Search Results (767)

Recombinant monoclonal antibody (mAb) botulinum neurotoxin (BoNT) antitoxins, consisting of three mAbs that bind non-overlapping epitopes, are highly potent. However, the three-mAb mixtures pose unique development and manufacturing challenges. Combining even more mAbs to create multivalent antitoxin drugs multiplies those challenges. We previously reported that a single tri-epitopic IgG1-based mAb (TeAb) containing the variable domains of the three parental BoNT/A mAbs and an Fc was as potent as the combination of three IgGs in the mouse neutralization assay (MNA). Here, we extended the tri-epitopic strategy to three other BoNT serotypes. Each TeAb (TeAb-B for BoNT/B, TeAb-E for BoNT/E, and TeAb-F for BoNT/F) binding was measured using fluorescence-activated cell sorting and flow fluorimetry, and the potency was tested in the MNA. The three TeAbs displayed binding affinities that were the same within error of the parental IgGs for each epitope, and all had higher avidity to each serotype of BoNT than that of the parental mAbs. The potency of the BoNT/B, BoNT/E, and BoNT/F TeAbs was similar to the combinations of the three parental IgGs binding BoNT/B, BoNT/E, and BoNT/F in the MNA. We now have four examples of a single TeAb recapitulating the affinity and in vivo potency of a three-mAb antitoxin. The tri-epitopic strategy could be applied to streamline the production and bioanalytics of antibody drugs where three-mAb binding is required for activity. Full article

Background/Objectives: Iron deficiency anaemia (IDA) is a common complication in patients with colorectal cancer presenting for surgery. Perioperative IDA is associated with increased post-operative mortality and morbidity. The impact on clinical outcomes for the active management of anaemia before surgery, with treatments such as intravenous (IV) iron, is uncertain. Methods: We performed a single-centre nested cohort study, analysing prospectively collected data from patients with colorectal cancer who were treated with IV iron prior to elective major abdominal surgery. Cox proportional hazard models were used to quantify the effect of anaemia treatment on length of stay. Other outcomes, including transfusion rates, were estimated using logistic regression analyses. Models were adjusted for age, sex, comorbidities and surgical details. Results: The length of stay was longer for patients with untreated anaemia compared to patients without anaemia (adjusted hazard ratio, HR 0.66 [95% confidence interval, CI 0.45, 0.95]). For patients with anaemia, the length of stay was shorter in those treated when compared to those not treated (adjusted HR 0.59 [95% CI 0.45, 0.78]). Patients with untreated anaemia had higher transfusion rates than patients with treated anaemia (adjusted odds ratio, OR 0.35 [95% CI 0.18, 0.66]) and non-anaemic patients (adjusted odds ratio, OR 0.20 [95% CI 0.07, 0.55]). Conclusions: This study suggests that treating iron deficiency anaemia with IV iron pre-operatively reduces length of stay and transfusion rates in colorectal cancer patients. Full article

Background: Gallbladder cancer (GBC) is a highly aggressive malignancy often diagnosed at an advanced stage due to its asymptomatic onset. Despite surgery being the only potentially curative option, recurrence and poor prognosis remain common, especially in advanced-stage diseases. There is limited consensus regarding the extent of lymphadenectomy, hepatic resection, and the role of adjuvant therapies. Identifying prognostic factors and optimizing treatment strategies are critical for improving outcomes. This multicenter retrospective study was conducted to evaluate the clinical and pathological predictors of survival and recurrence in GBC patients that underwent radical surgery and to assess the potential benefit of adjuvant therapies in advanced stages. Methods: This was a retrospective cohort study of GBC patients who underwent curative-intent resection for GBC between 2010 and 2022 at two tertiary medical centers in China. The baseline characteristics, surgical data, pathology, adjuvant therapy, and follow-up outcomes were analyzed. The survival outcomes were assessed using Kaplan–Meier methods and Cox regression models. Subgroup analyses were conducted to explore the impact of postoperative adjuvant chemotherapy, period of surgical treatment, and extent of resection. Multiple imputation was used to address missing data. Results: The 5-year overall survival (OS) rate was 57.4%. Independent predictors of a poorer OS included CA19-9 > 30 U/mL (HR = 1.861, p = 0.003), poor/moderate-to-poor differentiation (HR = 2.134, p = 0.004), T3–T4 stage (HR = 2.685, p = 0.001), N1–N2 stage (HR = 2.217, p = 0.002), M1 stage (HR = 2.308, p = 0.001), and a high CAN score (HR = 1.875, p = 0.009). Adjuvant chemotherapy improved the OS in the stage III–IV patients (24.8 vs. 17.3 months, p = 0.036), though the DFS improvement was not significant (p = 0.133). No survival difference was observed between the segment IVb + V resection and wedge resection in the T2b patients. The patients treated after 2017 had a better OS (p = 0.024), possibly due to improved surgical techniques and perioperative care. Conclusions: Radical surgery remains critical for GBC. Accurate staging and tailored perioperative strategies, including chemotherapy, may improve outcomes, though further prospective studies are needed to validate these findings. Full article

