Search Results for: Sindromi coronariche acute

Stroke, Ahead of Print. BACKGROUND:Studies in individuals with chronic stroke indicate high-intensity training (HIT) focused on walking improves locomotor function, which may be due to repeated activation of locomotor circuits and serotonin-dependent modulation of motor output. Separate studies in animals and individuals with spinal cord injury suggest acute intermittent hypoxia (AIH) can augment the effects of locomotor interventions through similar serotonin-dependent mechanisms, although no studies have coupled AIH with HIT in individuals poststroke. The goal of this study was to evaluate the safety and efficacy of AIH+HIT versus HIT alone in individuals with chronic stroke.METHODS:This phase II double-blind randomized, crossover trial recruited individuals between 18 and 85 years old, >6 months poststroke, and self-selected speeds 75% heart rate reserve. The control condition received normoxia for 30 minutes before HIT. Following the first training phase, participants performed the second phase >1 month later. The primary outcomes were self-selected speed and fastest speed, a 6-minute walk test, and peak treadmill speed. A 3-way mixed-model ANOVA assessed the effects of time, training, and order of interventions.RESULTS:Of 55 individuals screened, 35 were randomized to AIH+HIT or normoxia+HIT first, and 28 individuals completed both interventions, revealing greater gains in self-selected speeds (0.14 [0.08–0.18] versus 0.05 [0.01–0.10] m/s), fastest speed (0.16 [0.10–0.21] versus 0.06 [0.02–0.10] m/s), and peak treadmill speed (0.21 [0.14–0.29] versus 0.11 [0.06–0.16] m/s) following AIH+HIT versus normoxia+HIT (P

Introduction
Branch atheromatous disease (BAD)-related stroke is increasingly becoming a clinical entity and prone to early neurological deterioration (END) and poor prognosis. There are no effective regimens to reduce the disability caused by BAD-related stroke in acute phase. Recent studies have indicated the efficacy of tirofiban in acute ischaemic stroke; however, its efficacy has not been validated in patients with BAD-related stroke. Thus, we aim to test whether intravenous tirofiban initiated within 48 hours after the onset would improve the functional outcome in patients with acute BAD-related stroke, in comparison with the standard antiplatelet therapy based on the current guideline.

Methods and analysis
BRANT is a multicentre, randomised, open-label, blinded endpoint, parallel-controlled, phase III trial conducted in 21 hospitals in China. Participants aged 18–75 years with acute BAD-related stroke within 48 hours after the stroke onset are randomised in a 1:1 ratio to the tirofiban or control group. The treatment period is 48 hours in both groups. The primary outcome is the excellent functional outcome (modified Rankin Scale Score: 0–1) at 90 days. The secondary outcomes include END, major bleeding, stroke, death, functional status, serious adverse events and change in bleeding-related markers. Assuming the rates of the primary outcome to be 74% in the tirofiban group and 62% in the control group, a total of 516 participants are needed for 0.8 power (two-sided 0.05 alpha).

Ethics and dissemination
BRANT study has been approved by the Ethics Committee of the Peking Union Medical College Hospital (I-23PJ1242). Written informed consent is required for all the patients before enrolment. The results of the study will be published in a peer-reviewed journal.

Trial registration number
ClinicalTrials.gov (NCT06037889).

Objective
The objective of this study was to explore the perspectives with the decision-making process between surgery and palliative, non-operative management of geriatric hip fracture patients and their proxies.

Design
A qualitative interview study was performed. Patients and proxies were asked to participate in semi-structured interviews. Data were analysed using reflexive thematic analysis according to Braun and Clarke’s six-step guide.

Setting and participants
Hip fracture patients in the Netherlands were eligible for inclusion. For hip fracture patients with a pre-existing diagnosis of dementia and for patients who opted for palliative, non-operative management, proxies were included.

Results
A total of 16 interviews were conducted, consisting of 4 patient interviews and 12 proxy interviews. Five themes were identified during thematic analysis: (1) underlying patient values, (2) the provision of information, (3) reasons to consider either palliative, non-operative management or surgery, (4) involvement in decision and (5) realisation of expectations. Information provided by the physician varied in terms of desired level of detail but involved discussing the advantages and disadvantages of surgery and palliative, non-operative management. Patients and proxies underscored the importance of achieving optimal quality of life, and the disparity between expected and actual treatment outcomes was unpleasant and negatively influenced the overall experience.

