Novel biomarkers in the saliva of healthy young males and females in a randomized crossover study on sedentary time: An exploratory analysis.

Several known biomarkers have been used to understand the physiological responses of humans to various short and long-term interventions such as exercise or dietary interventions. However, little exploratory work has been conducted to identify novel biomarkers in human saliva that could enable non-invasive physiological research to understand acute responses to interventions such as reducing sedentary time. The purpose of this study was to identify novel biomarkers in the saliva (cytokines, growth factors and vascular factors) that respond to prolonged (4 hours) and interrupted sitting (4 hours of sitting interrupted by 3 minutes of walking at 60% of maximal heart rate every 27 minutes) in young, healthy males and females. We also sought to determine whether responsive biomarkers would differ by sex. Participants (n = 24, 21.2 ± 2.2 years, 50% female) completed a prolonged sitting (PS) session and an interrupted sitting (IS) session in random order. Individual saliva samples were pooled into a male sample and a female sample to identify responsive biomarkers using a human cytokine antibody membrane array (42 targets). Several novel biomarkers were responsive in both sexes (e.g., IL-8, Angiogenin, VEGF, and EGF), in females only (e.g., TNF-α and IL-13), and in males only (e.g., IL-3, RANTES, and IL-12p40/p70). Importantly, several biomarkers appear to be responsive to the 4-hour prolonged and interrupted sitting sessions (e.g., TNF-α, IL-8, IL-3, RANTES, EGF, Angiogenin, and VEGF). This work highlights new directions for researchers aiming to investigate the effect of short-term or acute interventions on different physiological pathways using non-invasive methods. Our work clearly indicates that human saliva samples can provide a wealth of insight into physiological responses, and that a number of biomarkers can be used to understand changes induced by acute interventions such as interrupting prolonged sitting.

Physically active pregnancies: Insights from the placenta.

Physical activity (PA) positively influences pregnancy, a critical period for health promotion, and affects placental structure and function in ways previously overlooked. Here, we summarize the current body of literature examining the association between PA, placenta biology, and physiology while also highlighting areas where gaps in knowledge exist. PA during pregnancy induces metabolic changes, influencing nutrient availability and transporter expression in the placenta. Hormones and cytokines secreted during PA contribute to health benefits, with intricate interactions in pro- and anti-inflammatory markers. Extracellular vesicles and placental "-omics" data suggest that gestational PA can shape placental biology, affecting gene expression, DNA methylation, metabolite profiles, and protein regulation. However, whether cytokines that respond to PA alter placental proteomic profiles during pregnancy remains to be elucidated. The limited research on placenta mitochondria of physically active gestational parents (gesP), has shown improvements in mitochondrial DNA and antioxidant capacity, but the relationship between PA, placental mitochondrial dynamics, and lipid metabolism remains unexplored. Additionally, PA influences the placenta-immune microenvironment, angiogenesis, and may confer positive effects on neurodevelopment and mental health through placental changes, vascularization, and modulation of brain-derived neurotrophic factor. Ongoing exploration is crucial for unraveling the multifaceted impact of PA on the intricate placental environment.

Isolated abdominal wall recurrence of pancreatic ductal adenocarcinoma: a rare case report.

A 76-year-old woman was investigated for epigastric pain on a background of a laparoscopic distal pancreatectomy and splenectomy for pancreatic ductal adenocarcinoma 4 years prior. Imaging revealed an isolated 32 mm fluorodeoxyglucose avid lesion contacting both the anterior abdominal wall and greater curvature of the stomach. Immunohistochemistry and fine needle biopsy confirmed a phenotype consistent with metastatic pancreatic adenocarcinoma. Laparoscopic excision of the mass and partial gastrectomy for clearance of margins was performed. Histopathology demonstrated a poorly differentiated pancreatic ductal adenocarcinoma, and the patient received adjuvant gemcitabine/capecitabine following an uncomplicated postoperative course. This article presents a rare case of isolated abdominal wall recurrence of pancreatic ductal adenocarcinoma, which was successfully treated with surgical resection and adjuvant chemotherapy.

Heat production during exercise in pregnancy: discerning the contribution of total body weight.

