Artificial intelligence scoring of liver biopsies in a phase II trial of semaglutide in nonalcoholic steatohepatitis.

BACKGROUND AND AIMS: Artificial intelligence-powered digital pathology offers the potential to quantify histological findings in a reproducible way. This analysis compares the evaluation of histological features of NASH between pathologists and a machine-learning (ML) pathology model. APPROACH AND RESULTS: This post hoc analysis included data from a subset of patients (n=251) with biopsy-confirmed NASH and fibrosis stage F1-F3 from a 72-week randomized placebo-controlled trial of once-daily subcutaneous semaglutide 0.1, 0.2, or 0.4 mg (NCT02970942). Biopsies at baseline and week 72 were read by 2 pathologists. Digitized biopsy slides were evaluated by PathAI's NASH ML models to quantify changes in fibrosis, steatosis, inflammation, and hepatocyte ballooning using categorical assessments and continuous scores. Pathologist and ML-derived categorical assessments detected a significantly greater percentage of patients achieving the primary endpoint of NASH resolution without worsening of fibrosis with semaglutide 0.4 mg versus placebo (pathologist 58.5% vs. 22.0%, p < 0.0001; ML 36.9% vs. 11.9%; p =0.0015). Both methods detected a higher but nonsignificant percentage of patients on semaglutide 0.4 mg versus placebo achieving the secondary endpoint of liver fibrosis improvement without NASH worsening. ML continuous scores detected significant treatment-induced responses in histological features, including a quantitative reduction in fibrosis with semaglutide 0.4 mg versus placebo ( p =0.0099) that could not be detected using pathologist or ML categorical assessment. CONCLUSIONS: ML categorical assessments reproduced pathologists' results of histological improvement with semaglutide for steatosis and disease activity. ML-based continuous scores demonstrated an antifibrotic effect not measured by conventional histopathology.

Safety Aspects of Postanesthesia Care Unit Discharge without Motor Function Assessment after Spinal Anesthesia: A Randomized, Multicenter, Semiblinded, Noninferiority, Controlled Trial.

BACKGROUND: Postanesthesia care unit (PACU) discharge without observation of lower limb motor function after spinal anesthesia has been suggested to significantly reduce PACU stay and enhance resource optimization and early rehabilitation but without enough data to allow clinical recommendations. METHODS: A multicenter, semiblinded, noninferiority randomized controlled trial of discharge from the PACU with or without assessment of lower limb motor function after elective total hip or knee arthroplasty under spinal anesthesia was undertaken. The primary outcome was frequency of a successful fast-track course (length of stay 4 days or less and no 30-day readmission). Noninferiority would be declared if the odds ratio (OR) for a successful fast-track course was no worse for those patients receiving no motor function assessment versus those patients receiving motor function assessment by OR = 0.68. RESULTS: A total of 1,359 patients (98.8% follow-up) were available for analysis (93% American Society of Anesthesiologists class 1 to 2). The primary outcome occurred in 92.2% and 92.0%, corresponding to no motor function assessment being noninferior to motor function assessment with OR 0.97 (95% CI, 0.70 to 1.35). Adverse events in the ward during the first 24 h occurred in 5.8% versus 7.4% with or without motor function assessment, respectively (OR, 0.77; 95% CI, 0.5 to 1.19, P = 0.24). CONCLUSIONS: PACU discharge without assessment of lower limb motor function after spinal anesthesia for total hip or knee arthroplasty was noninferior to motor function assessment in achieving length of stay 4 days or less or 30-day readmissions. Because a nonsignificant tendency toward increased adverse events during the first 24 h in the ward was discovered, further safety data are needed in patients without assessment of lower limb motor function before PACU discharge.

Dual mobility cup reduces dislocation and re-operation when used to treat displaced femoral neck fractures.

