Alcohol-related liver disease (ALD) refers to the liver damage occurring due to excessive alcohol consumption and involves a broad spectrum of diseases that includes liver steatosis, steatohepatitis, hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The progression of ALD is mainly associated with the amount and duration of alcohol usage; however, it is also influenced by genetic, epigenetic, and environmental factors. The definite diagnosis of ALD is based on a liver biopsy, although several non-invasive diagnostic tools and serum biomarkers have emerging roles in the early detection of ALD. While alcohol abstinence and nutritional support remain the cornerstone of ALD treatment, growing evidence has revealed that the therapeutic agents that target oxidative stress or gut-liver axis, inflammatory response inhibition, and liver regeneration enhancement also play a role in ALD management. Furthermore, microRNAs modulation and mesenchymal stem cell-based therapy have emerging potential as ALD therapeutic options. This review summarizes the updated understanding of the pathophysiology, diagnosis, and novel therapeutic approaches for ALD.

Sepsis remains the leading cause of death in critically ill patients. Thus, regular measurement of lactate levels has been proposed in sepsis guidelines. Elevated red cell distribution width (RDW) is associated with mortality risk in patients with sepsis. This study aimed to investigate the association between RDW and the risk of other adverse outcomes in patients with sepsis and to compare the mortality discriminative ability between lactate and RDW levels. This is a single-centered, retrospective, case-control study that included 504 adult patients with sepsis in the emergency department between 1 January 2020 and 31 December 2020. Eligible patients were divided into normal (RDW ≤ 14.5%) and high (RDW > 14.5%) groups. The baseline characteristics and adverse outcomes were recorded and compared. Compared with the normal RDW group, the patients in the high RDW group had a significantly higher rate of ICU admission (48.8% vs. 32.4%, p = 0.03), septic shock (39.2% vs. 23.5%, p < 0.01), and 30-day in-hospital mortality (32.0% vs. 20.7%, p < 0.01). Furthermore, the RDW (area under curve (AUC) = 0.71) had superior mortality discriminative ability compared to lactate (AUC = 0.63) levels (p = 0.02). Clinicians could rely on this simple and rapid parameter for risk stratification to initiate prompt treatment for patients with sepsis.

Neoadjuvant concurrent chemoradiotherapy (CCRT), followed by radical proctectomy, is the standard treatment for locally advanced rectal cancer. However, a poor response and therapeutic resistance continue to occur despite this treatment. In this study, we analyzed the microarray datasets (GSE68204) of rectal cancer from the Gene Expression Omnibus database, and identified CHD4 as one of the most significantly up-regulated genes among all subunits of the nucleosome remodeling and histone deacetylation (NuRD) complex, in non-responders to CCRT, among locally advanced rectal cancer (LARC) patients. We confirmed the predictive and prognostic significance of CHD4 expression in CCRT treatment, and its correlation with other clinicopathological features, such as tumor regression grade (TRG), therapeutic response, and patient survival. This was carried out by immunohistochemical studies on endoscopic biopsy tissues from 172 rectal cancer patients, receiving neoadjuvant concurrent chemoradiotherapy (CCRT). A high expression of CHD4 was significantly associated with pre-treatment tumor status (p < 0.001) and lymph node metastasis (p < 0.001), post-treatment tumor status (p < 0.001), and lymph node metastasis (p < 0.001), vascular invasion (p = 0.042), and tumor regression grade (p = 0.001). A high expression of CHD4 could also predict poor disease-specific survival and metastasis-free survival (log-rank test, p = 0.0373 and p < 0.0001, respectively). In multivariate Cox proportional-hazards regression analysis, CHD4 overexpression was an independent factor of poor prognosis for metastasis-free survival (HR, 4.575; 95% CI, 1.717–12.192; p = 0.002). By in vitro studies, based on cell line models, we also demonstrated that, the overexpression of CHD4 induced radio-resistance in microsatellite instability-high (MSI-H) colorectal cells (CRCs). On the contrary, the knockdown of CHD4 enhanced radiosensitivity in microsatellite stable (MSS) CRCs. Altogether, we have identified CHD4 as an important regulator of radio-resistance in both MSI-H and MSS CRC cell lines.