Studies have reported enhanced thermoregulatory function as pregnancy progresses; however, it is unclear if differences in thermoregulation are attributed to weight gain or other physiological changes. This study aimed to determine if total body weight will influence thermoregulation (heat production (Hprod)), heart rate, and perceptual measurements in response to weight-bearing exercise during early to late pregnancy. A cross-sectional design of healthy pregnant women at different pregnancy time points (early, T1; middle, T2; late, T3) performed a 7-stage weight-bearing incremental exercise protocol. Measurements of Hprod, HR, and RPE were examined. Two experimental groups were studied: (1) weight matched and (2) non-weight matched, in T1, T2, and T3. During exercise, equivalent Hprod at T1 (326 ± 88 kJ), T2 (330 ± 43 kJ), and T3 (352 ± 52 kJ) (p = 0.504); HR (p = 0.830); and RPE (p = 0.195) were observed in the WM group at each time point. In the NWM group, Hprod (from stages 1-6 of the exercise) increased across pregnancy time points, T1 (291 ± 76 kJ) to T2 (347 ± 41 kJ) and T3 (385 ± 47 kJ) (p < 0.001). HR increased from T1 to T3 in the warm-up to stage 6 (p = 0.009). RPE did not change as pregnancy time point progressed (p = 0.309). Total body weight, irrespective of pregnancy time point, modulates Hprod and HR during exercise. Therefore, accounting for total body weight is crucial when comparing thermoregulatory function during exercise across pregnancy.

Laparoscopic partial splenectomy in distal pancreatectomy may preserve splenic function.

INTRODUCTION: Splenectomy is known to carry a risk of infection with encapsulated organisms and associated sepsis. Current Australian guidelines recommend intensive vaccination schedules and long-term antibiotic therapy. We postulate that in some clinical scenarios where distal pancreatectomy (DP) and splenectomy is being performed, a partial splenectomy is feasible. This may preserve splenic function and help retain immunocompetence. METHODS: Five patients underwent laparoscopic distal pancreatectomy with partial splenectomy (LDPPS). The DP is performed with proximal division and resection of the splenic artery and vein. The inferior portion of the spleen is removed en bloc with the distal pancreas with ligasure and linear cutting staplers. The line of demarcation on the spleen after the division of the splenic artery identifies the portion supplied by the short gastric vessels. Temporary clamping of the short gastrics during splenic parenchymal transection reduces blood loss. All operations were completed laparoscopically and within 4 h. RESULTS: The pathology of resected lesions includes a serous cystadenoma, a pseudocyst, an IPMN and two small medial pancreatic ductal adenocarcinomas. The benign lesions involved splenic vessels at the hilum, making Kimura or Warshaw procedures untenable. No patient required blood transfusion. One patient suffered a postoperative collection consistent with postoperative pancreatic fistula requiring a drain for 10 days. Follow-up ranged from 6 to 24 months. Following surgery, all patients had a perfused splenic remnant on imaging and benign blood films, which suggests retained splenic function. CONCLUSION: Preserving some spleen when performing distal pancreatectomy may provide long-term benefits for patients.

3D-Printed Medical-Grade Polycaprolactone (mPCL) Scaffold for the Surgical Treatment of Vaginal Prolapse and Abdominal Hernias.

The expected outcome after a scaffold augmented hernia repair is the regeneration of a tissue composition strong enough to sustain biomechanical function over long periods. It is hypothesised that melt electrowriting (MEW) medical-grade polycaprolactone (mPCL) scaffolds loaded with platelet-rich plasma (PRP) will enhance soft tissue regeneration in fascial defects in abdominal and vaginal sheep models. A pre-clinical evaluation of vaginal and abdominal hernia reconstruction using mPCL mesh scaffolds and polypropylene (PP) meshes was undertaken using an ovine model. Each sheep was implanted with both a PP mesh (control group), and a mPCL mesh loaded with PRP (experimental group) in both abdominal and vaginal sites. Mechanical properties of the tissue-mesh complexes were assessed with plunger tests. Tissue responses to the implanted meshes were evaluated via histology, immunohistochemistry and histomorphometry. At 6 months post-surgery, the mPCL mesh was less stiff than the PP mesh, but stiffer than the native tissue, while showing equitable collagen and vascular ingrowth when compared to PP mesh. The results of this pilot study were supportive of mPCL as a safe and effective biodegradable scaffold for hernia and vaginal prolapse repair, hence a full-scale long-term study (over 24-36 months) with an adequate sample size is recommended.

Short bouts of walking attenuates the response of IL-8 to prolonged sitting in healthy adults.