Conclusions
In-depth analysis provided a unique insight into the patient and proxy perspectives in shared decision-making for geriatric hip fracture management in the acute setting. Overall, there were differences between reported experiences and preferences of participants. This heterogeneity stresses the importance of keeping a person-centred approach during shared decision-making. Other key considerations during shared decision-making include physicians informing patients from professional experience and communicating sensitively about both treatment options and prognosis. Physicians should aim to provide realistic, sensitive and timely information to both patients and proxies during the choice between curation and palliation for their hip fracture.

Objectives
This study aims to investigate the diagnostic value of heparin-binding protein (HBP) in sepsis and develop a sepsis diagnostic model incorporating HBP with key biomarkers and disease-related scores for rapid, and accurate diagnosis of sepsis in the intensive care unit (ICU).

Design
Clinical retrospective cross-sectional study.

Setting
A comprehensive teaching tertiary hospital in China.

Participants
Adult patients (aged ≥18 years) who underwent HBP testing or whose blood samples were collected when admitted to the ICU.

Main outcome measures
HBP, C reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), interleukin-6 (IL-6), lactate (LAC), Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) score were recorded.

Results
Between March 2019 and December 2021, 326 patients were enrolled in this study. The patients were categorised into a non-infection group (control group), infection group, sepsis group and septic shock group based on the final diagnosis. The HBP levels in the sepsis group and septic shock group were 45.7 and 69.0 ng/mL, respectively, which were significantly higher than those in the control group (18.0 ng/mL) and infection group (24.0 ng/mL) (p

Introduction
There is a lack of distinct and measurable outcomes in psychiatric and/or mental health nursing which negatively impacts guiding clinical practice, assessing evidence-based nursing interventions, ensuring future-proof nursing education and establishing visibility as a profession and discipline. Psychiatric and/or mental health nursing struggle to demonstrate patient-reported outcomes to assess the effectiveness of their practice. A systematic review that summarising patient-reported outcomes, associated factors, measured nursing care/interventions and used measurement scales of psychiatric and/or mental health nursing in the adult population in acute, intensive and forensic psychiatric wards in hospitals will capture important information on how care can be improved by better understanding what matters and what is important to patients themselves. This review can contribute to the design, planning, delivery and assessment of the quality of current and future nursing care

Methods and analysis
This protocol follows the Cochrane methodological guidance on systematic reviews of interventions and The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol. The search strategy will be identified by consultations with clinical and methodological experts and by exploring the literature. The databases Ovid MEDLINE, CINAHL, EMBASE, APA PsychARTICLES, Web of Science and Scopus will be searched for all published studies. Studies will be screened and selected with criteria described in the population, intervention, control and outcomes format after a pilot test by two researchers. Studies will be screened in two stages: (1) title and abstract screening and (2) full-text screening. Data extraction and the quality assessment based on the Johanna Briggs Institute guidelines will be conducted by two researchers. Data will be presented in a narrative synthesis.

Ethics and dissemination
No ethical approval is needed since all data are already publicly accessible. The results of this work will be published in a peer-reviewed scientific journal.

PROSPERO registration number
CRD42023363806.

Objective
Targeting bacterial translocation in cirrhosis is limited to antibiotics with risk of antimicrobial resistance. This study explored the therapeutic potential of a non-absorbable, gut-restricted, engineered carbon bead adsorbent, Yaq-001 in models of cirrhosis and acute-on-chronic liver failure (ACLF) and, its safety and tolerability in a clinical trial in cirrhosis.

Design
Performance of Yaq-001 was evaluated in vitro. Two-rat models of cirrhosis and ACLF, (4 weeks, bile duct ligation with or without lipopolysaccharide), receiving Yaq-001 for 2 weeks; and two-mouse models of cirrhosis (6-week and 12-week carbon tetrachloride (CCl4)) receiving Yaq-001 for 6 weeks were studied. Organ and immune function, gut permeability, transcriptomics, microbiome composition and metabolomics were analysed. The effect of faecal water on gut permeability from animal models was evaluated on intestinal organoids. A multicentre, double-blind, randomised, placebo-controlled clinical trial in 28 patients with cirrhosis, administered 4 gr/day Yaq-001 for 3 months was performed.

Results
Yaq-001 exhibited rapid adsorption kinetics for endotoxin. In vivo, Yaq-001 reduced liver injury, progression of fibrosis, portal hypertension, renal dysfunction and mortality of ACLF animals significantly. Significant impact on severity of endotoxaemia, hyperammonaemia, liver cell death, systemic inflammation and organ transcriptomics with variable modulation of inflammation, cell death and senescence in the liver, kidneys, brain and colon was observed. Yaq-001 reduced gut permeability in the organoids and impacted positively on the microbiome composition and metabolism. Yaq-001 regulated as a device met its primary endpoint of safety and tolerability in the clinical trial.

