Citations

INTRODUCTION: Management of hepatic encephalopathy relies on self-titration of lactulose. In this feasibility trial, we assess an artificial intelligence–enabled tool to guide lactulose use through a smartphone application. METHODS: Subjects with hepatic encephalopathy on lactulose captured bowel movement pictures during lead-in and intervention phases. During the intervention phase, daily feedback on lactulose titration was delivered through the application. Goals were determined according to number of bowel movement and Bristol Stool Scale reports. RESULTS: Subjects completed the study with more than 80% satisfaction. In the lead-in phase, less compliant subjects achieved Bristol Stool Scale goal on 62/111 (56%) of days compared with 107/136 (79%) in the intervention phase ( P = 0.041), while the most compliant subjects showed no difference. Severe/recurrent hepatic encephalopathy group achieved Bristol Stool Scale goal on 80/104 (77%) days in the lead-in phase and 90/110 (82%) days in the intervention phase ( P = NS), compared with 89/143 (62%) days and 86/127 (68%) days in the stable group. DISCUSSION: Dieta application is a promising tool for objective Bowel Movement/Bristol Stool Scale tracking for hepatic encephalopathy and may potentially be used to assist with lactulose titration.

Background Patients with peripheral artery disease are at increased risk for major adverse cardiac events, major adverse limb events, and all‐cause death. Developing tools capable of identifying those patients with peripheral artery disease at greatest risk for major adverse events is the first step for outcome prevention. This study aimed to determine whether computer‐assisted analysis of a resting Doppler waveform using deep neural networks can accurately identify patients with peripheral artery disease at greatest risk for adverse outcome events. Methods and Results Consecutive patients (April 1, 2015, to December 31, 2020) undergoing ankle–brachial index testing were included. Patients were randomly allocated to training, validation, and testing subsets (60%/20%/20%). Deep neural networks were trained on resting posterior tibial arterial Doppler waveforms to predict major adverse cardiac events, major adverse limb events, and all‐cause death at 5 years. Patients were then analyzed in groups based on the quartiles of each prediction score in the training set. Among 11 384 total patients, 10 437 patients met study inclusion criteria (mean age, 65.8±14.8 years; 40.6% women). The test subset included 2084 patients. During 5 years of follow‐up, there were 447 deaths, 585 major adverse cardiac events, and 161 MALE events. After adjusting for age, sex, and Charlson comorbidity index, deep neural network analysis of the posterior tibial artery waveform provided independent prediction of death (hazard ratio [HR], 2.44 [95% CI, 1.78–3.34]), major adverse cardiac events (HR, 1.97 [95% CI, 1.49–2.61]), and major adverse limb events (HR, 11.03 [95% CI, 5.43–22.39]) at 5 years. Conclusions An artificial intelligence–enabled analysis of Doppler arterial waveforms enables identification of major adverse outcomes among patients with peripheral artery disease, which may promote early adoption and adherence of risk factor modification.

Background Venoarterial extracorporeal membrane oxygenation (ECMO) provides full hemodynamic support for patients with cardiogenic shock, but optimal timing of ECMO initiation remains uncertain. We sought to determine whether earlier initiation of ECMO is associated with improved survival in cardiogenic shock. Methods and Results We analyzed adult patients with cardiogenic shock who received venoarterial ECMO from the international Extracorporeal Life Support Organization (ELSO) registry from 2009 to 2019, excluding those cannulated following an operation. Multivariable logistic regression evaluated the association between time from admission to ECMO initiation and in‐hospital death. Among 8619 patients (median, 56.7 [range, 44.8–65.6] years; 33.5% women), the median duration from admission to ECMO initiation was 14 (5–32) hours. Patients who had ECMO initiated within 24 hours (n=5882 [68.2%]) differed from those who had ECMO initiated after 24 hours, with younger age, more preceding cardiac arrest, and worse acidosis. After multivariable adjustment, patients with ECMO initiated >24 hours after admission had higher risk of in‐hospital death (adjusted odds ratio, 1.20 [95% CI, 1.06–1.36]; P =0.004). Each 12‐hour increase in the time from admission to ECMO initiation was incrementally associated with higher adjusted in‐hospital mortality rate (adjusted odds ratio, 1.06 [95% CI, 1.03–1.10]; P <0.001). The association between longer time to ECMO and worse outcomes appeared stronger in patients with lower shock severity. Conclusions Longer delays from admission to ECMO initiation were associated with higher a mortality rate in a large‐scale, international registry. Our analysis supports optimization of door‐to‐support time and the avoidance of inappropriately delayed ECMO initiation.

