We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound‐detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross‐sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, −0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40‐ligand (P = 0.0238), soluble Nox2‐derived peptide (sNox2‐dp; P < 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD40L (Spearman’s rank correlation coefficient [rs ], −0.33; P < 0.001), sNox2‐dp (rs , −0.57; P < 0.0001), and urinary excretion of isoprostanes (rs, −0.48; P < 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2‐dp, and urinary 8‐iso prostaglandin F2α‐III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2‐dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation.

Changes in immune and coagulation systems and possible viral spread through the blood–brain barrier have been described in SARS-CoV-2 infection. In this study, we evaluated the possible retinal involvement and ocular findings in severe COVID-19 pneumonia patients. A cross-sectional study was conducted on 46 patients affected by severe COVID-19 who were hospitalized in one intensive care unit (ICU) and in two infectious disease wards, including bedside eye screening, corneal sensitivity assessment and retinography. A total of 43 SARS-CoV-2-positive pneumonia patients affected with COVID-19 pneumonia were included, including 25 males and 18 females, with a median age of 70 years [IQR 59–78]. Except for one patient with unilateral posterior chorioretinitis of opportunistic origin, of whom aqueous tap was negative for SARS-CoV-2, no further retinal manifestation related to COVID-19 infection was found in our cohort. We found 3 patients (7%) with bilateral conjunctivitis in whom PCR analysis on conjunctival swabs provided negative results for SARS-CoV-2. No alterations in corneal sensitivity were found. We demonstrated the absence of retinal involvement in SARS-CoV-2 pneumonia patients. Ophthalmologic evaluation in COVID-19, particularly in patients hospitalized in an ICU setting, may be useful to reveal systemic co-infections by opportunistic pathogens.

Cirrhosis has been long considered a risk factor for bleeding due to the co-existence of the so-called ‘coagulopathy’.[1] [2] More recently, however, compelling evidences have been provided on the occurrence of thrombotic events in the portal and systemic circulation.[3] [4] [5] Portal vein thrombosis (PVT) is predominantly observed in patients with moderate to severe liver failure with a variable prevalence ranging from 0.6 to 25%.[6] [7] [8] Only few studies have provided a longitudinal assessment of the PVT incidence and its sequelae, including recurrence and survival.[9] [10] [11] [12] [13] [14] Due to the variability of PVT incidence and the paucity of data regarding recurrence and survival,[15] [16] [17] [18] [19] [20] we prospectively analysed the incidence and the recurrence of PVT in the population of Portal vein thrombosis Relevance On Liver cirrhosis: Italian Venous thrombotic Events Registry (PRO-LIVER), a multi-centre study,[8] which involved 43 enrolling centres in Italy (ClinicalTrials.gov Identifier: NCT01470547). The presence of PVT at baseline was assessed with Doppler ultrasound examination. By pre-set study criteria, PVT was first suspected when solid endoluminal material was detected in the main trunk of the portal vein and/or its branches, and it was confirmed by demonstration of a filling defect on the Doppler examination. Occlusive/complete PVT was defined by a thrombus leaving no channel for blood flow. Otherwise, PVT was considered non-occlusive/incomplete. In case of death, the circumstances and likely cause(s) were recorded. Survival curves were formally compared using the log-rank test. Cox proportional hazards analysis was used to calculate the adjusted relative hazards of outcome events by each clinical variable. Stochastic level of entry into the model was set at a p-value of 0.10, and interaction terms were explored for all the variables in the final model. Demographics and clinical characteristics of the population have been previously reported.[8] Seven hundred and fifty-three cirrhotic patients were followed up for a median of 21 (interquartile range [IQR]: 6.7–24) months yielding 1,008 patient-years of observation. During the observational period, 61 (8%) patients developed PVT (52% symptomatic): 36 (59%) of these were free from PVT at baseline and were considered as a new event (15.8 [9.4–21.0] months), 25 (41%) occurred in patients who displayed PVT at baseline and were, thus, classified as a recurrence (16.0 [12.0–24.0] months). The incidence rate of PVT was 6.05 per 100 patient-years in all patients, 4.1 per 100 patient-years in those without PVT at admission and 18.9 per 100 patient-years in those with PVT at admission. Among the 25 patients who displayed PVT recurrences, 7 (28%) were reported to take anticoagulants (n = 5, 20%) or anti-platelets (n = 2, 8%) at baseline. Complete thrombosis was detected in 15 (25%) patients; as for the location, in 33 (54%) patients PVT occurred only in the main trunk or one of its branches, while obstruction of more than one portal vein branches was present in 28 (46%) patients; an extension of thrombosis to the mesenteric–splenic veins was reported in 15 (24%) patients. [Table 1] reports the clinical characteristics of the patients according to the presence or not of PVT during the follow-up period; patients experiencing PVT had lower platelet count and previous PVT. Cox multivariable model showed that previous PVT (hazard ratio [HR]: 4.22, 95% confidence interval [CI]: 2.49–7.15, p < 0.001) ([Fig. 1A]) and being in the third lower tertile of platelets count (vs. the first) (HR: 3.52, 95% CI: 1.71–7.23, p = 0.001) were significantly and independently associated with the occurrence of PVT. During the study, 145 (19%) died (median [IQR] follow-up = 9.87 [3.6–16.3] months). Multivariable models demonstrated that only age (HR: 1.03, 95% CI: 1.02–1.05, p < 0.001), hepatocellular carcinoma (HR: 2.11, 95% CI: 1.49–2.98, p < 0.001), Child-Pugh classes B (HR: 5.61, 95% CI: 3.60–8.75, p < 0.001) and C (HR: 11.46, 95% CI: 6.95–18.88, p < 0.001) and PVT at the entry (HR: 1.70, 95% CI: 1.18–2.45, p = 0.004) ([Fig. 1B]) remained statistically significant as independent predictors of death. This study shows that in cirrhosis PVT is a risk factor for PVT recurrence and low survival. Previous analysis of PVT incidence in cirrhotic population was limited to patients with low to moderate cirrhosis and it was associated to an annual risk in average of 2%.[9] In this study, including patients with low to severe cirrhosis, the annual PVT incidence rate was 6.05%. This incidence, however, changes when a previous PVT is reported at the admission. Thus, the annual rate of PVT was much higher in patients with a history of PVT indicating that PVT per se carries a risk for recurrences. It is noteworthy that in the multivariable regression analysis, not only previous PVT, but also low platelet count independently predicted the occurrence of PVT event. This paradoxical association could reflect the platelet over-activation and consumption and consequent low platelet count due to a rapid platelet turnover.[21] During the follow-up, the survival rate of our population was 80.7%, which is consistent with other reports on this setting.[11] [20] In addition to the known association between hepatocellular carcinoma and liver failure versus low survival, we found that PVT at entry was per se an independent predictor of low survival. However, we have no element to suggest that PVT is a factor favouring low survival or is a mere reflection of disease severity as data regarding the mortality cause were incomplete. The study has implications and limitations. The study shows that cirrhosis is complicated by a high rate of PVT and that previous PVT is an independent predictor not only of PVT recurrence but also of low survival. The study opens...

