Variability in perfusion conditions and set-up parameters used in ex vivo human placenta models: A literature review.

The ex vivo human placenta perfusion model has proven to be clinically relevant to study transfer- and fetal exposure of various drugs. Although the method has existed for a long period, the setup of the perfusion model has not been generalized yet. This review aims to summarize the setups of ex vivo placental perfusion models used to examine drug transfer across the placenta to identify generalized properties and differences across setups. A literature search was carried out in PubMed September 26, 2022. Studies were labeled as relevant when information was reported, between 2000 and 2022, on the setups of ex vivo placental perfusion models used to study drug transfer across the placenta. The placenta perfusion process, and the data extraction, was divided into phases of preparation, control, drug, and experimental reflecting the chronological timeline of the different phases during the entire placental perfusion process. 135 studies describing an ex vivo human placental perfusion experiment were included. Among included studies, the majority (78.5%) analyzed drug perfusion in maternal to fetal direction, 18% evaluated bi-directional drug perfusion, 3% under equilibrium conditions, and one study investigated drug perfusion in fetal to maternal direction. This literature review facilitates the comparison of studies that employ similar placenta perfusion protocols for drug transfer studies and reveals significant disparities in the setup of these ex vivo placental perfusion models. Due to interlaboratory variability, perfusion studies are not readily comparable or interchangeable. Therefore, a stepwise protocol with multiple checkpoints for validating placental perfusion is needed.

Caloric restriction reduces proteinuria in male rats with established nephropathy.

Reducing proteinuria is a crucial approach in preventing kidney function loss. Previous preclinical studies indicated that caloric restriction (CR) imposed at a young age protects against age-related proteinuria. However, these studies have not explored CR in established renal disease. Therefore, this study aimed to investigate the impact of CR on established proteinuria. Rats, aged 12 ± 2 weeks, were administered 2.1 mg/kg of Adriamycin. Six weeks after injection, protein excretion was measured, and a [13 N]ammonia positron emission tomography (PET) scan was conducted to assess kidney perfusion. After 7 weeks rats were divided into four groups: ad libitum (AL) and CR groups fed either a 12% or a 20% protein diet. All groups were treated for 12 weeks. Blood pressure was measured and a second PET scan was acquired at the end of the study. The animals subjected to CR exhibited a 20.3% decrease in protein excretion (p = 0.003) compared to those in the AL groups. Additionally, blood pressure in the CR group was 21.2% lower (p < 0.001) than in the AL groups. While kidney function declined over time in all groups, the 20% CR group demonstrated the smallest decline. Thus CR effectively reduces urinary protein excretion and lowers blood pressure in rats with established proteinuria.

Development of pancreatic diseases during long-term follow-up after acute pancreatitis: a post-hoc analysis of a prospective multicenter cohort.

BACKGROUND AND AIM: More insight into the incidence of and factors associated with progression following a first episode of acute pancreatitis (AP) would offer opportunities for improvements in disease management and patient counseling. METHODS: A long-term post hoc analysis of a prospective cohort of patients with AP (2008-2015) was performed. Primary endpoints were recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), and pancreatic cancer. Cumulative incidence calculations and risk analyses were performed. RESULTS: Overall, 1184 patients with a median follow-up of 9 years (IQR: 7-11) were included. RAP and CP occurred in 301 patients (25%) and 72 patients (6%), with the highest incidences observed for alcoholic pancreatitis (40% and 22%). Pancreatic cancer was diagnosed in 14 patients (1%). Predictive factors for RAP were alcoholic and idiopathic pancreatitis (OR 2.70, 95% CI 1.51-4.82 and OR 2.06, 95% CI 1.40-3.02), and no pancreatic interventions (OR 1.82, 95% CI 1.10-3.01). Non-biliary etiology (alcohol: OR 5.24, 95% CI 1.94-14.16, idiopathic: OR 4.57, 95% CI 2.05-10.16, and other: OR 2.97, 95% CI 1.11-7.94), RAP (OR 4.93, 95% CI 2.84-8.58), prior pancreatic interventions (OR 3.10, 95% CI 1.20-8.02), smoking (OR 2.33, 95% CI 1.14-4.78), and male sex (OR 2.06, 95% CI 1.05-4.05) were independently associated with CP. CONCLUSION: Disease progression was observed in a quarter of pancreatitis patients. We identified several risk factors that may be helpful to devise personalized strategies with the intention to reduce the impact of disease progression in patients with AP.

