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SUMMARY: Background and aims: Preoperative fasting induces metabolic stress and leads to reduced postoperative insulin sensitivity, changes attenuated by preoperative carbohydrate loading. However, the mechanisms underlying these effects remain unknown. We investigated the dynamic changes in substrate metabolism and mononuclear cell mitochondrial function after fasting followed by refeeding with a drink [ONS (Fresenius Kabi, Germany)] designed to improve metabolic function preoperatively. Methods: Twelve healthy volunteers took part in this study. They were fed a standardized meal and studied 4h later (baseline ‘fed’ state), after 12 and 24h of fasting, and 2, 4 and 6h after ingestion of ONS (contained 100g carbohydrate, 30g glutamine, and antioxidants). Changes in liver and muscle glycogen and lipids were studied using 13C and 1H magnetic resonance spectroscopy. The activities of mitochondrial electron transport chain complexes I, II and IV in blood mononuclear cells were measured spectrophotometrically. Results: Compared to the baseline fed state, 12 and 24h fasts led to 29% and 57% decreases (P <0.001) in liver glycogen content, respectively. Fasting for 24h decreased mitochondrial membrane complexes I (−72%, P <0.05), II (−49%, P <0.01) and IV (−41%, P <0.05) activities compared to those following a 12h fast. A 23% increase (P <0.05) in calf intramyocellular lipid (IMCL) content occurred after a 24h fast. Liver glycogen reserves increased by 47% (P<0.05) by 2h following ingestion of ONS. Conclusions: Short-term fasting (up to 24h) affected mononuclear cell mitochondrial function adversely and increased IMCL content. Refeeding with ONS partially reversed the changes in liver glycogen. [ABSTRACT FROM AUTHOR]

BACKGROUND: Preoperative starvation results in the development of insulin resistance. Measures to attenuate the development of insulin resistance, such as preoperative carbohydrate loading, lead to clinical benefits. However, the mechanisms that underlie the development of insulin resistance during starvation and its attenuation by preoperative carbohydrate loading remain to be defined. Insulin resistance associated with type 2 diabetes and ageing has been linked to mitochondrial dysfunction. The metabolic consequences of preoperative starvation and carbohydrate loading and mechanisms linking insulin resistance to impaired mitochondrial function are discussed. METHODS: Searches of the Medline and Science Citation Index databases were performed using various key words in combinations with the Boolean operators AND, OR and NOT. Key journals, nutrition and metabolism textbooks and the reference lists of key articles were also hand searched. RESULTS: Animal studies have shown that short-term energy deprivation decreases mitochondrial ATP synthesis capacity and complex activity, and increases oxidative injury. Furthermore, evidence from human studies suggests that the development of insulin resistance during starvation may be linked to impaired mitochondrial function. CONCLUSIONS: There is evidence from animal studies that short-term starvation causes mitochondrial dysfunction. Future studies should investigate whether mitochondrial dysfunction underlies the development of insulin resistance in patients undergoing elective surgery. [ABSTRACT FROM AUTHOR]

Fluid and electrolyte balance is often poorly understood and inappropriate prescribing can cause increased post-operative morbidity and mortality. The efficiency of the physiological response to a salt or water deficit, developed through evolution, contrasts with the relatively inefficient mechanism for dealing with salt excess. Saline has a Na+:Cl- of 1:1 and can produce hyperchloraemic acidosis, renal vasoconstriction and reduced glomerular filtration rate. In contrast, the more physiological Hartmann's solution with a Na+:Cl- of 1.18:1 does not cause hyperchloraemia and Na excretion following infusion is more rapid. Salt and water overload causes not only peripheral and pulmonary oedema, but may also produce splanchnic oedema, resulting in ileus or acute intestinal failure. This overload may sometimes be an inevitable consequence of resuscitation, yet it may take 3 weeks to excrete this excess. It is important to avoid unnecessary additional overload by not prescribing excessive maintenance fluids after the need for resuscitation has passed. Most patients require 2-2.5 litres water and 60-100 mmol Na/d for maintenance in order to prevent a positive fluid balance. This requirement must not be confused with those for resuscitation of the hypovolaemic patient in whom the main aim of fluid therapy is repletion of the intravascular volume. Fluid and electrolyte balance is a vital component of the metabolic care of surgical and critically-ill patients, with important consequences for gastrointestinal function and hence nutrition. It is also of importance when prescribing artificial nutrition and should be given the same careful consideration as other nutritional and pharmacological needs. [ABSTRACT FROM AUTHOR]

The article presents the case study of a 59-year-old patient who was presented with gastric outlet obstruction.

Background: This study aims to study changes in blood volume after 1 litre infusions of Gelofusine(®) [4% succinylated gelatine in 0.7% saline, weight-average molecular weight (MWw) 30 kDa] and Voluven(®) (6% hydroxyethyl starch in 0.9% saline, MWw 130 kDa) in the presence of increased capillary permeability.Methods: In this randomized double-blind study, adults undergoing laparoscopic cholecystectomy received 1 litre of Gelofusine(®) (n=12) or Voluven(®) (n=13) over 1 h at the induction of anaesthesia. No other fluids were given. Haematocrit, serum electrolytes, and osmolality were measured before infusion and hourly thereafter for 4 h. Changes in blood volume were calculated from changes in haematocrit. The urinary albumin:creatinine ratio (ACR) was measured before and after operation.Results: Baseline parameters before the two infusions were similar (P>0.050). The urinary ACR increased significantly after operation after Gelofusine(®) (P=0.011) and Voluven(®) (P=0.002), indicating increased capillary permeability. Voluven(®) produced a greater increase in serum chloride concentration (P=0.028) and a larger decrease in strong ion difference (P=0.009) than Gelofusine(®). There were no significant differences in changes in haematocrit (P=0.523) and blood volume (P=0.404) over the study period when the two infusions were compared, nor were there any differences in serum sodium, potassium, bicarbonate, and albumin concentrations (P>0.050). Urine output, sodium concentration, and osmolality were similar after the two infusions (P>0.050).Conclusions: The blood volume-expanding effects of the two colloids were not significantly different, despite the increase in postoperative urinary ACR and the 100 kDa difference in MWw. [ABSTRACT FROM AUTHOR]