PURPOSE: Total hip arthroplasty (THA) as primary treatment for displaced femoral neck fractures is controversial as THA is associated with higher rates of dislocation but lower rates of re-operation compared to hemiarthroplasty (HA). A dual mobility cup (DMC) design is associated with lower dislocation and re-operation rates in elective surgery. Is this also the case when used to treat displaced femoral neck fractures? The aim of this study is to compare rates of dislocation and re-operation of any kind following treatment for displaced femoral neck fractures with either bipolar HA or THA with DMC. METHODS: Two consecutive groups of patients treated for displaced femoral neck fractures at the Regional Hospital in Viborg in Denmark were included. In 2007-2008 171 patients (mean age 84.1 years) were treated with bipolar HA. In 2009-2010 175 patients (mean age 75.2 years) were treated with THA with DMC. Data regarding rates of dislocation and re-operation were obtained by retrospective review of medical records. RESULTS: We found a statistically significant difference regarding rates of dislocation and re-operation of any kind in favour of THA with DMC. Dislocation occurred in 25/171 patients [95 % confidence interval (CI) 9.3-19.9 %] treated with bipolar HA and 8/175 patients (95 % CI 1.5-7.7 %) treated with THA with DMC (p = 0.002). Re-operations were required in 32/171 patients (95 % CI 12.9-24.6 %) treated with bipolar HA and 16/175 patients (95 % CI 4.8-13.4 %) treated with THA with DMC (p = 0.01). CONCLUSIONS: Our findings indicate that THA with DMC is superior to bipolar HA following treatment for displaced femoral neck fractures in regard to rates of dislocation and re-operation.

Semaglutide 2·4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial.

BACKGROUND: Patients with non-alcoholic steatohepatitis (NASH)-related cirrhosis are at high risk of liver-related and all-cause morbidity and mortality. We investigated the efficacy and safety of the glucagon-like peptide-1 analogue semaglutide in patients with NASH and compensated cirrhosis. METHODS: This double-blind, placebo-controlled phase 2 trial enrolled patients from 38 centres in Europe and the USA. Adults with biopsy-confirmed NASH-related cirrhosis and body-mass index (BMI) of 27 kg/m2 or more were randomly assigned (2:1) to receive either once-weekly subcutaneous semaglutide 2·4 mg or visually matching placebo. Patients were randomly allocated via an interactive web response system, stratified by presence or absence of type 2 diabetes. Patients, investigators, and those assessing outcomes were masked to treatment assignment. The primary endpoint was the proportion of patients with an improvement in liver fibrosis of one stage or more without worsening of NASH after 48 weeks, assessed by biopsy in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study drug. The trial is closed and completed, and registered with ClinicalTrials.gov, number NCT03987451. FINDINGS: 71 patients were enrolled between June 18, 2019, and April 22, 2021; 49 (69%) patients were female and 22 (31%) were male. Patients had a mean age of 59·5 years (SD 8·0) and mean BMI of 34·9 kg/m2 (SD 5·9); 53 (75%) patients had diabetes. 47 patients were randomly assigned to the semaglutide group and 24 to the placebo group. After 48 weeks, there was no statistically significant difference between the two groups in the proportion of patients with an improvement in liver fibrosis of one stage or more without worsening of NASH (five [11%] of 47 patients in the semaglutide group vs seven [29%] of 24 in the placebo group; odds ratio 0·28 [95% CI 0·06-1·24; p=0·087). There was also no significant difference between groups in the proportion of patients who achieved NASH resolution (p=0·29). Similar proportions of patients in each group reported adverse events (42 [89%] patients in the semaglutide group vs 19 [79%] in the placebo group) and serious adverse events (six [13%] vs two [8%]). The most common adverse events were nausea (21 [45%] vs four [17%]), diarrhoea (nine [19%] vs two [8%]), and vomiting (eight [17%] vs none). Hepatic and renal function remained stable. There were no decompensating events or deaths. INTERPRETATION: In patients with NASH and compensated cirrhosis, semaglutide did not significantly improve fibrosis or achievement of NASH resolution versus placebo. No new safety concerns were raised. FUNDING: Novo Nordisk A/S.

Quality of Cardiopulmonary Resuscitation and 5-Year Survival Following in-Hospital Cardiac Arrest.

