Concomitant Hepatorenal Dysfunction and Malnutrition in Valvular Heart Surgery:Long-Term Prognostic Implications for Death and Heart Failure

BACKGROUND: Strategies to improve long-term prediction of heart failure and death in valvular surgery are urgently needed because of an increasing number of procedures globally. This study sought to report the prevalence, changes, and prognostic implications of concomitant hepatorenal dysfunction and malnutrition in valvular surgery. METHODS AND RESULTS: In 909 patients undergoing valvular surgery, 3 groups were defined based on hepatorenal function (the modified model for end-stage liver disease excluding international normalized ratio score) and nutritional status (Controlling Nutritional Status score): normal hepatorenal function and nutrition (normal), hepatorenal dysfunction or malnutrition alone (mild), and concomitant hepatorenal dysfunction and malnutrition (severe). Overall, 32%, 46%, and 19% of patients were classified into normal, mild, and severe groups, respectively. Over a 4.1-year median follow-up, mild and severe groups in-curred a higher risk of mortality (hazard ratio [HR], 3.17 [95% CI, 1.40–7.17] and HR, 9.30 [95% CI, 4.09– 21.16], respectively), cardiovascular death (subdistribution HR, 3.29 [95% CI, 1.14– 9.52] and subdistribution HR, 9.29 [95% CI, 3.09– 27.99]), heart failure hospitalization (subdistribution HR, 2.11 [95% CI, 1.25– 3.55] and subdistribution HR, 3.55 [95% CI, 2.04– 6.16]), and adverse outcomes (HR, 2.11 [95% CI, 1.25– 3.55] and HR, 3.55 [95% CI, 2.04– 6.16]). Modified model for end-stage liver disease excluding international normalized ratio and controlling nutritional status scores improved the predictive ability of European System for Cardiac Operative Risk Evaluation (area under the curve: 0.80 versus 0.73, P<0.001) and Society of Thoracic Surgeons score (area under the curve: 0.79 versus 0.72, P=0.004) for all-cause mortality. One year following surgery (n=707), patients with persistent concomitant hepatorenal dysfunction and malnutrition (severe) experienced worse outcomes than those without.  CONCLUSIONS: Concomitant hepatorenal dysfunction and malnutrition was frequent and strongly linked to heart failure and mortality in valvular surgery

Trends in contemporary advanced heart failure management: an in-depth review over 30 years of heart transplant service in Hong Kong

Background : The year 2022 marks the 30th anniversary of heart transplant service in Hong Kong (HK). In this study, we describe prevailing trends and outcomes of advanced heart failure (AHF), including heart transplantations (HTx), in HK over the past 30 years. Methods : Trends in heart failure prevalence in HK from 1993 to 2021 were analyzed based on data from the Hospital Authority Clinical Data and Reporting System. All AHF patients referred for HTx consideration between 1992 and 2021 were reviewed. The bridge-to-transplant (BTT) utilization of short-term mechanical circulatory support (ST-MCS) devices, including venoarterial extracorporeal membrane oxygenation (VA-ECMO) and durable left ventricular assist devices (LVADs), from 2010 to 2021 was reviewed. Results : Overall, 237 heart transplants were performed in HK, with 10-year posttransplant and median survival of 68.1% and 18.7 years, respectively. An increase in AHF clinic referrals was correlated with increasing heart failure prevalence (R2=0.635, P<0.001). In total, 146 referrals were made for ST-MCS, and an observed increase in ST-MCS referrals was correlated with increasing VA-ECMO utilization (R2=0.849, P<0.001). Among 62 patients accepted for AHF therapy, those with durable LVAD implementation had better 1-year survival (71.5%) than those receiving an extracorporeal CentriMag (Levitronix) device as BTT (40%, P=0.008). In total, 143 LVADs were implanted, with 130 as BTT or bridge-to-candidacy (BTC) methods. The survival rate among the 130 BTT/BTC LVAD patients resembled that of HTx recipients (73.8% vs. 69.8% at 9 years, P=0.296). Conclusions: The burden of AHF management has increased and gained complexity over the past 30 years in Hong Kong

A bipotential organoid model of respiratory epithelium recapitulates high infectivity of SARS-CoV-2 Omicron variant

The airways and alveoli of the human respiratory tract are lined by two distinct types of epithelium, which are the primary targets of respiratory viruses. We previously established long-term expanding human lung epithelial organoids from lung tissues and developed a 'proximal' differentiation protocol to generate mucociliary airway organoids. However, a respiratory organoid system with bipotential of the airway and alveolar differentiation remains elusive. Here we defined a 'distal' differentiation approach to generate alveolar organoids from the same source for the derivation of airway organoids. The alveolar organoids consisting of type I and type II alveolar epithelial cells (AT1 and AT2, respectively) functionally simulate the alveolar epithelium. AT2 cells maintained in lung organoids serve as progenitor cells from which alveolar organoids derive. Moreover, alveolar organoids sustain a productive SARS-CoV-2 infection, albeit a lower replicative fitness was observed compared to that in airway organoids. We further optimized 2-dimensional (2D) airway organoids. Upon differentiation under a slightly acidic pH, the 2D airway organoids exhibit enhanced viral replication, representing an optimal in vitro correlate of respiratory epithelium for modeling the high infectivity of SARS-CoV-2. Notably, the higher infectivity and replicative fitness of the Omicron variant than an ancestral strain were accurately recapitulated in these optimized airway organoids. In conclusion, we have established a bipotential organoid culture system able to reproducibly expand the entire human respiratory epithelium in vitro for modeling respiratory diseases, including COVID-19