Conclusions
This study provides strong preclinical rationale and safety in patients with cirrhosis to allow clinical translation.

Trial registration number
NCT03202498.

Objective
Currently, there is no cure for chronic pancreatitis (CP). Germline loss-of-function variants in SPINK1 (encoding trypsin inhibitor) are common in patients with CP and are associated with acute attacks and progression of the disease. This preclinical study was conducted to explore the potential of adeno-associated virus type 8 (AAV8)-mediated overexpression of human SPINK1 (hSPINK1) for pancreatitis therapy in mice.

Design
A capsid-optimised AAV8-mediated hSPINK1 expression vector (AAV8-hSPINK1) to target the pancreas was constructed. Mice were treated with AAV8-hSPINK1 by intraperitoneal injection. Pancreatic transduction efficiency and safety of AAV8-hSPINK1 were dynamically evaluated in infected mice. The effectiveness of AAV8-hSPINK1 on pancreatitis prevention and treatment was studied in three mouse models (caerulein-induced pancreatitis, pancreatic duct ligation and Spink1 c.194+2T >C mouse models).

Results
The constructed AAV8-hSPINK1 vector specifically and safely targeted the pancreas, had low organ tropism for the heart, lungs, spleen, liver and kidneys and had a high transduction efficiency (the optimal expression dose was 2×1011 vg/animal). The expression and efficacy of hSPINK1 peaked at 4 weeks after injection and remained at significant level for up to at least 8 weeks. In all three mouse models, a single dose of AAV8-hSPINK1 before disease onset significantly alleviated the severity of pancreatitis, reduced the progression of fibrosis, decreased the levels of apoptosis and autophagy in the pancreas and accelerated the pancreatitis recovery process.

Conclusion
One-time injection of AAV8-hSPINK1 safely targets the pancreas with high transduction efficiency and effectively ameliorates pancreatitis phenotypes in mice. This approach is promising for the prevention and treatment of CP.

Postprandial, or meal-related, symptoms, such as abdominal pain, early satiation, fullness or bloating, are often reported by patients with disorders of gut-brain interaction, including functional dyspepsia (FD) or irritable bowel syndrome (IBS). We propose that postprandial symptoms arise via a distinct pathophysiological process. A physiological or psychological insult, for example, acute enteric infection, leads to loss of tolerance to a previously tolerated oral food antigen. This enables interaction of both the microbiota and the food antigen itself with the immune system, causing a localised immunological response, with activation of eosinophils and mast cells, and release of inflammatory mediators, including histamine and cytokines. These have more widespread systemic effects, including triggering nociceptive nerves and altering mood. Dietary interventions, including a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols, elimination of potential food antigens or gluten, IgG food sensitivity diets or salicylate restriction may benefit some patients with IBS or FD. This could be because the restriction of these foods or dietary components modulates this pathophysiological process. Similarly, drugs including proton pump inhibitors, histamine-receptor antagonists, mast cell stabilisers or even tricyclic or tetracyclic antidepressants, which have anti-histaminergic actions, all of which are potential treatments for FD and IBS, act on one or more of these mechanisms. It seems unlikely that food antigens driving intestinal immune activation are the entire explanation for postprandial symptoms in FD and IBS. In others, fermentation of intestinal carbohydrates, with gas release altering reflex responses, adverse reactions to food chemicals, central mechanisms or nocebo effects may dominate. However, if the concept that postprandial symptoms arise from food antigens driving an immune response in the gastrointestinal tract in a subset of patients is correct, it is paradigm-shifting, because if the choice of treatment were based on one or more of these therapeutic targets, patient outcomes may be improved.

Introduction
Approximately 40% of children with diabetic ketoacidosis (DKA) develop acute kidney injury (AKI), which increases the risk of chronic kidney damage. At present, there is limited knowledge of racial or ethnic differences in diabetes-related kidney injury in children with diabetes. Understanding whether such differences exist will provide a foundation for addressing disparities in diabetes care that may continue into adulthood. Further, it is currently unclear which children are at risk to develop worsening or sustained DKA-related AKI. The primary aim is to determine whether race and ethnicity are associated with DKA-related AKI. The secondary aim is to determine factors associated with sustained AKI in children with DKA.