Reproducibility and predictive value of three grading systems for intraoperative adverse events in a cohort of abdominal surgery.

INTRODUCTION: Intraoperative adverse events (iAEs) are increasingly recognized for their impact on patient outcomes. The Kaafarani classification and Surgical Apgar Score (SAS) were developed to assess the intraoperative course; however, both have their drawbacks. ClassIntra was validated for iAEs of any origin. This study compares the Kaafarani and SAS to ClassIntra considering predictive value and interrater reliability in a cohort of abdominal surgery to support implementation of a classification in clinical practice. METHODS: The authors made use of the LAParotomy or LAParoscopy and ADhesiolysis (LAPAD) study database of elective abdominal surgery. Detailed descriptions on iAEs were collected in real-time by a researcher. For the current research aim, all iAEs were graded according ClassIntra, Kaafarani, and SAS (score ≤4). The predictive value was assessed using univariable and multivariable linear regression and the area under the receiver operating curve (AUROC). Two teams graded ClassIntra and Kaafarani to assess the interrater reliability using Cohen's Kappa. RESULTS: A total of 755 surgeries were included, in which 335 (44%) iAEs were graded according to ClassIntra, 228 (30%) to Kaafarani, and 130 (20%) to SAS. All classifications were significantly correlated to postoperative complications, with an AUROC of 0.67 (95% CI: 0.62-0.72), 0.64 (0.59-0.70), and 0.71 (0.56-0.76), respectively. For the secondary endpoint, the interrater reliability of ClassIntra with κ 0.87 (95% CI: 0.84-0.90) and Kaafarani 0.90 (95% CI: 0.87-0.93) was both strong. CONCLUSION: ClassIntra, Kaafarani, and SAS can be used for reporting of iAEs in abdominal surgery with good predictive value for postoperative complications, with strong reliability. ClassIntra, compared with Kaafarani and SAS, included the most iAEs and has the most comprehensive definition suitable for uniform reporting of iAEs in clinical practice and research.

The effect of iron therapy on oxidative stress and intestinal microbiota in inflammatory bowel diseases: A review on the conundrum.

One in five patients with Inflammatory Bowel Disease (IBD) suffers from anemia, most frequently caused by iron deficiency. Anemia and iron deficiency are associated with worse disease outcomes, reduced quality of life, decreased economic participation, and increased healthcare costs. International guidelines and consensus-based recommendations have emphasized the importance of treating anemia and iron deficiency. In this review, we draw attention to the rarely discussed effects of iron deficiency and iron therapy on the redox status, the intestinal microbiota, and the potential interplay between them, focusing on the clinical implications for patients with IBD. Current data are scarce, inconsistent, and do not provide definitive answers. Nevertheless, it is imperative to rule out infections and discern iron deficiency anemia from other types of anemia to prevent untargeted oral or intravenous iron supplementation and potential side effects, including oxidative stress. Further research is necessary to establish the clinical significance of changes in the redox status and the intestinal microbiota following iron supplementation.

The relationship of peritubular capillary density with glomerular volume and kidney function in living kidney donors.

BACKGROUND: Peritubular capillary rarefaction plays an important role in the progression of chronic kidney disease. Little is known about the relation between peritubular capillary density, glomerular volume and filtration rate in the healthy kidney. METHODS: In this single-center study, we included 69 living kidney donors who donated between 2005 and 2008 and had representative renal biopsies available. In all donors, glomerular filtration rate was measured using 125I-Iothalamate before donation and at five years after donation. Before donation, the increase in glomerular filtration rate after dopamine stimulation was measured. Glomerular volume and peritubular capillary density were determined in biopsies taken at the time of transplantation. Pearson's correlation coefficient and linear regression were used to assess relations between parameters. RESULTS: Mean donor age was 52 ± 11 years and mean measured glomerular filtration rate was 119 ± 22 mL/min before donation and 82 ± 15 mL/min at five years after donation. While peritubular capillary density (measured by either number of peritubular capillaries/50,000 µm2 or number of peritubular capillaries/tubule) was not associated with measured glomerular filtration rate before or after donation, number of peritubular capillaries/tubule was associated with the increase in measured glomerular filtration rate after dopamine stimulation (St.ß = 0.33, p = 0.004), and correlated positively with glomerular volume (R = 0.24, p = 0.047). Glomerular volume was associated with unstimulated measured glomerular filtration rate before donation (St.ß = 0.31, p = 0.01) and at five years (St.ß = 0.30, p = 0.01) after donation, independent of age. CONCLUSIONS: In summary, peritubular capillary density was not related to unstimulated kidney function before or after kidney donation, in contrast to glomerular volume. However, number of peritubular capillaries/tubule correlated with the increase in glomerular filtration rate after dopamine stimulation in healthy kidneys, and with glomerular volume. These findings suggest that peritubular capillary density and glomerular volume differentially affect kidney function in healthy living kidney donors.