A good scientific poster should capture the interest and imagination of the viewer and the overall aim should be to make the target audience want to know more about the topic. A well prepared poster will speak for itself and significantly aid the presenter in sharing the findings of their work. It can often lead to new and exciting collaborative opportunities. Although a well presented poster cannot make up for poor data, a poorly presented poster can lessen the impact of the work and cause it to be overlooked. This article emphasises some of the considerations that need to be borne in mind to make a poster scientifically valid, have visual impact and be attractive to the viewer. The key points are brevity, clarity, neatness and readability., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: Prehabilitation combines exercise, nutritional, and psychological interventions administered before surgery to improve patient outcomes. This comprehensive review and meta-analysis examined the feasibility, adherence, and effectiveness of prehabilitation in frail, high-risk individuals undergoing major abdominal surgery., Methods: We searched the Cochrane Central Register of Controlled Trials, Web of Science, MEDLINE, Embase, and Cumulative Index to Nursing & Allied Health Literature (CINAHL) databases to identify relevant studies evaluating prehabilitation programs published between 2010 and 2023, either as observational studies or randomized clinical trials (RCTs)., Results: The 23 articles (13 RCTs and 10 observational studies) included 1849 older male and female patients aged 68.7 ± 7.2 years. Nineteen of the included studies reported on adherence to prehabilitation programmes, which was generally good (>75%) over different models, settings, and durations. Factors such as patients' desire for expedited surgery, self-assessment of fitness, personal and professional obligations, health issues, holidays, and advancement of surgery dates negatively affected adherence to prehabilitation programmes. When compared with rehabilitation or standard pre- and post-surgical care, prehabilitation was associated with a 25%, albeit not statistically significant reduction in postoperative complications, according to data from 14 studies reporting on postoperative complications (OR 0.75, 95% CI 0.48 to 1.17, P = 0.43; I 2  = 65%). Prehabilitation has been found to improve the 6-min walk test significantly by 29.4 m (MD +29.4 m, 95% CI 5.6 to 53.3, P = 0.02; I 2  = 39%), compared with rehabilitation or standard pre- and post-surgical care., Conclusion: Prehabilitation was acceptable to patients, with good adherence, and improved physical function., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Poor survival outcomes in periampullary cancer highlight the need for improvement in biomarkers and the development of novel therapies. Redox proteins, including the thioredoxin system, play vital roles in cellular antioxidant systems. Methods: In this retrospective study, thioredoxin (Trx), thioredoxin-interacting protein (TxNIP), and thioredoxin reductase (TrxR) protein expression was assessed in 85 patients with pancreatic ductal adenocarcinoma (PDAC) and 145 patients with distal bile duct or ampullary carcinoma using conventional immunohistochemistry. Results: In patients with PDAC, high cytoplasmic TrxR expression was significantly associated with lymph node metastasis ( p = 0.033). High cytoplasmic and nuclear Trx expression was significantly associated with better overall survival ( p = 0.018 and p = 0.006, respectively), and nuclear Trx expression remained significant in multivariate Cox regression analysis ( p < 0.0001). In distal bile duct and ampullary carcinomas, high nuclear TrxR expression was associated with vascular ( p = 0.001) and perineural ( p = 0.021) invasion, and low cytoplasmic TxNIP expression was associated with perineural invasion ( p = 0.025). High cytoplasmic TxNIP expression was significantly associated with better overall survival ( p = 0.0002), which remained significant in multivariate Cox regression analysis ( p = 0.013). Conclusions: These findings demonstrate the prognostic importance of Trx system protein expression in periampullary cancers.

