and DSM-BIA were performed in 91.2%, 69.2%, and 59.8% of patients, respectively. The main barrier for performing the 30-second STS and body composition measurements was an inability to mobilize the patient from the hospital bed. The assessment of HGS and PROs show excellent feasibility in clinical research including older patients, even when the patients are enrolled and tested within 24 hours of an acute admission. Assessments of DSM-BIA and the 30-second STS show good feasibility but are less feasible in immobile patients often presenting as more frail, weaker, and cognitively impaired. [ABSTRACT FROM AUTHOR]

Tracheostomy-related respiratory infections are common, though the diagnosis and management can be challenging in children. The goal of this review article was to provide an overview of the current knowledge known about recognizing and treating respiratory infections in this population and to emphasize future areas for further research. While several small and retrospective papers attempt to provide information, there remain more questions than answers. We have reviewed ten published articles to understand this topic, bringing to light significant variation in clinical practices across institutions. While identifying the microbiology is important, it is also crucial to recognize when to treat. Differentiating acute infection, chronic infection, and colonization are important features that influence the treatment of lower respiratory tract infection in children with a tracheostomy. [ABSTRACT FROM AUTHOR]

Copyright of Jurnal Veteriner is the property of Fakultas Kedokteran Hewan, Universitas Udayana and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Toxoplasmosis is a cosmopolitan parasitic infection caused by Toxoplasma gondii which is commonly treated by pyrimethamine (PYR) plus sulfadiazine (SDZ) with several adverse side effects. The present study evaluated the therapeutic effects of Urtica dioica L. aqueous extract (UDE) on acute and chronic toxoplasmosis in mice. Methods: For this purpose, mice were infected with 20 cysts (acute infection) or 10 cysts (chronic infection) of T. gondii (Me49 strain). The mice were treated with 200 mg/kg of UDE intraperitoneally (IP) and intragastric route (IG). The UDE-treated mice were compared with the PYR + SDZ treatment. The histopathological changes, cyst count, total antioxidant capacity (TAC), malondialdehyde (MDA) assay, and serum INF-γ were also evaluated. Results: In the acute toxoplasmosis, UDE by IP and IG administration significantly reduced the number of brain cysts by 93.74 and 92.55%, respectively, and increased the survival rate to 80% compared with 60% in untreated controls. In the chronic infection, cyst burden decreased at 88.2 and 83.4%, respectively, for IP and IG treatments. Moreover, UDE significantly increased INF- γ levels in acute and chronic toxoplasmosis. Tissue inflammatory lesions were reduced in the UDE-treated subgroups compared to the untreated group. UDE treatment significantly reduced MDA levels and elevated TAC in both acute and chronic infections. Conclusion: The results show that U. dioica possesses significant immunostimulant and antioxidant activity with a higher cyst reduction in the brain during acute toxoplasmosis. Further studies are required to investigate the fractionations of UDE against T. gondii and its combination with other standard drugs. [ABSTRACT FROM AUTHOR]

BackgroundImpairments in empathy are well established in anorexia nervosa (AN). It is unclear, however, whether these deficits only occur in the acute phases of AN due to neurocognitive impacts of starvation (often referred to as context-dependent, or state-like), or if deficits remain once remission has been achieved (trait-like). This debate is commonly referred to as the ‘state vs trait’ debate.ObjectiveThis systematic review aims to summarise existing literature regarding empathy in AN, and to investigate whether empathy deficits in AN are state- or trait-based.MethodA total of 1014 articles were identified, and seven articles remained after the screening process. These seven articles, comparing empathy across three groups (acute AN, remission of AN, and non-clinical controls), were evaluated and summarised in accordance with PRISMA guidelines. Articles were required to have included all three groups and report on either cognitive empathy and/or emotional empathy.ResultsThe majority of studies were of satisfactory quality. The results identified were inconsistent, with few articles lending some support to the ‘state’ hypothesis and others producing nonsignificant results.ConclusionsThere is minimal literature comparing empathy in acute and remission phases of AN. While there were some inconsistencies in included articles, some data indicate that there may be slight improvements to emotional and cognitive empathy following recovery of AN. Further research is needed to better enrich knowledge regarding the role of state vs trait with regard to neurocognitive difficulties experienced by individuals with AN.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=335669, identifier CRD42022335669.

