Serum Cytokine Levels for Predicting Immune-Related Adverse Events and the Clinical Response in Lung Cancer Treated with Immunotherapy

Analyses of the composition of peripheral cytokines hold promise for providing a basis for determining the prognosis of lung cancer treated with immunotherapy. In this study, we assessed correlations between interleukins in peripheral blood and the disease prognosis in patients with lung cancer. We retrospectively collected eligible adult patients with histologically confirmed lung cancer. Patients with immune-related adverse events (AE) from immunotherapy had higher pretreatment levels of IL-2 (p=0.002), IL-17 (p=0.01), and IFN-α (p=0.02) than patients with nonimmune-related adverse events (NAE). Univariate analysis showed that changes in IL-2 (p=0.04), IL-5 (p=0.007), IFN-α (p=0.003), IFN-γ (p=0.012) and TNF-α (p=0.049) levels were significantly increased in patients with AE compared with those with NAE before the second cycle of therapy. Patients with a clinical benefit had higher levels of IL-17 before the third cycle than patients without a clinical benefit. No significant cytokine differences were observed between patients with and without a clinical benefit undergoing ICI pretreatment or in the first two cycles of therapy. Plasma cytokines are related to immune-related adverse events and clinical responses, which are potential predictive markers for anti-PD-1/PD-L1 therapy in lung cancer patients and may play an important role in selecting patients who would benefit from PD-1/PD-L1 inhibitors.

Effusive–constrictive pericarditis after the second dose of BNT162b2 vaccine (comirnaty): a case report

Background Whereas effusive-constrictive pericarditis can rarely occur in COVID-19, to date no cases of effusive-constrictive pericarditis related to SARS-CoV2 vaccine have been documented. Case summary A 59-year-old caucasian man presented to our emergency department with effusive-constrictive pericarditis. Symptoms occurred shortly after the second dose of BNT162b2 (Comirnaty) vaccine. No other etiological causes were identified. Guidelines directed therapy for acute pericarditis was implemented, with clinical benefit. Discussion Systemic inflammatory response to COVID-19 can rarely trigger pericarditis. In our case a strong temporal relation between the second dose of BNT162b2 vaccine and symptoms occurrence was documented, indicating a possible rare adverse reaction to the vaccine, similarly to natural infection. Further research is needed to confirm a causal relationship.

Health technology assessment-informed pricing negotiation in China: higher negotiated price for more effective targeted anticancer medicines?

Background In China, health technology assessment (HTA) has recently been adopted in pricing negotiation for medicine listing in the National Reimbursement Drug List. At present, how HTA is applied to inform the decision-making process remains underreported. In order to explore how the adoption of HTA was translated into listing and price negotiation results in light of the confidential nature of the negotiating process, this study aimed to compare the negotiated price and the clinical benefit of selected targeted anticancer medicines (TAMs) involved in the 2019 negotiation. Main text Among 16 TAMs successfully negotiated, only four TAMs representing four indication groups had appropriate reference medicines for comparison and were, therefore, included in the analysis. The price and clinical benefit of the four TAMs were compared against one or two reference medicines with the same initial indications. The sales prices for nine TAMs before and after the negotiation were extracted from the centralized medication procurement system. Clinical benefits were evaluated based on evidence from published articles and clinical guidelines. The results suggested that, despite the application of HTA, both rational and irrational decisions had been made about the reimbursement of TAMs in the 2019 negotiation, warranting further investigation. Conclusion While the development and adoption of HTA has seen significant progress in China, actions are needed to ensure that the adoption of HTA is effectively applied in decisions on the reimbursement of medicines.

