NEJM evidence最新文献

Background: Patients with advanced chronic liver disease (ACLD) are at high risk of developing hepatocellular carcinoma (HCC). Therefore, biannual surveillance is recommended. This large-scale multicenter study aimed to stratify the risk of HCC development in ACLD.

Methods: From 3016 patients with ACLD screened in 17 European and Chinese centers, 2340 patients with liver stiffness measurement (LSM) determined using different techniques (two-dimensional shear-wave elastography [2D-SWE], transient elastography, and point shear-wave elastography) and with different disease severities were included. Cox regression was used to explore risk factors for HCC. We used these data to create an algorithm, named PLEASE, but referred to in this manuscript as "the algorithm"; the algorithm was validated in internal and two external cohorts across elastography techniques.

Results: HCC developed in 127 (5.4%) patients during follow-up. LSM by 2D-SWE (hazard ratio: 2.28) was found to be associated with developing HCC, alongside age, sex, etiology, and platelet count (C-index: 0.8428). We thus established the algorithm with applicable cutoffs, assigning a maximum of six points: platelet count less than 150×10⁹/l, LSM greater than or equal to 15 kPa, age greater than or equal to 50 years, male sex, controlled/uncontrolled viral hepatitis, or presence of steatotic liver diseases. Within 2 years, with a median follow-up of 13.7 months, patients in the high-risk group (≥4 points) had an HCC incidence of 15.6% (95% confidence interval [CI], 12.1% to 18.7%) compared with the low-risk group, at 1.7% (95% CI, 0.9% to 2.5%).

Conclusions: Our algorithm stratified patients into two groups: those at higher risk of developing HCC and those at lower risk. Our data provide equipoise to test the prospective utility of the algorithm with respect to clinical decisions about screening patients with ACLD for incident HCC. (Funded by the German Research Foundation and others; ClinicalTrials.gov number, NCT03389152.).

Background: Cyclophosphamide and infliximab are recommended as induction therapies for severe Behçet's syndrome. Whether infliximab is safer and more effective than cyclophosphamide in treating severe Behçet's syndrome is not known.

Methods: In this phase 2, Bayesian, multicenter randomized controlled trial, we assigned patients fulfilling the International Study Group's criteria for Behçet's syndrome who had major vascular or central nervous system involvement to receive either intravenous infliximab (5 mg/kg at weeks 0, 2, 6, 12, and 18) or cyclophosphamide (0.7 g/m² intravenously at weeks 0, 4, 8, 12, 16, and 20, with a maximal dose of 1.2 g/infusion). All patients received the same glucocorticoid regimen. The primary outcome was complete response (clinical, biological, and radiological remission with a daily prednisone dose ≤0.1 mg/kg) at week 22.

Results: Between May 2018 and April 2021, 52 patients with severe Behçet's syndrome (n=37 [71%] with vascular Behçet's syndrome and n=15 [29%] with neuro-Behçet's syndrome) were randomly assigned to receive either infliximab or cyclophosphamide. Complete response was achieved by 22 out of 27 (81%) and 14 out of 25 (56%) patients in the infliximab and cyclophosphamide treatment groups, respectively (estimated difference, 29.8 percentage points; 95% credible interval, 6.6 to 51.7). The posterior probability that at least 70% of treated individuals achieved complete response by week 22 was 97.4% for infliximab and 6.0% for cyclophosphamide. Overall, adverse events were recorded in 8 out of 27 (29.6%) patients receiving infliximab and 16 out of 25 (64%) patients receiving cyclophosphamide (estimated difference, -32.3 percentage points; 95% credible interval, -55.2 to -6.6). Serious adverse events were reported in 15% and 12% of patients receiving infliximab and cyclophosphamide, respectively.

Conclusions: Among patients with severe Behçet's syndrome, induction therapy with infliximab had a superior complete response rate at 22 weeks and fewer adverse events than induction with cyclophosphamide. (Funded by the French Ministry of Health.).

Background: People with human immunodeficiency virus (HIV) smoke at much higher rates than the general population, resulting in higher risk for tobacco-related morbidity and mortality. The efficacy of smoking cessation interventions among people with HIV in lower-middle-income countries remains unclear.

