Preclinical assessment and randomized Phase I study of CT-P63, a broadly neutralizing antibody targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in significant morbidity and mortality worldwide. Despite a successful vaccination programme, the emergence of mutated variants that can escape current levels of immunity mean infections continue. Herein, we report the development of CT-P63, a broad-spectrum neutralizing monoclonal antibody. In vitro studies demonstrated potent neutralizing activity against the most prevalent variants, including Delta and the BA.1 and BA.2 sub-lineages of Omicron. In a transgenic mouse model, prophylactic CT-P63 significantly reduced wild-type viral titres in the respiratory tract and CT-P63 treatment proved efficacious against infection with Beta, Delta, and Omicron variants of SARS-CoV-2 with no detectable infectious virus in the lungs of treated animals. A randomized, double-blind, parallel-group, placebo-controlled, Phase I, single ascending dose study in healthy volunteers (NCT05017168) confirmed the safety, tolerability, and pharmacokinetics of CT-P63. Twenty-four participants were randomized and received the planned dose of CT-P63 or placebo. The safety and tolerability of CT-P63 were evaluated as primary objectives. Eight participants (33.3%) experienced a treatment-emergent adverse event (TEAE), including one grade ≥3 (blood creatine phosphokinase increased). There were no deaths, treatment-emergent serious adverse events, TEAEs of special interest, or TEAEs leading to study drug discontinuation in the CT-P63 groups. Serum CT-P63 concentrations rapidly peaked before declining in a biphasic manner and systemic exposure was dose proportional. Overall, CT-P63 was clinically safe and showed broad-spectrum neutralizing activity against SARS-CoV-2 variants in vitro and in vivo.

Predictive performance of the quick Sequential Organ Failure Assessment score as a screening tool for sepsis, mortality, and intensive care unit admission in patients with febrile neutropenia.

PURPOSE: In Sepsis-3, the quick Sequential Organ Failure Assessment (qSOFA) score was developed as criteria to use for recognizing patients who may have poor outcomes. This study was performed to evaluate the predictive performance of the qSOFA score as a screening tool for sepsis, mortality, and intensive care unit (ICU) admission in patients with febrile neutropenia (FN). We also tried to compare its performance with that of the systemic inflammatory response syndrome (SIRS) criteria and Multinational Association of Supportive Care in Cancer (MASCC) score for FN. METHODS: We used a prospectively collected adult FN data registry. The qSOFA and SIRS scores were calculated retrospectively using the preexisting data. The primary outcome was the development of sepsis. The secondary outcomes were ICU admission and 28-day mortality. RESULTS: Of the 615 patients, 100 developed sepsis, 20 died, and 38 were admitted to ICUs. In multivariate analysis, qSOFA was an independent factor predicting sepsis and ICU admission. However, compared to the MASCC score, the area under the receiver operating curve of qSOFA was lower. qSOFA showed a low sensitivity (0.14, 0.2, and 0.23) but high specificity (0.98, 0.97, and 0.97) in predicting sepsis, 28-day mortality, and ICU admission. CONCLUSIONS: Performance of the qSOFA score was inferior to that of the MASCC score. The preexisting risk stratification tool is more useful for predicting outcomes in patients with FN.

Ultrasonographic assessment of optic nerve sheath diameter during pediatric laparoscopy.

This study investigated the extent of the raised intracranial pressure resulting from carbon dioxide (CO2) pneumoperitoneum by ultrasonographically measuring optic nerve sheath diameter (ONSD) in children undergoing laparoscopic surgery. Twenty-five children aged less than 9 y (53.1 ± 23.3 mo, mean ± standard deviation) and scheduled for an elective laparoscopic surgery participated. ONSD was assessed using ocular ultrasonography 10 min after induction of anesthesia (T0), 10 min after induction of CO2 pneumoperitoneum at 10 mm Hg intra-abdominal pressure (T1) and in an anesthetized state without CO2 pneumoperitoneum at the conclusion of the surgery (T2). During CO2 pneumoperitoneum, ONSD increased significantly compared with ONSD after anesthesia induction (T0: 4.3 ± 0.3 mm, T1: 4.6 ± 0.3 mm, p < 0.05). In all enrolled patients, any neurologic complications were not observed during the intra-operative or post-operative period. In children undergoing laparoscopic surgery, an increase in ONSD was ascertained during CO2 pneumoperitoneum, and thus the corresponding increase in intracranial pressure could be predicted.

Assessment of liver stiffness measurement: novel intraoperative blood loss predictor?

BACKGROUND: The risks of massive intraoperative blood loss are of major concern during liver surgery. Various predictors of massive intraoperative blood loss were reported for identifying patients preoperatively with high risk of suffering massive intraoperative blood loss during liver surgery. The assessment of the extent of fibrosis may be a way to predict the risk of the intraoperative blood loss in patients undergoing liver surgery. Liver stiffness measurement by transient elastography is a noninvasive method for assessing liver fibrosis in patients with chronic liver disease. The purpose of this retrospective, single-center study was to assess a correlation between liver stiffness measurement and intraoperative blood loss during liver surgery for determining the role of liver stiffness measurement as a predictor of intraoperative blood loss. METHODS: A total of 45 patients who underwent elective right hepatectomy from August 2007 to July 2011 were selected. Liver stiffness measurement, tumor size, intraoperative data, and perioperative laboratory data were retrospectively investigated. Correlation analysis was used to find the correlations between variables. RESULTS: Among the 45 patients enrolled in this study, 43 were ultimately investigated. A statistically positive correlation was found between the intraoperative blood loss and the median liver stiffness measurements (r = 0.420, p = 0.005). CONCLUSIONS: The liver stiffness measurement is a possible predictor of intraoperative blood loss through the correlation between liver stiffness measurement and the intraoperative blood loss during right hepatectomy.

Decision-making model for early diagnosis of congestive heart failure using rough set and decision tree approaches.

The accurate diagnosis of heart failure in emergency room patients is quite important, but can also be quite difficult due to our insufficient understanding of the characteristics of heart failure. The purpose of this study is to design a decision-making model that provides critical factors and knowledge associated with congestive heart failure (CHF) using an approach that makes use of rough sets (RSs) and decision trees. Among 72 laboratory findings, it was determined that two subsets (RBC, EOS, Protein, O2SAT, Pro BNP) in an RS-based model, and one subset (Gender, MCHC, Direct bilirubin, and Pro BNP) in a logistic regression (LR)-based model were indispensable factors for differentiating CHF patients from those with dyspnea, and the risk factor Pro BNP was particularly so. To demonstrate the usefulness of the proposed model, we compared the discriminatory power of decision-making models that utilize RS- and LR-based decision models by conducting 10-fold cross-validation. The experimental results showed that the RS-based decision-making model (accuracy: 97.5%, sensitivity: 97.2%, specificity: 97.7%, positive predictive value: 97.2%, negative predictive value: 97.7%, and area under ROC curve: 97.5%) consistently outperformed the LR-based decision-making model (accuracy: 88.7%, sensitivity: 90.1%, specificity: 87.5%, positive predictive value: 85.3%, negative predictive value: 91.7%, and area under ROC curve: 88.8%). In addition, a pairwise comparison of the ROC curves of the two models showed a statistically significant difference (p<0.01; 95% CI: 2.63-14.6).