Liver disease is frequently asymptomatic, challenging early identification in the primary care setting. The fibrosis 4 (FIB4) index is a liver fibrosis biomarker that is a potential alternative to liver biopsy for diagnosing and managing liver disease. This study aimed to calculate the FIB4 index for screening individuals at high risk of liver disease at the community level. This was a retrospective real-world study analyzing blood and serum test results from a central laboratory. The primary outcome was the number of individuals within each risk category for hepatic fibrosis: high risk (FIB4 ≥ 3.25) and low risk (FIB4 < 1.3). The analysis included samples from 31,753 patients, of which 18,102 were aged 40 to 75 years. In these patients, the FIB4 index had been explicitly requested in 1852 (10.2%) cases and estimated ad hoc in the rest. Of the 263 (1.5%) cases with FIB4 ≥ 3.25, the FIB4 index was requested in 46 (17.5%), and 52 (19.8%) showed evidence of liver fibrosis in their medical records, while the rest did not report any data regarding liver fibrosis. FIB4 is a simple score that can play a role as a “red flag” for early identification of patients at high risk of advanced liver fibrosis and their referral to specialized care.

Few validated biomarker or clinical score combinations exist which can discriminate between cases of infection and other non-infectious conditions following activation of an in-hospital sepsis code, as well as provide an accurate severity assessment of the corresponding host response. This study aimed to identify suitable blood biomarker (MR-proADM, PCT, CRP and lactate) or clinical score (SOFA and APACHE II) combinations to address this unmet clinical need. A prospective, observational study of patients activating the Vall d’Hebron University Hospital sepsis code (ISC) within the emergency department (ED), hospital wards and intensive care unit (ICU). Area under the receiver operating characteristic (AUROC) curves, logistic and Cox regression analysis were used to assess performance. 148 patients fulfilled the Vall d’Hebron ISC criteria, of which 130 (87.8%) were retrospectively found to have a confirmed diagnosis of infection. Both PCT and MR-proADM had a moderate-to-high performance in discriminating between infected and non-infected patients following ISC activation, although the optimal PCT cut-off varied significantly across departments. Similarly, MR-proADM and SOFA performed well in predicting 28- and 90-day mortality within the total infected patient population, as well as within patients presenting with a community-acquired infection or following a medical emergency or prior surgical procedure. Importantly, MR-proADM also showed a high association with the requirement for ICU admission after ED presentation [OR (95% CI) 8.18 (1.75–28.33)] or during treatment on the ward [OR (95% CI) 3.64 (1.43–9.29)], although the predictive performance of all biomarkers and clinical scores diminished between both settings. Results suggest that the individual use of PCT and MR-proADM might help to accurately identify patients with infection and assess the overall severity of the host response, respectively. In addition, the use of MR-proADM could accurately identify patients requiring admission onto the ICU, irrespective of whether patients presented to the ED or were undergoing treatment on the ward. Initial measurement of both biomarkers might therefore facilitate early treatment strategies following activation of an in-hospital sepsis code.

Slow-release delivery systems are needed to ensure long-term sustained treatments for retinal diseases such as age-related macular degeneration and diabetic retinopathy, which are currently treated with anti-angiogenic agents that require frequent intraocular injections. These can cause serious co-morbidities for the patients and are far from providing the adequate drug/protein release rates and required pharmacokinetics to sustain prolonged efficacy. This review focuses on the use of hydrogels, particularly on temperature-responsive hydrogels as delivery vehicles for the intravitreal injection of retinal therapies, their advantages and disadvantages for intraocular administration, and the current advances in their use to treat retinal diseases.

Nonalcoholic steatohepatitis (NASH) is a leading cause of cirrhosis in western countries. Insulin resistance (IR), type 2 diabetes (T2D), and the polymorphisms patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 and transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 are independent risk factors of NASH. Nevertheless, little is known about the interaction between IR and T2D with these polymorphisms in the pathogenesis of NASH and the development of advanced fibrosis. Thus, our study aimed to investigate this relationship. This is a cross-sectional study including NASH patients diagnosed by liver biopsy, at the Vall d’Hebron University Hospital. A total of 140 patients were included (93 T2D, 47 non-T2D). T2D (OR = 4.67; 95%CI 2.13–10.20; p < 0.001), PNPLA3 rs738409 and TM6SF2 rs58542926 polymorphisms (OR = 3.94; 95%CI 1.63–9.54; p = 0.002) were independently related with advanced liver fibrosis. T2D increased the risk of advance fibrosis on top of the two polymorphisms (OR = 14.69; 95%CI 3.03–77.35; p = 0.001 for PNPLA3 rs738409 and OR = 11.45; 95%CI 3.16–41.55; p < 0.001 for TM6SF2 rs58542926). In non-T2D patients, the IR (HOMA-IR ≥ 5.2, OR = 14.33; 95%CI 2.14–18.66; p = 0.014) increased the risk of advanced fibrosis when the polymorphisms were present (OR = 19.04; 95%CI 1.71–650.84; p = 0.042). The T2D and IR status increase the risk of advanced fibrosis in patients with NASH carrying the PNPLA3 rs738409 and/or TM6SF2 rs58542926 polymorphisms, respectively.

Early diagnosis and appropriate treatments are crucial to reducing mortality risk in septic patients. Low SOFA scores and current biomarkers may not adequately discern patients that could develop severe organ dysfunction or have an elevated mortality risk. The aim of this prospective observational study was to evaluate the predictive value of the biomarkers mid-regional pro-adrenomedullin (MR-proADM), procalcitonin (PCT), C-reactive protein (CRP), and lactate for 28-day mortality in patients with sepsis, and patients with a SOFA score ≤6. 284 were included, with a 28-day all-cause mortality of 8.45% (n = 24). Non-survivors were older (p = 0.003), required mechanical ventilation (p = 0.04), were ventilated for longer (p = 0.02), and had higher APACHE II (p = 0.015) and SOFA (p = 0.027) scores. Lactate showed the highest predictive ability for all-cause 28-day mortality, with an area under the receiver-operating characteristic curve (AUROC) of 0.67 (0.55–0.79). The AUROC for all-cause 28-day mortality in patients with community-acquired infection was 0.69 (0.57–0.84) for SOFA and 0.70 (0.58–0.82) for MR-proADM. A 2.1 nmol/L cut-off point for this biomarker in this subgroup of patients discerned, with 100% sensibility, survivors from non-survivors at 28 days. In patients with community-acquired sepsis and initial SOFA score ≤ 6, MR-proADM could help identify patients at risk of 28-day mortality.

Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) have been traditionally linked to one another. Recent studies suggest that NAFLD may be increasingly common in other types of diabetes such as type 1 diabetes (T1DM) and less frequently ketone-prone and Maturity-onset Diabetes of the Young (MODY) diabetes. In this review, we address the relationship between hyperglycemia and insulin resistance and the onset and progression of NAFLD. In addition, despite the high rate of patients with T2DM and other diabetes phenotypes that can alter liver metabolism and consequently develop steatosis, fibrosis, and cirrhosis, NALFD screening is not still implemented in the daily care routine. Incorporating a clinical algorithm created around a simple, non-invasive, cost-effective model would identify high-risk patients. The principle behind managing these patients is to improve insulin resistance and hyperglycemia states with lifestyle changes, weight loss, and new drug therapies.