We aimed to evaluate the diagnostic role of Alzheimer’s disease (AD) biomarkers in tears as well as their association with retinal and choroidal microstructures. In a cross-sectional study, 35 subjects (age 71.7 ± 6.9 years) were included: 11 with prodromal AD (MCI), 10 with mild-to-moderate AD, and 14 healthy controls. The diagnosis of AD and MCI was confirmed according to a complete neuropsychological evaluation and PET or MRI imaging. After tear sample collection, β-amyloid peptide Aβ1-42 concentration was analyzed using ELISA, whereas C-terminal fragments of the amyloid precursor protein (APP-CTF) and phosphorylated tau (p-tau) were assessed by Western blot. Retinal layers and choroidal thickness (CT) were acquired by spectral-domain optical coherence tomography (SD-OCT). Aβ1-42 levels in tears were able to detect both MCI and AD patients with a specificity of 93% and a sensitivity of 81% (AUC = 0.91). Tear levels of Aβ1-42 were lower, both in the MCI (p < 0.01) and in the AD group (p < 0.001) when compared to healthy controls. Further, Aβ1-42 was correlated with psychometric scores (p < 0.001) and CT (p < 0.01). CT was thinner in the affected patients (p = 0.035). No differences were observed for APP-CTF and p-tau relative abundance in tears. Testing Aβ1-42 levels in tears seems to be a minimally invasive, cost-saving method for early detection and diagnosis of AD.

Purpose: To investigate the incidence and risk factors for the main complications in patients with rhegmatogenous retinal detachment treated with scleral buckling (SB) or pars plana vitrectomy (PPV). Methods: A retrospective, comparative, observational study was conducted. The medical records of 107 patients with primary rhegmatogenous retinal detachment who were managed with SB (n = 57) or PPV (n = 50) were reviewed. Scleral buckling was performed using scleral encircling solid silicone band and circumferential solid silicone exoplant to support the break. Pars plana vitrectomy was combined with phacoemulsification in phakic eyes and with scleral encircling in inferior detachments. Follow-ups, including spectral-domain optical coherence tomography examination, were scheduled at 1, 3, and 12 months after surgery. Propensity score matching was used to adjust for potential preoperative selection bias. Results: The overall incidence of postoperative cystoid macular edema (CME) and epiretinal membrane was 14.95% and 30.84%, respectively. Compared with SB, CME was more frequent in the PPV (P = 0.021) and in the PPV pseudophakic eyes (P = 0.027). Postoperative CME was an early, predominantly transient complication and regressed in 67% of SB and in 77% of PPV eyes within 12 months after surgery. No differences were observed regarding epiretinal membrane development. Except for the surgical technique, no preoperative factors associated with CME were identified. A correlation between epiretinal membrane and patients' age was found (P = 0.028). Conclusion: The incidence of CME after rhegmatogenous retinal detachment repair was higher in patients who underwent PPV, either alone or combined with phacoemulsification, than in those treated with SB. Epiretinal membrane development was correlated to older age, regardless of the surgical procedure.