Methods and analysis
This retrospective, multicentre, cross-sectional study of children with type 1 or type 2 diabetes with DKA will be conducted through the Paediatric Emergency Medicine Collaborative Research Committee. Children aged 2–18 years who were treated in a participating emergency department between 1 January 2020 and 31 December 2023 will be included. Children with non-ketotic hyperglycaemic-hyperosmolar state or who were transferred from an outside facility will be excluded. The relevant predictor is race and ethnicity. The primary outcome is the presence of AKI, defined by Kidney Disease: Improving Global Outcomes criteria. The secondary outcome is ‘sustained’ AKI, defined as having AKI ≥48 hours, unresolved AKI at last creatinine measurement or need for renal replacement therapy. Statistical inference of the associations between predictors (ie, race and ethnicity) and outcomes (ie, AKI and sustained AKI) will use random effects regression models, accounting for hospital variation and clustering.

Ethics and dissemination
The Institutional Review Board of Children’s Minnesota approved this study. 12 additional sites have obtained institutional review board approval, and all sites will obtain local approval prior to participation. Results will be presented at local or national conferences and for publication in peer-reviewed journals.

In Reply We thank Drs Schoenmakers and Fraser for their comments on our study. We reported the US experience with denosumab administration among dialysis-dependent patients, finding the weighted cumulative incidence of severe hypocalcemia (ie,

In this issue of JAMA, Jabbour and colleagues report results from the interim analysis of the PhALLCON randomized trial with ponatinib vs imatinib, combined with reduced-intensity chemotherapy. They found ponatinib to have superior efficacy and a comparable safety profile for frontline treatment of adults with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL). On the heels of these results, the US Food and Drug Administration granted ponatinib accelerated approval for this indication on March 19, 2024.

This randomized trial assesses the effect of ponatinib vs imatinib combined with low-intensity chemotherapy on disease remission in adults with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia (ALL).

Introduction
Intraoperative opioids have been used for decades to reduce negative responses to nociception. However, opioids may have several, and sometimes serious, adverse effects. Cardiac surgery exposes patients to a high risk of postoperative complications, some of which are common to those caused by opioids: acute respiratory failure, postoperative cognitive dysfunction, postoperative ileus (POI) or death. An opioid-free anaesthesia (OFA) strategy, based on the use of dexmedetomidine and lidocaine, may limit these adverse effects, but no randomised trials on this issue have been published in cardiac surgery.
We hypothesised that OFA versus opioid-based anaesthesia (OBA) may reduce the incidence of major opioid-related complications after cardiac surgery.

Methods and analysis
Multicentre, randomised, parallel and single-blinded clinical trial in four cardiac surgical centres in France, including 268 patients scheduled for coronary artery bypass grafting under cardiac bypass, with or without aortic valve replacement. Patients will be randomised to either a control OBA protocol using remifentanil or an OFA protocol using dexmedetomidine/lidocaine. The primary composite endpoint is the occurrence of at least one of the following: (1) postoperative cognitive disorder evaluated by the Confusion Assessment Method for the Intensive Care Unit test, (2) POI, (3) acute respiratory distress or (4) death within the first 48 postoperative hours. Secondary endpoints are postoperative pain, morphine consumption, nausea–vomiting, shock, acute kidney injury, atrioventricular block, pneumonia and length of hospital stay.

Ethics and dissemination
This trial has been approved by an independent ethics committee (Comité de Protection des Personnes Ouest III–Angers on 23 February 2021). Results will be submitted in international journals for peer reviewing.

Trial registration number
NCT04940689, EudraCT 2020-002126-90.

This case series reports durable remissions in 2 patients with relapsed/refractory B-cell acute lymphoblastic leukemia treated with allogeneic bispecific CD19/CD22-targeting chimeric antigen receptor T cells.

In this issue of JAMA Internal Medicine, Woodruff et al present a cross-sectional study of patients 50 years and older who were hospitalized and tested positive for respiratory syncytial virus (RSV), reporting that 22% experienced an acute cardiac event, including acute exacerbation of heart failure or myocardial injury. The already high in-hospital mortality rate of 5% for older adults with RSV-associated hospitalizations was doubled among those experiencing a concurrent acute cardiac event.

This nonrandomized controlled trial investigates the acute toxic effects of treatment with hypofractionated pelvic intensity-modulated radiotherapy and concurrent chemotherapy among women who experienced lymph node metastasis, parametrial invasion, or positive resection margins after radical hysterectomy for treatment of confirmed cervical cancer.