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.
INTRODUCTION Adhesion formation is the most common complication following peritoneal surgery and the leading cause of small bowel obstruction, acquired infertility and inadvertent organ injury at ...reoperation. Using a 'good surgical technique' is advocated as a first step in preventing adhesions. However, the evidence for different surgical techniques to reduce adhesion formation needs confirmation. METHODS Pubmed, Embase and CENTRAL were searched to identify randomized controlled trials that investigated the effect of various aspects of surgical technique on adhesion-related outcomes. Clinical outcomes and incidence of adhesions were the primary endpoints. Identification of papers and data extraction were performed by two independent researchers. RESULTS There were 28 papers with 27 studies included for a systematic review. Of these, 17 studies were eligible for meta-analysis and 11 for qualitative assessment only. None of the techniques that were compared significantly reduced the incidence of adhesive small bowel obstruction. In a small low-quality trial, the pregnancy rate increased after subserous fixation of suture knots. However, the incidence of adhesions was lower after laparoscopic compared with open surgery relative risk (RR) 0.14; 95% confidence interval (CI): 0.03-0.61 and when the peritoneum was not closed (RR 0.36; 95% CI: 0.21-0.63). CONCLUSIONS None of the specific techniques that were compared reduced the two main adhesion-related clinical outcomes, small bowel obstruction and infertility. The meta-analysis provides little evidence for the surgical principle that using less invasive techniques, introducing less foreign bodies or causing less ischaemia reduces the extent and severity of adhesions.
Background
Postoperative adhesion formation is a common consequence of abdominal surgery, and constitutes a major source of morbidity and mortality. This study evaluated an ultrapure alginate‐based ...antiadhesive barrier gel.
Methods
Experiments were performed in a rat model with caecal abrasion and peritoneal side wall excision. The primary endpoint was the incidence of adhesions at 14 days after surgery. In experiment 1 (24 rats), animals treated with alginate gel were compared with controls that had no antiadhesive barrier. In experiment 2 (42 rats), alginate gel was compared with sodium hyaluronate carboxymethyl cellulose (HA/CMC) membrane and with no antiadhesive barrier. To check for any remote action of the gel, in experiment 3 (45 rats) application of alginate gel to the ipsilateral versus contralateral side of injury was compared with no antiadhesive barrier.
Results
In experiment 1, ultrapure alginate gel reduced the incidence of adhesions from eight of 12 in control animals to one in 12 (P = 0·009). Tissue healing assessed by histology was similar in both groups. In experiment 2, ultrapure alginate gel and HA/CMC membrane showed similar antiadhesive effectiveness, reducing the incidence of adhesions from ten of 14 rats in the control group to three of 14 (P = 0·021) and two of 14 (P = 0·006) respectively. In experiment 3, ultrapure alginate gel reduced the incidence of adhesions at the site of direct application (1 of 15) compared with controls (13 of 15; P = 0·001), but not if applied remotely (9 of 15; P = 0·214).
Conclusion
Ultrapure alginate gel decreased the incidence of postoperative adhesion formation in this rat model.
Alginate gel was effective
Background
The contribution of animal research to a reduction in clinical intestinal anastomotic leakage is unknown, despite numerous experimental studies. In view of the current societal call to ...replace, reduce and refine animal experiments, this study examined the quality of animal research related to anastomotic healing and leakage.
Methods
Animal studies on intestinal anastomotic healing were retrieved systematically from PubMed and Embase. Study objective, conclusion and animal model were recorded. Reporting quality and internal validity (reporting of randomization and blinding) were assessed.
Results
A total of 1342 studies were identified, with a rising publication rate. The objectives of most studies were therapeutic interventions (64·8 per cent) and identification of risk factors (27·5 per cent). Of 350 articles studying experimental therapies, 298 (85·1 per cent) reported a positive effect on anastomotic healing. On average, 44·7 per cent of relevant study characteristics were not reported, in particular details on anastomotic complications (31·6 per cent), use of antibiotics (75·7 per cent), sterile surgery (83·4 per cent) and postoperative analgesia (91·4 per cent). The proportion of studies with randomization, blinding of surgery and blinding of primary outcome assessment has increased in the past two decades but remains insufficient, being included in only 62·4, 4·9 and 8·5 per cent of publications respectively. Animal models varied widely in terms of species, method to compromise healing, intestinal segment and outcome measures used.
Conclusion
Animal research on anastomotic leakage is of poor quality and still increasing, contrary to societal aims. Reporting and study quality must improve if results are to impact on patients.
Too many poor‐quality, repetitious studies
Atherosclerotic plaques are classically divided into stable and vulnerable plaques. Vulnerable plaques are prone to rupture with a risk for infarction. High intraplaque microvessel density ...predisposes to plaque vulnerability. Hydrogen sulfide (H
S) is a proangiogenic gasotransmitter which is endogenously produced by cystathionine γ-lyase (CSE), and is believed to have vasculoprotective effects. However, due to its proangiogenic effects, H
S may result in pathological angiogenesis in atherosclerotic plaques, thereby increasing plaque vulnerability. The aim of this study was to determine CSE expression pattern in atherosclerotic plaques, and investigate whether CSE is involved in micro-angiogenesis in vitro. Endarterectomy plaques were studied for CSE expression, and the role of CSE in micro-angiogenesis was studied in vitro. CSE is expressed in plaques with similar levels in both stable and vulnerable plaques. CSE co-localized with von Willebrand Factor-positive microvessel endothelial cells and alpha-smooth-muscle actin-positive SMCs. In vitro, inhibition of CSE in HMEC-1 reduced tube formation, cell viability/proliferation, and migration which was restored after culture in the presence of H
S donor GYY4137. CSE is expressed in intraplaque microvessels, and H
S is a stimulator of micro-angiogenesis in vitro. Due to this pro-angiogenic effect, high levels of CSE in atherosclerotic plaques may be a potential risk for plaque vulnerability.