Inter-Rater Agreement of the Classification of Intraoperative Adverse Events (ClassIntra) in Abdominal Surgery.

OBJECTIVE AND SUMMARY OF BACKGROUND DATA: Adverse events in surgical patients can occur preoperatively, intraoperatively, and postoperatively. Universally accepted classification systems are not yet available for intraoperative adverse events (iAEs). ClassIntra has recently been developed and validated as a tool for grading iAEs that occur between skin incision and skin closure irrespective of the origin, that is, surgery, anesthesia, or organizational. The aim of this study is to assess the inter-rater agreement of ClassIntra and assess its predictive value for postoperative complications in elective abdominal surgery. METHODS: This study is a secondary use of data from the LAParotomy or LAParoscopy and ADhesiolysis (LAPAD) study, with detailed data on incidence and management of intra-operative and post-operative complications. Data were collected in a cohort of elective abdominal surgeries. Two teams graded all recorded events in the LAPAD study according to ClassIntra. Cohen Kappa coefficient was calculated to determine inter-rater agreement. Uni- and multivariable linear regression was used to assess the predictive value of the ClassIntra grades for postoperative complications. RESULTS: IAEs were rated in 333 of 755 (44%) surgeries by team 1, and in 324 of 755 (43%) surgeries by team 2. Cohen kappa coefficient for ClassIntra grades was 0.87 [95% confidence interval (CI) 0.84-0.90]. Discrepancies in grading were most frequent for intraoperative bleeding and adhesions' associated injuries. At least 1 postoperative complication was observed in 278 (37%) patients. The risk of a postoperative complications increased with every increase in severity grade of ClassIntra. Intraoperative hypotension [mean difference (MD) 23.41, 95% CI 12.93-33.90] and other organ injuries (MD 18.90, 95% CI -4.22 - 42.02) were the strongest predictors for postoperative complications. CONCLUSIONS: ClassIntra has an almost perfect inter-rater agreement for the classification of iAEs. An increasing grade of ClassIntra was associated with a higher incidence of postoperative complications. Discrepancies in grading related to common complications in abdominal procedures mostly consisted of intraoperative bleeding and adhesion-related injuries. Grading of interoperative events in abdominal surgery might further improve by consensus regarding the definitions of a number of frequent events.

[18F]Sodium Fluoride PET has the potential to identify active formation of calcinosis cutis in limited cutaneous systemic sclerosis.

OBJECTIVES: Calcinosis cutis affects 20-40% of patients with systemic sclerosis (SSc). When calcinosis cutis becomes clinically apparent, it is irreversible in most cases. Detection of active calcification formation might allow early disease-modifying interventions. We assessed the feasibility of visualizing active calcifications using [18F]Sodium Fluoride ([18F]NaF) PET/low-dose CT (LDCT) in SSc patients with calcinosis cutis. METHODS: In this cross-sectional, observational pilot study patients underwent a whole body [18F]NaF PET/LDCT. All patients met the 2013 ACR/EULAR SSc criteria and had clinically detectable calcinosis cutis. (Sub)cutaneous calcifications were described by three investigators. RESULTS: Nine female patients were included (median age 59.0 years [IQR 51.5-70.5]). [18F]NaF uptake was mostly visible in the fingers (n=7) and knees (n=5). [18F]NaF PET showed calcifications in the fingers of 3 patients where calcifications were undetected on LDCT and in the clinic. Ninety-seven percent of [18F]NaF positive lesions was visible on LDCT. Of all lesions visible on LDCT, 70% was also visible on [18F]NaF PET. CONCLUSION: Imaging of active calcifications in SSc is feasible using [18F]NaF PET/LDCT. Seventy percent of calcifications on LDCT were [18F]NaF PET positive. Although these findings require replication, [18F]NaF PET/LDCT may detect active calcification formation, being potentially suitable for early disease-modifying interventions.