Background: Hepatic resection is performed for liver lesions and requires careful preoperative planning to minimize bleeding. Blood type O, associated with lower von Willebrand factor (vWF) levels, may increase bleeding risk. This study investigates the relationship between the ABO blood type and perioperative bleeding in partial hepatectomy for colorectal liver metastases (CRLMs). Methods: Out of 563 patients who underwent hepatectomy, 135 cases were analyzed for CRLM at Carmel Medical Center (2013–2023). Patients were categorized into blood type O (61 patients) and non-O (74 patients) groups. Data on perioperative hemoglobin levels, blood loss, coagulation parameters, transfusion needs, and complications were assessed using χ², t-tests, and ANOVA (p < 0.05). Results: No significant differences were observed for estimated blood loss (474.3 ± 696 mL for O vs. 527.8 ± 599 mL for non-O; p = 0.29), intraoperative hemoglobin drop (p = 0.613), or transfusion rates (24.59% for O vs. 28.37% for non-O; p = 0.698). Although non-O patients had a higher postoperative INR (p = 0.035), this did not correlate with increased bleeding or transfusion needs. Conclusions: Blood type O does not significantly affect perioperative bleeding or transfusion requirements in partial hepatectomy for CRLM. Further research is needed to better understand the significance of the ABO blood type. Full article

Background: Bile leakage remains a significant challenge following major liver resection, with potential for improvement depending on the transection technique used. In this study, we aimed to evaluate the effectiveness of our hybrid resection technique—utilizing both LigaSure and stapler devices—in reducing bile leakage after major liver resection compared to our conventional stapler-only technique. As a secondary aim, we compared overall morbidity, costs, and reimbursements. Method: Patients who underwent major hepatectomy without biliary reconstruction using either the hybrid or stapler technique between August 2014 and December 2021 were included in the study. Propensity score matching was performed using a one-to-two algorithm. Perioperative data, bile leakage rates, and cost and reimbursement information based on the diagnosis-related group (DRG) system were analyzed. Results: In total, data from 492 patients were evaluated (hybrid = 152; stapler = 340). After one-to-two propensity score matching, the operation time was significantly longer in the hybrid group (p = 0.005). A cost analysis showed no significant difference in total operative costs between the two techniques (p = 0.092). However, the hybrid group had a significantly lower rate of bile leakage (p = 0.002), as well as shorter intensive care unit (ICU) and overall hospital stays (p = 0.034 and p = 0.007, respectively). Consequently, ICU and ward costs were significantly lower in the hybrid group (p = 0.024 and p = 0.014, respectively) compared to the stapler group. The financial difference calculated as DRG reimbursement minus costs was two-fold higher in the hybrid group (p = 0.02). Conclusions: Although the hybrid technique resulted in a longer operating time, it proved superior to the stapler technique in reducing postoperative bile leakage and shortening ICU and hospital stays. Furthermore, the use of the hybrid technique was more cost efficient and resulted in a greater positive financial margin. Full article