PURPOSE: To improve cardiac arrest survival, international resuscitation guidelines emphasize measuring the quality of cardiopulmonary resuscitation (CPR). We aimed to investigate CPR quality during in-hospital cardiac arrest (IHCA) and study long-term survival outcomes. PATIENTS AND METHODS: This was a cohort study of IHCA from December 2011 until November 2014. Data were collected from the hospital switch board, patient records, and from defibrillators. Impedance data from defibrillators were analyzed manually at the level of single compressions. Long-term survival at 1-, 3-, and 5 years is reported. RESULTS: The study included 189 IHCAs; median (interquartile range (IQR)) time to first rhythm analysis was 116 (70-201) seconds and median (IQR) time to first defibrillation was 133 (82-264) seconds. Median (IQR) chest compression rate was 126 (119-131) per minute and chest compression fraction (CCF) was 78% (69-86). Thirty-day survival was 25%, while 1-year-, 3-year-, and 5-year survival were 21%, 14%, and 13%, respectively. There was no significant association between any survival outcomes and CCF, whereas chest compression rate was associated with survival to 30 days and 3 years. Overall, 5-year survival was associated with younger age (median 68 vs 74 years, p=0.003), less comorbidity (Charlson comorbidity index median 3 vs 5, p<0.001), and witnessed cardiac arrest (96% vs 77%, p=0.03). CONCLUSION: We established a systematic collection of IHCA CPR quality data to measure and improve CPR quality and long-term survival outcomes. Median time to first rhythm check/defibrillation was <3 minutes, but median chest compression rate was too fast and median CCF slightly below 80%. More than half of 30-day survivors were still alive at 5 years.

A comparison of pediatric basic life support self-led and instructor-led training among nurses.

OBJECTIVE: Pediatric cardiac arrest carries a poor prognosis. Basic life support improves survival. Studies on pediatric basic life support (PBLS) training are sparse. The aim of our study was to investigate the effect of self-training in PBLS. PARTICIPANTS AND METHODS: We conducted a prospective controlled trial enrolling nurses from pediatric and maternity wards (n=29 in each group). Self-training, including a manikin and access to a web-based video on PBLS, was compared with a 2-h instructor-led course. Two weeks after training, all participants were tested in a mock scenario of pediatric cardiac arrest. Fifteen parameters equivalent to the steps in the PBLS algorithm - for example, effective ventilations, effective chest compressions, calling for help, and correct sequence of actions, were evaluated and rated dichotomously (1=approved or 0=not approved). RESULTS: No difference was observed in the baseline demographics between the self-training group and the instructor-led group. The participants in the self-training group accessed the website 2±1.5 times (mean±SD) and spent 41±25 min on the site. There was no significant difference between the two groups in the overall average score (10.5 in the self-training group vs. 10.0 in the instructor-led group, P=0.51) or in any of the 15 parameters. After the study, all participants felt that they had improved their skills and felt capable of performing PBLS. CONCLUSION: Self-training is not statistically different to instructor-led training in teaching PBLS. Self-evaluated confidence improved, but showed no difference between groups. PBLS may be disseminated through self-training.

A Cancer That Went Up in Smoke: Pulmonary Reaction to e-Cigarettes Imitating Metastatic Cancer.

e-Cigarettes have gained worldwide popularity as a substitute for smoking, but concern has been raised regarding the long-term effects associated with their use. We report a case of a 45-year-old female consumer of e-cigarettes who presented with 4 months of abdominal pain and fever. Initial imaging discovered multiple pulmonary nodules and liver lesions suspicious of widespread metastases; however, an extensive evaluation found no evidence of malignancy. Results of a lung biopsy revealed an area with multinucleated giant cells suggestive of a foreign body reaction to a lipophilic material. Upon cessation of e-cigarette use (known as vaping), the lung nodules disappeared, and the liver lesions regressed. Our case report suggests that vaping can induce an inflammatory reaction mimicking metastatic cancer.

Lower reoperation rate for cemented femoral stem than for uncemented femoral stem in primary total hip arthroplasty following a displaced femoral neck fracture.

