Mixed Methods EvAluation of the high-volume low-complexity Surgical hUb pRogrammE (MEASURE): a mixed methods study protocol.

INTRODUCTION: The waiting list for elective surgery in England recently reached over 7.8 million people and waiting time targets have been missed since 2010. The high-volume low complexity (HVLC) surgical hubs programme aims to tackle the backlog of patients awaiting elective surgery treatment in England. This study will evaluate the impact of HVLC surgical hubs on productivity, patient care and the workforce. METHODS AND ANALYSIS: This 4-year project consists of six interlinked work packages (WPs) and is informed by the Consolidated Framework for Implementation Research. WP1: Mapping current and future HVLC provision in England through document analysis, quantitative data sets (eg, Hospital Episodes Statistics) and interviews with national service leaders. WP2: Exploring the effects of HVLC hubs on key performance outcomes, primarily the volume of low-complexity patients treated, using quasi-experimental methods. WP3: Exploring the impact and implementation of HVLC hubs on patients, health professionals and the local NHS through approximately nine longitudinal, multimethod qualitative case studies. WP4: Assessing the productivity of HVLC surgical hubs using the Centre for Health Economics NHS productivity measure and Lord Carter's operational productivity measure. WP5: Conducting a mixed-methods appraisal will assess the influence of HVLC surgical hubs on the workforce using: qualitative data (WP3) and quantitative data (eg, National Health Service (NHS) England's workforce statistics and intelligence from WP2). WP6: Analysing the costs and consequences of HVLC surgical hubs will assess their achievements in relation to their resource use to establish value for money. A patient and public involvement group will contribute to the study design and materials. ETHICS AND DISSEMINATION: The study has been approved by the East Midlands-Nottingham Research Ethics Committee 23/EM/0231. Participants will provide informed consent for qualitative study components. Dissemination plans include multiple academic and non-academic outputs (eg, Peer-reviewed journals, conferences, social media) and a continuous, feedback-loop of findings to key stakeholders (eg, NHS England) to influence policy development. TRIAL REGISTRATION: Research registry: Researchregistry9364 (https://www.researchregistry.com/browse-the-registry%23home/registrationdetails/64cb6c795cbef8002a46f115/).

Permissive Weight Bearing in Patients With Surgically Treated Periprosthetic Femoral Fractures Around Total Hip Arthroplasty: A Scoping Review.

Periprosthetic femoral fractures (PPFF) around total hip arthroplasty (THA) are one of the leading causes of hip revision. High mortality rates are observed after revision in case of PPFF around THA. To modify risk factors, early postoperative mobilization is necessary. Permissive weight bearing (PWB) is designed to optimize clinical recovery in aftercare. This study aimed to perform a scoping review to summarize the current available evidence on postoperative weight bearing in late PPFF around THA and the implementation of PWB in aftercare. A systematic search was performed on the Cochrane Library, Web of Science, Ovid MEDLINE, EMBASE, and CINAHL databases on January 26th, 2023. Articles were screened in two stages by two independent reviewers. Studies describing adult patients with a history of primary THA who were surgically treated for late PPFF and mentioning prescribed postoperative weight-bearing protocols with relevant outcome measures were included. Seven studies were included, reporting data on 22 patients (age range 47-97 years, BMI range 19-32 kg/m2, ASA classification range 2-3). No studies used PWB in aftercare. The non-weight-bearing group showed no complications. The restricted weight-bearing group had one death and one implant failure. The full weight-bearing group experienced one deep infection and one plate removal because of impingement. The main finding was that, after an extensive systematic search, no articles could be included focusing on PWB in patients with a late PPFF after THA. Addressing this gap in the literature is essential to advancing the understanding of postoperative weight-bearing protocols and PWB for late PPFF around THA.

Linking genetic counseling communication skills to patient outcomes and experiences using a community-engagement and provider-engagement approach: research protocol for the GC-PRO mixed methods sequential explanatory study.