Increased frequency of proangiogenic tunica intima endothelial kinase 2 (Tie2) expressing monocytes in individuals with type 2 diabetes mellitus.

BACKGROUND: Individuals with type 2 diabetes mellitus (T2DM) have an increased risk for developing macrovascular disease (MVD) manifested by atherosclerosis. Phenotypically and functionally different monocyte subsets (classical; CD14++CD16-, non-classical; CD14+CD16++, and intermediate; CD14++CD16+) including pro-angiogenic monocytes expressing Tie2 (TEMs) can be identified. Here we investigated monocyte heterogeneity and its association with T2DM and MVD. METHODS: Individuals with (N = 51) and without (N = 56) T2DM were recruited and allocated to "non-MVD" or "with MVD" (i.e., peripheral or coronary artery disease) subgroups. Blood monocyte subsets were quantified based on CD14, CD16 and Tie2 expression levels. Plasma levels of Tie2-ligands angiopoietin-1 and angiopoietin-2 were determined using ELISA. Carotid endarterectomy samples from individuals with (N = 24) and without (N = 22) T2DM were stained for intraplaque CD68+ macrophages (inflammation) and CD34+ (angiogenesis), as plaque vulnerability markers. RESULTS: Monocyte counts were similar between individuals with T2DM and healthy controls (non-diabetic, non-MVD). Non-classical monocytes were reduced (p < 0.05) in T2DM, whereas the percentage of TEMs within the intermediate subset was increased (p < 0.05). T2DM was associated with increased angiopoietin-1 (p < 0.05) and angiopoietin-2 (p = 0.0001) levels. Angiopoietin-2 levels were higher in T2DM individuals with MVD compared with non-MVD (p < 0.01). Endarterectomized plaques showed no differences in macrophage influx and microvessel number between individuals with and without T2DM. CONCLUSIONS: Monocyte subset distribution is altered in T2DM with reduced non-classical monocytes and increased TEM percentage in the intermediate monocyte subset. Increased angiopoietin-2 levels together with increased frequency of TEMs might promote plaque vulnerability in T2DM which could however not be confirmed at tissue level in advanced atherosclerotic lesions.

Oxidative Stress Predicts Post-Surgery Complications in Gastrointestinal Cancer Patients.

INTRODUCTION: An excessive perioperative inflammatory reaction can lead to more postoperative complications in patients treated for gastrointestinal cancers. It has been suggested that this inflammatory reaction leads to oxidative stress. The most important nonenzymatic antioxidants are serum free thiols. The purpose of this study was to evaluate whether high preoperative serum free thiol levels are associated with short-term clinical outcomes. METHODS: Blood samples were drawn before, at the end of, and 1 and 2 days after surgery of a consecutive series of patients with gastrointestinal cancer. Serum free thiols were detected using a colorimetric detection method using Ellman's reagent. Short-term clinical outcomes were defined as 30-day complications (Clavien-Dindo ≥2) and length of hospital stay. Logistic regression was applied to examine the association between serum free thiol levels and short-term patient outcomes. RESULTS: Eighty-one patients surgically treated for gastrointestinal cancer were included in the study. Median age was 68 (range 26-87) years, and 28% were female. Patients in the lowest tertile of preoperative serum free thiols had a threefold higher risk to develop postoperative complications (odds ratio [OR]: 3.4; 95% confidence interval [CI]:1.1-10.7) and a fourfold higher risk to have an increased length of stay in the hospital (OR 4.0; 95% CI 1.3-12.9) compared with patients in the highest tertile. CONCLUSIONS: Patients with lower preoperative serum free thiol levels, indicating a decrease in extracellular antioxidant capacity and therefore an increase in systemic oxidative stress, are more likely to develop postoperative complications and show a longer in hospital stay than patients with higher serum free thiol levels.

Analgesia in patients with adhesion-related chronic abdominal and pelvic pain after surgery: a systematic review.