Methods: We conducted a randomized, 2 × 2 factorial design trial based in Nairobi, Kenya, to evaluate the efficacy of bupropion versus placebo, and a culturally tailored behavioral cessation therapy, called Positively Smoke Free (PSF), versus standard of care for people with HIV who smoke. The primary outcome was 7-day point prevalence abstinence confirmed by exhaled carbon monoxide <7 ppm at 36 weeks.

Results: Between June 2020 and August 2023, 300 participants were randomly assigned. Most participants were men (71.4%) who were moderately dependent on nicotine (Fagerström Test of Cigarette Dependence, mean [SD]: 4.5 [2.3]; range: 0-10; higher scores represent greater physical dependence on nicotine); nearly all participants (99.7%) were taking antiretroviral medication. At 36 weeks, 31.3% of participants who received bupropion were abstinent from smoking, compared with 13.3% in the placebo group (odds ratio, 2.95; 95% confidence interval [CI], 1.64-5.32, P<0.001). Among participants randomized to receive PSF therapy, 29.5% were abstinent from smoking, compared with 14.9% in the standard of care group (odds ratio, 2.39; 95% CI, 1.34-4.25, P=0.003). The combination of bupropion+PSF was associated with increased abstinence compared with either bupropion (38.9% vs. 23.6%; odds ratio, 2.06; 95% CI, 1.00-4.23) or PSF (38.9% vs. 20.3%; odds ratio, 2.50; 95% CI, 1.20-5.24) alone. Participants randomized to receive bupropion were significantly more likely to report excessive sweating compared with placebo (50.7% vs. 37.6%; P=0.024).

Conclusions: Both bupropion and PSF cessation counseling were effective in promoting abstinence from smoking at 36 weeks. The combined intervention was associated with higher abstinence rates than either therapy alone. (The National Cancer Institute provided support for this trial through grant R01CA225419.).

Background: Cardiogenic shock remains highly associated with early mortality, with mortality often exceeding 50%. We sought to determine the association between prognostic factors and in-hospital and 30-day mortality in cardiogenic shock.

Methods: We performed a systematic review and meta-analysis of prognostic factors in cardiogenic shock, searching MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for records up to June 5, 2023. English-language studies that investigated prognostic factors and in-hospital and/or 30-day mortality in cardiogenic shock were included. Studies were excluded if they evaluated the pediatric population, were postmortem studies, or included fewer than 100 patients. The primary aim was to identify modifiable and non-modifiable prognostic factors associated with in-hospital and 30-day mortality in cardiogenic shock.

Results: We identified 160 studies, including 2,459,703 patients with a median in-hospital mortality of 41.4% (interquartile range, 33.6% to 49.2%). The majority were retrospective cohort studies. Patient factors potentially associated with an increase in early mortality included an age greater than or equal to 75 years of age, peripheral arterial disease, chronic kidney disease, and female sex. Procedural and presentation factors potentially associated with increased mortality included out-of-hospital cardiac arrest, left main culprit artery, left ventricular ejection fraction less than 30%, dialysis, and need for mechanical circulatory support. Revascularization in the form of coronary artery bypass graft and percutaneous coronary intervention were potentially associated with reduced in-hospital mortality.

Conclusions: This analysis quantifies the association between patient, presentation, and treatment-related factors and early mortality in cardiogenic shock. Increased certainty in the association of these prognostic factors with cardiogenic shock outcomes can aid in clinical risk assessment, development of risk tools, and analysis of clinical trials.

AbstractIn response to the Covid-19 pandemic, the National Heart, Lung, and Blood Institute launched five multisite clinical trials testing candidate host tissue-directed medical interventions to hasten recovery, improve function, and reduce morbidity and mortality. Speed, flexibility, and collaboration were essential. This article from the Steering and Executive committees describes the Collaborating Network of Networks for Evaluating Covid-19 and Therapeutic Strategies (CONNECTS) research program that enrolled 6690 participants and evaluated 18 intervention strategies using 10 molecular agents across the care continuum (outpatient, inpatient, and post discharge), and reports lessons learned from this initiative. Successes include rapid trial execution through collaboration and adaptive platform designs. Challenges that impeded efficiency included time required to execute subcontracts, constraints on clinical research workforce, and limited research infrastructure in nonacademic settings.