INTRODUCTION: In over 50 years since the genetic counseling (GC) profession began, a systematic study of GC communication skills and patient-reported outcomes in actual sessions across multiple clinical specialties has never been conducted. To optimize GC quality and improve efficiency of care, the field must first be able to comprehensively measure GC skills and determine which skills are most critical to achieving positive patient experiences and outcomes. This study aims to characterise GC communication skills using a novel and pragmatic measure and link variations in communication skills to patient-reported outcomes, across clinical specialties and with patients from diverse backgrounds in the USA. Our community-engagement and provider-engagement approach is crucial to develop recommendations for quality, culturally informed GC care, which are greatly needed to improve GC practice. METHODS AND ANALYSIS: A mixed methods, sequential explanatory design will be used to collect and analyze: audio-recorded GC sessions in cancer, cardiac, and prenatal/reproductive genetic indications; pre-visit and post-visit quantitative surveys capturing patient experiences and outcomes and post-visit qualitative interview data. A novel, practical checklist will measure GC communication skills. Coincidence analysis will identify patterns of GC skills that are consistent with high scores on patient-reported measures. Two-level, multilevel models will be used to evaluate how GC communication skills and other session/patient characteristics predict patient-reported outcomes. Four community advisory boards (CABs) and a genetic counselor advisory board will inform the study design and analysis. ETHICS AND DISSEMINATION: This study has been approved by the single Institutional Review Board of the University of Minnesota. This research poses no greater than minimal risk to participants. Results from this study will be shared through national and international conferences and through community-based dissemination as guided by the study's CABs. A lay summary will also be disseminated to all participants.

Enhanced recovery after cardiac surgery: A literature review.

Enhanced recovery after cardiac surgery (ERACS) represents a constellation of evidence-based peri-operative methods aimed to reduce the physiological and psychological stress patients experience after cardiac surgery, with the primary objective of providing an expedited recovery to pre-operative functional status. The method involves pre-operative, intra-operative, and post-operative interventions as well as direct patient engagement to be successful. Numerous publications in regard to the benefits of enhanced recovery have been presented, including decreased post-operative complications, shortened length of stay, decreased overall healthcare costs, and higher patient satisfaction. Implementing an ERACS program undeniably requires a culture change, a methodical shift in the approach of these patients that ultimately allows the team to achieve the aforementioned goals; therefore, team-building, planning, and anticipation of obstacles should be expected.

REporting quality of PilOt randomised controlled trials in surgery (REPORTS): a methodological survey protocol.

INTRODUCTION: The aim of this methodological review is to evaluate the completeness of reporting of surgical pilot and feasibility randomised trials as per the Consolidated Standards of Reporting Trials (CONSORT) extension to randomised pilot and feasibility trials. Moreover, we aim to assess for the presence of spin reporting and inconsistency between abstract and main text reporting in surgical pilot and feasibility randomised trials. METHODS AND ANALYSIS: A comprehensive, electronic search strategy will be used to identify studies indexed in Medline, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Studies will be included if they are pilot or feasibility randomised trials of surgical interventions. The primary outcome will be overall CONSORT statement extension to randomised pilot and feasibility trials checklist completeness. This will be defined as trials reporting each of the 40 items in the CONSORT statement extension to randomised pilot and feasibility trials checklist. Secondary outcomes will include the reporting of individual studies as per the CONSORT extension to randomised pilot and feasibility trials, the use of spin reporting strategies, trial factors associated with reporting quality and spin strategy use, and consistency between abstract and main text reporting. Poisson and logistic regressions will be performed to explore the association between trial factors and completeness of reporting as measured by the number of reported CONSORT items. ETHICS AND DISSEMINATION: This is a methodological survey that has been registered a priori on the International Prospective Register for Systematic Reviews (PROSPERO) (CRD42023475512). Local ethics approval is not required. We plan to disseminate study results through peer-reviewed publication and conference presentations.

Updates in traumatic brain injury management: brain oxygenation, middle meningeal artery embolization and new protocols.

