Acute Deterioration Research Articles

643 THE HEART WAS MADE TO BE BROKEN: RECURRENT TAKOTSUBO SYNDROME IN AMYOTROPHIC LATERAL SCLEROSIS

Abstract Takotsubo syndrome (TTS) is a rare cardiac disease, characterized by transient regional wall motion abnormalities without evidence of obstructive coronary artery stenoses, mainly triggered by emotion or physical stressors. Reverse Takotsubo syndrome (rTTS), an atypical variant with basal segments involvement, is frequently associated with neurological disorders, including patients with amyotrophic lateral sclerosis (ALS). We reported the case of a 54 years old woman who experienced two consecutive episodes of TTS with different wall motion patterns, complicated by a recurrent episode and arrhythmic events. A Caucasian woman, affected by ALS, was hospitalized in our department due to anemia and recurrent episodes of hematochezia. Following a week of relative clinical stability, the patient experienced acute deterioration with generalized malaise and worsening dyspnea. CT scan excluded pulmonary causes, whereas EKG (ST segment depression in the lower and lateral leads), blood test (increase in high-sensitive cardiac troponins) and TTE (severe impairment of LVEF, with akinesia of basal segments) revealed a cardiac etiology. Coronary angiography and left ventriculography were performed, documenting a wall motion pattern consistent with rTTS. After an initial management in intensive care unit, clinical stability was obtained with a complete recovery of left ventricular systolic function. The patient was discharged but one month later, due to bacterial pneumonia, she was readmitted in our ward and antibiotic therapy was started. Two days later an acute deterioration of clinical status occurred, characterized by dyspnea, altered state of consciousness and marked hypotension. TTE revealed a severe left ventricular systolic dysfunction with apical akinesia and preserved contractility of basal segments, so a diagnosis of typical TTS was made. Three weeks later the clinical scenario became more complicated due to advanced atrioventricular block, with phases of atrioventricular dissociation and ventricular escape-rhythm. Therefore, in light of the increased risk of infectious complications, she underwent implantation of a leadless pacemaker (PMK). This clinical case represents the first report of recurrent episodes of TTS, one of which as rTTS, in a patient affected by ALS. It is worth noting that the first episode of TTS had atypical clinical presentation (dyspnea without chest pain), the EKG showed diffuse ST-segment depression (totally different from classical TTS typical electrocardiographic alterations), and TTE confirmed a different phenotype of segment involvement (unsurprisingly InterTAK Diagnostic Score was low). TTS recurrence is an extremely rare event, even if in this case there were two well defined triggers such as anemia and pneumonia. On the other hand it is reasonable to think that non-use of BBs after the first episode may have contributed to the occurrence of the next event, affecting different segments compared to the previous episode. Furthermore, advanced atrioventricular (AV) block represents a rare complication of TTS, most probably due to catecholamine stress or increased vagal tone, often requiring PMK implantation. In conclusion TTS represents an important frequent cardiac complication in patients affected by ALS, often still underdiagnosed. Therefore clinicians must keep their guard up with TTS, especially in the cases with atypical clinical presentation.