Introduction: Distinguishing between ruptured and non-ruptured acute appendicitis presents a significant challenge. This study aimed to validate the accuracy of RAMA-WeRA Risk Score in predicting ruptured appendicitis (RA) in emergency department. Methods: This study was a multicenter diagnostic accuracy study conducted across six hospitals in Thailand from February 1, 2022, to January 20, 2023. The eligibility criteria included individuals aged >15 years suspected of acute appendicitis, presenting to the ED, and having an available pathology report following appendectomy or intraoperative diagnosis by the surgeon. We assessed the screening performance characteristics of RAMA-WeRA Risk Score, in detecting the ruptured appendicitis (RA) cases. Results: 860 patients met the study criteria. 168 (19.38%) had RA and 692 (80.62%) patients had non-RA. The area under the receiver operating characteristic curve (AuROC) of RAMA-WeRA Risk Score was 75.11% (95% CI: 71.10, 79.11). The RAMA-WeRA Risk Score > 6 points (high-risk group) demonstrated a positive likelihood ratio (LR) of 3.22 in detecting the ruptured cases. The sensitivity and specificity of score in > 6 cutoff point was 43.8% (95%CI: 36.2, 51.6) and 86.4% (95%CI: 83.6, 88.9), respectively. Conclusions: The RAMA-WeRA Risk Score can predict rupture in patients presenting with suspected acute appendicitis in the emergency department with total accuracy of 75% for high-risk cases.

IntroductionTraditionally, cancer pain has often been viewed as an independent third major category in pain medicine alongside acute pain and chronic non-cancer pain. However, the new chronic pain category MG30 in the eleventh version of International Classification of Diseases (ICD-11) includes cancer-related pain as one of its seven subgroups. In light of this, the aim of the paper is to investigate whether the traditional trichotomy should be replaced by a dichotomy between acute pain and chronic pain, cancer-related pain being part of both groups depending on the duration of pain.MethodsThe rationale for viewing cancer pain as a separate category is reviewed.ResultsCancer being a deadly disease, cancer pain has a life-and-death and existential dimension that is different from non-cancer pain. It seems sensible to believe that this is an additional dimension to the suffering caused by cancer pain, and that clinicians should therefore take this existential dimension into consideration when assessing pain.ConclusionWithout challenging the place of chronic cancer-related pain under the MG30 heading, it is concluded that while using ICD-11 in the future, pain clinicians should continue being mindful of the fact that the reality of death shapes the experience of cancer pain. The traditional trichotomy is therefore still valid and mirrors the fact that human beings are vulnerable (acute pain), temporal (chronic pain) and mortal (cancer pain).

Abstract Under European Union legislation (Article 32, Regulation (EC) No 396/2005), the European Food Safety Authority provides an annual report assessing the pesticide residue levels in foods on the European market. In 2022, 96.3% of the overall 110,829 samples analysed fell below the maximum residue level (MRL), 3.7% exceeded this level, of which 2.2% were non‐compliant, i.e. results in a given sample exceeded the MRL after taking into account the measurement uncertainty. For the EU‐coordinated multiannual control programme subset, 11,727 samples were analysed of which 0.9% were non‐compliant. To assess acute and chronic risk to consumer health, dietary exposure to pesticide residues was estimated and compared with available health‐based guidance values (HBGV). Continuation of the probabilistic assessment methodology was consolidated to all pesticides listed in the 2022 EU Regulation providing the probability of a consumer being exposed to an exceedance of the HBGV. Overall, the assessed risk to EU consumer's health is low. Recommendations to risk managers are given to increase the effectiveness of European control systems and to ensure a high level of consumer protection throughout the EU.