Traumatic brain injury (TBI) confers significant morbidity and mortality, and is a pathology often encountered by trauma surgeons. Several recent trials have evaluated management protocols of patients with severe TBI. The Brain Oxygen Optimization in Severe Traumatic Brain Injury Phase-II trial (BOOST-II) evaluated efficacy and feasibility of brain oxygen measurement in severe TBI. BOOST phase 3 trial (BOOST-3) and two ongoing trials look to measure functional outcomes in this population. Furthermore, middle meningeal artery embolization has now become standard therapy for adult patients with chronic subdural hematoma (SDH) and has increasing popularity in those with recurrent SDH as an alternative to surgical intervention. In this manuscript, we review the literature, ongoing trials, and discuss current updates in the management of TBI.

eviQ Cancer Treatments Online: Providing evidence-based information to improve cancer patient outcomes.

AIM: To understand the current usage of eviQ Cancer Treatments Online (www.eviQ.org.au), an Australian, open-access website providing evidence-based and consensus-driven cancer treatment protocols and information, and the extent to which it is meeting its intended outcomes and providing value to its users. METHODS: A mixed-method evaluation was conducted in 2020-2022 which included a review of key program documentation and website usage data, and delivery of a focused online survey to its users. RESULTS: In 2022, 329 clinicians representing all Australian states and territories contributed to eviQ content development and review. eviQ content continues to grow with a 15.2% increase in total content from 2019 to 2022.  eviQ website users continue to grow with 90,000 total monthly users in 2022, representing a 166% increase from 2018. The proportion of international users compared to Australian users continues to grow with 57% of total users in Australia and 43% international in 2022. Of 466 survey responses, the most cited reason for eviQ use was for information on side effects/toxicity (67%). Ninety-three percent (93%) of respondents either agreed or strongly agreed that eviQ contributed to both health professionals providing the best evidence-based treatment and care and improving the standardization of treatment and care provided. CONCLUSION:  eviQ is embedded in Australian clinical practice, highly valued, and relied upon by users. Users agree that eviQ has a positive impact on patients by supporting the delivery of evidence-based treatment and that eviQ contributed to patients' improved health outcomes and quality of life. eviQ's increasing international usage should be explored.

Accuracy and usability of artificial intelligence chatbot generated chemotherapy protocols.

Background: Medical practitioners are increasingly using artificial intelligence (AI) chatbots for easier and faster access to information. To our knowledge, the accuracy and availability of AI-generated chemotherapy protocols has not yet been studied. Methods: Nine simulated cancer patient cases were designed and AI chatbots, ChatGPT version 3.5 (OpenAI) and Bing (Microsoft), were used to generate chemotherapy protocols for each case. Results: Generated chemotherapy protocols were compared with the original protocols for nine simulated cancer patients. ChatGPT's overall performance was 5 out of 9 on protocol generation, and Bing's was 4 out of 9; this was statistically nonsignificant (p = 1). Conclusion: AI chatbots show both potential and limitations in generating chemotherapy protocols. The overall performance is low, and they should be used carefully in oncological practice.

Implementation of the Fast-track Protocol for Total Hip Arthroplasty in a Public Hospital in the State of São Paulo - Brazil.

Objective Evaluate the results of the implementation of the Fast Track Protocol (FTP), a medical practice based on scientific evidence, for elective total hip arthroplasty surgery, mainly comparing the National Average Hospital Admission Rate of 7.1 days. Methods 98 patients who underwent elective total hip arthroplasty surgery via the direct anterior approach, anterolateral approach and posterior approach were included in the FTP from December 2018 to March 2020, being followed up preoperatively, intraoperatively and immediately postoperatively. Results The average length of hospital stay was 2.8 days, being 2.1 days for the direct anterior approach, 3.0 days for the anterolateral access approach and 4.1 days for the posterior access approach. The average surgery time was 90 minutes, 19 (19.39%) of the patients were referred to the ICU in the postoperative period, however, none of them underwent surgery using the direct anterior approach. We had no cases of deep vein thrombosis (DVT), pulmonary embolism (PTE) or neurological injury, 19 (19.39%) patients had postoperative bleeding requiring dressing change, 4 (4.08%) needed blood transfusion, 2 (2.04%) patients had implant instability, 1 (1.02%) patient had a fracture during surgery and 1 (1.02%) patient died of cardiac complications. Conclusion FTP may be a viable alternative to reduce the length of stay and immediate postoperative complications for elective total hip arthroplasty surgery decreasing the length of stay of patients by 2 to 3 times when compared to the national average of 7.1 days.