Background and Aims: Citation scores (CS) have been traditionally used to measure the impact of scientific publications. Sourced from the Internet, Altmetric Attention Scores (AAS) are complementary metrics that assess how often publications are discussed and used globally. We compared by rank the top 500 papers by CS and AAS published in Clinical Nutrition with corresponding AAS and CS., Methods: A search for all publications in Clinical Nutrition was performed on Dimensions (https://app.dimensions.ai/discover/publication) on 3rd April 2024. Outputs were ranked according to CS and then by AAS with the top 500 in each category selected. Scores, year and type of publication were recorded. Correlation was expressed as the Spearman's rank coefficient (ϱ)., Results: We identified 18,790 outputs. Within the top 500 publications ranked by CS, there was a significant weak positive correlation (ϱ = 0.235, P < 0.0001) between CS [median (IQR) 149 (116-223)] and AAS [7 (3-22)]. Ranked by AAS, there was a non-significant very weak positive correlation (ϱ = 0.072, P = 0.106) between AAS [55.5 (36-115)] and CS [42 (16.5-94.5)]. Trends remained similar when grouped by publication type. Guidelines, ranked by CS, had the highest CS and ranked by AAS, the highest CS and AAS. Publications per year, by year, ranked by CS, had a negatively skewed distribution peaking in 2012 and declined thereafter, but when ranked by AAS, had a moderately positive linear trend from 2001 to 2024 (ϱ = 0.513, P < 0.0001)., Conclusion: Correlation between CS and AAS was weak. Guidelines had the highest CS and AAS. CS are iterative taking years to mature while AAS are immediate., Competing Interests: Conflict of interest DNL has received an unrestricted educational grant from B. Braun for unrelated work. He has also received speaker's honoraria for unrelated work from Abbott, Nestlé and Corza. He is also an Associate Editor of Clinical Nutrition. No other competing interests declared., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Nearly half of adult patients undergoing surgery experience moderate or severe postoperative pain. Inadequate pain management hampers postoperative recovery and function and may be associated with adverse outcomes. This multidisciplinary consensus statement provides principles that might aid postoperative recovery, and which should be applied throughout the entire peri-operative pathway by healthcare professionals, institutions and patients., Methods: We conducted a directed literature review followed by a four-round modified Delphi process to formulate recommendations for organisations and individuals., Results: We make recommendations for the entire peri-operative period, covering pre-admission; admission; intra-operative; post-anaesthetic care unit; ward; intensive care unit; preparation for discharge; and post-discharge phases of care. We also provide generic principles of peri-operative pain management that clinicians should consider throughout the peri-operative pathway, including: assessing pain to facilitate function; use of multimodal analgesia, including regional anaesthesia; non-pharmacological strategies; safe use of opioids; and use of protocols and training for staff in caring for patients with postoperative pain., Conclusions: We hope that with attention to these principles and their implementation, outcomes for adult patients having surgery might be improved., (© 2024 Association of Anaesthetists.)

Background: Gastric fluid plays a key role in food digestion and drug dissolution, therefore, the amount of gastric fluid present in a fasted state may influence subsequent digestion and drug delivery. We aimed to describe intra- and interindividual variation in fasted gastric content volume (FGCV) and to determine the association with age, sex, and body size characteristics., Methods: Data from 24 MRI studies measuring FGCV in healthy, mostly young individuals after an overnight fast were pooled. The analysis included 366 participants who had up to 6 repeated measurements, with a total of 870 measurements. Linear mixed model analysis was performed to calculate intra- and interindividual variability and to assess the effects of age, sex, weight, height, weight*height as a proxy for body size, and body mass index (BMI)., Results: FGCV ranged from 0 to 156 mL, with a mean (± SD) value of 33 ± 25 mL. The overall coefficient of variation within the study population was 75.6%, interindividual SD was 15 mL, and the intraindividual SD was 19 mL. Age, weight, height, weight*height, and BMI had no effect on FGCV. Women had lower volumes compared to men (MD: -6 mL), when corrected for the aforementioned factors., Conclusion: FGCV is highly variable, with higher intraindividual compared to interindividual variability, indicating that FGCV is subject to day-to-day and within-day variation and is not a stable personal characteristic. This highlights the importance of considering FGCV when studying digestion and drug dissolution. Exact implications remain to be studied., (© 2024 The Author(s). Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Common bile duct duplications represent exceptionally rare congenital anomalies of the biliary tract. In this case report we document an unusual variant of common bile duct duplication in a 79-year-old man who underwent a pancreaticoduodenectomy for ampullary cancer. The duplication consisted of two unseparated, completely-layered, common bile ducts which originated above the cystic duct junction and terminated prior to the point of insertion into the pancreas, where the two lumens converged into a single duct. Duplication of the bile duct is rare and often goes undetected. In the present case, the anomaly was found incidentally in a patient who had a pancreaticoduodenectomy for an ampullary carcinoma. However, duplication may be associated with choledocholithiasis, cholangitis, pancreatitis, and pancreaticobiliary malignancies and it is important to be aware of the condition., Competing Interests: None of the authors has a direct conflict of interest to declare. DNL has received an unrestricted educational grant from B. Braun for unrelated work. He has also received speaker’s honoraria for unrelated work from Abbott, Nestlé and Corza.