Background
Chronic abdominal pain is common in chronic pancreatitis (CP) and may involve altered central pain processing. This study evaluated the relationship between pain processing and pain ...outcome after pancreatic duct decompression and/or pancreatic resection in patients with CP.
Methods
Patients with CP underwent quantitative sensory testing. Pain processing was measured via electrical pain detection (ePDT) and electrical pain tolerance (ePTT) thresholds in dermatomes C5 and L4. Inhibitory descending pain control mechanisms were assessed using the conditioned pain modulation (CPM) paradigm. Healthy controls and patients with CP were compared, and patients with CP and a poor pain outcome (visual analogue scale (VAS) score greater than 30) were compared with those with a good pain outcome (VAS score 30 or less).
Results
Forty‐eight patients with CP had lower ePDT, ePTT and CPM responses compared with values in 15 healthy controls (P < 0·030). The sum of ePDT values was lower in patients with a poor pain outcome than in those with a good outcome (median 7·1 versus 11·2 mA; P = 0·008). There was a correlation with the VAS score and the sum of ePDT values (rs = −0·45, P = 0·016) and ePTT values (rs = −0·46, P = 0·011), and CPM response (rs = −0·43, P = 0·006) in patients with CP.
Conclusion
After pain‐relieving pancreatic surgery, patients with CP exhibit altered central pain processing compared with that in healthy controls. Poor pain outcomes are associated with more central sensitization and more pronociceptive descending pain modulation, and this should be considered when managing persistent pain after pain‐relieving surgery for CP.
Presented in part to the 7th Alpine Liver and Pancreatic Surgery Meeting, Madonna di Campiglio, Italy, January 2012, and the American Pancreatic Association/International Association of Pancreatology Joint Annual Meeting, Miami, Florida, USA, October–November 2012; published in form as Pancreas 2012; 41: 1350
New approach to pain control
The surgical treatment of patients with complex ventral hernias is challenging. The aim of this study was to present an international overview of expert opinions on current practice.
A survey ...questionnaire was designed to investigate preoperative risk management, surgical approach and mesh choice in patients undergoing complex hernias repair, and treatment strategies for infected meshes. Geographical location of practice, experience and annual volumes of the surgeons were compared.
Of 408 surgeons, 234 (57.4 per cent) were practising in the USA, 116 (28.4 per cent) in Europe, and 58 (14.2 per cent) in other countries. Some 412 of 418 surgeons (98.6 per cent) performed open repair and 322 of 416 (77.4 per cent) performed laparoscopic repair. Most recommended preoperative work-up/lifestyle changes such as smoking cessation (319 of 398, 80.2 per cent) and weight loss (254 of 399, 63.7 per cent), but the consequences of these strategies varied. American surgeons and less experienced surgeons were stricter. Antibiotics were given at least 1 h before surgery by 295 of 414 respondents (71.3 per cent). Synthetic and biological meshes were used equally in contaminated primary hernia repair, whereas for recurrent hernia repair synthetic mesh was used in a clean environment and biological or no mesh in a contaminated environment. American surgeons and surgeons with less experience preferred biological mesh in contaminated environments significantly more often. Percutaneous drainage and antibiotics were the first steps recommended in treating mesh infection. In the presence of sepsis, most surgeons favoured synthetic mesh explantation and further repair with biological mesh.
There remains a paucity of good-quality evidence in dealing with these hernias, leading to variations in management. Patient optimization and issues related to mesh choice and infections require well designed prospective studies.
Background. The renoprotective effect of vasopressin V2 receptor antagonist (V2RA) is currently being tested in a clinical trial in early autosomal dominant polycystic kidney disease (ADPKD). If ...efficacious, this warrants life-long treatment with V2RA, however, with associated side effects as polydipsia and polyuria. We questioned whether we could reduce the side effects without influencing the renoprotective effect by starting the treatment later in the disease or by lowering drug dosage.
Methods. To investigate this, we administered V2RA OPC-31260 at a high (0.1%) and low (0.05%) dose to a tamoxifen-inducible kidney epithelium-specific Pkd1-deletion mouse model starting treatment at Day 21 (early) or 42 (advanced). After 3 and 6 weeks of treatment, we monitored physiologic and potential renoprotective effects.
Results. Initiation of V2RA treatment at advanced stage of the disease lacked renoprotective effects and had less pronounced physiologic effects than early initiation. After 3 weeks on a high dose, cyst ratio and kidney weight were reduced versus untreated controls (18 versus 25%, P = 0.05, and 0.33 versus 0.45 g, P = 0.03, respectively). After 6 weeks of treatment, however, this did not reach significance anymore, even at a high dose (cyst ratio 24 versus 27%, P = 0.12, and kidney weight 0.55 versus 0.66 g, P = 0.38).
Conclusions. Our results suggest that intervention with V2RA should be instituted early in ADPKD and that it might be necessary to further increase the dosage of this drug later in the disease to decrease cyst growth.
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
125
I-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 μm
2
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.
β
= 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.
β
= 0.31,
p
= 0.01) and at five years (St.
β
= 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.
Graphical abstract
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