BackgroundNasal septal perforations (NSP) can have a heterogeneous appearance on endoscopic examination with varying degrees of crusting, inflammatory change, and associated septal deviation. The clinical applicability of these findings as contributors to patient symptoms may be enhanced by use of a standardized assessment.MethodsVideo nasal endoscopy recordings were obtained from 40 patients with NSP. Five raters with varied levels of training ranging from a senior resident to an experienced septal perforation surgeon independently reviewed the videos for the following exam findings: crusting, scarring, granulation tissue, septal deviation, and edema. Scoring for each item was reported on a 3‐point (0–2) scale, and each reviewer repeated scoring at a 14‐day interval. Interrater and intrarater agreement were calculated using Fleiss kappa for each item and the total scores. Additionally, endoscopy scores were correlated with patient‐reported NOSE‐Perf symptom scores.ResultsInterrater agreement for the overall instrument was in the “fair‐to‐moderate” range with the following interrater agreement for each item: crusting (0.458–0.575), scarring (0.286–0.308), granulation (0.403–0.406), deviation (0.487–0.494), and edema (0.253–0.406). Intrarater agreement was generally “substantial” for individual items as well as the overall instrument (0.688). The NSP endoscopy scores were moderately correlated with NOSE‐Perf scores (r = 0.44, p = 0.008).ConclusionsAn endoscopic evaluation of NSP comprising five exam findings has acceptable interrater and intrarater reliability and correlates with patient‐reported outcomes. NSP endoscopy may be applied to future clinical studies for characterization of NSP and assessment of treatment outcomes.Level of Evidence3 Laryngoscope, 134:3049–3053, 2024

Prediabetes is a risk factor for ischemic stroke in atrial fibrillation (AF) patients, yet, its impact on recurrent stroke in AF patients remains understudied. Using the 2018 National Inpatient Sample, we investigated the link between Prediabetes and recurrent stroke in AF patients with prior stroke or transient ischemic attack (TIA). Among 18,905 non-diabetic AF patients, 480 (2.5%) had prediabetes. The prediabetic group, with a median age of 78, exhibited a two-fold higher risk of recurrent stroke compared to the non-prediabetic cohort (median age 82), as evidenced by both unadjusted (OR 2.14, 95% CI 1.72–2.66) and adjusted (adjusted for socio-demographics/comorbidities, OR 2.09, 95% CI 1.65–2.64, p < 0.001). The prediabetes cohort, comprising more male and Black patients, demonstrated associations with higher Medicaid enrollment, admissions from certain regions, and higher rates of hyperlipidemia, smoking, peripheral vascular disease, obesity, and chronic obstructive pulmonary disease (all p < 0.05). Despite higher rates of home health care and increased hospital costs in the prediabetes group, the adjusted odds of all-cause mortality were not statistically significant (OR 0.55, 95% CI 0.19–1.56, p = 0.260). The findings of this study suggest that clinicians should be vigilant in managing prediabetes in AF patients, and strategies to prevent recurrent stroke in this high-risk population should be considered.