Background: The aim of this study was to establish features of inflammation in histologically normal gallbladders with gallstones and compare the expression of inflammatory markers in acutely and chronically inflamed gallbladders., Methods: Immunohistochemistry was performed on formalin-fixed paraffin-embedded gallbladders for tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-2R, and substance p in three groups: Group I (n = 60) chronic cholecystitis, Group II (n = 57) acute cholecystitis and Group III (n = 45) histologically normal gallbladders with gallstones. Expression was quantified using the H-scoring system., Results: Median, interquartile range expression of mucosal IL-2R in Groups I (2.65, 0.87-7.97) and II (12.30, 6.15-25.55) was significantly increased compared with group III (0.40, 0.10-1.35, p < 0.05). Submucosal IL-2R expression in Groups I (2.0, 1.12-4.95) and II (10.0, 5.95-14.30) was also significantly increased compared with Group III (0.50, 0.15-1.05, p < 0.05). There was no difference in the lymphoid cell IL-6 expression between Groups I (5.95, 1.60-18.15), II (6.10, 1.1-36.15) and III (8.30, 2.60-26.35, p > 0.05). Epithelial IL-6 expression of Group III (8.3, 2.6-26.3) was significantly increased compared with group I (0.5, 0-10.2, p < 0.05) as was epithelial TNF-α expression in Group III (85.0, 70.50-92.0) compared with Groups I (72.50, 45.25.0-85.50, p < 0.05) and II (61.0, 30.0-92.0, p < 0.05). Lymphoid cell Substance P expression in Groups I (1.90, 1.32-2.65) and II (5.62, 2.50-20.8) was significantly increased compared with Group III (1.0,1.0-1.30, p < 0.05). Epithelial cell expression of Substance P in Group III (121.7, 94.6-167.8) was significantly increased compared with Groups I (75.7, 50.6-105.3, p < 0.05) and II (78.9, 43.5-118.5, p < 0.05)., Conclusion: Histologically normal gallbladders with gallstones exhibited features of inflammation on immunohistochemistry., (© 2024 The Author(s). World Journal of Surgery published by John Wiley & Sons Ltd on behalf of International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Background: Diabetes mellitus is a significant modulator of postoperative outcomes and is an important risk factor in the patient selection process. We aimed to investigate the effect of diabetes mellitus and use of insulin on outcomes after colorectal resection using a national cohort., Methods: Adults with a recorded colorectal resection in England between 2010 and 2020 were identified from Hospital Episode Statistics data linked to the Clinical Practice Research Database. The primary outcome was 90-day mortality. Secondary outcomes included hospital length of stay (LOS) and readmission within 90 days., Results: Of the 106 139 (52 875, 49.8% male) patients included, diabetes mellitus was prevalent in 10 931 (10.3%), 2145 (19.6%) of whom had a record of use of insulin. Unadjusted 90-day mortality risk was 5.7%, with an increased adjusted hazard ratio (aHR) for people with diabetes mellitus (aHR 1.28, 95% confidence interval [CI] 1.19-1.37, P<0.001). This risk was higher in both people with diabetes using insulin (aHR 1.51, 95% CI 1.31-1.74, P<0.001) and not using insulin (aHR 1.22, 95% CI 1.13-1.33, P<0.001), compared with those without diabetes. Ninety-day readmission occurred in 20 542 (19.4%) patients and this was more likely in those with diabetes mellitus (aHR 1.23, 95% CI 1.18-1.29, P<0.001). Median (inter-quartile range) LOS was 8 (5-15) days and was higher in people with diabetes mellitus (adjusted time ratio 1.10, 95% CI 1.08-1.11, P<0.001)., Conclusions: People with diabetes mellitus undergoing colorectal resection are at a higher risk of 90-day mortality, prolonged LOS, and 90-day readmission, with use of insulin associated with additional risk., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aims: Cytological classification systems provide a standardised interpretation framework for reporting cytological specimens. Three well-known classification systems can be applied when reporting pancreatic cytology. This study aimed to compare the accuracy of these classification systems (C1-C5 system, the Papanicolaou system and the WHO classification) for the assessment of pancreatic neuroendocrine lesions., Methods: We analysed 73 pancreatic neuroendocrine tumour resections, 49 of which had corroborative cytology available, reported over a 12-year period, at a single UK tertiary referral centre. Each cytology case was classified using the aforementioned systems. The final tumour grade allocated at resection was used to assess and compare the accuracy of each cytological classification system., Results: Cytological assessment accurately reported 77.6% of neuroendocrine lesions as category IVB (neoplastic - other) on Papanicolaou grading, 77.6% as C5 (malignant) lesions and 85.7% as VII (malignant) on WHO grading. 74.3% of resected tumours were grade 1, 17.1% grade 2 and 8.6% grade 3. Complete resection was achieved in 80.8% of cases., Conclusions: The results demonstrated that the WHO classification appeared to provide reduced ambiguity when compared with both 'C' and Papanicolaou classification systems; with a lower proportion of cases being classified as suspicious of malignancy as opposed to malignant. The Papanicolaou system was able to supersede the other two systems through its ability to distinguish neuroendocrine tumours from more aggressive entities such as pancreatic adenocarcinoma, thus, offering flexibility in management while still retaining a similar level of accuracy to the WHO classification system in distinguishing benign from malignant lesions., Competing Interests: Competing interests: DNL has received an unrestricted educational grant from B. Braun for unrelated work. He has also received speaker’s honoraria for unrelated work from Abbott, Nestlé and Corza. No other competing interests declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: Decoding pancreatic ductal adenocarcinoma heterogeneity and the consequent therapeutic selection remains a challenge. We aimed to characterize epigenetically regulated pathways involved in pancreatic ductal adenocarcinoma progression., Methods: Global DNA methylation analysis in pancreatic cancer patient tissues and cell lines was performed to identify differentially methylated genes. Targeted bisulfite sequencing and in vitro methylation reporter assays were employed to investigate the direct link between site-specific methylation and transcriptional regulation. A series of in vitro loss-of-function and gain-of function studies and in vivo xenograft and the KPC ( LSL-Kras G12D/+ ; LSL-Trp53 R172H/+ ; Pdx1-Cre ) mouse models were used to assess pancreatic cancer cell properties. Gene and protein expression analyses were performed in 3 different cohorts of pancreatic cancer patients and correlated to clinicopathological parameters., Results: We identify Hepatocyte Nuclear Factor 4A (HNF4A) as a novel target of hypermethylation in pancreatic cancer and demonstrate that site-specific proximal promoter methylation drives HNF4A transcriptional repression. Expression analyses in patients indicate the methylation-associated suppression of HNF4A expression in pancreatic cancer tissues. In vitro and in vivo studies reveal that HNF4A is a novel tumor suppressor in pancreatic cancer, regulating cancer growth and aggressiveness. As evidenced in both the KPC mouse model and human pancreatic cancer tissues, HNF4A expression declines significantly in the early stages of the disease. Most importantly, HNF4 loss correlates with poor overall patient survival., Conclusion: HNF4A silencing, mediated by promoter DNA methylation, drives pancreatic cancer development and aggressiveness leading to poor patient survival., (© 2024 The Authors.)