IntroductionStroke is a detrimental condition associated with long-term functional impairments that restrict community reintegration, which is an indicator of successful post-stroke functional recovery and rehabilitation. Additionally, trunk control is an understudied factor that may contribute to community mobility and participation after stroke. This study aimed to identify predictors of community mobility among stroke survivors in the acute phase, with a primary focus on trunk control, in addition to exploring the mediating and moderating role of predictive factors.MethodsA longitudinal observational study included 61 participants with acute stroke. Trunk control test (TCT) during sitting, stroke severity, quality of life, fear of falls, depression, and age was assessed during the acute phase as potential predictors. The community mobility outcome measure was assessed 3 months after baseline using the Reintegration to Normal Living Index (RNLI). Statistical analyses included correlation, linear regression, mediation, and moderation analyses.ResultsTrunk control test was the strongest predictor of RNLI among all factors (β = 0.72; 95%CI = 0.004–0.007; p ≤ 0.0001). Stroke severity, quality of life, fear of falls, and age significantly predicted RNLI (p

ObjectivesThe diameter, area, and volume of the true lumen and false lumen (FL) have been measured in previous studies to evaluate the extent of DeBakey type I aortic dissection. However, these indicators have limitations because of the irregular shapes of the true and false lumens and the constant oscillation of intimal flap during systole and diastole. The ratio of arch lengths seems to be a more reliable indicator. FL% was defined as the ratio of the arch length of FL to the circumference of the aorta at the different levels of the aorta. The purpose of this article was to investigate whether FL% is a predictor of the severity of acute DeBakey type I aortic dissection in patients undergoing frozen elephant trunk (FET) and total arch replacement.MethodsIn this retrospective observational study, we analyzed a total of 344 patients with acute DeBakey type I aortic dissection that underwent FET and total arch replacement at our center from October 2015 to October 2019. The patients were divided into two groups by cluster analysis according to the perioperative course. Binary logistic regression analyses were performed to determine whether FL% could predict the severity of acute DeBakey type I aortic dissection. The area under the receiver operating characteristic curve (AUROC) was used to assess the power of the multivariate logistic regression model for the severity of acute DeBakey type I aortic dissection.ResultsThe patients in the ultra-high-risk group (109 patients) had significantly more severe clinical comorbidities and complications than the patients in the high-risk group (235 patients). The ascending aortic FL% [odds ratio (OR), 11.929 (95% CI: 1.421–100.11); P = 0.022], location of initial tear [OR, 0.68 (95% CI: 0.47–0.98); P = 0.041], the degree of left iliac artery involvement [OR, 1.95 (95% CI: 1.15–3.30); P = 0.013], and the degree of right coronary artery involvement [OR, 1.46 (95% CI: 1.01–2.12); P = 0.045] on preoperative computed tomography angiography were associated with the severity of acute DeBakey type I aortic dissection. The AUROC value of this multivariate logistic regression analysis was 0.940 (95% CI: 0.914–0.967; P

Abstract is missing (Short communication)

Toxoplasmosis continues to be a prevalent parasitic zoonosis with a global distribution. This disease is caused by an intracellular parasite known as Toxoplasma gondii, and the development of effective novel drug targets to combat it is imperative. There is limited information available on the potential advantages of wheat germ oil (WGO) and propolis, both individually and in combination, against the acute phase of toxoplasmosis. In this study, acute toxoplasmosis was induced in Swiss albino mice, followed by the treatment of infected animals with WGO and propolis, either separately or in combination. After 10 days of experimental infection and treatment, mice from all groups were sacrificed, and their brains, uteri, and kidneys were excised for histopathological assessment. Additionally, the average parasite load in the brain was determined through parasitological assessment, and quantification of the parasite was performed using Real-Time Polymerase Chain Reaction targeting gene amplification. Remarkably, the study found that treating infected animals with wheat germ oil and propolis significantly reduced the parasite load compared to the control group that was infected but not treated. Moreover, the group treated with a combination of wheat germ oil and propolis exhibited a markedly greater reduction in parasitic load compared to the other groups. Similarly, the combination treatment effectively restored the histopathological changes observed in the brain, uterus, and kidney, and the scoring of these reported lesions confirmed these findings. In summary, the present results reveal intriguing insights into the potential therapeutic benefits of wheat germ oil and propolis in the treatment of acute toxoplasmosis.