Degree of swallowing impairment in the elderly: clinical and instrumental assessment.

OBJECTIVE: To classifying the degree of swallowing impairment in the elderly, comparing clinical and instrumental assessment. METHODS: This is a cross-sectional study with quantitative and qualitative analysis of clinical and instrumental assessment of 37 elderly, aged 60-82 years, of both genders without neurological, oncological or systemic diseases, participated in this study. All participants were submitted to clinical evaluation and their results compared through fiberoptic endoscopic evaluation of swallowing considering liquid, pudding and solid food consistencies. Data were analyzed descriptively and statistically using the analysis of variance test (two-way ANOVA) and Tukey's post hoc test (p <  0.05). RESULTS: In the clinical evaluation there was a higher occurrence of moderate swallowing impairment, followed by functional swallowing, while in fiberoptic endoscopic evaluation of swallowing the severity of the impairment was greater for moderate and mild degrees. There was no statistical difference between the clinical and instrumental evaluation methods. However, there was a significant interaction between the variables, with a difference for liquid consistency in the instrumental evaluation method. CONCLUSION: Healthy elderly have different degree of swallowing impairment according to food consistency. The clinical assessment using a scale that considers the physiological changes of the elderly, presented results similar to those found in the instrumental examination.

Role of patient characteristics in adherence to first-line treatment guidelines in breast, lung and prostate cancer: insights from the Nordic healthcare system.

OBJECTIVES: This study investigates the influence of socioeconomic status, health literacy, and numeracy on treatment decisions and the occurrence of adverse events in patients with breast, lung, and prostate cancer within a Nordic healthcare setting. DESIGN: A follow-up to a cross-sectional, mixed-methods, single-centre study. SETTING: A Nordic, tertiary cancer clinic. PARTICIPANTS: A total of 244 participants with breast, lung and prostate cancer were initially identified, of which 138 first-line treatment participants were eligible for this study. First-line treatment participants (n=138) surpassed the expected cases (n=108). INTERVENTIONS: Not applicable as this was an observational study. PRIMARY AND SECONDARY OUTCOME MEASURES: The study's primary endpoint was the rate of guideline adherence. The secondary endpoint involved assessing treatment toxicity in the form of adverse events. RESULTS: Guideline-adherent treatment was observed in 114 (82.6%) cases. First-line treatment selection appeared uninfluenced by participants' education, occupation, income or self-reported health literacy. A minority (3.6%) experienced difficulties following treatment instructions, primarily with oral cancer medications. CONCLUSIONS: The findings indicated lesser cancer health disparities regarding guideline adherence and treatment toxicity within the Nordic healthcare framework. A causal connection may not be established; however, the findings contribute to discourse on equitable cancer health provision.

Effects of home-based exercise on the health of patients with fibromyalgia syndrome: a systematic review of randomized clinical trials.

PURPOSE: Analyze the effects of interventions with home-based physical exercise on the health of patients with fibromyalgia and the characteristics of the protocols used. METHODS: This systematic review was registered at PROSPERO and followed the PRISMA recommendations. Searches were performed in six electronic databases. Eligibility criteria for the selection of studies were compiled using the acronym PICOS. Data were extracted and checked in a Microsoft Excel® spreadsheet and the risk of bias was assessed using the Rob 2 tool. RESULTS: The search resulted in seven studies included for analysis. Among them, the most common modality was aerobic exercise. The analyzed outcomes were: pain, quality of life, depression, anxiety, disease severity, physical function, pain catastrophizing, self-efficacy, psychological well-being, sleep quality and somatosensory and temporal discrimination. The effects of home-based exercise are limited, and improvements in pain and quality of life was found. For the other outcomes, the results were inconclusive. Most studies presented some concerns about the risk of bias. CONCLUSION: It is necessary to expand the evidence on home-based exercises for fibromyalgia, as this is the first systematic review on the subject. Subsequent research should focus on methodological rigor and protocol detail, allowing findings to be replicated.