Albumin is a relatively small molecule with a radius of 7.5 nm and a molecular weight of 65 kDa. It is the most abundant protein in plasma, accounting for 60-75% of its oncotic pressure. Its concentration in plasma is merely one static measurement reflecting a dynamic and complex system of albumin physiology, and is the net result of several different processes, one or more of which may become deranged by disease or its treatment. It is also unsurprising that hypoalbuminaemia has proved to be an indicator of morbidity and mortality risk since the underlying conditions which cause it, including protein energy malnutrition, crystalloid overload, inflammation, and liver dysfunction are themselves risk factors. In some cases, its underlying cause may require treatment but mostly it is just a parameter to be monitored and used as one measure of clinical progress or deterioration. While malnutrition, associated with a low protein intake, may be a contributory cause of hypoalbuminaemia, in the absence of inflammation and/or dilution with crystalloid its development in response to malnutrition alone is slow compared with the rapid change caused by inflammatory redistribution or dilution with crystalloids. Other significant causes include liver dysfunction and serous losses. These causal factors may occur singly or in combination in any particular case. Treatment is that of the underlying causes and associated conditions such as a low plasma volume, not of hypoalbuminaemia per se., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Despite being a commonly performed surgical procedure, pain management for appendicectomy is often neglected because of insufficient evidence on the most effective treatment options., Objective: To provide evidence-based recommendations by assessing the available literature for optimal pain management after appendicectomy., Design and Data Sources: This systematic review-based guideline was conducted according to the PROSPECT methodology. Relevant randomised controlled trials, systematic reviews and meta-analyses in the English language from January 1999 to October 2022 were retrieved from MEDLINE, Embase and Cochrane Databases using PRISMA search protocols., Eligibility Criteria: We included studies on adults and children. If articles reported combined data from different surgeries, they had to include specific information about appendicectomies. Studies needed to measure pain intensity using a visual analogue scale (VAS) or a numerical rating scale (NRS). Studies that did not report the precise appendicectomy technique were excluded., Results: Out of 1388 studies, 94 met the inclusion criteria. Based on evidence and consensus, the PROSPECT members agreed that basic analgesics [paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs)] should be administered perioperatively for open and laparoscopic appendicectomies. A laparoscopic approach is preferred because of lower pain scores. Additional recommendations for laparoscopic appendicectomies include a three-port laparoscopic approach and the instillation of intraperitoneal local anaesthetic. For open appendicectomy, a preoperative unilateral transverse abdominis plane (TAP) block is recommended. If not possible, preincisional infiltration with local anaesthetics is an alternative. Opioids should only be used as rescue analgesia. Limited evidence exists for TAP block in laparoscopic appendicectomy, analgesic adjuvants for TAP block, continuous wound infiltration after open appendicectomy and preoperative ketamine and dexamethasone. Recommendations apply to children and adults., Conclusion: This review identified an optimal analgesic regimen for open and laparoscopic appendicectomy. Further randomised controlled trials should evaluate the use of regional analgesia and wound infiltrations with adequate baseline analgesia, especially during the recommended conventional three-port approach., Registration: The protocol for this study was registered with the PROSPERO database (Registration No. CRD42023387994)., (Copyright © 2024 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Background & Aims: Prehabilitation comprises multidisciplinary preoperative interventions including exercise, nutritional optimisation and psychological preparation aimed at improving surgical outcomes. The aim of this systematic review and meta-analysis was to determine the impact of prehabilitation on postoperative outcomes in frail and high-risk patients undergoing major abdominal surgery., Methods: Embase, Medline, CINAHAL and Cochrane databases were searched from January 2010 to January 2023 for randomised clinical trials (RCTs) and observational studies evaluating unimodal (exercise) or multimodal prehabilitation programmes. Meta-analysis was limited to length of stay (primary end point), severe postoperative complications (Clavien-Dindo Classification ≥ Grade 3) and the 6-minute walk test (6MWT). The analysis was performed using RevMan v5.4 software., Results: Sixteen studies (6 RCTs, 10 observational) reporting on 3339 patients (1468 prehabilitation group, 1871 control group) were included. The median (interquartile range) age was 74.0 (71.0-78.4) years. Multimodal prehabilitation was applied in fifteen studies and unimodal in one. Meta-analysis of nine studies showed a reduction in hospital length of stay (weighted mean difference -1.07 days, 95 % CI -1.60 to -0.53 days, P < 0.0001, I 2  = 19 %). Ten studies addressed severe complications and a meta-analysis suggested a decline in occurrence by up to 44 % (odds ratio 0.56, 95 % CI 0.37 to 0.82, P < 0.004, I 2  = 51 %). Four studies provided data on preoperative 6MWT. The pooled weighted mean difference was 40.1 m (95 % CI 32.7 to 47.6 m, P < 0.00001, I 2  = 24 %), favouring prehabilitation., Conclusion: Given the significant impact on shortening length of stay and reducing severe complications, prehabilitation should be encouraged in frail, older and high-risk adult patients undergoing major abdominal surgery., Competing Interests: Conflict of interest None of the authors has a direct conflict of interest to declare. DNL has received an unrestricted educational grant from B. Braun for unrelated work. He has also received speaker's honoraria for unrelated work from Abbott, Nestlé and Corza. KF has received honoraria for unrelated work from Abbott Nutrition., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

