Risk factors for acute kidney injury and impact of earlier anticoagulation on renal function in patients with normotensive pulmonary embolism: a retrospective cohort study.

OBJECTIVE: We aimed to investigate the risk factors for acute kidney injury (AKI) after normotensive pulmonary embolism (PE) and the impact of anticoagulation on renal recovery. DESIGN: Multicentred, retrospective cohort study. SETTING: Data from four tertiary hospitals in China were captured. All available measurements of serum creatinine (SCr) during hospitalisation and follow-up were collected. PARTICIPANTS: Patients with acute PE and those without haemodynamic instability were enrolled. All recruited patients were followed up for up to 2 years. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the occurrence of AKI, defined by the Kidney Disease Improving Global Outcomes criteria. The secondary outcome was the recovery of renal function. The time interval between PE onset and the initiation of anticoagulation was analysed to obtain its influence on the recovery of renal function. RESULTS: A total of 461 patients with acute normotensive PE were enrolled. A transient elevation of SCr during hospitalisation was observed. The incidence of AKI among normotensive patients was 18.9%. Brain natriuretic peptide (BNP) NT-proBNP elevation (adjusted HR (aHR) 2.27, 95% CI 1.33 to 3.86) and history of chronic kidney disease (aHR 4.81, 95% CI 2.44 to 9.48) were associated with the development of AKI during hospitalisation. Earlier initiation of anticoagulation therapy (within 5 days after PE onset, compared with over 6 days) promoted an early recovery of renal function (adjusted OR 0.26, 95% CI 0.08 to 0.84, p=0.025). CONCLUSIONS: Renal impairment and AKI were highly prevalent among patients with normotensive patients. The occurrence of AKI was associated with right heart function. Patients who developed AKI after PE would benefit from earlier anticoagulation therapy for an early recovery of renal function.

Efficacy and safety of anticoagulant for treatment and prophylaxis of VTE patients with renal insufficiency: a systemic review and meta-analysis.

Patients with venous thromboembolism (VTE) comorbid renal insufficiency (RI) are at higher risk of bleeding and thrombosis. Recommendations in guidelines on anticoagulation therapy for those patients remain ambiguous. The goal of this study is to compare the efficacy and safety between different anticoagulant regimens in VTE patients comorbid RI at different stages of treatment and prophylaxis. We performed English-language searches of Pubmed, EMBASE, and Web of Science (inception to Nov 2022). RCTs evaluated anticoagulants for VTE treatment at the acute phase, extension phase, and prophylaxis in patients with RI and reported efficacy and safety outcomes were selected. The methodological quality of the studies was assessed at the outcome level using the risk-of-bias assessment tool developed by the Cochrane Bias Methods Group. A meta-analysis of twenty-five RCTs was conducted, comprising data from twenty-three articles, encompassing a total of 9,680 participants with RI. In the acute phase, the risk of bleeding was increased with novel oral anticoagulants (NOACs) compared to LMWH (RR 1.29, 95% CI 1.04-1.60). For the prophylaxis of VTE, NOACs were associated with an elevated risk of bleeding compared with placebo (RR 1.31, 95%CI 1.02-1.68). In comparison to non-RI patients, both NOACs and vitamin K antagonists (VKA) could increase the risk of bleeding among RI patients (RR 1.45, 95%CI 1.14-1.84 and RR 1.53, 95%CI 1.25-1.88, respectively) during acute phase, while NOACs may increase the incidence of VTE in RI population (RR 1.74, 95%CI 1.29-2.34). RI patients who are under routine anticoagulation have a significantly higher risk of adverse outcomes. LMWH is the most effective and safe option for VTE treatment or prophylaxis in patients with RI.

The relationship between VDR polymorphisms and keratinocyte carcinomas: a systematic review and meta-analysis.

Aim: To perform a meta-analysis to assess the association between common VDR polymorphisms (Fok1, Taq1, Apa1, Bsm1) and keratinocyte carcinomas (KCs) susceptibility. Methods & materials: databases were searched up to November 2021. Odds ratios (ORs) with 95% CIs were evaluated in the association. Results: This meta-analysis included seven articles. KC (and its subtypes) risks are found to be associated with Fok1 (BCC: ff vs FF+Ff: OR = 2.13, 95% CI = 1.14-3.97; SCC: ff vs FF+Ff: OR = 1.54, 95% CI = 1.09-2.18) and Taq1 (BCC: Tt vs TT: OR = 1.99, 95% CI = 1.35-2.93; tt vs TT: OR = 2.09, 95% CI = 1.27-3.43; Tt +tt vs TT: OR = 2.02, 95% CI = 1.41-2.90) polymorphisms. Conclusion: This study suggests that the Fok1 f allele and the Taq1 t allele are associated with increased susceptibility to KC and its subtypes.

Growth and Viability of Cutaneous Squamous Cell Carcinoma Cell Lines Display Different Sensitivities to Isoform-Specific Phosphoinositide 3-Kinase Inhibitors.

Cutaneous squamous cell carcinomas (cSCCs) account for about 20% of keratinocyte carcinomas, the most common cancer in the UK. Therapeutic options for cSCC patients who develop metastasis are limited and a better understanding of the biochemical pathways involved in cSCC development/progression is crucial to identify novel therapeutic targets. Evidence indicates that the phosphoinositide 3-kinases (PI3Ks)/Akt pathway plays an important role, in particular in advanced cSCC. Questions remain of whether all four PI3K isoforms able to activate Akt are involved and whether selective inhibition of specific isoform(s) might represent a more targeted strategy. Here we determined the sensitivity of four patient-derived cSCC cell lines to isoform-specific PI3K inhibitors to start investigating their potential therapeutic value in cSCC. Parallel experiments were performed in immortalized keratinocyte cell lines. We observed that pan PI3Ks inhibition reduced the growth/viability of all tested cell lines, confirming the crucial role of this pathway. Selective inhibition of the PI3K isoform p110α reduced growth/viability of keratinocytes and of two cSCC cell lines while affecting the other two only slightly. Importantly, p110α inhibition reduced Akt phosphorylation in all cSCC cell lines. These data indicate that growth and viability of the investigated cSCC cells display differential sensitivity to isoform-specific PI3K inhibitors.