INTRODUCTION: Acute displaced femoral neck fractures are often treated with cemented hemiarthroplasty (HA). There is increasing evidence that total hip arthroplasty (THA) may be a better alternative, but the degree to which the fixation of the femoral stem used affects the outcome is not fully known. The aim of this study is to compare rates of operative complications and implant survival following THA treatment of displaced femoral neck fractures with either a cemented or an uncemented femoral stem. METHODS: The study consists of two groups of patients (N = 334), who were treated for a displaced femoral neck fracture with THA at the Regional Hospital of Viborg during 2007-2012. The first group (50.9%) had uncemented (Corail (®) ) stem while the second group (49.1%) had cemented (Exeter (®) ) stem implanted. Nearly all patients had uncemented dual mobility cup (Saturne (®) ) as acetabular component and were followed up to three months postoperatively. Data regarding rates of implant survival and operative complications were obtained by retrospective review of medical records. RESULTS: We found a statistically significant difference regarding rates of postoperative reoperation with 1.2% (95% CI 0.005-0.03) for cemented and 5.9% (95% CI 0.02-0.09) for uncemented stem (p = 0.02). The main causes for reoperation were peri-prosthetic fractures and deep infections. There was no difference regarding dislocation or peroperative complications. Rates of dislocation were 4.3% (95% CI 0.012-0.07) for cemented and 3.5% (95% CI 0.008-0.06) for uncemented stem (p = 0.72). Rates of peroperative complications were 6.1% (95% CI 0.024-0.1) for cemented and 8.2% (95% CI 0.04-0.12) for uncemented stem (p = 0.1). DISCUSSION: Our results indicate that cemented femoral stem is superior to cementless when rates of reoperation are compared.

The dislocating hip replacement - revision with a dual mobility cup in 56 consecutive patients.

INTRODUCTION: Recurrent dislocations of hip replacements are a difficult challenge. One treatment option for recurrent dislocations is the use of a dual mobility cup. The aim of this study was to retrospective investigate the effect of dual mobility cups as a treatment for recurrent dislocations in a consecutive series. Materials and. METHODS: 56 consecutive patients were revised in the period November 2000 to December 2010. The mean age at revision was 72 years (SD 11, range 37-92)) and median number of dislocations before revision surgery were 4 (IQR, 2-11). In all cases, revision was made with a Saturne dual mobility cup (Amplitude, Neyron, France). The mean follow-up period was 44 months (SD 30, range 0.1-119). RESULTS: One patient (1.8%) experienced a re-dislocation. Three patients (5.3%) had to be revised. One due to disintegration between the femoral head and inner shell, one due to loosening of the acetabular component, and one due to infection. Harris Hip Score improved from a mean of 76 before index surgery to 87 within one year after index surgery. CONCLUSION: This study advocates the use of a dual mobility cup for treatment of recurrent dislocations of THR. However, studies with a longer follow up are needed in order to evaluate implant survival.

[Data from automated external defibrillators provide important information on the quality of in-hospital resuscitation].

International guidelines recommend monitoring the outcome following in-hospital cardiac arrest. Using data from automatic external defibrillators (AED) prospectively collected during a three-year period in a regional hospital, we evaluated the treatment quality of resuscitation. Time to defibrillation was acceptable, but quality of chest compressions did not comply with current international recommendations. AED use led to a high fraction of time with no chest compressions. Survival to discharge was 11%. Consequently, training in basic and advanced life support of hospital staff has been modified.

Initial assessment and treatment with the Airway, Breathing, Circulation, Disability, Exposure (ABCDE) approach.

The Airway, Breathing, Circulation, Disability, Exposure (ABCDE) approach is applicable in all clinical emergencies for immediate assessment and treatment. The approach is widely accepted by experts in emergency medicine and likely improves outcomes by helping health care professionals focusing on the most life-threatening clinical problems. In an acute setting, high-quality ABCDE skills among all treating team members can save valuable time and improve team performance. Dissemination of knowledge and skills related to the ABCDE approach are therefore needed. This paper offers a practical "how-to" description of the ABCDE approach.

[Registries of in-hospital cardiac arrest are a challenge in daily clinical practice]. / Registrering af hjertestop på hospital er en udfordring i den kliniske hverdag.

In-hospital cardiac arrest carries a poor prognosis. Registries of in-hospital cardiac arrest provide the opportunity to improve quality of care and conduct research of disease mechanisms and treatment. This paper describes the preliminary experience with systematic registration of in-hospital cardiac arrest at Aarhus University Hospital, Denmark. Data from 102 patients are presented and practical aspects and challenges of establishing a registry and implementing the collection of data in daily clinical practice are discussed.