Background: Liver transplantation has become the standard of care for patients with end-stage liver disease. Despite advances in surgical techniques, immunosuppression, and perioperative care, disparities in access and outcomes persist across demographic and socioeconomic lines. Objective: To assess trends and disparities in liver transplant admissions in the United States from 2016 to 2021, examining demographic patterns, in-hospital mortality, hospital charges, length of stay, and socioeconomic factors. Methods: Using the National Inpatient Sample (NIS) from 2016 to 2021, we identified liver transplant admissions using ICD-10 PCS codes 0FY00Z1 and 0FY00Z2. Demographic characteristics (age, sex, race, insurance status, and income quartile), clinical outcomes, and resource utilization metrics were analyzed. One-way ANOVA and Hensel’s test were used to assess variance and distribution homogeneity, with a significance threshold of p < 0.05. Results: A total of 9677 liver transplant admissions were analyzed. The mean recipient age remained stable (51–52 years), with males comprising ~62% of transplants. White patients constituted the largest group of recipients (~66–68%), followed by Hispanic (~14–17%) and Black patients (~7–10%). The proportion of transplants relative to liver failure admissions remained stable across racial groups, indicating no widening racial gap during the study period. In-hospital mortality post-transplant remained low (2.37–3.52%) and did not differ significantly by race (p = 0.23), sex (p = 0.24), or income quartile (p = 0.13). Similarly, Charlson Comorbidity Index > 5 did not predict inpatient mortality (p = 0.154). Hospital charges ranged from $578,000 to $766,000, with an average stay of ~21 days. Conclusions: Liver transplantation outcomes, including in-hospital mortality, appear consistent across demographic and socioeconomic groups once patients are admitted for transplant. However, broader disparities in access persist, necessitating further research into pre-transplant barriers and long-term outcomes. These findings support the need for equitable healthcare strategies aimed at optimizing transplant candidacy and survival across all populations. Full article

Background: This systematic review aimed to evaluate the efficacy of immunoenhancing nutritional therapy compared to conventional nutritional care in reducing perioperative complications in adult patients undergoing surgery for oral cancer. Given the unclear role of immunonutrition in this specific surgical setting, we synthesized available randomized controlled trials to assess outcomes such as surgical site infections, wound healing complications, hospital stay, and adverse events. Methods: Patients who underwent planned oral cancer surgery were included. The intervention group received oral or enteral immunoenhancing nutritional agents preoperatively, postoperatively, or both, while the control group received standard care (intravenous fluids) and/or macromolecular nutritional supplements. PubMed, Cochrane CENTRAL, and Central Medical Journal were comprehensively searched for randomized controlled trials (RCTs); eight RCTs were included. The primary outcomes were mortality, suture/healing failure, surgical site infection (SSI), and hospital stay length, with evidence certainty assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Results: Although mortality estimation was not feasible, hazard ratios from the meta-analysis showed that the intervention significantly improved suture/healing failure, SSI, and hospital stay length. The certainty of evidence was “low” for suture/healing failure and SSI and “moderate” for hospital stay length. Conclusions: Perioperative management with enteral nutritional agents fortified with immunonutrients should be considered in adult patients scheduled for (advanced) oral cancer surgery. Full article

Background: The timing of anesthesia administration may affect drug efficacy and recovery outcomes. Understanding these variations is important for optimizing anesthetic care. Aim: To assess how spinal anesthesia timing affects block duration, postoperative pain, and CRP and cortisol levels in cesarean deliveries. Methods: Ninety women were divided into three groups based on spinal anesthesia timing: Group A (08:00–16:00), Group B (16:00–00:00), and Group C (00:00–08:00). Standardized spinal anesthesia was administered. Sensory/motor blockade and pain (NRS) were assessed every 10 min. Blood samples for CRP and cortisol were collected preoperatively and at 2, 4, 24, and 48 h post operation. Results: Group C showed shorter sensory and motor blockade than Groups A and B (p < 0.05). The time to first analgesic request was longest in Group A, while Group C reported the highest pain scores (p < 0.05). CRP levels were significantly higher in Group B vs. Group A at 24 and 48 h, and vs. Group C at 48 h (p < 0.05). Group B demonstrated the steepest CRP velocity, indicating a more rapid physiological stress response. BMI differences may have influenced biomarker dynamics. Conclusions: Spinal anesthesia timing significantly impacts block duration, pain experience, and the rate of the physiological stress response. CRP velocity may offer additional insights into perioperative inflammation. Circadian considerations should be integrated into anesthetic planning for cesarean deliveries. Full article