Background: Current guidelines recommend proceeding with cardioversion, without the explicit need for preprocedural transesophageal echocardiography (TEE), in patients compliant with oral anticoagulation for at least 3 weeks. The relevance of these guidelines remains unclear in those undergoing repeat cardioversion. Case summary: A 66-year-old male with a history of atrial fibrillation (AF) and a left atrial appendage occlusion (LAAO) device, compliant with apixaban, presented with dyspnea and lightheadedness. He was cardioverted into sinus rhythm, 10 days before symptom onset, with TEE unremarkable at the time. An ECG revealed that the patient converted back into AF and a repeat cardioversion was scheduled. At the patient’s request, a TEE was obtained, revealing a new 2 cm×1 cm thrombus in the left atrium above the WATCHMAN device. Cardioversion was canceled and the patient was hospitalized for AF management. Discussion: Cardioverted patients are at risk for thrombus formation due to atrial stunning, a transitory dysfunction of the atrial appendage and atrium, which occurs immediately after cardioversion and can persist for several weeks. The likelihood of a thrombus is further propagated by individual risk factors for stroke. Conclusion: Anticoagulation does not eliminate the risk of thrombus formation in those with increased risk factors for stroke. Further studies are warranted to assess the need for routine TEE, after cardioversion, in those with stroke risk factors on anticoagulation or who have LAAO.

Abstract The canonical non-homologous end joining (c-NHEJ) repair pathway has generally been considered a highly efficient and stochastic repair process. Yet recent studies indicated that c-NHEJ-mediated CRISPR-Cas9 mutagenesis, primarily leading to 1-bp insertions and small deletions, may be highly predictable. This observation has spurred the development of in-silico programs with remarkable accuracy in various animal species. Nevertheless, the predictability of CRISPR-induced mutation profiles across species and the associated mechanisms remained elusive. Through comparison of CRISPR-Cas9 repair outcomes between human and plant species, we discovered significant differences in 1-bp insertion profiles across species, governed by an X-family DNA polymerase, DNA Pol λ. The high predictability observed in human cells seemed linked to the template-dependent activity of human DNA Pol λ. However, this predictability cannot be directly extended to plants due to the dual activities of the plant homolog, capable of generating 1-bp insertions through both templated and non-templated manners. While knocking out DNA Pol λ led to deletion-only mutations, its overexpression enhanced 1-bp insertion by 1.2 - 2 folds at multiple target sites in plants. These findings unveiled the underlying mechanism dictating unique CRISPR-Cas9-induced insertion profiles across species and presented new strategies for achieving predictable and precise genome editing through c-NHEJ.

Colorectal cancer is a leading cause of cancer-related mortality worldwide. Approximately 3–5% of colorectal tumors harbor human epidermal growth factor receptor ( HER2) amplification which is associated with a higher incidence of intracranial metastasis and overall worse outcomes. In the setting of refractory metastatic RAS wild-type tumors, evidence supports the use of various HER2-blocking agents, including monoclonal antibodies, tyrosine kinase inhibitors, and novel antibody–drug conjugates. With a number of relatively active agents clinically available and even more in development, it is crucial for clinicians to familiarize themselves with the mechanisms of action, efficacy data, and safety profiles of these treatments. In this review, we aim to summarize key findings from past and ongoing trials with anti-HER2 agents in metastatic colorectal cancer.

As the availability of extracorporeal membrane oxygenation (ECMO) expands, so has the need for interfacility transfer to ECMO centers. However, the impact of these transfers is unknown. We hypothesized that interfacility transfers would be associated with increased complications and mortality. This retrospective cohort study includes adult patients treated with venovenous (VV) ECMO at all four adult ECMO centers comprising our statewide registry. Complications, mortality, ECMO duration, length of stay, and disposition were compared based on cannulation at an ECMO center versus outside hospital and transferred by air versus ground after adjusting for baseline covariates/parameters. The study included 420 adult patients, 36% of whom were cannulated at an outside institution before transfer. Of these, 63% were transported by ground and the remainder by air. Risk adjusted logistic regression revealed similar odds of mortality between those cannulated at ECMO centers versus referring hospital and then transported (odds ratio [OR] = 0.77, confidence interval [CI] = 0.49–1.22). This study supports the practice of interfacility ECMO transfer.