PURPOSE: Experimental studies have shown that prolonged sitting for 2-8 h can cause changes to vascular and metabolic markers; the response of pro-inflammatory cytokines is relatively unexplored. The purpose of this study is to determine the response of interleukin-8 (IL-8) to prolonged and interrupted sitting. METHODS: Healthy participants (n = 24, 21.1 years ± 2.2, 50% female) completed a prolonged sitting session (4 h) and an interrupted sitting session (4 h of sitting with 3 min of walking at 60%HRmax, every 30 min) in random order. Saliva and capillary plasma were collected at the beginning (T1) and at the end of each session (T2). RESULTS: Salivary concentrations of IL-8 increased during the prolonged (T1 median: 22.09 pg/mL, T2 median: 86.18 pg/mL; p = < 0.01, ES - 0.55) and interrupted (T1 median: 22.09 pg/mL, T2 median: 51.99 pg/mL; p = 0.021, ES - 0.34) sessions; however, the increase during interrupted sitting was lower (PS median: 134.4%, range: - 43.96 to 1115.69 and IS median: 50.8%, range: - 75.5 to 356.35; p = 0.011, ES - 0.53). In the sub-sample of males, salivary IL-8 did not increase in the interrupted session (T1 median: 22.09, range: 3.496-699.12, and T2 median: 24.96, range: 5.11-533.5, p = > 0.05, ES - 0.16). No significant findings were observed for IL-8 in the plasma. CONCLUSION: Prolonged sitting appears to increase concentrations of the pro-inflammatory cytokine IL-8 while interrupting this sitting with short bouts of walking blunts this response. Sex appears to moderate this relationship; however, there appears to be a large amount of individual variability.

High SUVmax on routine pre-operative FDG-PET predicts early recurrence in pancreatic and peri-ampullary cancer.

BACKGROUND: SUVmax of a primary pancreatic tumour on FDG-PET/CT (SUVmax-p) may predict early post-operative recurrence. This has not been tested in the context of routine pre-operative FDG-PET/CT. It is also unknown whether this association exists independent of local residual tumour. METHODS: FDG-PET/CT was performed routinely prior to resection of pancreatic or peri-ampullary adenocarcinoma between 2008 and 2012 as part of a previous prospective study. We compared SUVmax-p according to whether recurrence was diagnosed within 6 months of resection. We also determined the odds ratio for recurrence within 6 months for multiple cut-points of SUVmax-p. This analysis was repeated exclusively for patients who had resection with clear surgical margins (R0). RESULTS: Of 56 patients from the initial study 23 underwent resection and were eligible. Recurrence within 6 months was associated with higher median SUVmax-p (5.9 vs 3.5; p = 0.04). This was also observed in 12 patients who underwent R0 resection (6.5 vs 2.2; p = 0.05). The cut-point with the highest odds for recurrence within 6 months for both groups was SUVmax-p ≥ 5.5 (OR = 10.8, CI = 1.56-109; OR[R0] = 24.0, CI = 1.64-1020). CONCLUSION: SUVmax-p on routine FDG-PET/CT is useful for identifying patients likely to benefit from additional pre-operative staging or neoadjuvant therapy, even where clear margins can confidently be achieved.

Ventral hernia repair with a hybrid laparoscopic technique.

BACKGROUND: Ventral hernias are increasingly managed with minimally invasive laparoscopic surgery. Invasive open surgery is typically used for the repair of large-sized hernias (>10 cm diameter). The two methods are often considered mutually exclusive. We report a hybrid technique for repair of medium to large-sized hernias. METHODS: Data was collected prospectively from 44 hernias repaired using the hybrid technique from 2012 to 2020. Operative data was examined and follow-up conducted by both clinical and phone review. As for surgical technique, laparoscopic access was established via a 5 mm optical port and two (or more) 5 mm ports were added under vision. Hernia contents were reduced and extraperitoneal fat excised around the defect. Hernias with diameters ranging from 5 to 10 cm were fixed using the hybrid technique. A small incision was made directly over the hernia and polyester mesh was placed intraabdominally before defect closure with a transfascial suture. Pneumoperitoneum was re-established and mesh fixation achieved using absorbable tacks and/or fixation sutures. RESULTS: Of the 44 ventral hernias repaired with the hybrid technique, 43 were secondary hernias from incisional defects. Average hernia diameter was 6.6 cm. 86% of patients were discharged within the first 48 h. Four patients (9%) had recurrences during the study period. Minor complications occurred in 8 patients (18%): 3 (7%) had post-operative wound infection, 3 patients (7%) developed post-operative seroma. Two patients (5%) had clinically significant wound haematoma. CONCLUSION: Laparoscopic hybrid ventral hernia repair can be safely performed by a combination of laparoscopic and open techniques, offering an alternative method in the management of medium-sized ventral hernias.