The genetics of relapsed pediatric acute myeloid leukemia (AML) has yet to be comprehensively defined. Here, we present the spectrum of genomic alterations in 136 relapsed pediatric AMLs. We identified recurrent exon 13 tandem duplications (TD) in upstream binding transcription factor (UBTF) in 9% of relapsed AML cases. UBTF-TD AMLs commonly have normal karyotype or trisomy 8 with cooccurring WT1 mutations or FLT3-ITD but not other known oncogenic fusions. These UBTF-TD events are stable during disease progression and are present in the founding clone. In addition, we observed that UBTF-TD AMLs account for approximately 4% of all de novo pediatric AMLs, are less common in adults, and are associated with poor outcomes and MRD positivity. Expression of UBTF-TD in primary hematopoietic cells is sufficient to enhance serial clonogenic activity and to drive a similar transcriptional program to UBTF-TD AMLs. Collectively, these clinical, genomic, and functional data establish UBTF-TD as a new recurrent mutation in AML.SignificanceWe defined the spectrum of mutations in relapsed pediatric AML and identified UBTF-TDs as a new recurrent genetic alteration. These duplications are more common in children and define a group of AMLs with intermediate-risk cytogenetic abnormalities, FLT3-ITD and WT1 alterations, and are associated with poor outcomes. See related commentary by Hasserjian and Nardi, p. 173. This article is highlighted in the In This Issue feature, p. 171.

Small-molecule FLT3 inhibitors have recently improved clinical outcomes for patients with FLT3-mutant acute myeloid leukemia (AML) after many years of development, but resistance remains an important clinical problem. FF-10101 is the first irreversible, covalent inhibitor of FLT3 which has previously shown activity against FLT3 tyrosine kinase inhibitor resistance-causing FLT3 F691L and D835 mutations. We report that FF-10101 is also active against an expanded panel of clinically identified FLT3 mutations associated with resistance to other FLT3 inhibitors. We also demonstrate that FF-10101 can potentially address resistance mechanisms associated with growth factors present in the bone marrow microenvironment but is vulnerable to mutation at C695, the amino acid required for covalent FLT3 binding. These data suggest that FF-10101 possesses a favorable resistance profile that may contribute to improved single-agent efficacy when used in patients with FLT3-mutant AML.

BackgroundThis study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic.MethodsCHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality.ResultsThis study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121).ConclusionCHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic.

Survival outcomes for relapsed/refractory pediatric acute myeloid leukemia (R/R AML) remain dismal. Epigenetic changes can result in gene expression alterations which are thought to contribute to both leukemogenesis and chemotherapy resistance. We report results from a phase I trial with a dose expansion cohort investigating decitabine and vorinostat in combination with fludarabine, cytarabine, and G-CSF (FLAG) in pediatric patients with R/R AML [NCT02412475]. Thirty-seven patients enrolled with a median age at enrollment of 8.4 (range, 1-20) years. There were no dose limiting toxicities among the enrolled patients, including two patients with Down syndrome. The recommended phase 2 dose of decitabine in combination with vorinostat and FLAG was 10 mg/m2 . The expanded cohort design allowed for an efficacy evaluation and the overall response rate among 35 evaluable patients was 54% (16 complete response (CR) and 3 complete response with incomplete hematologic recovery (CRi)). Ninety percent of responders achieved minimal residual disease (MRD) negativity (