1235: ABBCC8 (SULFONYLUREA RECEPTOR 1) KO CONFERS NEUROPROTECTION IN SEPSIS-ASSOCIATED BRAIN INJURY

Introduction: Sepsis-Associated Brain Injury (SABI) Is Characterized by an Acute Deterioration of Mental Status Resulting in Cognitive Impairment and Acquisition of New and Persistent Functional Limitations in Sepsis Survivors. Previously, We Reported That Septic Mice Had Evidence of Axonal Injury, Robust Microglial Activation, and Cytotoxic Edema in the Cerebral Cortex, Thalamus, and Hippocampus in the Absence of Blood-Brain Barrier Disruption. In Central Nervous System Injury, Sulfonylurea Receptor 1 (SUR1), a Member of the Adenosine Triphosphate (ATP)-Binding Cassette Protein Superfamily, Associates With the Transient Receptor Potential Melastatin 4 (TRPM4) Cation Channel to Play a Crucial Role in Cerebral Edema Development. Therefore, We Hypothesized That Knockout (KO) of Abcc8 (Sur1 Gene) Is Associated With a Decrease in Microglial Activation, Cerebral Edema, and Improved Neurobehavioral Outcomes in a Murine Cecal Ligation and Puncture (CLP) Model of Sepsis. Methods: Sepsis Was Induced in 4-6-Week-Old Abcc8 KO and Wild-Type (WT) Littermate Control Male Mice by CLP. We Used Immunohistochemistry to Define Microglial Activation Along With Parallel Studies Using Magnetic Resonance Imaging, Focusing on Cerebral Edema on Days 1 and 4 Days After CLP. Results: Abcc8 KO Mice Exhibited a Decrease in Axonal Injury and Cytotoxic Edema vs. WT on Day 1. Abcc8 KO Mice Also Had Decreased Microglial Activation in the Cerebral Cortex vs WT. These Findings Were Associated With Cognitive Improvement on Days 7–8 After CLP. Conclusions: Our Study Challenges a Key Concept in Sepsis and Suggests That Brain Injury Does Not Merely Happen as an Extension of Systemic Inflammation, but Upregulation of the SUR1-TRPM4 Channel in the Brain Directly Contributes to the CNS Pathobiology Previously Demonstrated. Benefits Conferred by Abcc8 KO in the Murine CLP Model Warrant Studies of Pharmacological Abcc8 Inhibition as a New Potential Therapeutic Strategy for SABI.

Progressive pulmonary fibrosis: an expert group consensus statement.

This expert group consensus statement emphasises the need for standardising the definition of progressive fibrosing interstitial lung diseases (F-ILDs), with an accurate initial diagnosis being of paramount importance in ensuring appropriate initial management. Equally, case-by-case decisions on monitoring and management are essential, given the varying presentations of F-ILDs and the varying rates of progression. The value of diagnostic tests in risk stratification at presentation and, separately, the importance of a logical monitoring strategy, tailored to manage the risk of progression, are also stressed. The term "progressive pulmonary fibrosis" (PPF) exactly describes the entity that clinicians often face in practice. The importance of using antifibrotic therapy early in PPF (once initial management has failed to prevent progression) is increasingly supported by evidence. Artificial intelligence software for high-resolution computed tomography analysis, although an exciting tool for the future, awaits validation. Guidance is provided on pulmonary rehabilitation, oxygen and the use of non-invasive ventilation focused specifically on the needs of ILD patients with progressive disease. PPF should be differentiated from acute deterioration due to drug-induced lung toxicity or other forms of acute exacerbations. Referral criteria for a lung transplant are discussed and applied to patient needs in severe diseases where transplantation is not realistic, either due to access limitations or transplantation contraindications. In conclusion, expert group consensus guidance is provided on the diagnosis, treatment and monitoring of F-ILDs with specific focus on the recognition of PPF and the management of pulmonary fibrosis progressing despite initial management.

Prolonged neurologic deficits with brain MRI changes following ECT in an adolescent with a CACNA1a-related disorder; a case report

Electroconvulsive therapy is used to treat depression and schizophrenia with infrequent use in pediatric patients. We report a case of an adolescent with autism spectrum disorder and acute catatonia that presented with status epilepticus (SE) and prolonged neurologic deficits with unilateral left cerebral edema on imaging following unilateral electroconvulsive therapy (ECT) on the right side, subsequently found to have a CACNA1a pathogenic variant. This case highlights a potential adverse effect of ECT in patients with CACNA1a related disorders. The patient received unilateral ECT to the right side and subsequently had an episode of SE with right-sided hemiplegia for 72h prior to regaining some function with persistent mild right-hand weakness that persisted for at least 1-2weeks. A brain MRI 2days after ECT was unremarkable, but a repeat MRI on day four of admission showed left hemisphere cortical diffusion restriction, increased perfusion and T2 prolongation suggestive of cortical edema. They had whole exome genetic testing sent after discharge that showed a known pathogenic CACNA1a variant (p.I1709T). CACNA1a encodes the P/Q type calcium channels and deleterious variants in this gene result in a channelopathy associated with a spectrum of neurodevelopmental disorders that include autism spectrum disorder, hemiplegic migraine with unilateral cerebral edema, epileptic encephalopathies, or episodic ataxia syndromes. A literature review of ECT and neurologic deficits showed that most neurologic deficits resolve within 30min of ECT. Case reports of prolonged deficits are rare and there are no prior reports of acute MRI changes related to ECT. Thus, the acute deterioration and MRI findings in this patient are likely related to the underlying CACNA1a channelopathy disorder with ECT as a precipitating event. This case report suggests care should be taken when using ECT in patients with pathogenic variants in CACNA1a. Furthermore, it reinforces the utility and importance of expanded genetic testing in patients with neurodevelopmental disorders as findings can provide valuable information that can guide treatment decisions.