"Enhanced recovery after surgery" is a multimodal effort to control perioperative pathophysiology and improve outcome. However, despite advances in perioperative care, postoperative complications and the need for hospitalisation and prolonged recovery continue to be challenging. This is further complicated by procedure-specific and patient-associated risk factors, given the increase in the number of elderly and frail patients with multiple comorbidities undergoing surgery. This paper is a critical assessment of current methodology for trials in perioperative medicine. We make a plea to reconsider the design of future interventional trials to improve surgical outcome, based upon studies of potentially effective interventions, but often without improvements in recovery. The complexity of perioperative pathophysiology necessitates a procedure- and patient-specific approach whenever outcome is assessed or interventions are planned. With improved understanding of perioperative pathophysiology, the way to improve outcomes looks promising, provided that knowledge and established enhanced recovery programmes are integrated in trial design., Funding: None., Competing Interests: HK has no conflicts of interest to declare. DNL has received an unrestricted educational grant from B Braun and speaker's honoraria from Nestlé, Abbott and Corza for unrelated work. DNL is also the Scientific Chair of the ERAS® Society., (© 2024 Elsevier Ltd.)

Both acute and chronic pancreatitis are frequent diseases of the pancreas, which, despite being of benign nature, are related to a significant risk of malnutrition and may require nutritional support. Acute necrotizing pancreatitis is encountered in 20 % of patients with acute pancreatitis, is associated with increased morbidity and mortality, and may require artificial nutrition by enteral or parenteral route, as well as additional endoscopic, radiological or surgical interventions. Chronic pancreatitis represents a chronic inflammation of the pancreatic gland with development of fibrosis. Abdominal pain leading to decreased oral intake, as well as exocrine and endocrine failure are frequent complications of the disease. All of the above represent risk factors related to malnutrition. Therefore, patients with chronic pancreatitis should be considered at risk, screened and supplemented accordingly. Moreover, osteoporosis and increased facture risk should be acknowledged in patients with chronic pancreatitis, and preventive measures should be considered., Competing Interests: Conflict of Interest The expert members of the working group were accredited by the ESPEN Guidelines Group, the ESPEN Education and Clinical Practice Committee, and the ESPEN executive. All expert members have declared their individual conflicts of interest according to the rules of the International Committee of Medical Journal Editors (ICMJE). If potential conflicts were indicated, they were reviewed by the ESPEN guideline officers and, in cases of doubts, by the ESPEN executive. None of the expert panel had to be excluded from the working group or from co-authorship because of serious conflicts. The conflict of interest forms are stored at the ESPEN guideline office and can be reviewed with legitimate interest upon request to the ESPEN executive., (Copyright © 2023 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

We provide comprehensive insights into the peer review process and guide potential reviewers through the steps of reviewing scientific manuscripts. We discuss essential aspects such as the reviewer's responsibility in responding to invitations and maintaining confidentiality throughout the process, the criteria for accepting or rejecting papers, and efficient review of resubmissions. We emphasize the importance of prioritizing the review responsibility within other commitments, communication using professional and courteous language, and adherence to deadlines. We also offer practical tips on evaluating the abstract, introduction, materials and methods, results, and discussion section and summarizing the critiques in the review report., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

The presence of inhibitory immune cells and difficulty in generating activated effector T cells remain obstacles to development of effective cancer vaccines. We designed a vaccine regimen combining human telomerase reverse transcriptase (hTERT) peptides with concomitant therapies targeting regulatory T cells (Tregs) and cyclooxygenase-2 (COX2)-mediated immunosuppression. This Phase 1 trial combined an hTERT-derived 7-peptide library, selected to ensure presentation by both HLA class-I and class-II in 90% of patients, with oral low-dose cyclophosphamide (to modulate Tregs) and the COX2 inhibitor celecoxib. Adjuvants were Montanide and topical TLR-7 agonist, to optimise antigen presentation. The primary objective was determination of the safety and tolerability of this combination therapy, with anti-cancer activity, immune response and detection of antigen-specific T cells as additional endpoints. Twenty-nine patients with advanced solid tumours were treated. All were multiply-pretreated, and the majority had either colorectal or prostate cancer. The most common adverse events were injection-site reactions, fatigue and nausea. Median progression-free survival was 9 weeks, with no complete or partial responses, but 24% remained progression-free for ≥6 months. Immunophenotyping showed post-vaccination expansion of CD4 + and CD8 + T cells with effector phenotypes. The in vitro re-challenge of T cells with hTERT peptides, TCR sequencing, and TCR similarity index analysis demonstrated the expansion following vaccination of oligoclonal T cells with specificity for hTERT. However, a population of exhausted PD-1 + cytotoxic T cells was also expanded in vaccinated patients. This vaccine combination regimen was safe and associated with antigen-specific immunological responses. Clinical activity could be improved in future by combination with anti-PD1 checkpoint inhibition to address the emergence of an exhausted T cell population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zareian, Eremin, Pandha, Baird, Kwatra, Funingana, Verma, Choy, Hargreaves, Moghimi, Shepherd, Lobo, Eremin, Farzaneh, Kordasti and Spicer.)