[Coronary angiography should be considered after out-of-hospital cardiac arrest]. / Koronarangiografi bør overvejes efter hjertestop uden for hospital.

Cardiac arrest has a poor prognosis. Ischaemic heart disease is the main cause of out-of-hospital cardiac arrest. This paper is a review of the essential studies on acute coronary angiography and angioplasty in post resuscitation care. No randomised studies were found. Observational studies support the use of acute angiography in ST-segment elevation myocardial infarction. The negative predictive value of ST-segment elevation can be low after out-of-hospital cardiac arrest, and acute angiography should be considered regardless of electrocardiographic findings.

Quality of cardiopulmonary resuscitation in out-of-hospital cardiac arrest is hampered by interruptions in chest compressions--a nationwide prospective feasibility study.

AIM OF THE STUDY: Quality of cardiopulmonary resuscitation (CPR) is a critical determinant of outcome following out-of-hospital cardiac arrest. The aim of our study was to evaluate the quality of CPR provided by emergency medical service providers (Basic Life Support (BLS) capability) and emergency medical service providers assisted by paramedics, nurse anesthetists or physician-manned ambulances (Advanced Life Support (ALS) capability) in a nationwide, unselected cohort of out-of-hospital cardiac arrest cases. METHODS: We conducted a prospective, observational study of out-of-hospital cardiac arrest with non-traumatic etiology (>18 years of age) occurring from the 1st to the 31st of January 2009 and treated by the primary Danish emergency medical service operator, covering approximately 85% of the population. One hundred and ninety-one cases were eligible for analysis. Follow-up was up to one year or death. Quality of CPR was evaluated using measurements of transthoracic impedance. RESULTS: The majority of patients were treated by ambulances with ALS capability (54%). Interruptions in CPR related to loading of the patient into the emergency medical service vehicle were substantial, but independent of whether patients were managed by ALS or BLS capable units (222s versus 224s, P = 0.76) as were duration of interruptions during rhythm analysis alone (20s versus 22s, P = 0.33) and defibrillation (24s versus 26s, P = 0.07). CONCLUSIONS: Nationwide, routine monitoring of transthoracic impedance is feasible. CPR is hampered by extended interruptions, particularly during loading of the patient into the emergency medical service vehicle, rhythm analysis and defibrillation.

[ABCDE--a systematic approach to critically ill patients]. / ABCDE--systematisk tilgang til patienter med kritisk sygdom.

This systematic approach to the immediate assessment and treatment of the critically ill or injured patient is applicable in all clinical emergencies. The aim of the ABCDE approach is to facilitate immediate life-saving treatment and thus buy time for definite diagnosis and treatment by breaking down complex clinical situations into manageable parts. Application of the ABCDE approach may improve treatment quality.

[Rescue breathing is still a part of basic life support]. / Kunstigt åndedraet udgør fortsat en del af basal genoplivning.

Bystander cardiopulmonary resuscitation (CPR) consisting of mouth-to-mouth ventilation and chest compressions improves survival from cardiac arrest. Bystanders perform CPR only in a minority of cardiac arrests. To improve the number of bystanders initiating CPR, the American Heart Association recommends that laypersons omit rescue breathing and perform Hands-only CPR. In this paper studies on Hands-only CPR are reviewed. Currently, the evidence is insufficient to herald immediate changes to CPR guidelines and further research is warranted.

[Where is the automated external defibrillator? Development and education]. / Hvor er den automatiske eksterne defibrillator? Udvikling og uddannelse.

The International Liaison Committee on Resuscitation has presented a universal sign to indicate the presence of automated external defibrillators (AED). To disseminate the knowledge of this important signage, a review in a Danish context is presented. It is essential that the public in general and health care professionals in particular know where to locate on AEDs.

[In-hospital resuscitation with automated external defibrilliator]. / Genoplivning med automatisk ekstern defibrillator på hospital.

Early defibrillation is a determinant of survival in cardiac arrest. We report a Danish case of successful in-hospital resuscitation using an automated external defibrillator (AED). This case illustrates important aspects of implementation of in-hospital use of an AED, i.e. location of the AED, education of the staff, systematic registration and data collection and technical aspects of AED use. If in-hospital AED implementation is carefully executed, its use may provide a safe and effective way of obtaining early defibrillation.