ObjectivesSoluble receptor for advanced glycation end products is a known plasma marker of alveolar epithelial injury. However, RAGE is also expressed on cell types beyond the lung, and its activation leads to up-regulation of pro-inflammatory mediators. We sought to examine the relationship between plasma soluble receptor for advanced glycation end products and primary pulmonary dysfunction, extrapulmonary organ dysfunction, and mortality in pediatric acute respiratory distress syndrome patients at two early time points following acute respiratory distress syndrome diagnosis and compare these results to plasma surfactant protein-D, a marker of pure alveolar epithelial injury.DesignProspective observational study.SettingFive academic PICUs.PatientsTwo hundred fifty-eight pediatric patients 30 days to 18 years old meeting Berlin Criteria for acute respiratory distress syndrome.InterventionsNone.Measurements and main resultsPlasma was collected for soluble receptor for advanced glycation end products and surfactant protein-D measurements within 24 hours (day 1) and 48 to 72 hours (day 3) after acute respiratory distress syndrome diagnosis. Similar to surfactant protein-D, plasma soluble receptor for advanced glycation end products was associated with a higher oxygenation index (p < 0.01) and worse lung injury score (p < 0.001) at the time of acute respiratory distress syndrome diagnosis. However, unlike surfactant protein-D, plasma soluble receptor for advanced glycation end products was associated with worse extrapulmonary Pediatric Logistic Organ Dysfunction score during ICU stay (day 3; p < 0.01) and positively correlated with plasma levels of interleukin-6 (p < 0.01), tumor necrosis factor-α (p < 0.01), and angiopoietin-2 (p < 0.01). Among children with indirect lung injury, plasma soluble receptor for advanced glycation end products was associated with mortality independent of age, sex, race, cancer/bone marrow transplant, and Pediatric Risk of Mortality score (day 3; odds ratio, 3.14; 95% CI, 1.46-6.75; p < 0.01).ConclusionsUnlike surfactant protein-D, which is primarily localized to the alveolar epithelium plasma soluble receptor for advanced glycation end products is systemically expressed and correlates with markers of inflammation, extrapulmonary multiple organ dysfunction, and death in pediatric acute respiratory distress syndrome with indirect lung injury. This suggests that unlike surfactant protein-D, soluble receptor for advanced glycation end products is a multifaceted marker of alveolar injury and increased inflammation and that receptor for advanced glycation end products activation may contribute to the pathogenesis of multiple organ failure among children with indirect acute respiratory distress syndrome.

Effective reinduction regimens are needed for children with relapsed and refractory acute myeloid leukemia (AML), as outcomes remain poor. Therapeutic options are limited in this heavily pretreated patient population, many of whom have reached lifetime recommended doses of anthracycline chemotherapy. The development of effective non-anthracycline-based salvage regimens is crucial to these patients who are at significant risk of life-threatening cardiotoxicity. We previously reported results of a phase 2 trial of a clofarabine-based regimen with topotecan, vinorelbine, and thiotepa (TVTC) in patients with relapsed acute leukemias. Here we report on an expanded bicenter cohort of 33 patients,

MicroRNAs (miRNAs) have been shown to hold prognostic value in acute myeloid leukemia (AML); however, the temporal dynamics of miRNA expression in AML are poorly understood. Using serial samples from a mouse model of AML to generate time-series miRNA sequencing data, we are the first to show that the miRNA transcriptome undergoes state-transition during AML initiation and progression. We modeled AML state-transition as a particle undergoing Brownian motion in a quasi-potential and validated the AML state-space and state-transition model to accurately predict time to AML in an independent cohort of mice. The critical points of the model provided a framework to align samples from mice that developed AML at different rates. Our mathematical approach allowed discovery of dynamic processes involved during AML development and, if translated to humans, has the potential to predict an individual's disease trajectory.