Home-based physical exercise can improve pain and quality of life in patients with fibromyalgia.Among the modalities, combinations of aerobic exercise, resistance training and stretching are recommended.The weekly frequency should be two or three times, with an average duration of 40 minutes.Programs from four weeks onwards may already show improvement in symptoms, but the practice should be maintained in the long term.

Preparation of a universally usable, animal product free, defined medium for 2D and 3D culturing of normal and cancer cells.

Since 1958, cell culture media supplemented with fetal bovine serum is used, despite the well-known concerns about animal welfare, reproducibility, reliability, relevance, and safety. To obliterate these concerns and increase scientific accuracy, we recently published an open access, publicly available paper on a defined medium composition to make it possible for any lab to prepare this medium. The medium supports routine culturing and cell banking as well as investigations of growth curves, dose response testing of compounds of cells in 2D and 3D, and cell migration; all important aspects for research and toxicology. Here we give a detailed description of how to mix the defined universal cell culture medium in 14 simple steps to support any entity that wishes to make it. We also list different normal and cancer cell lines that have been cultured in the defined medium.•Open source composition of animal product free universal cell culture medium•Protocols for mixing solutions of small xeno free molecules for supplementation•Protocols for mixing solutions of human proteins for supplementation.

Impact of evidence-based guidelines on healthcare utilisation and costs for disc related sciatica in the Netherlands: a population-based, cross-sectional study.

OBJECTIVE: The aim of this study was to assess the impact of high-quality evidence supporting surgical treatment of lumbar disc herniation (LDH) on healthcare practice in the Netherlands by examining changes in healthcare utilisation, including the timing of surgery, and the healthcare costs for patients with LDH. DESIGN: A retrospective, cross-sectional study was performed using population-based, longitudinal data obtained from the Dutch Healthcare Authority (2007-2020) and NIVEL's primary care (2012-2020) administrative databases. SETTING: The study was conducted within the healthcare system of the Netherlands. PARTICIPANTS: We included adults (≥18 years) who visited a Dutch hospital or a general practitioner (GP) for lumbar degenerative disc disease. Patients with LDH were identified based on registered diagnosis code, type of surgery (discectomy) and age (<56 years). MAIN OUTCOME MEASURES: The primary outcome measure was the difference in the annual number of LDH procedures following the publication of evidence-based guidelines in 2009 (comparing the periods 2007-2009 to 2017-2019). Secondary outcome measures focused on the timing of surgery and associated healthcare costs. To validate the outcomes, secondary outcomes also include the number of discectomies and the number of procedures in the younger age group (discectomies, laminectomies, and fusion surgery). RESULTS: The number of patients suffering from LDH increased from 55 581 to 68 997 (+24%) between 2007 and 2019. A decrease was observed in the annual number of LDH procedures (-18%), in the number of discectomies (-22%) and in the number of procedures for patients aged <56 years (-18%). This resulted in lower healthcare costs by €10.5 million annually. In 2012, 31% of all patients <56 years had surgery before 12 weeks from diagnosis at the GP, whereas 20% did in 2019. CONCLUSIONS: Healthcare utilisation for LDH changed tremendously in the Netherlands between 2007 and 2020 and seemed to be associated with the publication and implementation of evidence-based guidelines. The observed decrease in the number of procedures has been accompanied by a corresponding reduction in healthcare costs. These findings underscore the importance of adhering to evidence-based guidelines to optimise the management of patients with LDH.

[Consensus for the diagnosis and management of extramedullary plasmacytoma in China(2024)].

Extramedullary plasmacytoma (EMP) is a special type of malignant plasmacytosis, which is complex and heterogeneous. Most EMP patients have poor prognosis and lack a stratified prognostic system or ideal treatment strategy supported by evidence-based medical evidence, which cannot meet clinical needs. In order to improve the understanding of this disease entity, Plasma Cell Disease Group, Chinese Society of Hematology, Chinese Medical Association and Chinese Myeloma Committee-Chinese Hematology Association developed the "Chinese Expert Consensus on the diagnosis and treatment of extramedullary plasmacytoma", which aims to standardize the clinical diagnosis and treatment of EMP and ultimately improve the overall survival of patients with plasmacytoma.