The outbreak of coronavirus disease-2019 (COVID-19) has resulted in a global public health emergency. Patients with cirrhosis were deemed more susceptible to viral infection because of their dysregulated immune response. Similar to the general population, cirrhotic patients exhibit various degrees of COVID-19-related liver injury, which could be attributed to direct virus cytotoxicity, systemic immune system activation, drug-related liver injury, reactivation of pre-existing liver disease, and hypoxic hepatitis. The clinical symptoms in patients with cirrhosis and COVID-19 were similar to those in the general population with COVID-19, with a lower proportion of patients with gastrointestinal symptoms. Although respiratory failure is the predominant cause of mortality in cirrhotic patients with COVID-19, a significant proportion of them lack initial respiratory symptoms. Most evidence has shown that cirrhotic patients have relatively higher rates of morbidity and mortality associated with COVID-19. Advanced cirrhosis was also proposed as an independent factor affecting a poor prognosis and the need to consider COVID-19 palliative care. General measures implemented to prevent the transmission of the virus are also essential for cirrhotic patients, and they should also receive standard cirrhosis care with minimal interruptions. The efficacy of the available COVID-19 vaccines in cirrhotic patients still needs investigation.

Cirrhotic patients with bacteremia are at an increased risk of organ failure and mortality. In addition, they can develop serious infection without fever because of their impaired immune response. Our study aimed to investigate the clinical characteristics and outcomes in afebrile bacteremic patients with liver cirrhosis. A single-center, retrospective cohort study was performed on adult patients who visited the emergency department from January 2015 to December 2018. All patients with bacteremia and diagnosis of liver cirrhosis were enrolled and classified as either afebrile or febrile. In total, 104 bacteremic patients with liver cirrhosis (afebrile: 55 patients and, febrile: 49) were included in the study. Compared with the febrile group, patients in the afebrile group showed a significantly higher rate of inappropriate antibiotics administration (43.6% vs. 20.4%,p = 0.01). They were also at an increased risk of 30-day mortality (40% vs. 18.4%,p = 0.02), intensive care unit transfer (38.2% vs. 18.4%,p = 0.03) and endotracheal intubation (27.3% vs. 10.2%,p = 0.03). The afebrile state was also an independent risk factor associated with 30-day mortality in cirrhotic patients with bacteremia. Clinicians should perform a prudent evaluation in cirrhotic patients and carefully monitor for possible signs of serious infection even in the absence of fever.

The increasing prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections is a global concern. Elderly patients have a diminished immune response and functional reserve, and are thus more vulnerable to bacterial infection. This study aimed to investigate the risk factors and outcomes in elderly patients with community-acquired CRKP infections. We performed a retrospective cohort study in a tertiary medical center between 1 January 2021, and 31 December 2021. All elderly patients who visited the emergency department during this period with culture-positive K. pneumoniae were enrolled, and their baseline demographics, laboratory profiles, management strategies, and outcomes were recorded and analyzed. We identified 528 elderly patients with K. pneumonia infection, and the proportion of patients with CRKP infection was 10.2% (54/528). Recent intensive care unit (ICU) admission and prior carbapenem use are independent risk factors for CRKP infection in elderly patients. Compared to patients with carbapenem-sensitive K. pneumoniae infection, those with CRKP infection had a significantly higher risk of adverse outcomes, including ICU care, respiratory failure, septic shock, and 90-day mortality. CRKP infection was also identified as an independent risk factor for 90-day mortality. Clinicians should be aware of the increasing prevalence of CRKP infections in elderly patients and judiciously choose appropriate antibiotics for these patients.