The Safety of Direct Oral Anticoagulants Compared to Warfarin in Patients Hospitalized With Acute Kidney Injury.

Direct oral anticoagulants (DOACs) are preferred over warfarin for many indications, though their safety has not been well established in patients with acute renal impairment. The purpose of this study was to evaluate the frequency of bleeding complications associated with DOACs compared with warfarin in patients admitted to the hospital with acute kidney injury (AKI). This was a retrospective cohort study evaluating patients admitted to the Penn Medicine Lancaster General Hospital with a diagnosis of AKI from October 2017 through September 2021 and receiving therapy with oral anticoagulants. Comparing DOACs with warfarin, the primary endpoint was the percent frequency of composite major and minor bleeding during the admission and within 30 days of discharge. There were 112 hospitalization encounters included in the study. Of these, 42 (37.5%) patients were receiving warfarin and 70 (62.5%) patients were receiving DOAC therapy before admission. There was a higher frequency of the primary endpoint of bleeding in patients receiving DOACs as compared with warfarin, though this was not statistically significant (18.5% vs. 11.9%, respectively, P = 0.432). There were no differences between groups in the frequency of major bleeding, minor bleeding, or transfusions. Patients receiving DOAC therapy were more likely to experience anticoagulation-related readmissions or emergency department visits compared with patients on warfarin therapy (11.4% vs. 0%, P = 0.024). Direct oral anticoagulants and warfarin were associated with statistically similar rates of bleeding in patients presenting with AKI. Further research is necessary to elucidate if DOACs are safer than warfarin in this patient population.

The Australian New Zealand Spontaneous Coronary Artery Dissection (ANZ-SCAD) Registry - A Multi-Centre Cohort Study: Protocol, Background and Significance.

Spontaneous coronary artery dissection (SCAD) is an under-recognised cause of acute coronary syndrome (ACS) with a strong female predominance. There are currently limited prospective studies and no randomised controlled trials that inform on SCAD's best clinical care. Little is also known about predictors of acute SCAD deterioration or recurrence. We describe the study design of a multi-centre prospective and historical cohort study recruiting patients with SCAD across 15-20 sites in Australia/New Zealand (NZ). The primary aim is to describe the clinical presentation, management and outcomes along with predictors of acute deterioration and recurrence in a large Australian/NZ SCAD cohort, with international data pooling. Consented patients diagnosed with SCAD during a hospital admission for an ACS will be prospectively followed at 30 days then yearly, for up to 5 years. Each recruiting site will also retrospectively identify historical cases of SCAD from the proceeding 10 years, with a waiver of consent. For historical cases, data will be collected in a de-identified manner with date of last follow-up or death obtained from the medical records. All cases undergo core laboratory adjudication of coronary angiography and any accompanying imaging to confirm SCAD diagnosis. The primary endpoint will be occurrence of major adverse cardiovascular events; a composite of all-cause mortality, recurrent myocardial infarction (including SCAD recurrence), stroke/transient ischaemic attack, heart failure, cardiogenic shock, cardiac arrest/ventricular arrhythmia, heart transplantation and, repeat/unplanned revascularisation. Secondary endpoints will include each individual primary outcome as well as acute SCAD extension and quality of life/Seattle Angina Score in prospectively recruited participants. Endpoints will be assessed at the end of the hospital admission and at 30-days, 1 year, and median long-term follow-up. Multicentre ethics approval has been granted from the Western Sydney Local Health District Human Research Ethics Committee (2021/ETH00040). The analysed results will be published in peer-reviewed journals on completion of the historical data collection and then on completion of the prospective data collection. The ANZ-SCAD registry has been prospectively registered with the Australia and New Zealand Clinical Trials Registry (ACTRN12621000824864).