Background: Early defibrillation improves outcomes in cardiac arrest, but the optimal defibrillation strategy and energy requirements remain debated. This study investigated whether arterial blood gas (ABG) parameters could predict optimal defibrillation energy requirements for achieving the highest first-shock success rates in an animal model. Our study focused on clinical scenarios where ABG measurements are readily available, such as ventricular tachycardia and ventricular fibrillation storms requiring multiple shock deliveries. Materials and Methods: In the experimental setting, ventricular fibrillation was induced by 50 Hz direct current (DC), and the defibrillation threshold (DFT) was determined using a stepwise defibrillation protocol. ABG parameters were measured before each defibrillation attempt, recording partial arterial pressure of carbon dioxide (PaCO₂) and oxygen (PaO₂), pH, hematocrit (Hct), sodium (Na⁺), potassium (K⁺), and bicarbonate (HCO₃⁻) levels. The relationships between ABG parameters and the DFT were analyzed for 15 subjects using classical data analysis techniques and machine learning (ML) algorithms. Multiple ML models were trained and tested to predict the higher energy needed for successful defibrillation based on the ABG parameters. Results: Statistically significant differences were found in Hct and Na⁺ levels between the two DFT categories, above 130 Joules (J) and below 40 J (p < 0.01). The DFT negatively correlated with PaO₂ and positively correlated with Hct and Na⁺. However, other ABG parameters did not show significant correlations with DFT. Using ML, we predicted cases requiring higher defibrillation E. Our best-performing model, the Extra Trees Classifier, achieved 83% overall accuracy, with 100% and 67% precision rates for higher and lower DFT categories, respectively. We validated the model using bootstrap resampling and 10-fold cross-validation, confirming consistent performance. We identified Hct, PaCO₂, and PaO₂ as significant contributors to model prediction based on the feature importance value. Conclusions: Modern data analysis techniques applied to ABG parameters may guide personalized defibrillation energy selection, particularly in controlled clinical environments such as catheterization laboratories and intensive care units where ABG measurements are readily available. Full article

Background: Nutritional management has become an integral part of Inflammatory Bowel Disease (IBD) care, with growing evidence supporting specific dietary interventions alongside pharmacologic therapy. However, clinical guidance remains fragmented due to heterogeneous study designs and variable endpoints. Objectives: This review critically examines the current evidence on dietary strategies and oral nutritional supplementation (ONS) in both Crohn’s Disease (CD) and Ulcerative Colitis (UC), highlighting their clinical applications, mechanisms of action, and limitations. Methods: A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science databases, analyzing studies on various dietary approaches and ONS in IBD. Results: Exclusive Enteral Nutrition (EEN) is a first-line therapy in pediatric CD, while partial enteral nutrition (PEN) and the Crohn’s Disease Exclusion Diet (CDED) show promising efficacy and better adherence in both children and adults. Whole-food-based interventions, including the Mediterranean Diet, Specific Carbohydrate Diet, plant-based diets, and emerging strategies such as CD-TREAT and the Tasty & Healthy diet, have demonstrated varying levels of benefit in disease maintenance and symptom control. Targeted exclusion diets—such as low-FODMAP, low-emulsifier, and low-sulfur diets—may relieve functional symptoms and influence inflammatory activity, although evidence remains preliminary. ONS plays a pivotal role in addressing malnutrition and improving outcomes in perioperative and hospitalized patients. Conclusions: Dietary interventions and ONS represent valuable therapeutic tools in IBD management. Future research should prioritize standardized, well-powered clinical trials and personalized nutritional approaches to better define their role within integrated care pathways. Full article

The COVID-19 pandemic disrupted healthcare delivery worldwide, potentially impacting the management of urolithiasis. This study aimed to evaluate changes in referral patterns, perioperative care, and surgical outcomes among patients undergoing ureteroscopic treatment for upper ureteral stones at a Japanese institution. A retrospective cohort of 467 patients who underwent ureteroscopic lithotripsy or retrograde intrarenal surgery between March 2018 and May 2022 was analyzed. The patients were divided into pre-pandemic (March 2018–March 2020, n = 244) and post-pandemic (April 2020–May 2022, n = 223) groups. Clinical characteristics and outcomes were compared. Baseline demographics were similar. After the pandemic onset, preoperative ureteral stenting increased (30.3% vs. 42.6%, p = 0.006), while surgical waiting times (36 days vs. 28 days, p = 0.005) and operative durations (77 min vs. 67 min, p = 0.018) decreased. Referral sources shifted (p = 0.045), with fewer primary care referrals and more from emergency or higher-level hospitals. Stone-free rates (65.6% vs. 58.7%, p = 0.128) and postoperative complication rates were comparable. Despite systemic constraints during the pandemic, timely adaptations in scheduling and perioperative management allowed for the continued delivery of safe and effective ureteroscopic treatment. These findings emphasize the importance of flexible clinical strategies during healthcare crises. Full article