BACKGROUND AND OBJECTIVE: Adhesions are the most common cause of chronic abdominal pain after surgery. Surgical adhesiolysis can relieve symptoms in selected patients, but many require other treatments. The aim of this study is to evaluate analgesic treatments other than abdominal surgery in chronic pain related to adhesions. DATABASE AND DATA TREATMENT: A search was conducted in PubMed, Embase, and Central. Studies with patients suffering from chronic postoperative pain related to adhesions and undergoing all types' analgesic treatment were included. The primary outcome was the number of patients who improved in pain at long-term follow-up (at least 1 year). Secondary outcomes included improvement in pain at 3 months follow-up, quality of life, and physical functioning. RESULTS: Searches identified 3022 citations. Four studies were included, one trial, one cohort study, and two case reports. The primary outcome was not reported. In a small trial (n = 18) pregabalin tended to have a benefit over placebo improving pain at 3 months. In the cohort study, 17 patients with chronic pelvic pain underwent a trial of sacral nerve stimulation. Eight patients who responded positively received an implanted device for continuous modulation, reporting sustainable improvement during follow-up (range: 6-36 months). One case report described improved pain at 6 months with trans-abdominis plane stimulation. The second report described improvement of physical function with manual therapy at long-term follow-up. CONCLUSIONS: Low level of evidence is available regarding analgesic treatments of chronic abdominal and pelvic pain related to adhesions. The benefit of pregabalin is doubtful; nerve modulation is promising in a selected group.HighlightsAdhesions are a frequent cause of chronic abdominal and pelvic pain after surgery.Many patients are not good candidates for surgery (Adhesiolysis) or have relapses of pain.There is an important knowledge gap regarding non-surgical analgesic treatment.Analgesia in adhesion-related chronic abdominal pain after surgery.

Can continuous remote vital sign monitoring reduce the number of room visits to patients suspected of COVID-19: A quasi-experimental study.

BACKGROUND: Continuous remote monitoring of vital signs on the hospital ward gained popularity during the Severe Acute Respiratory Syndrome coronavirus 2 pandemic due to its ability to support early detection of respiratory failure, and the possibility to do so without physical contact between patient and clinician. The effect of continuous monitoring on patient room visits has not been established yet. OBJECTIVES: To assess the impact of continuous monitoring on the number of patient room visits for patients suspected of Corona Virus Disease 2019 (COVID-19) and the use of personal protection equipment. DESIGN AND METHODS: We performed a before-after study at a ward with private rooms for patients suspected of COVID-19 at a tertiary hospital in Nijmegen, The Netherlands. Non-participant observers observed hospital staff during day, evening and night shifts to record patient room visits and personal protection equipment usage. After eleven days, wearable continuous vital sign monitoring was introduced. An interrupted time series analysis was applied to evaluate the effect of continuous monitoring on the number of patient room visits, visits for obtaining vital signs (Modified Early Warning Score visits) and the amount of personal protection equipment used. RESULTS: During the 45 day study period, 86 shifts were observed. During each shift, approximately six rooms were included. A total of 2347 patient room visits were recorded. The slope coefficient for the number of patient room visits did not change after introducing continuous vital sign monitoring (B -0.003, 95% confidence interval -0.022/0.016). The slope coefficients of the number of Modified Early Warning Score visits and the amount of personal protection equipment used did not change either (B -0.002, 95% confidence interval -0.021/0.017 and B 0.046, 95% confidence interval -0.008/0.099). The number of Modified Early Warning Score visits did show a decline over the entire study period, however this decline was not influenced by the intervention. Evening and night shifts were associated with fewer patient room visits compared to day shifts. CONCLUSION: Introduction of continuous vital sign monitoring at a general ward for patients with suspected COVID-19 did not reduce the number of patient room visits or the usage of personal protection equipment by hospital staff. The number of Modified Early Warning Score visits declined over time, but this was not related to the introduction of continuous monitoring. Detailed analysis of the influence of continuous monitoring on the workflow of hospital staff reveals key points to increase efficacy of this intervention.

Low body weight and involuntary weight loss are associated with Raynaud's phenomenon in both men and women.