Benefits of Robotic Assisted vs. Traditional Laparoscopic Partial Nephrectomy: A Single Surgeon Comparative Study

The current study aims to compare peri-operative and post-operative outcomes between robotic assisted vs. laparoscopic partial nephrectomy. Multiple reviews of the current literature have detailed the lack of single surgeon studies in this domain. To limit inter-operator bias, we utilise a single surgeon experienced in both approaches to reduce this bias seen in other multi-centre studies. We retrospectively compared patient demographics, tumour characteristics, peri-operative and post-operative outcomes of all partial nephrectomies undertaken by a single surgeon between 2014 and 2021 with experience in both laparoscopic and robotic surgery. The Da Vinci surgical system was utilized. Statistical analysis was carried out using GraphPad prism software version 7.03, San Diego, CA, USA. Warm ischemia time was reduced by 2.6 min, length of stay reduced by 1.3 days and acute renal function deterioration was reduced by 55% with all these results being significant with robotic assisted partial nephrectomy compared to laparoscopic partial nephrectomy. This study highlights the benefits of robotic assisted in comparison to laparoscopic partial nephrectomy. Further large-scale prospective studies and cost-benefit analysis of robotic assisted partial nephrectomy would be valuable in confirming these findings and justifying the usage against their financial cost.

Clinical Decision-Making in Practice with New Critical Care Ultrasound Methods for Assessing Respiratory Function and Haemodynamics in Critically Ill Patients.

Situations often arise in intensive care units (ICUs) for which only sparse primary evidence or guidelines are applicable or to which existing evidence cannot be applied owing to interactions of multiple disease states. To improve and guide intensive care management in complex scenarios, ultrasonography and echocardiography are invaluable. In five clinical scenarios involving acute deterioration, serial ultrasound examinations of the respiratory system, general critical care ultrasound (GCCUS), and non-invasive haemodynamic critical care echocardiography (CCE) were used routinely. Ultrasonographic results were used to guide further management and initiate experimental therapy or transition from curative to supportive care. The process of initiation of ultrasound examinations to clinical decision-making in these complex scenarios is outlined. These case vignettes highlight the utility of ultrasound and echocardiography. When clinical management is not clear, or evidence is not available, the use of ultrasound for the evaluation of the respiratory system, GCCUS, and non-invasive haemodynamic CCE can help to guide management, reveal newly developed pathologies, lead to clinical management changes, and support the decision for employing experimental therapy approaches in a dynamic way of which few other imaging modalities or monitoring tools are currently capable.

Ethical Prioritization of Patients to CAR T-Cell Therapies: Tool Development and Process

Introduction: CAR T-cell therapy is a novel and expensive anti-cancer treatment marked by limited availability and an expanding eligible patient population. This situation requires an ethical framework and priority-setting process to guide fair allocation of limited healthcare resources. The purpose of this health services and quality initiative was to develop an ethical prioritization tool to support oncology clinicians in making fair and equitable decisions about patient prioritization to CAR T-cell therapies. Methods: Accountability for reasonableness (A4R) is a well-developed ethical approach to resource allocation when there are values-disagreements between stakeholders about the principles that should govern priority setting. A4R supports a democratic decision-making process, enabling stakeholders to agree on what is legitimate and fair, rather than articulating principles that should govern decision-making a priori. Key elements of the process include: transparency about the rationale for decisions, rationales and evidence that all can accept as relevant to meeting health needs fairly, and procedures for revisiting decisions. Following the A4R approach, we engaged a strong multi-disciplinary team to form a CAR T-cell therapy Ethics Working Group that included physicians, nurses, patients, coordinators, social work, managers, operations, flow, quality, bioethics, and fellows/trainees. Stakeholders from the myeloma, lymphoma and leukemia programs were represented. Through two deliberative events and one patient focus group we established an ethical framework, prioritization tools based on the ethical framework, and an assessment process to support fair and equitable decision making. Results: Stakeholders agreed the following ethical principles are relevant to the decision-making process: beneficence, non-maleficence, equity/consistency, stewardship, autonomy, evidence-informed, and utility. Beneficence and non-maleficence were identified as inherent to the process and equity/consistency and stewardship were also identified as extremely important, especially as more patients become eligible for CAR-T cell therapy. Stakeholders then identified prioritization criteria and categorized them into four major themes: medical benefit, safety/risk of complications, medical urgency, and psychosocial factors. Although the relative weights were not determined, the sequence of application of these criteria were deemed important. Determination of medical benefit was primary, as no patient should proceed further if they did not have any potential for medical benefit. Safety/Risk and psychosocial evaluation would follow using existing tools (e.g., ECOG) and allowing for summative objectives, when possible. Lastly, medical urgency as defined by rapid pace of disease progression, refractoriness to prior therapy, and development of serious disease-related complications, was considered critical in prioritizing patients for therapy. However, stakeholders agreed and cautioned that medical urgency does not equate medical benefit, as patients with rapidly expanding disease and acute deterioration frequently have dismal outcomes, despite all attempts to expedite their treatment course. Recognizing the importance of sequencing in the assessment of criteria, stakeholders developed a 3-Step assessment process: (1) Medical Benefit Assessment, (2) Safety/Risk and Psychosocial Assessment and (3) referral to the Cell Therapy Review Committee for review and prioritization based on medical urgency. Patients who may gain medical benefit, have reasonable risk of toxicity, and have adequate psychosocial capacity and support from Steps 1 and 2, proceed to 3 where consensus decisions are documented on an existing intake form. Conclusions: An ethical framework to support CAR T-cell priority-setting is necessary to ensure transparent and equitable decision making, thus allowing fair patient access to these important therapies. It also enhances the cancer care experience for all by promoting public trust and confidence in the healthcare system and therapeutic relationships by ensuring that decisions are based on sound rationales and that individual clinician biases are minimized.

