Integrated SegFlow, µSIA, and UPLC for Online Sialic Acid Quantitation of Glycoproteins Directly from Bioreactors.

This study emphasizes the critical importance of closely monitoring and controlling the sialic acid content in therapeutic glycoproteins, including EPO, interferon-γ, Orencia, Enbrel, and others, as the level of sialylation directly impacts their pharmacokinetics (PK), immunogenicity, potency, and overall clinical performance due to its influence on protein clearance via hepatic asialoglycoprotein receptors (ASGPR). The ASGPR recognizes and binds to glycoproteins exposed to terminal galactose or N-acetylgalactosamine residues, leading to receptor-mediated endocytosis. Recent studies have demonstrated that sialylation of O-linked glycan plays a role in protecting against macrophage galactose lectin (MGL)-mediated clearance.

Harnessing the power of AI in precision medicine: NGS-based therapeutic insights for colorectal cancer cohort.

Purpose: Developing innovative precision and personalized cancer therapeutics is essential to enhance cancer survivability, particularly for prevalent cancer types such as colorectal cancer. This study aims to demonstrate various approaches for discovering new targets for precision therapies using artificial intelligence (AI) on a Polish cohort of colorectal cancer patients.

Methods: We analyzed 71 patients with histopathologically confirmed advanced resectional colorectal adenocarcinoma.

Remote, automatic, digital preanesthetic evaluation - are we there yet?

Recent years have witnessed multiple advancements in the field of information technology in medicine. The need to ensure patient and doctor safety during COVID-19 resulted in improved telemedicine adaptation across various fields, including anaesthesiology. In this review, the authors examine the current state of the elements of preanesthetic evaluation and their remote execution using current and future telemedical facilities and technologies, as well as the potential of future advancements in this field.

Analysis of Factors Determining Spleen Preservation during Laparoscopic Distal Pancreatectomy - A Cohort Study.

Background: Spleen preservation during laparoscopic distal pancreatectomy (LSPDP) should be pursued if safe and oncologically justified. The aim of the presented study was to compare surgical outcomes and identify risk factors for unplanned splenectomy during laparoscopic distal pancreatectomy and evaluate short and long-terms outcomes.

Methods: The following study is a retrospective cohort study of consecutive patients who underwent laparoscopic distal pancreatectomy, with the intention of preserving the spleen, for benign tumors of the body and tail of the pancreas between August 2012 and December 2022.

Rapid total sialic acid monitoring during cell culture process using a machine learning model based soft sensor.

Total sialic acid content (TSA) in biotherapeutic proteins is often a critical quality attribute as it impacts the drug efficacy. Traditional wet chemical assays to quantify TSA in biotherapeutic proteins during cell culture typically takes several hours or longer due to the complexity of the assay which involves isolation of sialic acid from the protein of interest, followed by sample preparation and chromatographic based separation for analysis. Here, we developed a machine learning model-based technology to rapidly predict TSA during cell culture by using typically measured process parameters.

Nutritional responsiveness affects novel neutrophil parameters and reduces in-hospital mortality and costs in elective cancer oesophagectomy - a single centre, prospective, observational study.

Introduction: Malnutrition in surgical patients remains a common issue affecting the perioperative period. Oesophageal cancer is a disease associated with one of the highest malnutrition rates. Assessment of patient nutritional status remains a challenge due to limited validated tools.

Use of spectroscopic process analytical technology for rapid quality evaluation during preparation of CHO cell culture media.

Media preparation parameters contribute significantly to media quality, cell culture performance, productivity, and product quality. Establishing proper media preparation procedures is critical for ensuring a robust CHO cell culture process. Process analytical technology (PAT) enables unique ways to quantify assessments and improve media quality.

Validation of a CFD model for cell culture bioreactors at large scale and its application in scale-up.