Capacity building for pediatric neuro-oncology in Pakistan- a project by my child matters program of Foundation S.

Introduction: Initiated in June 2019, this collaborative effort involved 15 public and private sector hospitals in Pakistan. The primary objective was to enhance the capacity for pediatric neuro-oncology (PNO) care, supported by a My Child Matters/Foundation S grant. Methods: We aimed to establish and operate Multidisciplinary Tumor Boards (MTBs) on a national scale, covering 76% of the population (185.7 million people). In response to the COVID-19 pandemic, MTBs transitioned to videoconferencing. Fifteen hospitals with essential infrastructure participated, holding monthly sessions addressing diagnostic and treatment challenges. Patient cases were anonymized for confidentiality. Educational initiatives, originally planned as in-person events, shifted to a virtual format, enabling continued implementation and collaboration despite pandemic constraints. Results: A total of 124 meetings were conducted, addressing 545 cases. To augment knowledge, awareness, and expertise, over 40 longitudinal lectures were organized for healthcare professionals engaged in PNO care. Additionally, two symposia with international collaborators and keynote speakers were also held to raise national awareness. The project achieved significant milestones, including the development of standardized national treatment protocols for low-grade glioma, medulloblastoma, and high-grade glioma. Further protocols are currently under development. Notably, Pakistan's first pediatric neuro-oncology fellowship program was launched, producing two graduates and increasing the number of trained pediatric neuro-oncologists in the country to three. Discussion: The initiative exemplifies the potential for capacity building in PNO within low-middle income countries. Success is attributed to intra-national twinning programs, emphasizing collaborative efforts. Efforts are underway to establish a national case registry for PNO, ensuring a comprehensive and organized approach to monitoring and managing cases. This collaborative initiative, supported by the My Child Matters/Foundation S grant, showcases the success of capacity building in pediatric neuro-oncology in low-middle income countries. The establishment of treatment protocols, fellowship programs, and regional tumor boards highlights the potential for sustainable improvements in PNO care.

Evolution of European prostate cancer screening protocols and summary of ongoing trials.

Population-based organised repeated screening for prostate cancer has been found to reduce disease-specific mortality, but with substantial overdiagnosis leading to overtreatment. Although only very few countries have implemented a screening programme on a national level, individual prostate-specific antigen (PSA) testing is common. This opportunistic testing may have little favourable impact, while stressing the side-effects. The classic early detection protocols as were state-of-the-art in the 1990s applied a PSA and digital rectal examination threshold for sextant systematic prostate biopsy, with a fixed interval for re-testing, and limited indication for expectant management. In the three decades since these trials were started, different important improvements have become available in the cascade of screening, indication for biopsy, and treatment. The main developed aspects include: better identification of individuals at risk (using early/baseline PSA, family history, and/or genetic profile), individualised re-testing interval, optimised and individualised starting and stopping age, with gradual invitation at a fixed age rather than invitation of a wider range of age groups, risk stratification for biopsy (using PSA density, risk calculator, magnetic resonance imaging, serum and urine biomarkers, or combinations/sequences), targeted biopsy, transperineal biopsy approach, active surveillance for low-risk prostate cancer, and improved staging of disease. All these developments are suggested to decrease the side-effects of screening, while at least maintaining the advantages, but Level 1 evidence is lacking. The knowledge gained and new developments on early detection are being tested in different prospective screening trials throughout Europe. In addition, the European Union-funded PRostate cancer Awareness and Initiative for Screening in the European Union (PRAISE-U) project will compare and evaluate different screening pilots throughout Europe. Implementation and sustainability will also be addressed. Modern screening approaches may reduce the burden of the second most frequent cause of cancer-related death in European males, while minimising side-effects. Also, less efficacious opportunistic early detection may be indirectly reduced.

Evaluation of the efficacy and safety of a precise thymalfasin-regulated PRaG regimen for advanced refractory solid tumours: protocol for the open-label, prospective, multicentre study (PRaG5.0 study).