Predicting the survival benefit of liver transplantation in HBV-related acute-on-chronic liver failure: an observational cohort study

Liver transplantation (LT) is an effective therapy for acute-on-chronic liver failure (ACLF) but is limited by organ shortages. We aimed to identify an appropriate score for predicting the survival benefit of LT in HBV-related ACLF patients. Hospitalized patients with acute deterioration of HBV-related chronic liver disease (n=4577) from the Chinese Group on the Study of Severe Hepatitis B (COSSH) open cohort were enrolled to evaluate the performance of five commonly used scores for predicting the prognosis and transplant survival benefit. The survival benefit rate was calculated to reflect the extended rate of the expected lifetime with vs. without LT. In total, 368 HBV-ACLF patients received LT. They showed significantly higher 1-year survival than those on the waitlist in both the entire HBV-ACLF cohort (77.2%/52.3%, p<0.001) and the propensity score matching cohort (77.2%/27.6%, p<0.001). The area under the receiver operating characteristic curve (AUROC) showed that the COSSH-ACLF II score performed best (AUROC 0.849) at identifying the 1-year risk of death on the waitlist and best (AUROC 0.864) at predicting 1-year outcome post-LT (COSSH-ACLFs/CLIF-C ACLFs/MELDs/MELD-Nas: AUROC 0.835/0.825/0.796/0.781; all p<0.05). The C-indexes confirmed the high predictive value of COSSH-ACLF IIs. Survival benefit rate analyses showed that patients with COSSH-ACLF IIs 7-10 had a higher 1-year survival benefit rate from LT (39.2%-64.3%) than those with score <7 or >10. These results were prospectively validated. COSSH-ACLF IIs identified the risk of death on the waitlist and accurately predicted post-LT mortalityand survival benefit for HBV-ACLF. Patients with COSSH-ACLF IIs 7-10 derived a higher net survival benefit from LT. This study was supported by the National Natural Science Foundation of China (No. 81830073, No. 81771196) and the National Special Support Program for High-Level Personnel Recruitment (Ten-thousand Talents Program).

Abstract 14241: Feasibility and Safety of Non-Contrast Optical Coherence Tomography Imaging Using Hydroxyethyl Starch in Coronary Arteries