Portal vein thrombosis following elective laparoscopic splenectomy: incidence and analysis of risk factors.

BACKGROUND: Minimally invasive splenectomy is now well established for a wide range of pathologies. Portal vein thrombosis (PVT) is increasingly being recognised as a complication of splenectomy. The aim was to determine the incidence and risk factors for PVT after laparoscopic splenectomy. METHODS: All cases of elective laparoscopic splenectomy performed from 1993 to 2020 were reviewed. Parameters recorded included demographics, diagnostic criterion and post-operative outcomes. Data were analysed using Minitab V18 with a p < 0.05 considered significant. RESULTS: 210 patients (103 female, 107 male) underwent laparoscopic splenectomy (14 to 85 years). A major proportion of cases were performed for ITP (n = 77, p = 0.012) followed by lymphoma (n = 28), indeterminate lesions (n = 21) and myelofibrosis (n = 19). Ten patients developed symptomatic portal vein thrombosis (4.8%). Patients presented most commonly with pain and fever and diagnosis was confirmed by computed tomography (CT) or ultrasonography (USS). There were 10 conversions (4.8%) to open and two postoperative deaths, one from PVT and one from pneumonia. The remaining nine patients were successfully treated with anticoagulation. Of 19 patients with myelofibrosis, six patients developed PVT (p = 0.0002). Patients who developed PVT had significantly greater specimen weights (1773 g vs 348 g, p < 0.001). Forty-three patients had a specimen weight of 1 kg or greater, and of these 9 developed portal vein thrombosis (21%), versus one with PVT of 155 with a specimen weight of less than 1 kg (p < 0.0001). Myelofibrosis (p = 0.0039), specimen weight (p < 0.001) and mean platelet count (p = 0.0049) were predictive of PVT. CONCLUSION: A high index of suspicion for this complication should be maintained and prompt treatment with anticoagulation. High-risk patients should be considered for prophylactic anticoagulation and routine imaging of the portal vein.

Comparison of lipid-normalised concentrations of persistent organic pollutants (POPs) between serum and adipose tissue.

Human biomonitoring of persistent organic pollutants (POPs) is typically based on serum analysis and for comparison and modelling purposes, data are often normalised to the lipid content of the serum. Such approach assumes a steady state of the compound between the serum lipids and for example lipid-rich adipose tissue. Few published data are available to assess the validity of this assumption. The aim of this study was to measure concentrations of POPs in both serum and adipose tissue samples from 32 volunteers and compare the lipid-normalised concentrations between serum and adipose tissue. For p,p'-DDE, PCB-138, PCB-153 and PCB-180, lipid-normalised adipose tissue concentrations were positively correlated to the respective serum concentrations but generally were more highly concentrated in adipose tissue. These results suggest that the investigated legacy POPs that were consistently found in paired samples may often not be in a steady state between the lipid compartments of the human body. Consequently, the analysis of serum lipids as a surrogate for adipose tissue exposure may more often than not underestimate total body burden of POPs. Further research is warranted to confirm the findings of this study.

Managing valproic acid toxicity-related hyperammonaemia: an unpredicted course.

A 20-year-old woman presented following an intentional overdose of valproic acid. Use of valproic acid, either acute or chronic, can result in hyperammonaemia. Mild hyperammonaemia with chronic use is mostly asymptomatic but can also present with concern for encephalopathy. Acute valproic acid toxicity results in significant hyperammonaemia, which can contribute to encephalopathy. Levocarnitine is the treatment of choice in valproic acid toxicity-related hyperammonaemia. For severe cases of encephalopathy, intermittent haemodialysis can also be considered. To our knowledge, this is the first case report to clearly show symptom relapse and hyperammonaemia after discontinuing levocarnitine. We recommend levocarnitine therapy for at least 72 hours, followed by an additional 24 hours of monitoring for symptom relapse and hyperammonaemia after levocarnitine discontinuation.

Body mass index and surgical outcomes in laparoscopic liver resections: a systematic review.

