The utility of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) utility in predicting immune-related adverse events (irAEs) and survival have not been well studied in the context of treatment with immune checkpoint inhibitors (ICIs). We performed a case-control study of cancer patients who received at least one dose of ICI in a tertiary hospital. We examined NLR and PLR in irAE cases and controls. Logistic and Cox regression models were used to identify independent risk factors for irAEs, progression-free survival (PFS), and overall survival (OS). The study included 91 patients with irAEs and 56 controls. Multiple logistic regression showed that NLR < 3 at baseline was associated with higher occurrence of irAEs. Multivariate Cox regression showed that development of irAEs and reduction in NLR from baseline to week 6 were associated with longer PFS. Higher NLR values at baseline and/or week 6 were independently associated with shorter OS. A reduction in NLR from baseline to week 6 was associated with longer OS. In this study of cancer patients treated with ICIs, NLR has a bidirectional relationship with adverse outcomes. Lower NLR was associated with increased occurrence of irAEs while higher NLR values were associated with worse clinical outcomes.
Although the incidence of venous thromboembolism (VTE) in Asian populations is lower than in Western countries, the overall burden of VTE in Asia has been considerably underestimated. Factors that may explain the lower prevalence of VTE in Asian populations relative to Western populations include the limited availability of epidemiological data in Asia, ethnic differences in the genetic predisposition to VTE, underdiagnoses, low awareness toward thrombotic disease, and possibly less symptomatic VTE in Asian patients. The clinical assessment, diagnostic testing, and therapeutic considerations for VTE are, in general, the same in Asian populations as they are in Western populations. The management of VTE is based upon balancing the treatment benefits against the risk of bleeding. This is an especially important consideration for Asian populations because of increased risk of intracranial hemorrhage with vitamin K antagonists. Non-vitamin K antagonist oral anticoagulants have shown advantages over current treatment modalities with respect to bleeding outcomes in major phase 3 clinical trials, including in Asian populations. Although anticoagulant therapy has been shown to reduce the risk of postoperative VTE in Western populations, VTE prophylaxis is not administered routinely in Asian countries. Despite advances in the management of VTE, data in Asian populations on the incidence, prevalence, recurrence, risk factors, and management of bleeding complications are limited and there is need for increased awareness. To that end, this review summarizes the available data on the epidemiology, risk stratification, diagnosis, and treatment considerations in the management of VTE in Asia.
Iptacopan (LNP023) is a novel, oral selective inhibitor of complement factor B under clinical development for paroxysmal nocturnal hemoglobinuria (PNH). In this ongoing open-label phase 2 study, PNH patients with active hemolysis were randomized to receive single-agent iptacopan twice daily at a dose of either 25 mg for 4 weeks followed by 100 mg for up to 2 years (cohort 1) or 50 mg for 4 weeks followed by 200 mg for up to 2 years (cohort 2). At the time of interim analysis, of 13 PNH patients enrolled, all 12 evaluable for efficacy achieved the primary endpoint of reduction in serum lactate dehydrogenase (LDH) levels by ≥60% by week 12 compared with baseline; mean LDH levels dropped rapidly and durably, namely by 77% and 85% at week 2 and by 86% and 86% at week 12 in cohorts 1 and 2, respectively. Most patients achieved a clinically meaningful improvement in hemoglobin (Hb) levels, and all but 1 patient remained transfusion-free up to week 12. Other markers of hemolysis, including bilirubin, reticulocytes, and haptoglobin, showed consistent improvements. No thromboembolic events were reported, and iptacopan was well tolerated, with no severe or serious adverse events reported until the data cutoff. In addition to the previously reported beneficial effect of iptacopan add-on therapy to eculizumab, this study showed that iptacopan monotherapy in treatment-naïve PNH patients resulted in normalization of hemolytic markers and rapid transfusion-free improvement of Hb levels in most patients. This trial was registered at www.clinicaltrials.gov as #NCT03896152.
18 May 2019 in Journal of Thrombosis and Haemostasis
The early identification of patients at risk of severe dengue infection (DI) is critical to guide clinical management. There is currently no validated laboratory test which can predict severe complications of DI. The Atypical lymphocyte count (ALC) is a research parameter generated at no extra cost when an automated Full Blood Count (FBC) is performed. The purpose of this study was to assess the association of ALC with the severity of DI. We prospectively collected data on patients admitted to Nawaloka Hospital Sri Lanka (NH) with DI between December 2016 and November 2017. DI was diagnosed based on a positive Non-structural antigen 1 (NS1) or dengue IgM antibody. ALC (absolute ALC and percentage) data were extracted from the Sysmex XS500i automated full blood count (FBC) analyzer (Sysmex Corporation Kobe, Japan). Clinical data was recorded from medical records and the computerized data base maintained by NH. 530 patients were enrolled. Patients with clinical manifestations of severe dengue have a significantly higher AL % compared to dengue without warning signs. Patients who presented with respiratory compromise had statistically significantly higher AL% compared to those without. (AL%; 8.65±12.09 vs 2.17±4.25 [p = 0.01]). Similarly, patients who developed hypotension had higher AL% compared to those who did not suffered from shock (AL%; 8.40±1.26 vs 2.18±4.25 [p = 0.001]). The AL% of dengue patients presenting with bleeding, at 4.07%, is also higher than those without bleeding complications, at 2.15%. There was a significant negative association between platelet count and AL% (p = 0.04). Clinical manifestations of severe dengue have a significantly higher AL % compared to dengue without warning signs. AL % at presentation may be predictive of severe DI and future larger prospective longitudinal studies should be done to determine if AL % on admission is predictive of the complications of DI.
Since emerging in China in December 2019, the infection caused by SARS‐CoV‐2, COVID‐19, has infected more than 3 million people worldwide (Johns Hopkins University and Medicine: Coronavirus Resource Center). Since then, clusters of infections have emerged in Singapore, particularly among younger workers in communal living environments. The spectrum of COVID‐19 infection ranges from mild respiratory illness, to viral pneumonia and life‐threatening acute respiratory distress syndrome in up 15‐20% (Huang, et al 2020, Wu and McGoogan 2020).