MiR-126 and miR-155 are key microRNAs (miRNAs) that regulate, respectively, hematopoietic cell quiescence and proliferation. Herein we showed that in acute myeloid leukemia (AML), the biogenesis of these two miRNAs is interconnected through a network of regulatory loops driven by the FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD). In fact, FLT3-ITD induces the expression of miR-155 through a noncanonical mechanism of miRNA biogenesis that implicates cytoplasmic Drosha ribonuclease III (DROSHA). In turn, miR-155 down-regulates SH2-containing inositol phosphatase 1 (SHIP1), thereby increasing phosphor-protein kinase B (AKT) that in turn serine-phosphorylates, stabilizes, and activates Sprouty related EVH1 domain containing 1 (SPRED1). Activated SPRED1 inhibits the RAN/XPO5 complex and blocks the nucleus-to-cytoplasm transport of pre-miR-126, which cannot then complete the last steps of biogenesis. The net result is aberrantly low levels of mature miR-126 that allow quiescent leukemia blasts to be recruited into the cell cycle and proliferate. Thus, miR-126 down-regulation in proliferating AML blasts is downstream of FLT3-ITD–dependent miR-155 expression that initiates a complex circuit of concatenated regulatory feedback (i.e., miR-126/SPRED1, miR-155/human dead-box protein 3 [DDX3X]) and feed-forward (i.e., miR-155/SHIP1/AKT/miR-126) regulatory loops that eventually converge into an output signal for leukemic growth.

The phase 3 Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FMS-like Tyrosine Kinase (FLT3) Mutation (ADMIRAL) trial demonstrated the superiority of the FLT3 inhibitor, gilteritinib, to salvage chemotherapy (SC) in patients with FLT3-mutated relapsed or refractory (R/R) AML. Baseline comutations, FLT3-internal tandem duplication (ITD) allelic ratio and length, and treatment-emergent mutations were analyzed in patients in the ADMIRAL trial. Baseline comutations were grouped according to gene subgroups (DNA methylation/hydroxymethylation, transcription, chromatin-spliceosome, receptor tyrosine kinase-Ras signaling, TP53-aneuploidy, NPM1, DNMT3A, DNMT3A/NPM1, WT-1, and IDH1/IDH2). Across all but 1 gene subgroup (TP53-aneuploidy), higher pretransplant response rates and a trend toward longer overall survival were observed with gilteritinib vs SC. Patients with DNMT3A/NPM1 comutations who received gilteritinib had the most favorable outcomes of any molecular subgroup analyzed. Survival outcomes with gilteritinib were not adversely affected by FLT3-ITD allelic ratio, FLT3-ITD length, or multiple FLT3-ITD mutations. Among patients who relapsed on gilteritinib, Ras/mitogen-activated protein kinase (MAPK) pathway and FLT3 F691L gene mutations were the most common mutational events associated with treatment resistance. However, the occurrence of Ras/MAPK pathway gene mutations at baseline did not preclude a clinical benefit from gilteritinib. Acquisition of multiple Ras/MAPK pathway gene mutations at relapse suggests a high level of pathway reactivation is needed to overcome the gilteritinib treatment effect. These findings provide insight into the R/R AML molecular profile and the impact of FLT3 inhibitors on mutational evolution associated with treatment resistance and benefit of gilteritinib across a wide spectrum of molecular and genetic subgroups in FLT3-mutated R/R AML. This trial was registered at www.clinicaltrials.gov as #NCT02421939.

Cancer vaccines are promising treatments to prevent relapse after chemotherapy in acute myeloid leukemia (AML) patients, particularly for those who cannot tolerate intensive consolidation therapies. Here, we report the development of an AML cell membrane-coated nanoparticle (AMCNP) vaccine platform, in which immune-stimulatory adjuvant-loaded nanoparticles are coated with leukemic cell membrane material. This AMCNP vaccination strategy stimulates leukemia-specific immune responses by co-delivering membrane-associated antigens along with adjuvants to antigen-presenting cells. To demonstrate that this AMCNP vaccine enhances leukemia-specific antigen presentation and T cell responses, we modified a murine AML cell line to express membrane-bound chicken ovalbumin as a model antigen. AMCNPs were efficiently acquired by antigen-presenting cells in vitro and in vivo and stimulated antigen cross-presentation. Vaccination with AMCNPs significantly enhanced antigen-specific T cell expansion and effector function compared with control vaccines. Prophylactic vaccination with AMCNPs enhanced cellular immunity and protected against AML challenge. Moreover, in an AML post-remission vaccination model, AMCNP vaccination significantly enhanced survival in comparison to vaccination with whole leukemia cell lysates. Collectively, AMCNPs retained AML-specific antigens, elicited enhanced antigen-specific immune responses, and provided therapeutic benefit against AML challenge.