Background/Objectives: Dexmedetomidine, an alpha-2 adrenergic agonist, has gained significant attention for its sedative, analgesic, and anxiolytic properties in paediatric anaesthesia. This review explores its pharmacokinetics and pharmacodynamics, perioperative applications and efficacy, and safety profile in paediatric patients. Findings: Dexmedetomidine has emerged as a highly effective adjunct in paediatric anaesthesia, offering significant advantages across various perioperative settings. It reduces the need for other anaesthetics and opioids, leading to smoother recoveries with lower postoperative pain and agitation. Studies highlight its role in enhancing procedural sedation, improving patient cooperation, and providing superior analgesia in neuraxial and general anaesthesia. Its neuroprotective properties and stable haemodynamic profile make it particularly valuable in the perioperative and critical care settings. Conclusions: Dexmedetomidine has shown a favourable safety and efficacy profile in paediatric anaesthesia when doses are carefully titrated within the ranges recommended in the literature. While its use remains off-label in paediatric populations, increasing clinical experience and evidence support its integration into perioperative protocols. Full article

Hepatectomies play a crucial role in the multidisciplinary management of primary and secondary liver malignancies but are associated with significant risks, including 30-day mortality, morbidity, prolonged hospitalization, and increased resource utilization. Optimizing perioperative care remains a challenge; however, enhanced recovery programs have shown improved patient outcomes. The EUPEMEN (EUropean PErioperative MEdical Networking) protocol focuses on improving the perioperative management of liver resections through the establishment of interdisciplinary principles based on practical experience and theoretical frameworks from five European countries. This paper outlines the core elements of the EUPEMEN protocol, emphasizing strategies to minimize surgical stress, optimize perioperative care, and enhance postoperative recovery. The protocol is systematically designed to reduce postoperative mortality and morbidity, shorten hospital stays, and improve patient outcomes. The EUPEMEN guidelines address inconsistencies in surgical practice across Europe and are structured for implementation in various healthcare environments. “The protocol’s approach is designed to support improvements in perioperative care standards in liver resections and may serve as a practical and efficient tool for healthcare professionals, pending further clinical validation. The EUPEMEN protocol offers a standardized, evidence-based framework to enhance perioperative management in hepatectomies. By integrating multidisciplinary principles, the main target is to eliminate complications, improve surgical outcomes, and promote faster recovery. Its implementation across diverse clinical settings may contribute to advancing perioperative care standards for liver resections in Europe. Full article

Synchronous colorectal cancer (SCRC) is characterized by the simultaneous occurrence of two or more primary colorectal malignancies, diagnosed either preoperatively, intraoperatively, or within six months postoperatively. The rare prevalence of SCRC makes it an uncommon scenario among colorectal malignancies. Since the majority of SCRC patients have been reported to have two concurrent malignancies, triple synchronous malignancies are extremely rare. We report the case of a 65-year-old male individual presenting with a history of abdominal pain, anemia, anorexia, and unintentional weight loss. He was diagnosed with synchronous colorectal cancer with three distinct tumors: two located in the splenic flexure and sigmoid colon, respectively, and another in the rectum that caused partial obstruction. This case highlights the importance of intraoperative evaluation and an appropriate choice of surgical intervention in colorectal cancer. The early identification and proper management of multiple colorectal cancers remain essential for better survival rates. Full article

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality. Exploration of the tumor microenvironment (TME) has resulted in dramatic advancements in the treatment of NSCLC through the advent of immunotherapy. Indeed, anti-programmed death (PD) ligand 1/PD-1 checkpoint inhibitor therapy has substantially improved survival for advanced, unresectable disease and is now being increasingly utilized in the perioperative setting for early-stage, resectable tumors. This success has generated vigorous interest in exploring other cellular players in the NSCLC TME that could be potentially targeted for therapeutic benefit. In this review, we discuss the current state of therapeutic targets in the NSCLC TME, reflect on the revolution of immunotherapy and future directions for its utilization, and reflect on how the current investigations into TME-specific targets may impact thoracic surgical care. Full article