Objectives: Low body weight is an easily assessable cause of Raynaud's phenomenon (RP), and is frequently overlooked by clinicians. We aim to investigate the association of low body weight (body mass index < 18.5 kg/m2), involuntary weight loss, and nutritional restrictions with the presence of RP.Method: Participants from the Lifelines Cohort completed a validated self-administered connective tissue disease questionnaire. Subjects who reported cold-sensitive fingers and biphasic or triphasic colour changes were considered to suffer from RP. Patient characteristics, anthropometric measurements, and nutritional habits were collected. Statistical analyses was stratified for gender.Results: Altogether, 93 935 participants completed the questionnaire. The prevalence of RP was 4.2% [95% confidence interval (CI) 4.1-4.4%], and was three-fold higher in women than in men (5.7% vs 2.1%, p < 0.001). Subjects with RP had a significantly lower daily caloric intake than those without RP. Multivariate analysis, correcting for creatinine level, daily caloric intake, and other known aetiological factors associated with RP, revealed that low body weight [men: odds ratio (OR) 5.55 (95% CI 2.82-10.93); women: 3.14 (2.40-4.10)] and involuntary weight loss [men: OR 1.32 (1.17-1.48); women: 1.31 (1.20-1.44)] were significantly associated with the presence of RP. Low-fat diet was also associated with RP in women [OR 1.27 (1.15-1.44)].Conclusion: Low body weight and prior involuntary weight loss are associated with an increased risk of RP in both men and women. This study emphasizes that low body weight and weight loss are easily overlooked risk factors for RP, and should be assessed and monitored in subjects with RP.

[Early Warning Scores at the nursing ward: what do you really want to know?] / 'Early warning scores' op de verpleegafdeling.

Early Warning Scores (EWSs) are based on the assumption that critical illness is preceded by physical deterioration. The question is whether measuring 5 vital parameters several times a day can predict changes in a highly complex and dynamic clinical condition. Little evidence has yet been found for clinical superiority of current EWSs over good clinical assessment. If we want to predict better and act structurally proactively, the measurement frequency of vital parameters must increase and much more complex scores are needed to identify specific changes in individual patients at an early stage. It is plausible that the many innovative developments in this area are the stepping stone to an era in which care in regular nursing wards is increasingly directed in the right direction by predictive algorithms. Integration of such super EWSs in new working methods may contribute to continuously adaptive care that is ultimately better and more efficient and relieves the care provider.

The effect of Virtual Reality on evoked potentials following painful electrical stimuli and subjective pain.

BACKGROUND: Virtual reality (VR) has been shown to reduce pain, however outcome parameters of previous studies have primarily been of a subjective nature and susceptible to bias. This study investigated the effect of VR on cortical processing of evoked potentials (EPs) and subjectively reported pain. Additionally, we explored whether subjects' demographic and personal characteristics modulated the effect of VR analgesia. METHODS: Three VR conditions were compared in a randomized cross-over study of 30 healthy volunteers: Passive VR (i.e. no interaction possible with the virtual world), active VR (interactive virtual environment) and no VR (black screen). Subjects received noxious electrical stimuli at random intervals during all conditions. EPs, recorded at Cz, were extracted time locked to stimuli. Pain scores were reported after each condition. RESULTS: Active VR significantly decreased pain scores and amplitudes of N1 and P3. Passive VR had no analgesic effect. Age was significantly correlated to pain scores, with older subjects demonstrating larger effects of VR. Gender, game experience, and susceptibility for immersion, did not influence VR analgesia. CONCLUSION: Active VR decreases pre-perceptual and perceptual brain activity following painful electrical stimuli, corresponding with reduced pain experience. VR has potential to serve as a non-pharmacologic treatment for pain, particularly in elderly patients.

Hypomagnesemia in persons with type 1 diabetes: associations with clinical parameters and oxidative stress.