SARS-CoV-2 Omicron Spike recognition by plasma from individuals receiving BNT162b2 mRNA vaccination with a 16-weeks interval between doses

Continuous emergence of SARS-CoV-2 variants of concern (VOC) is fueling the COVID-19 pandemic. Omicron (B.1.1.529), is rapidly spreading worldwide. The large number of mutations in its Spike raised concerns about a major antigenic drift that could significantly decrease vaccine efficacy and infection-induced immunity. A long interval between BNT162b2 mRNA doses was shown to elicit antibodies that efficiently recognize Spikes from different VOCs. Here we evaluated the recognition of Omicron Spike by plasma from a cohort of SARS-CoV-2 naive and previously-infected individuals that received their BNT162b2 mRNA vaccine 16-weeks apart. Omicron Spike was recognized less efficiently than D614G, Alpha, Beta, Gamma and Delta Spikes. We compared to plasma activity from participants receiving a short (4-weeks) interval regimen. Plasma from individuals of the long interval cohort neutralized better the Omicron Spike compared to those that received a short interval. Whether this difference confers any clinical benefit against Omicron remains unknown.

Development and Internal Validation of a Nomogram to Predict Mortality During the ICU Stay of Thoracic Fracture Patients Without Neurological Compromise: An Analysis of the MIMIC-III Clinical Database

Background: This study aimed to develop and validate a nomogram for predicting mortality in patients with thoracic fractures without neurological compromise and hospitalized in the intensive care unit.Methods: A total of 298 patients from the Medical Information Mart for Intensive Care III (MIMIC-III) database were included in the study, and 35 clinical indicators were collected within 24 h of patient admission. Risk factors were identified using the least absolute shrinkage and selection operator (LASSO) regression. A multivariate logistic regression model was established, and a nomogram was constructed. Internal validation was performed by the 1,000 bootstrap samples; a receiver operating curve (ROC) was plotted, and the area under the curve (AUC), sensitivity, and specificity were calculated. In addition, the calibration of our model was evaluated by the calibration curve and Hosmer-Lemeshow goodness-of-fit test (HL test). A decision curve analysis (DCA) was performed, and the nomogram was compared with scoring systems commonly used during clinical practice to assess the net clinical benefit.Results: Indicators included in the nomogram were age, OASIS score, SAPS II score, respiratory rate, partial thromboplastin time (PTT), cardiac arrhythmias, and fluid-electrolyte disorders. The results showed that our model yielded satisfied diagnostic performance with an AUC value of 0.902 and 0.883 using the training set and on internal validation. The calibration curve and the Hosmer-Lemeshow goodness-of-fit (HL). The HL tests exhibited satisfactory concordance between predicted and actual outcomes (P = 0.648). The DCA showed a superior net clinical benefit of our model over previously reported scoring systems.Conclusion: In summary, we explored the incidence of mortality during the ICU stay of thoracic fracture patients without neurological compromise and developed a prediction model that facilitates clinical decision making. However, external validation will be needed in the future.

Atezolizumab alone or in combination did not demonstrate a favorable risk-benefit profile in myelodysplastic syndrome

We present here primary results from the phase Ib GO29754 study (NCT02508870) evaluating the safety and tolerability of atezolizumab, a PD-L1 inhibitor, alone and in combination with azacitidine, a hypomethylating agent (HMA), in patients with relapsed/refractory (R/R) or HMA-naïve myelodysplastic syndrome (MDS). R/R MDS patients received atezolizumab for 12 months (Cohort A), or atezolizumab plus azacitidine for six cycles followed by atezolizumab as maintenance for eight cycles (Cohort B). HMA-naïve MDS patients received atezolizumab plus azacitidine until loss of clinical benefit (Cohort C). Safety, activity, and exploratory endpoints were investigated. Forty-six patients were enrolled and received treatment (11 in Cohort A, 14 in Cohort B, 21 in Cohort C). All patients experienced ≥1 adverse event (AE) on study, and all patients discontinued atezolizumab. In Cohort A, seven patients (63.6%) died, and no patients responded. In Cohort B, eight patients (57.1%) discontinued azacitidine, 11 patients (78.6%) died, and two patients (14.3%) responded. In Cohort C, all 21 patients discontinued azacitidine, 13 patients died (61.9%), and 13 patients (61.9%) responded. The study was terminated by the sponsor prior to completing recruitment due to the unexpected high early death rate in Cohort C (6/13 deaths [46.2%] were due to AEs and occurred within the first four treatment cycles.). The high death rate and poor efficacy observed in this study do not support a favorable risk-benefit profile for atezolizumab as a single agent or in combination with azacitidine in R/R or HMA-naïve MDS.