Among all the operating parameters that control the cell culture environment inside bioreactors, appropriate mixing and aeration are crucial to ensure sufficient oxygen supply, homogeneous mixing, and CO stripping. A model-based manufacturing facility fit approach was applied to define agitation and bottom air flow rates during the process scale-up from laboratory to manufacturing, of which computational fluid dynamics (CFD) was the core modeling tool. The realizable k-ε turbulent dispersed Eulerian gas-liquid flow model was established and validated using experimental values for the volumetric oxygen transfer coefficient (ka).

An innovative hybrid modeling approach for simultaneous prediction of cell culture process dynamics and product quality.

The use of hybrid models is extensively described in the literature to predict the process evolution in cell cultures. These models combine mechanistic and machine learning methods, allowing the prediction of complex process behavior, in the presence of many process variables, without the need to collect a large amount of data. Hybrid models cannot be directly used to predict final product critical quality attributes, or CQAs, because they are usually measured only at the end of the process, and more mechanistic knowledge is needed for many classes of CQAs.

Fed-batch performance profiles for mAb production using different intensified N - 1 seed strategies are CHO cell-line dependent.

Recent optimizations of cell culture processes have focused on the final seed scale-up step (N - 1 stage) used to inoculate the production bioreactor (N-stage bioreactor) to enable higher inoculation cell densities (2-20 × 10 cells/mL), which could shorten the production culture duration and/or increase the volumetric productivity. N - 1 seed process intensification can be achieved by either non-perfusion (enriched-batch or fed-batch) or perfusion culture to reach those higher final N - 1 viable cell densities (VCD). In this study, we evaluated how different N - 1 intensification strategies, specifically enriched-batch (EB) N - 1 versus perfusion N - 1, affect cell growth profiles and monoclonal antibody (mAb) productivity in the final N-stage production bioreactor operated in fed-batch mode.

Laparoscopic radical antegrade modular pancreatosplenectomy (RAMPS) for adenocarcinoma of the body and tail of the pancreas - technical considerations with analysis of surgical outcomes.

Purpose: The aim of this study was to establish whether laparoscopic RAMPS (L-RAMPS) is a safe procedure with better oncological outcomes compared to laparoscopic distal pancreatectomy (LDP) with splenectomy among patients with distal pancreatic ductal adenocarcinoma (PDAC).

Methods: This is a retrospective study performed on consecutive patients who underwent L-RAMPS and LDP with splenectomy for resectable or borderline resectable PDAC of the body and tail. In this paper, we presented our technique of laparoscopic RAMPS and analyzed intraoperative and perioperative complications, oncological efficacy, and long-term survival.

Splenectomy and tumor size are risk factors for serious perioperative morbidity of laparoscopic distal pancreatectomies.

<b><br>Introduction:</b> The determinants influencing the risk for complications of laparoscopic distal pancreatectomies (LDP) are not yet fully defined, thus we aimed to determine risk factors for serious perioperative morbidity after LDP with spleen preservation, LDP and radical antegrade modular pancreatosplenectomy for adenocarcinoma of the body and tail of the pancreas (RAMPS).</br> <b><br>Material and methods:</b> Retrospective cohort study of consecutive patients that underwent LDP between January 2019 and December 2022. The study group included cases of serious perioperative morbidity (III-V grades in Clavien-Dindo classification) during a 30-day period after operation.

The use of the ERAS protocol in malnourished and properly nourished patients undergoing elective surgery: a questionnaire study.

Introduction: Enhanced recovery after surgery (ERAS) is a modern approach to perioperative management. This study aimed to evaluate compliance with certain aspects of the ERAS protocol in malnourished and properly nourished patients undergoing elective surgery.

Material And Methods: A questionnaire study was conducted among 197 patients undergoing elective surgery at the university hospital.

Continuous lumbar erector spinae plane block as an alternative to epidural analgesia in pain treatment in patients undergoing hip replacement surgery - a prospective pilot study.

Introduction: Postoperative pain associated with hip replacement surgery can be severe, decreasing the patient's mobility and satisfaction with perioperative treatment. Regional techniques are commonly used as postoperative analgesia in hip surgery patients.