BACKGROUND: Among persons with type 1 diabetes mellitus (T1DM) low concentrations of magnesium have been reported. Previous (small) studies also suggested a relation of hypomagnesemia with (poor) glycaemic control and complications. We aimed to investigate the magnitude of hypomagnesemia and the associations between magnesium with parameters of routine T1DM care in a population of unselected outpatients. METHODS: As part of a prospective cohort study, initially designed to measure quality of life and oxidative stress, data from 207 patients with a mean age of 45 [standard deviation (SD) 12] years, 58% male, diabetes duration 22 [interquartile range (IQR) 16, 31] years and glycated haemoglobin (HbA1c) of 60 (SD 11) mmol/mol [7.6 (SD 1.0)%] were examined. Hypomagnesemia was defined as a concentration below <0.7 mmol/l. RESULTS: Mean magnesium concentration was 0.78 (SD 0.05) mmol/l. A deficiency was present in 4.3% of participants. Among these persons, mean concentration was 0.66 (SD 0.03) mmol/l. There was no correlation between magnesium and HbA1c at baseline (r = -0.014, p = 0.843). In multivariable analysis, free thiols (reflecting the degree of oxidative stress) were significantly and negatively associated with magnesium concentrations. CONCLUSION: In this cohort of T1DM outpatients, the presence of hypomagnesemia was infrequent and, if present, relative mild. Magnesium was not associated with glycaemic control nor with presence of micro- and macrovascular complications. Although these results need confirmation, in particular the negative association of magnesium with free thiols, this suggests that hypomagnesemia is not a relevant topic in routine care for people with T1DM.

Low-fat/high-fibre diet prehabilitation improves anastomotic healing via the microbiome: an experimental model.

BACKGROUND: Both obesity and the presence of collagenolytic bacterial strains (Enterococcus faecalis) can increase the risk of anastomotic leak. The aim of this study was to determine whether mice chronically fed a high-fat Western-type diet (WD) develop anastomotic leak in association with altered microbiota, and whether this can be mitigated by a short course of standard chow diet (SD; low fat/high fibre) before surgery. METHODS: Male C57BL/6 mice were assigned to either SD or an obesogenic WD for 6 weeks followed by preoperative antibiotics and colonic anastomosis. Microbiota were analysed longitudinally after operation and correlated with healing using an established anastomotic healing score. In reiterative experiments, mice fed a WD for 6 weeks were exposed to a SD for 2, 4 and 6 days before colonic surgery, and anastomotic healing and colonic microbiota analysed. RESULTS: Compared with SD-fed mice, WD-fed mice demonstrated an increased risk of anastomotic leak, with a bloom in the abundance of Enterococcus in lumen and expelled stool (65-90 per cent for WD versus 4-15 per cent for SD; P = 0·010 for lumen, P = 0·013 for stool). Microbiota of SD-fed mice, but not those fed WD, were restored to their preoperative composition after surgery. Anastomotic healing was significantly improved when WD-fed mice were exposed to a SD diet for 2 days before antibiotics and surgery (P < 0·001). CONCLUSION: The adverse effects of chronic feeding of a WD on the microbiota and anastomotic healing can be prevented by a short course of SD in mice. Surgical relevance Worldwide, enhanced recovery programmes have developed into standards of care that reduce major complications after surgery, such as surgical-site infections and anastomotic leak. A complementary effort termed prehabilitation includes preoperative approaches such as smoking cessation, exercise and dietary modification. This study investigated whether a short course of dietary prehabilitation in the form of a low-fat/high-fibre composition can reverse the adverse effect of a high-fat Western-type diet on anastomotic healing in mice. Intake of a Western-type diet had a major adverse effect on both the intestinal microbiome and anastomotic healing following colonic anastomosis in mice. This could be reversed when mice received a low-fat/high-fibre diet before operation. Taken together, these data suggest that dietary modifications before major surgery can improve surgical outcomes via their effects on the intestinal microbiome.

