Inbreeding and population bottlenecks in the ancestry of Friesian horses has led to health issues such as dwarfism. The limbs of dwarfs are short and the ribs are protruding inwards at the ...costochondral junction, while the head and back appear normal. A striking feature of the condition is the flexor tendon laxity that leads to hyperextension of the fetlock joints. The growth plates of dwarfs display disorganized and thickened chondrocyte columns. The aim of this study was to identify the gene defect that causes the recessively inherited trait in Friesian horses to understand the disease process at the molecular level.
We have localized the genetic cause of the dwarfism phenotype by a genome wide approach to a 3 Mb region on the p-arm of equine chromosome 14. The DNA of two dwarfs and one control Friesian horse was sequenced completely and we identified the missense mutation ECA14:g.4535550C > T that cosegregated with the phenotype in all Friesians analyzed. The mutation leads to the amino acid substitution p.(Arg17Lys) of xylosylprotein beta 1,4-galactosyltransferase 7 encoded by B4GALT7. The protein is one of the enzymes that synthesize the tetrasaccharide linker between protein and glycosaminoglycan moieties of proteoglycans of the extracellular matrix. The mutation not only affects a conserved arginine codon but also the last nucleotide of the first exon of the gene and we show that it impedes splicing of the primary transcript in cultured fibroblasts from a heterozygous horse. As a result, the level of B4GALT7 mRNA in fibroblasts from a dwarf is only 2 % compared to normal levels. Mutations in B4GALT7 in humans are associated with Ehlers-Danlos syndrome progeroid type 1 and Larsen of Reunion Island syndrome. Growth retardation and ligamentous laxity are common manifestations of these syndromes.
We suggest that the identified mutation of equine B4GALT7 leads to the typical dwarfism phenotype in Friesian horses due to deficient splicing of transcripts of the gene. The mutated gene implicates the extracellular matrix in the regular organization of chrondrocyte columns of the growth plate. Conservation of individual amino acids may not be necessary at the protein level but instead may reflect underlying conservation of nucleotide sequence that are required for efficient splicing.
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/m
2
), 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.
Background
Inadvertent bowel injury during adhesiolysis is a major cause of increased morbidity and mortality following abdominal surgery. Identification of risk factors predicting this complication ...would guide preoperative counselling and surgical decision‐making. The aim of this study was to identify predictive preoperative factors for inadvertent bowel injury occurring during adhesiolysis.
Methods
All patients undergoing elective abdominal surgery between June 2008 and June 2010 were evaluated prospectively as part of the LAPAD study. Data on adhesiolysis and inadvertent organ injury were gathered by direct observation during operation. Univariable logistic regression was used to investigate factors that increased the risk of inadvertent bowel injury. Independent predictors of bowel injury were identified using multivariable logistic regression and used to create a clinical nomogram.
Results
Of 715 patients eligible for analysis, 48 (6·7 per cent) had inadvertent bowel injuries. In 42 patients the defect was detected during operation and in nine at a later time (3 patients had both). Bowel resection was required for almost two‐thirds of the enterotomies. The number of previous laparotomies, anatomical site of the operation, presence of bowel fistula and laparotomy via a pre‐existing median scar were independent predictors of bowel injury. A clinical scoring system was constructed using a nomogram incorporating these risk factors; this had a predictive discrimination, measured as the area under the receiver operating characteristic curve, of 0·85.
Conclusion
A nomogram based on four independent factors predicted the risk of inadvertent bowel injury. Registration number: NCT01236625 (http://www.clinicaltrials.gov).
Predicts up to 50 per cent risk of bowel injury
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.
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.
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.
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.
Local renal complement activation by the donor kidney plays an important role in the pathogenesis of renal injury inherent to kidney transplantation. Contradictory results were reported about the ...protective effects of the donor C3F allotype on renal allograft outcome. We investigated the influence of the donor C3F allotype on renal transplant outcome, taking all different donor types into account. C3 allotypes of 1265 donor–recipient pairs were determined and divided into four genotypic groups according to the C3F allotype of the donor and the recipient. The four genotypic groups were analyzed for association with primary nonfunction (PNF), delayed graft function, acute rejection, death‐censored graft survival and patient survival. Considering all donor types, multivariable analysis found no association of the donor C3F allotype with renal allograft outcome. Also, for living and deceased brain‐dead donors, no association with allograft outcome was found. Post hoc subgroup analysis within deceased cardiac dead (DCD) donors revealed an independent protective association of donor C3F allotype with PNF. This study shows that the donor C3F allotype is not associated with renal allograft outcome after kidney transplantation. Subgroup analysis within DCD donors revealed an independent protective association of the donor C3F allotype with PNF, which is preliminary and warrants further validation.
The donor complement C3F allotype is not associated with renal allograft outcome after kidney transplantation; however, post‐hoc analyses within donation after cardiac death donors suggests its protective association with primary nonfunction.
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.
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.
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.
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.
Highlights
Adhesions 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.
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 18FSodium Fluoride (18FNaF) PET/low-dose CT (LDCT) in SSc patients with calcinosis cutis.
In this cross-sectional, observational pilot study patients underwent a whole body 18FNaF 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.
Nine female patients were included (median age 59.0 years IQR 51.5-70.5). 18FNaF uptake was mostly visible in the fingers (n=7) and knees (n=5). 18FNaF PET showed calcifications in the fingers of 3 patients where calcifications were undetected on LDCT and in the clinic. Ninety-seven percent of 18FNaF positive lesions was visible on LDCT. Of all lesions visible on LDCT, 70% was also visible on 18FNaF PET.
Imaging of active calcifications in SSc is feasible using 18FNaF PET/LDCT. Seventy percent of calcifications on LDCT were 18FNaF PET positive. Although these findings require replication, 18FNaF PET/LDCT may detect active calcification formation, being potentially suitable for early disease-modifying interventions.
PDF
![[18F]Sodium Fluoride PET ha...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0049-0172/small "[18F]Sodium Fluoride PET has the potential to identify active formation of calcinosis cutis in limited cutaneous systemic sclerosis")