PurposeThere is limited evidence on the clinical utility of monitoring measurable residual disease (MRD) in patients with acute myeloid leukemia treated with lower-intensity therapy. Herein, we explored the outcomes of patients treated with venetoclax and azacitidine who achieved composite complete remission (CRc; complete remission + complete remission with incomplete hematologic recovery) and MRD < 10-3 in the VIALE-A trial.MethodsThe patients included in this report were treated with venetoclax and azacitidine. Bone marrow aspirate samples for multiparametric flow cytometry assessments were collected for central analysis at baseline, end of cycle 1, and every three cycles thereafter. MRD-negative response was defined as < 1 residual blast per 1,000 leukocytes (< 10-3 or 0.1%) with an estimated analytic sensitivity of 0.0037%-0.0027%. CRc, duration of remission (DoR), event-free survival (EFS), and overall survival (OS) were assessed. A multivariate Cox regression analysis identified prognostic factors associated with OS.ResultsOne hundred sixty-four of one hundred ninety (86%) patients with CRc were evaluable for MRD. MRD < 10-3 was achieved by 67 of 164 (41%), and 97 of 164 (59%) had MRD ≥ 10-3. The median DoR, EFS, and OS were not reached in patients with CRc and MRD < 10-3, and the 12-month estimates for DoR, EFS, and OS in this group were 81.2%, 83.2%, and 94.0%. Among patients with CRc and MRD ≥ 10-3, the median DoR, EFS, and OS were 9.7, 10.6, and 18.7 months. Multivariate analysis showed that CRc with MRD < 10-3 was a strong predictor of OS (adjusted hazard ratio = 0.285; 95% CI, 0.159 to 0.510; P < .001).ConclusionPatients who achieved CRc and MRD < 10-3 with venetoclax and azacitidine had longer DoR, EFS, and OS, than responding patients with MRD ≥ 10-3.

Gene expression profiling and proteome analysis of normal and malignant hematopoietic stem cells (HSCs) point to shared core stemness properties. However, discordance between mRNA and protein signatures highlights an important role for post-transcriptional regulation by microRNAs (miRNAs) in governing this critical nexus. Here, we identify miR-130a as a regulator of HSC self-renewal and differentiation. Enforced expression of miR-130a impairs B lymphoid differentiation and expands long-term HSCs. Integration of protein mass spectrometry and chimeric AGO2 crosslinking and immunoprecipitation (CLIP) identifies TBL1XR1 as a primary miR-130a target, whose loss of function phenocopies miR-130a overexpression. Moreover, we report that miR-130a is highly expressed in t(8;21) acute myeloid leukemia (AML), where it is critical for maintaining the oncogenic molecular program mediated by the AML1-ETO complex. Our study establishes that identification of the comprehensive miRNA targetome within primary cells enables discovery of genes and molecular networks underpinning stemness properties of normal and leukemic cells.