ANTECEDENTES: Tanto la obesidad como la presencia de cepas bacterianas colagenolíticas (Enterococcus faecalis) pueden aumentar el riesgo de fuga anastomótica. El objetivo de este estudio fue determinar si los ratones alimentados durante un tiempo prolongado con una dieta de tipo occidental con alto contenido en grasas (western type diet, WD) desarrollaban una fuga anastomótica en asociación con una microbiota alterada, así como determinar si una dieta estándar preoperatoria de corta duración baja en grasa/alta en fibra (standard diet, SD) podía mitigar la aparición de fuga. MÉTODOS: Ratones machos C57BL/6 obtenidos de Charles River fueron asignados aleatoriamente a una dieta chow estándar (SD) o a una dieta de tipo occidental obesogénica (WD) durante 6 semanas, seguida de la administración preoperatoria de antibióticos y la realización de una anastomosis en el colon. La microbiota se analizó longitudinalmente después de la operación y se correlacionó con la curación utilizando una puntuación de cicatrización anastomótica ya establecida. En experimentos repetidos, los ratones con una WD durante 6 semanas fueron expuestos a una SD durante 2, 4 y 6 días antes de la cirugía de colon, analizándose la cicatrización de la anastomosis y la microbiota del colon. RESULTADOS: Los ratones alimentados con WD en comparación con los alimentados con SD presentaron un mayor riesgo de fuga anastomótica con un rápido incremento en la abundancia de Enterococcus (65-90% para WD versus 4-15% para SD, P < 0,01). La microbiota de ratones alimentados con SD, pero no con WD, se restableció a su composición preoperatoria después de la operación. La cicatrización anastomótica mejoró significativamente cuando los ratones alimentados con WD fueron expuestos a una dieta SD durante 2 días antes del tratamiento antibiótico y de la cirugía (P < 0,01). CONCLUSIÓN: En ratones, los efectos adversos de una alimentación crónica con una WD sobre la microbiota y la cicatrización anastomótica se pueden prevenir mediante una SD de corta duración.

Pre-operative CT scan measurements for predicting complications in patients undergoing complex ventral hernia repair using the component separation technique.

BACKGROUND: The component separation technique (CST) is considered an excellent technique for complex ventral hernia repair. However, postoperative infectious complications and reherniation rates are significant. Risk factor analysis for postoperative complication and reherniation has focused mostly on patient history and co-morbidity and shows equivocal results. The use of abdominal morphometrics derived from CT scans to assist in risk assessment seems promising. The aim of this study is to determine the predictability of reherniation and surgical site infections (SSI) using pre-operative CT measurements. METHODS: Electronic patient records were searched for patients who underwent CST between 2000 and 2013 and had a pre-operative CT scan available. Visceral fat volume (VFV), subcutaneous fat volume (SFV), loss of domain (LOD), rectus thickness and width (RT, RW), abdominal volume, hernia sac volume, total fat volume (TFV), sagittal distance (SD) and waist circumference (WC) were measured or calculated. Relevant variables were entered in multivariate regression analysis to determine their effect on reherniation and SSI as separate outcomes. RESULTS: Sixty-five patients were included. VFV (p = 0.025, OR = 1.65) was a significant predictor regarding reherniation. Hernia sac volume (p = 0.020, OR = 2.10) and SFV per 1000 cm3 (p = 0.034, OR = 0.26) were significant predictors of SSI. CONCLUSION: Visceral fat volume, subcutaneous fat volume and hernia sac volume derived from CT scan measurements may be used to predict reherniation and SSI in patients undergoing complex ventral hernia repair using CST. These findings may aid in optimizing patient-tailored preoperative risk assessment.

Modulation of tactile perception by Virtual Reality distraction: The role of individual and VR-related factors.

BACKGROUND: Virtual reality (VR) has shown to be an effective distraction method in health care. However, questions remain regarding individual and VR-related factors that may modulate the effect of VR. PURPOSE: To explore the effect of VR distraction on tactile perception thresholds in healthy volunteers, in relation to personal characteristics and interactivity of VR applications. METHODS: A randomized three way cross-over study was conducted to investigate the effects of active and passive VR applications in 50 healthy participants. Main outcome measures were monofilament detection thresholds (MDT) and electrical detection thresholds (EDT). Personal characteristics (e.g. age, gender, susceptibility for immersion) and immersion in the VR conditions were analyzed for their effect on VR induced threshold differences. RESULTS: The use of VR caused a significant increase in both MDT and EDT compared to the control condition (MDT: F (2, 76) = 20.174, p < 0.001; EDT F (2, 76) = 6.907, p = 0.002). Furthermore, a significant difference in favour of active VR compared to passive VR was found in MDT (p = 0.012), but not in EDT. No significant gender effect was found. There was a significant positive correlation between age and active VR distraction (r = 0.333, p = 0.018). Immersion in the VR world was positively correlated with the effect of VR, whereas visualization and daydreaming were negatively correlated with VR effects. CONCLUSION: VR increased tactile perception thresholds, with active VR having the largest effect. Results indicate that the efficacy of VR may increase with increasing age. Gender did not affect VR susceptibility.