Background: Burnout arising from chronic work-related stress is endemic among surgeons in the UK. Identification of contributory and modifiable psychosocial work characteristics could inform risk reduction activities., Aims: We aimed to assess the extent to which surgeons' psychosocial working conditions met aspirational Management Standards delineated by the UK Health and Safety Executive, draw comparisons with national general workforce benchmarks and explore associations with burnout., Methods: Surgeons (N = 536) completed the Management Standards Indicator Tool and a single-item measure of burnout. Descriptive data were computed for each Standard, independent t-tests were used to examine differences between trainees and consultants, and hierarchical linear regression was applied to explore relations between psychosocial work environment quality and burnout., Results: Psychosocial work environment quality fell short of each Management Standard. Trainee surgeons (n = 214) reported significantly poorer psychosocial working conditions than consultant surgeons (n = 322) on the control, peer support and change Standards. When compared with UK workforce benchmarks, trainees' psychosocial working conditions fell below the 10th percentile on four Standards and below the 50th percentile on the remainder. Consultant surgeons were below the 50th percentile on five of the seven Standards. Psychosocial working conditions accounted for 35% of the variance in burnout over that accounted for by socio- and occupational-demographic characteristics., Conclusions: Surgeons' psychosocial working conditions were poor in comparison with benchmark data and associated with burnout. These findings suggest that risk management activities based on the Management Standards approach involving modification of psychosocial working conditions would help to reduce burnout in this population., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Occupational Medicine.)

Background: Evidence suggests that physical fitness interventions, mental health support and nutritional advice before surgery (prehabilitation) could reduce hospital stay and improve quality of life of patients with cancer. In this study we captured the opinions of a group of patients with cancer undergoing these interventions after treatment to discover what a prehabilitation programme should encompass., Methods: Patients from the Cancer and Rehabilitation Exercise (CARE) programme based in Nottingham took part in a 26-point online questionnaire about the design of prehabilitation programmes., Results: The questionnaire was completed over a 2-week period in December 2021 by 54 patients from the CARE programme. Their responses were as follows: 44 (81.5%) participants would have participated in prehabilitation had it been available to them and 28 (51.9%) ranked physical exercise as the most important component. Forty (74.1%) participants believed the counselling aspect of prehabilitation would have contributed to a successful outcome and 35 (64.8%) thought dietary advice would have benefitted them before surgery. Thirty-one (57.4%) participants preferred the programme to take place in a fitness centre, rather than at home or hospital and 43 (79.6%) would have liked to have known about prehabilitation from their doctor at the time of diagnosis., Conclusions: Patients are interested in prehabilitation to become more physically fit and mentally prepared for surgery. They expressed the need for a focus on physical exercise, counselling to improve mental health and personalised nutritional advice. Tailoring a prehabilitation programme, with input from patients, could contribute to improving patient outcomes following cancer treatments., (© 2023. The Author(s).)

The procedure-specific postoperative pain management (PROSPECT) working group develops evidence-based pain management recommendations. PROSPECT methodology is unique and rigorous. However, several limitations were recognised that needed to be addressed, and several new factors were identified that improved PROSPECT methodology. The aim of this article is to present updated PROSPECT methodology for development of recommendations for procedure-specific pain management, focusing on the methodological revisions we will implement. In future, included randomised clinical trials will need to be prospectively registered on a publicly accessible clinical trials database and the study design, including the primary outcome in the registration, should coincide with that in the published manuscript. Placebo-controlled studies in which the analgesic intervention of interest is solely paracetamol, non-steroidal anti-inflammatory drugs, cyclo-oxygenase-2-specific inhibitors or opioids will not be included. Studies comparing one drug in a particular class with another in the same class will also not be included. Future projects will use the Cochrane Collaboration risk of bias tool for quality of reporting of methodology and results. A modified Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach will be used for grading of level of evidence and strength of recommendations. Finally, the updated PROSPECT methodology addresses several other limitations and implements new factors that all add rigour and transparency to developing procedure-specific pain management recommendations., (© 2023 Association of Anaesthetists.)

Background: While opioid analgesics are often necessary for the management of acute postoperative pain, appropriate prescribing practices are crucial to avoid harm. The aim was to investigate the changes in the proportion of people receiving initial opioid prescriptions after hospital discharge following colectomy, and describe trends and patterns in prescription characteristics., Methods: This was a retrospective cohort study. Patients undergoing colectomy in England between 2010 and 2019 were included using electronic health record data from linked primary (Clinical Practice Research Datalink Aurum) and secondary (Hospital Episode Statistics) care. The proportion of patients having an initial opioid prescription issued in primary care within 90 days of hospital discharge was calculated. Prescription characteristics of opioid type and formulation were described., Results: Of 95 155 individuals undergoing colectomy, 15 503 (16.3%) received opioid prescriptions. There was a downward trend in the proportion of patients with no prior opioid exposure (opioid naive) who had a postdischarge opioid prescription (P <0.001), from 11.4% in 2010 to 6.7% in 2019 (-41.3%, P <0.001), whereas the proportions remained stable for those prescribed opioids prior to surgery, from 57.5% in 2010 to 58.3% in 2019 (P = 0.637). Codeine represented 44.5% of all prescriptions and prescribing increased by 14.5% between 2010 and 2019. Prescriptions for morphine and oxycodone rose significantly by 76.6% and 31.0% respectively, while tramadol prescribing dropped by 48.0%. The most commonly prescribed opioid formulations were immediate release (83.9%), followed by modified release (5.8%) and transdermal (3.2%). There was a modest decrease in the prescribing of immediate-release formulations from 86.0% in 2010 to 82.0% in 2019 (P <0.001)., Conclusion: Over the 10 years studied, there was a changing pattern of opioid prescribing following colectomy, with a decrease in the proportion of opioid-naive patients prescribed postdischarge opioids., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd.)