Background/Objectives: Contemporary high-resolution intracoronary optical coherence tomography (OCT) requires injection of flushing media for image acquisition. There is a growing need for an alternative flushing media other than iodine contrast to reduce the risk of acute kidney injury. To address this issue, we investigated the safety and feasibility of hydroxyethyl starch (pentastarch) as a flushing media for OCT image acquisition and compared with the contrast media flushed images. Methods: We prospectively enrolled 43 patients with 70 coronary lesions (46 stented and 24 pre-stented or non-culprit lesions). Paired OCT images were obtained by manual injection of iodine contrast (average 12 mL), followed by pentastarch (average 15 mL). A total of 162 runs (81 pairs) were analyzed and each OCT pullback was assessed on a frame-by-frame basis by automated customized lumen contour and stent strut segmentation algorithm. Results: Image quality as assessed by proportion of clear image segments were comparable between the contrast media and pentastarch flushed images (93.3% vs. 93.7%; p=0.501). Pixel-based flushing capability showed no significant difference between the paired image segments (median(IQR), 0.951(0.947-0.953) vs. 0.951(0.949-0.952), p=0.264; Figure). Quantitative measurements of minimal stent area (R 2 =0.977, p&lt;0.001), minimal lumen area (R 2 =0.983, p&lt;0.001) correlated well between the paired OCT runs. There were no clinically relevant complications associated with OCT imaging with pentastarch such as anaphylaxis, life-threatening arrhythmia, or acute renal deterioration. Conclusions: Intracoronary OCT using pentastarch is safe and technically feasible without affecting the optical signal intensity and overall image quality. Non-contrast imaging with pentastarch significantly reduces the obligatory iodine contrast load, therefore, could be considered as a promising strategy in high-risk patients for renal impairment.

Serious adverse reaction associated with the COVID-19 vaccines of BNT162b2, Ad26.COV2.S, and mRNA-1273: Gaining insight through the VAERS.

Background and purpose: Serious adverse events following immunization (AEFI) associated with the COVID-19 vaccines, including BNT162b2 (Pfizer-BioNTech), Ad26.COV2.S (Janssen), and mRNA-1273 (Moderna), have not yet been fully investigated. This study was designed to evaluate the serious AEFI associated with these three vaccines. Methods: A disproportionality study was performed to analyze data acquired from the Vaccine Adverse Event-Reporting System (VAERS) between 1 January 2010 and 30 April 2021. The reporting odds ratio (ROR) method was used to identify the association between the COVID-19 vaccines BNT162b2, Ad26.COV2.S, and mRNA-1273 and each adverse event reported. Moreover, the ratio of the ROR value to the 95% CI span was applied to improve the credibility of the ROR. The median values of time from vaccination to onset (TTO) for the three vaccines were analyzed. Results: Compared with BNT162b2 and mRNA-1273, Ad26.COV2.S vaccination was associated with a lower death frequency (p < 0.05). Ad26.COV2.S vaccination was associated with a lower birth defect and emergency room visit frequency than BNT162b2 (p < 0.05). There were 6,605, 830, and 2,292 vaccine recipients who suffered from COVID-19-related symptoms after vaccination with BNT162b2, Ad26.COV2.S, and mRNA-1273, respectively, including people who were infected by COVID-19, demonstrated a positive SARS-CoV-2 test, and were asymptomatic. Serious AEFI, including thromboembolism, hemorrhage, thrombocytopenia, cardiac arrhythmia, hypertension, and hepatotoxicity, were associated with all three vaccines. Cardiac failure and acute renal impairment events were associated with BNT162b2 and mRNA-1273, while seizure events were associated with BNT162b2 and Ad26.COV2.S. The median values of TTO associated with the three vaccinations were similar. Conclusion: These findings may be useful for health workers and the general public prior to inoculation, especially for patients with underlying diseases; however, the risk/benefit profile of these vaccines remains unchanged. The exact mechanism of SARS-CoV-2 vaccine-induced AEFI remains unknown, and further studies are required to explore these phenomena.