INTRODUCTION: The PRaG regimen, which consists of hypofractionated radiotherapy combined with a programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitor and granulocyte-macrophage colony stimulating factor (GM-CSF), has been demonstrated to have a survival benefit in patients with advanced solid tumours who have failed at least two lines of treatment. Nonetheless, lymphopenia poses an impediment to the enduring efficacy of PD-1/PD-L1 inhibitor therapy. Adequate lymphocyte reserves are essential for the efficacy of immunotherapy. Coupling the PRaG regimen with immunomodulatory agents that augment the number and functionality of lymphocytes may yield further survival benefits in this cohort of patients. OBJECTIVE: The aim of this study is to investigate the effectiveness and safety of a meticulously thymalfasin-controlled PRaG regimen in patients with advanced and chemotherapy-resistant solid tumours. METHODS AND ANALYSIS: The study has a prospective, single-arm, open-label, multicentre design and aims to recruit up to 60 patients with histologically confirmed advanced solid tumours that have relapsed or metastasised. All eligible patients will receive a minimum of two cycles of the PRaG regimen comprising thymalfasin followed by maintenance treatment with a PD-1/PD-L1 inhibitor and thymalfasin for 1 year or until disease progression. Patients will be monitored according to the predetermined protocol for a year or until disease progression after initiation of radiotherapy. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of the Second Affiliated Hospital of Soochow University, on 25 November 2022 (JD-LK-2022-151-01) and all other participating hospitals. Findings will be disseminated through national and international conferences. We also plan to publish our findings in high-impact peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05790447.

Efficacy and safety of terlipressin infusion during liver surgery: a protocol for systematic review and meta-analysis.

INTRODUCTION: Liver disease causes 2 million deaths annually, accounting for 4% of all deaths worldwide. Liver surgery is one of the effective therapeutic options. Bleeding is a major complication during liver surgery. Perioperative bleeding and allogeneic blood transfusion may deteriorate the prognosis. Terlipressin (TP), a synthetic analogue of the antidiuretic hormone, may reduceblood loss during abdominal surgery. Several clinical centres have attempted to use TP during liver surgery, but the evidence for its effectiveness in reducing blood loss and the need for allogeneic blood transfusion, as well as its safety during the perioperative period, remains unclear. The aim of this systematic review and meta-analysis is to evaluate the efficacy and safety of TP in reducing blood loss and allogeneic blood transfusion needs during liver surgery. METHODS AND ANALYSIS: We will search PubMed, EMBASE, the Cochrane Library and Web of Science for studies on perioperative use of TP during liver surgery from inception to July 2023. We will limit the language to English, and two reviewers will independently screen and select articles. The primary study outcomes are estimated blood loss and the need for allogeneic blood transfusion. Secondary outcomes include operating time, intensive care unit stay, length of stay, intraoperative urine output, acute kidney injury rate, postoperative complications, hepatic and renal function during follow-up, and TP-related adverse effects. We will include studies that met the following criteria: (1) randomised controlled trials (RCTs), cohort studies or case-control studies; (2) the publication time was till July 2023; (3) adult patients (≥18 years old) undergoing elective liver surgery; (4) comparison of TP with other treatments and (5) the study includes at least one outcome. We will exclude animal studies, case reports, case series, non-original articles, reviews, paediatric articles, non-controlled trials, unpublished articles, non-English articles and other studies that are duplicates. We will use Review Manager V.5.3 software for meta-analysis and perform stratification analysis for the study quality of RCTs based on the Jadad score. For cohort or case-control studies, the study quality will be analysed based on Newcastle-Ottawa Scale scores. Grading of Recommendations, Assessment, Development and Evaluation will be used to assess confidence in the cumulative evidence. For primary outcomes, we will conduct subgroup analyses based on meta-regression. We will also perform leave-one-out sensitivity analyses to evaluate the effect of each individual study on the combined results by removing the individual studies one by one for outcomes with significant heterogeneity. The protocol follows the Cochrane Handbook for Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols guidelines. ETHICS AND DISSEMINATION: This study is a secondary analysis of existing data; therefore, it does not require ethical approval. We will disseminate the results through peer-reviewed publications. PROSPERO REGISTRATION NUMBER: CRD42023450333.