This review summarises some of my work on fluid and electrolyte balance over the past 25 years and shows how the studies have influenced clinical practice. Missing pieces in the jigsaw are filled in by summarising the work of others. The main theme is the biochemical, physiological and clinical problems caused by inappropriate use of saline solutions including the hyperchloraemic acidosis caused by 0.9% saline. The importance of accurate and near-zero fluid balance in clinical practice is also emphasised. Perioperative fluid and electrolyte therapy has important effects on clinical outcome in a U-shaped dose response fashion, in which excess or deficit progressively increases complications and worsens outcome. Salt and water overload, with weight gain in excess of 2.5 kg worsens surgical outcome, impairs gastrointestinal function and increases the risk of anastomotic dehiscence. Hyperchloraemic acidosis caused by overenthusiastic infusion of 0.9% saline leads to adverse outcomes and dysfunction of many organ systems, especially the kidney. Salt and water deficit causes similar adverse effects as fluid overload at the cellular level and also leads to worse outcomes. Serum albumin is shown to be affected mainly by dilution and inflammation and is not a good nutritional marker. These findings have been incorporated in the British consensus Guidelines on Intravenous Fluid Therapy for Adult Surgical Patients (GIFTASUP) and National Institute for Health and Care Excellence (NICE) guidelines on intravenous fluid therapy in adults in hospital and are helping change clinical practice and improve outcomes., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Polymeric immunoglobulin receptor (PIGR) has a major role in mucosal immunity as a transporter of polymeric immunoglobulin across the epithelial cells. The aim of this study was to determine the effect of PIGR on cellular behaviours and chemo-sensitivity of MCF7 and MDA-MB468 breast cancer cell lines. Basal levels of PIGR mRNA and protein expression in MCF7 and MDA-MB468 cells were evaluated by real time quantitative polymerase chain reaction and Western blotting, respectively. MCF7/PIGR and MDA-MB468/PIGR stable cell lines, overexpressing the PIGR gene, were generated using a lentiviral vector with tetracycline dependent induction of expression. Cell viability, cell proliferation and chemo-sensitivity of PIGR transfected cells were evaluated and compared with un-transfected cells to determine the effect of PIGR overexpression on cell phenotype. The levels of PIGR mRNA and protein expression were significantly higher in MDA-MB468 cells than in MCF7 cells (380-fold, p < 0.0001). However, the differential expression of PIGR in these two cell lines did not lead to significant differences in chemosensitivity. Viral overexpression of PIGR was also not found to change any of the parameters measured in either cell line. PIGR per se did not affect cellular behaviours and chemosensitivity of these breast cancer cell lines., (© 2023. Springer Nature Limited.)

Getting your scientific paper published can be a difficult process. The quality of the paper relates to the quality of the design of the study, the questions asked, and defining an excellent primary endpoint that is easy to understand, and data obtained from a sufficiently large population. Before submitting your paper, go over all requirements like ethical approval, registration in public databases, and conflict of interest declarations. Manuscripts are structured in several sections. The introduction section should mainly focus on why the study was done. The materials and methods section should describe what was used and the results section provides a good representation of all data. Specifically, attention needs to be paid to high quality tables and figures. The discussion section should focus on putting the results in perspective. The abstract should cover all aspects in a condensed and focused manner. The publication process is handled by editors, reviewers, and the publisher. The first impression is the most important factor that decides whether the paper is sent out for review. If revisions are requested, a thoughtful response to the reviewers is needed. Hopefully, it all will lead to acceptance of the paper and publication., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

There are several pitfalls in the publication process that researchers can fall victim to, and these can occur knowingly or unknowingly. Although some of these errors may have occurred in good faith, disregard of publication governance is a dangerous practice and could bring authors and their co-authors into disrepute. We highlight some of these potential pitfalls, acquaint the reader with some rules that need to be adhered to in research and publishing, and help the reader learn how to avoid tripping-up on the road to publication., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Presenting a paper to a small or large audience should match both the knowledge level of your audience and the title and abstract you submitted to the conference. Your slides should give context to your work. Simpler slides and talks are easier to follow than a highly complex presentation. You must keep to the time scheduled for your talk and remember to Keep It Short and Simple (KISS). Your slides should be readable from the back of the room by keeping them simple but informative. Practice the talk (preferably with an audience of your colleagues) and be prepared to amend as necessary. Know your talk "by heart", so you can relax and enjoy the experience., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

In this education paper, we want to give some advice to aid in successful scientific grant writing. Besides defining an important research hypothesis and how to support this hypothesis, there are also technical aspects in grant writing that need to be fulfilled. Therefore, read carefully the requirements before starting to write the proposal. You must also determine what skilled people, equipment and consumables are needed in order to reach your research goal. It is advised to develop a timeline with the key milestones (background, partnership, budget, writing, peer-evaluation, submission). Spend enough time on the summary, title and acronyms, in order to make them attractive to the reader. The research objectives must be SMART (Specific, Measurable, Achievable, Realistic, Time-Sensitive), not DUMB (Diverse, Unmeasurable, Mediocre and Basically-Unachievable). In the end, understand that also non-experts will review your grant and therefore they should be able to understand what your goals are, but also at the same time add sufficient details of your proposed methodology to convince the experts., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)