Prognostic study of acute-on-chronic liver failure patients: Usefulness of the fibrosis-4 index.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by an acute deterioration of liver function in cirrhotic patients. Since treatment of this condition is difficult, its prevention is of paramount importance. The predictors of ACLF are yet to be identified. To determine the prognosis of cirrhotic and ACLF patients, we conducted a retrospective study to analyze each parameter in ACLF patients. Cirrhotic patients with serum total-bilirubin level ≥5.0 mg/dL and prothrombin time (PT) value ≤40% after acute insults were diagnosed with ACLF, whereas patients who met one of the above criteria were diagnosed with extended type of ACLF (EX-ACLF). Overall, in this study, 18 ACLF and 16 EX-ACLF patients retrospectively investigated between 2008 and 2020, and each data was analyzed during and before acute insults. In the analysis during acute insults, renal and coagulation functions showed significant differences between the ACLF and EX-ACLF groups. Furthermore, the mortality rate in the ACLF group was higher than that in the EX-ACLF group. In the analysis before acute insults, aspartate aminotransferase (AST), Fibrosis-4 (FIB-4) index score, and AST to platelet ratio index (APRI) showed significant differences between the two groups. Among these, the FIB-4 index score correlated best with ACLF severity for identifying cirrhotic patients with poor prognosis. The FIB-4 index is the most useful predictor of ACLF severity. Careful management of cirrhotic patients with a high FIB-4 index score is considered beneficial to prevent ACLF occurrence.

The National Early Warning Score: from concept to NHS implementation

This year is the 10th anniversary since the launch of the National Early Warning Score (NEWS) by the Royal College of Physicians in 2012. This review reflects on the journey, from the nascent concept of a standardised system to detect acute illness severity and clinical deterioration through to the adoption of NEWS2 by the NHS and, ultimately, its incorporation into quality indicators of acute care provision. The impact of NEWS/NEWS2 on the transformation of provision and configuration and training of acute care teams in hospitals is reviewed. User feedback has been key in iterating guidance on the use of NEWS/NEWS2 and key elements of this are discussed. The ultimate aim of NEWS was to improve patient outcomes with acute illness or deterioration and the impact on outcomes is now becoming apparent but, paradoxically, an effective response can eliminate the link between the score and the ultimate outcome. This review concludes with a reflection on what the next 10 years may bring, particularly with the digital transformation of healthcare and its potential impact on scoring systems, as well as the necessary permeation of NEWS2 beyond the acute hospital setting into emergency response triage in primary and community care settings.Ten years on, via NEWS/NEWS2, the NHS is the first healthcare system globally with a 'common language' of illness severity and a standardised early warning system for acute clinical illness and deterioration, a system that is now being replicated in many other areas of the world.

Acute Neurologic Deterioration Associated with Multiple Dural Arteriovenous Fistula Improved by Endovascular Procedure

Acute Neurologic Deterioration Associated with Multiple Dural Arteriovenous Fistula Improved by Endovascular Procedure

Evaluation of the utility of NEWS2 during the COVID-19 pandemic

The emergence of the COVID-19 pandemic resulted in a dramatic increase in acutely ill patients presenting to hospitals with life-threatening acute respiratory disease. There was an immediate need for effective triage systems to facilitate clinical decision making. This review assesses the performance of the National Early Warning Score 2 (NEWS2) in two contexts. Firstly, the ability to detect acute illness severity and likely clinical deterioration in patients presenting to hospitals with COVID-19. Secondly, the use of NEWS2 in the longitudinal monitoring to detect acute clinical deterioration in hospitalised patients with COVID-19. NEWS2 appeared to be at least comparable and, often, superior to other scoring systems (such as qSOFA and CURB-65), and provided an earlier alert of deterioration. A NEWS2 of 5 had high short-term sensitivity within and was unlikely to miss patients with COVID-19 who go on to deteriorate, but this comes with moderate specificity. However, the specificity of these systems is likely underestimated because preventing deterioration is their purpose.NEWS2 is an adjunct to clinical decision making and has served that purpose during the COVID-19 pandemic, playing an important role in communicating illness severity, clinical deterioration, triaging patients to appropriate levels of care and prompting completion of treatment escalation plans for those with high scores and at imminent risk of deterioration.

NEWS2 and the older person

The National Early Warning Score (NEWS), published in 2012, made no specific adjustments for older people. The updated NEWS2 (2017) incorporated new confusion as a category for consciousness. In this article, we consider the role of NEWS2 in detection of acute clinical deterioration in older people and how the score may be used to inform care, highlighting the additional aspects, such as care escalation decisions, that may ensue. We consider the evidence of NEWS and NEWS2 in assessment of the older person in different settings, including the potential benefits and limitations for care home residents. We suggest that NEWS2 may need adaptation for older people in future iterations, and that it should be used in conjunction with other clinical assessments, such as the Clinical Frailty Scale and the four 'A's test (4AT) for delirium.