Material And Methods: We performed a prospective pilot study on patients undergoing hip replacement surgery.

Malnutrition risk in elective surgery patients and effectiveness of preoperative nutritional interventions at a pre-anaesthetic clinic: a 4-year apart, single-centre, observational study.

Introduction: Approximately 44% of all patients hospitalised for an elective surgical procedure have a malnutrition risk. In this study, we assessed the prevalence of malnutrition risk at a pre-anaesthetic clinic and the feasibility of introducing nutritional support. The primary objective of this study was to assess malnutrition risk prevalence in patients referred to a pre-anaesthetic clinic.

The impact of bacterial superinfections on the outcome of critically ill patients with COVID-19 associated acute respiratory distress syndrome (ARDS) - a single-centre, observational cohort study.

Introduction: Bacterial superinfections are common in severely ill COVID-19 patients and could be associated with a significant increase in morbidity and mortality.

Material And Methods: We assessed 29 critically ill patients treated in a university hospital's intensive care unit (ICU). Each patient required mechanical ventilation due to COVID-19-induced acute respiratory distress syndrome (ARDS).

Recent advances in upstream process development for production of recombinant adeno-associated virus.

Recombinant adeno-associated virus (rAAV) is rapidly emerging as the preferred delivery vehicle for gene therapies, with promising advantages in safety and efficacy. Key challenges in systemic in-vivo rAAV gene therapy applications are the gap in production capabilities versus potential market demand and complex production process. This review summarizes current available information on rAAV upstream manufacturing processes and proposed optimizations for production.

Initial experience with laparoscopic revisional single anastomosis duodeno-ileal bypass (SADI-S) after failed sleeve gastrectomy.

Introduction: Laparoscopic sleeve gastrectomy (SG) is currently the most commonly performed bariatric operation, but re-do surgery may be necessary in up to half of the patients. Single anastomosis duodeno-ileal bypass (SADI-S) is quickly gaining recognition as a revisional procedure after failed SG.

Aim: To discuss the surgical technique and analyze initial outcomes after introduction of SADI-S after SG with 1-year follow-up.

Creating an Innovative Artificial Intelligence-Based Technology (TCRact) for Designing and Optimizing T Cell Receptors for Use in Cancer Immunotherapies: Protocol for an Observational Trial.

Background: Cancer continues to be the leading cause of mortality in high-income countries, necessitating the development of more precise and effective treatment modalities. Immunotherapy, specifically adoptive cell transfer of T cell receptor (TCR)-engineered T cells (TCR-T therapy), has shown promise in engaging the immune system for cancer treatment. One of the biggest challenges in the development of TCR-T therapies is the proper prediction of the pairing between TCRs and peptide-human leukocyte antigen (pHLAs).

Population Pharmacokinetics and Probability of Target Attainment Analysis of Nadroparin in Different Stages of COVID-19.

Background And Objective: The risk of thrombotic complications in critical patients with COVID-19 remains extremely high, and multicenter trials failed to prove a survival benefit of escalated doses of low-molecular-weight heparins (nadroparin calcium) in this group. The aim of this study was to develop a pharmacokinetic model of nadroparin according to different stages of COVID-19 severity.

Methods: Blood samples were obtained from 43 patients with COVID-19 who received nadroparin and were treated with conventional oxygen therapy, mechanical ventilation, and extracorporeal membrane oxygenation.

Strategies for controlling afucosylation in monoclonal antibodies during upstream manufacturing.

Core fucosylation is a highly prevalent and significant feature of N-glycosylation in therapeutic monoclonal antibodies produced by mammalian cells where its absence (afucosylation) plays a key role in treatment safety and efficacy. Notably, even slight changes in the level of afucosylation can have a considerable impact on the antibody-dependent cell-mediated cytotoxicity. Therefore, implementing control over afucosylation levels is important in upstream manufacturing to maintain consistent quality across batches of product, since standard downstream processing does not change afucosylation.