CC-90002 is an anti-CD47 antibody that inhibits CD47-SIRPα interaction and enables macrophage-mediated killing of tumor cells in hematological cancer cell lines. In this first clinical, phase 1, dose-escalation and -expansion study (CC-90002-AML-001; NCT02641002), we evaluated CC-90002 in patients with relapsed/refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS). CC-90002 was administered in escalating doses of 0.1-4.0 mg/kg, using a modified 3 + 3 design. Primary endpoints included dose-limiting toxicities (DLTs), non-tolerated dose (NTD), maximum tolerated dose (MTD), and recommended phase 2 dose. Secondary endpoints included preliminary efficacy, pharmacokinetics, and presence/frequency of anti-drug antibodies (ADAs). Between March 2016 and July 2018, 28 patients were enrolled (24 with AML and 4 with MDS) at 6 sites across the USA. As of July 18, 2018, all patients had discontinued, mainly due to death or progressive disease. The most common treatment-emergent adverse events were diarrhea (46.4%), thrombocytopenia (39.3%), febrile neutropenia (35.7%), and aspartate aminotransferase increase (35.7%). Four patients experienced DLTs (1 patient had grade 4 disseminated intravascular coagulation and grade 5 cerebral hemorrhage, 1 had grade 3 purpura, 1 had grade 4 congestive cardiac failure and grade 5 acute respiratory failure, and another had grade 5 sepsis). The NTD and MTD were not reached. No objective responses occurred. CC-90002 serum exposure was dose-dependent. ADAs were present across all doses, and the proportion of ADA-positive patients in cycle 1 increased over time. Despite no unexpected safety findings, the CC-90002-AML-001 study was discontinued in dose escalation for lack of monotherapy activity and evidence of ADAs. However, as other anti-CD47 agents in clinical trials are showing promising early results for AML and MDS, understanding preclinical and clinical differences between individual agents in this class will be of high importance.

Background: The purpose of this study was to perform a narrative review of acute elbow dislocation (AED). There are certain aspects of the management of AED that are controversial, including type and length of immobilization, indications for surgery, type of surgery, and new evidence available. Material and methods: A literature search was performed using MEDLINE and Embase databases for studies regarding AED. Preference was given to studies according to their level of evidence. Studies regarding the outcome of conservative and surgical treatment, including patient-reported outcomes, complications, and conversion to stabilization or revision surgery were included. Results: We found only 1 level I study and 3 level II randomized clinical trials. The rest consisted of level III-V evidence. Conservative care continues to be the standard of care for stable AEDs. Shorter immobilization periods are favored when possible. A consensus definition of an unstable elbow still needs to be improved. Unstable simple elbow dislocation may benefit from surgical intervention with different techniques showing similar outcomes. Advances in surgical procedures and suture designs, including tapes, and ligament augmentation, need to prove their role in managing acute elbow instability. Conclusion: There is a need for higher quality studies after the reduction of an AED, including discerning the outcome of specific patterns of injury and particular groups of patients like high-level athletes or people with preoperative laxity. Comparison between different surgical techniques is warranted, including arthroscopic techniques and types of ligament augmentation to promote early motion and reduce postoperative stiffness.

Abstract Background Data on the prevalence and clinical impact of extrapulmonary findings at screening computed tomography (CT) on initiation of veno-venous extracorporeal membrane oxygenation (V-V ECMO) are limited. We aimed to identify the prevalence of extrapulmonary findings on screening CT following V-V ECMO initiation. We hypothesized that extrapulmonary findings would influence clinical management and outcome. Methods Retrospective analysis (2011–2021) of admission screening CT including head, abdomen and pelvis with contrast of consecutive patients on initiation of V-V ECMO. CT findings identified by the attending consultant radiologist were extracted. Demographics, admission physiological and laboratory data, clinical decision-making following CT and ECMO ICU mortality were recorded from the electronic medical record. We used multivariable logistic regression and Kaplan–Meier curves to evaluate associations between extrapulmonary findings and ECMO ICU mortality. Results Of the 833 patients receiving V-V ECMO, 761 underwent routine admission CT (91.4%). ECMO ICU length of stay was 19 days (IQR 12–23); ICU mortality at the ECMO centre was 18.9%. An incidental extrapulmonary finding was reported in 227 patients (29.8%), leading to an invasive procedure in 12/227 cases (5.3%) and a change in medical management (mainly in anticoagulation strategy) in 119/227 (52.4%). Extrapulmonary findings associated with mortality were intracranial haemorrhage (OR 2.34 (95% CI 1.31–4.12), cerebral infarction (OR 3.59 (95% CI 1.26–9.86) and colitis (OR 2.80 (95% CI 1.35–5.67). Conclusions Screening CT frequently identifies extrapulmonary findings of clinical significance. Newly detected intracranial haemorrhage, cerebral infarction and colitis were associated with increased ICU mortality.