The Frail Patient in a Fictitious Case Study

Various limitations in everyday life can indicate a frailty syndrome. These limitations are not always directly visible and result from a wide variety of domains. Fried et al. described these limitations of different domains as frailty syndrome. This syndrome can be acutely worsened by different influencing factors. One major risk factor is an upcoming anesthesia and surgery. Frailty is associated with a significantly increased risk of peri- and postoperative complications. To avoid acute deterioration due to anesthesia and surgery, the concept of prehabilitation was developed. The aim is to specifically address the respective deficits and to develop an individual training concept together with the patient. Prehabilitation can significantly improve the risk of complications and the outcome of frail patients. In this context, it is important to establish routine screening in order to detect a frailty syndrome in everyday clinical practice and to create opportunities for prehabilitation.

On Natural History and Management of Colloid Cysts: Time to Rethink?

Colloid cysts, although benign, may occasionally cause obstructive hydrocephalus and sudden death. Reliable prognostic factors for symptomatic progression have been sought, with heterogenous results. We conducted a retrospective review of all cases of colloid cysts of the third ventricle managed at our center between 2009 and 2019. Clinical and neuroimaging characteristics were analyzed using logistic regression in relation to symptomatic status and hydrocephalus. The cutoff values for outcome prediction were calculated using the receiver operating characteristic curve analysis. There were 82 patients with colloid cysts, of whom 60 were asymptomatic and 22 symptomatic. None of the asymptomatic patients experienced acute neurologic decline or hydrocephalus during follow-up, whereas half (n= 11) of the symptomatic patients presented with hydrocephalus, 8 of whom had acute hydrocephalus. We found 3 putative candidate risk factors for symptomatic colloid cysts: T1-weighted magnetic resonance imaging hyperintense/mixed signal appearance (P= 0.004), location in risk zone I (P= 0.007), and a volume >236.49 mm3 (P= 0.007). Cyst diameter and volume/foramen of Monro diameter ratios had a decreasing trend over time among asymptomatic patients, providing new insights into the natural history of the disease. Only a few asymptomatic colloid cysts showed progression requiring surgery, with no acute deterioration or fatal events, whereas the rest remained stable over time, thus supporting a more conservative approach for this group of patients. Higher risk for developing symptomatic colloid cyst was defined by a risk score that included T1-weighted magnetic resonance imaging appearance, risk zone, and colloid cyst volume, aiding the detection of patients at risk of clinical deterioration.

Rapid Response Team Activations in Oncologic Ambulatory Sites: Characteristics, Interventions, and Outcomes.

Patients with cancer are vulnerable to clinical deterioration. Rapid response teams (RRTs) identify and manage patients with acute changes in clinical status. Although RRTs have been well studied in the hospital setting, there are limited data on patients who require support in the ambulatory or outpatient oncologic settings. Describe baseline characteristics, reasons for activations, interventions, and outcomes of ambulatory oncologic patients receiving RRT activation in a tertiary cancer center. We conducted a retrospective review of adult (age ≥ 18 years) patients requiring RRT activation at multiple ambulatory sites between July 2020 and June 2021. Demographic and clinical data captured include age, sex, race, ethnicity, do not resuscitate status, vital signs, receipt of active cancer treatment within 30 days, and cancer type. Using Kaplan-Meier survival analysis and multivariable Cox proportion hazard ratio regression models, outcomes of 90-day mortality and hospitalization were assessed. There were 322 RRT activations among 427,734 visits to 10 ambulatory sites (0.75 RRTs/1,000 visits). The most frequent reasons were syncope (25.2%), fall (24.5%), and adverse reaction to cancer therapy or intravenous contrast (16.5%). One hundred thirty-seven (42.5%) required transfer to an emergency department, of which 81 (59.1%) required hospital admission. At 90 days, 51 (15.8%) had died, with 44 (86.3%) receiving comfort measures. Kaplan-Meier survival analysis and multivariable Cox proportional hazard ratio regression showed that heart rate > 100 at RRT presentation and hospitalization after a RRT event were significantly associated with 90-day mortality. Although uncommon, patients with cancer undergoing care at ambulatory sites can suffer acute clinical deterioration needing RRT review. The rates of hospitalization and mortality among such patients are high, suggesting the need for improved end-of-life care.