BACKGROUND: Laparoscopic liver resection is gaining momentum; however, there is limited evidence on its efficacy and safety in obese patients. The aim of this study was to examine the relationship between BMI and outcomes after laparoscopic liver resection (LLR) using a systematic review of the existing literature. METHODS: A systematic search of Medline (Ovid 1946-present), PubMed (NCBI), Embase (Ovid 1966-present) and Cochrane Library was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement for parameters of LLR and BMI. Operative, post-operative and oncological outcomes were recorded. RESULTS: Of 1460 abstracts, seven retrospective studies were analysed, published between 2015 and 2017 (study periods 1998-2017). Total patient cohort were classified as 481 obese and 1180 non-obese with a median age range of 42.5-69.4 years. Variations existed in definitions of obesity (Asia BMI >25 kg/m2 , Western BMI >30 kg/m2 ). Rates of conversion were examined in four studies (0-31%) with one reporting BMI >28 kg/m2 as an independent risk factor. Estimated blood loss and transfusion rates were similar. Operative time was increased in obese patients in one study (P = 0.02). Mortality rates ranged from 0% to 4.3% with no difference between BMI classes. No difference in major morbidity was demonstrated. Bile leak rates were increased in obese groups in one study (0-3.44%, P < 0.05). Wound infections were reported in five studies, with higher rates in obese patients (0-5.8% versus 0-1.9%). Tumour size was comparable in both groups. Completeness of resection was analysed in four studies with one study reporting increased R0 rates in obese patients (P = 0.012). CONCLUSION: This systematic review highlights that current evidence shows LLR in obese patients is safe, however, further studies are required.

The Patenting and Technological Trends in Hernia Mesh Implants.

Described as a projection (prolapse) of tissue through a fascial defect in the abdominal wall, hernias are associated with significant rates of complications, recurrence, and reoperations. This literature review is aimed at providing an overview of the prosthetic surgical meshes used for the repairing of hernia defects. The review was carried out using two specialized online databases: Espacenet, from the European Patent Office (EPO), and WIPO from the World Intellectual Property Organization. Of the 56 patents selected from 2008 to 2018, China was the largest contributor with 55% (31 patents) of the total patent applicant filings, followed by the United States of America (US), with 29% (16 patents). Although the majority of patent applications (39 documents) had at least one company (industry) assigned to the patent application, 4 patents were solely from academic research. Our data showed that only 13 industry applicants have had their products included in the market, and the majority of meshes available on the market are still made from polypropylene. Chemical, physical, and mesh surface modifications have been implemented, and a few reviews describing mesh design, composition, and mechanical properties are available. However, to date, the ideal mesh implant from a clinical point of view has not been developed.

Diagnostic and therapeutic considerations in biopsy-proven type 2 autoimmune pancreatitis: comparative analysis with biopsy-proven type 1 autoimmune pancreatitis.

BACKGROUND: Autoimmune processes are now an increasingly recognized cause of acute and chronic pancreatitis. Autoimmune pancreatitis is a rare, benign pathology with two distinct clinicopathologic subtypes. The aim of this study was to compare the presentation, diagnostic considerations and outcomes of patients with biopsy-proven type 1 and 2 autoimmune pancreatitis (AIP). METHODS: A retrospective review of the Queensland Health pathology database of histologically proven AIP was conducted. Parameters compared included demographics, diagnostic criterion and post-treatment outcomes. RESULTS: Twenty-three patients had a confirmed histological diagnosis of AIP (type 1 = 13, type 2 = 10). Patients with type 2 AIP were younger (median age 49 versus 59 years, P < 0.05). There was no significant difference in gender distribution of disease at presentation. Type 2 AIP presented with significant increased focal pancreatic changes on cross-sectional imaging (80% versus 54%, P < 0.05). Serum IgG4 levels were raised (>1.40 g/L) in 69% of patients with type 1 AIP and not detected in type 2 (P < 0.01). Concurrent underlying inflammatory bowel disease was present in a higher proportion of type 2 AIP (40% versus 15%, P < 0.05). A significantly increased proportion of patients with type 2 AIP underwent surgical resection (70% versus 30%, P < 0.05). Conservative management was utilized in more patients with type 1 disease (54% versus 30%). On follow-up, two patients have experienced symptomatic relapse at 6-18 months. CONCLUSIONS: Diagnostic challenges do exist and clinicians must suspect 2 type AIP in young, serum IgG4-negative inflammatory bowel disease patients with recurrent pancreatitis.