Non-operated Controls Research Articles

Epithelial changes of congenital intestinal obstruction in a rat model.

Intestinal atresia is a rare congenital affliction that is often associated with severe bacterial infections despite adequate neonatal surgery. Previous studies have focused on enteric nervous system variations. We hypothesized that epithelial systems (ES) may also be involved in the pathophysiology of postnatal disorders. Global gene expression was measured by transcriptomic analysis in a rat model of induced intestinal atresia. The analyses then focused on genes involved in ES (enterocytes and goblet cells). Rat fetus small intestines at various stages of development (ED15, ED17, ED19, and ED21, n = 22), were used as non-operated controls and compared to the upper and lower segments of rat fetus small intestines with an induced atresia (n = 14; ligature at ED18). The pattern of gene expression was then confirmed by histochemistry, electron microscopy, and RT-qPCR. From ED15 to ED21, the expression of several genes exhibited a physiological increase of ES markers, with a significant increase at the end of gestation. The operated embryos exhibited significantly higher variations of gene expression in the proximal segment than in the distal segment in terms of absorption and the epithelial barrier. An increase in goblet cells and markers was observed in the proximal segment compared to the controls. Fetal intestinal obstruction accelerates maturation in the proximal segment and disrupts the intestinal wall in the distal segment, with a decrease in the number of mucosal cells. Moreover, the epithelial cells underwent significant changes, supporting the notion that intestinal disorders involve more than the ENS.

Abstract 154: Technique And Morphologic Evaluation Of Component Restoration In The Bilateral Intermediate Cleft Tip Rhinoplasty

Purpose: The bilateral cleft nose (BCN) deformity is characterized by a broad nasal tip and shortened columella due to structural defects that include cartilage weakness and malpositioning, in addition to nasal vestibular lining deficits. Corrective rhinoplasty to address anomalies of the BCN is stratified into the primary, intermediate, and secondary phases. This study describes a novel intermediate cleft tip rhinoplasty (ICTR) component restoration technique for BCN and includes an evaluation of the chronologic postoperative morphometric changes for surgical patients in comparison with non-operated age-matched controls. Methods: The ICTR component restoration technique involves repositioning and fixation of the bilateral cleft lower lateral cartilages through composite auricular cartilage grafting to address BCN lining and structural anomalies. Photographic analysis of patients with BCN who had ICTR (n=12) and age-matched controls who did not have ICTR (n=8) were assessed at timepoints T0 = preoperative, T1= less than 2 years postoperative, T2 = more than 2 years postoperative. Evaluation includes alar symmetry, nasal tip projection, nostril dimensions, nasofacial angle, and facial symmetry. Independent sample T-tests compared morphometric measurements of ICTR patients to control groups at T0 to assess baseline morphology. One-way analyses of variance with posthoc corrections using the Tukey criterion were performed to compare morphometrics over all time points. P<0.05 was considered statistically significant. Results: No significant differences in any demographic characteristics were found between the two groups. At baseline, ICTR patients had decreased nasal tip projection (40.2±9.5 vs 50.8±9.8, p=0.03). No differences were seen in alar symmetry, nostril dimensions, nasofacial angle, or facial symmetry. ICTR technique resulted in statistically significant improvements in nasal tip protrusion based on nasofacial angle representing lateral view (32.9±4.7 vs 37.5±4.9, p=0.04) and nasal tip projection representing basal view (40.2±9.5 vs 51.7±6.6, p=0.04), in addition to improvements in nostril dimensions (67.7±14.4 vs 81.9±12.8, p=0.02) when comparing timepoints T0 with T2. On the other hand, non-operated control patients did not demonstrate statistically significant changes in any morphometrics. Conclusion: Baseline assessment reveals a greater degree of nasal deformity for patients who received ICTR. Also, this technique improves bilateral cleft nasal tip protrusion that is sustained over time. In contrast, patients who did not receive ICTR did not show improvements in nasal morphology, suggesting that these changes were not secondary to growth.

Refining the unilateral ureteral obstruction mouse model: No sham, no shame.

Fibrosis, as a common final pathway in many renal diseases, contributes significantly to the decline of organ function and to progression to end-stage renal disease. To establish therapeutic interventions that target fibrosis, animal models are essential. The most widely used model of renal fibrosis is the unilateral ureteral obstruction (UUO) model. Typically, the control for this model is a sham-operated animal. Sham surgery causes pain and distress to these control animals, and here we aim to show that there is no difference in the main read-outs of this model between sham-operated animals and non-operated C57BL/6J mice. In five experiments, quantification of Picro Sirius Red stained collagen in the renal cortex did not show any difference between 15 sham and 25 non-operated individuals. A comparison of the regulation of genes involved with fibrosis did not show any difference between sham and non-operated groups at 21 days post surgery either. We conclude that there are no significant differences between non-operated controls and sham animals with respect to collagen deposition and fibrosis pathways in the UUO mouse model.

Machine Learning Classification of Articular Cartilage Integrity Using Near Infrared Spectroscopy

IntroductionAssessment of cartilage integrity during arthroscopy is limited by the subjective visual nature of the technique. To address this shortcoming in diagnostic evaluation of articular cartilage, near infrared spectroscopy (NIRS) has been proposed. In this study, we evaluated the capacity of NIRS, combined with machine learning techniques, to classify cartilage integrity.MethodsRabbit (n = 14) knee joints with artificial injury, induced via unilateral anterior cruciate ligament transection (ACLT), and the corresponding contra-lateral (CL) joints, including joints from separate non-operated control (CNTRL) animals (n = 8), were used. After sacrifice, NIR spectra (1000–2500 nm) were acquired from different anatomical locations of the joints (nTOTAL = 313: nCNTRL = 111, nCL = 97, nACLT = 105). Machine and deep learning methods (support vector machines–SVM, logistic regression–LR, and deep neural networks–DNN) were then used to develop models for classifying the samples based solely on their NIR spectra.ResultsThe results show that the model based on SVM is optimal of distinguishing between ACLT and CNTRL samples (ROC_AUC = 0.93, kappa = 0.86), LR is capable of distinguishing between CL and CNTRL samples (ROC_AUC = 0.91, kappa = 0.81), while DNN is optimal for discriminating between the different classes (multi-class classification, kappa = 0.48).ConclusionWe show that NIR spectroscopy, when combined with machine learning techniques, is capable of holistic assessment of cartilage integrity, with potential for accurately distinguishing between healthy and diseased cartilage.

Responses of gut and pancreatic hormones, bile acids, and fibroblast growth factor-21 differ to glucose, protein, and fat ingestion after gastric bypass surgery.

Postprandial gut hormone responses change after Roux-en-Y gastric bypass (RYGB), and we investigated the impact of glucose, protein, and fat (with and without pancreas lipase inhibition) on plasma responses of gut and pancreas hormones, bile acids, and fibroblast growth factor 21 (FGF-21) after RYGB and in nonoperated control subjects. In a randomized, crossover study 10 RYGB operated and 8 healthy weight-matched control subjects were administered 4 different 4-h isocaloric (200 kcal) liquid meal tests containing >90 energy (E)% of either glucose, protein (whey protein), or fat (butter with and without orlistat). The primary outcome was glucagon-like peptide-1 (GLP-1) secretion (area under the curve above baseline). Secondary outcomes included responses of peptide YY (PYY), glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin (CCK), glicentin, neurotensin, ghrelin, insulin, glucagon, bile acids, and FGF-21. In the RYGB group the responses of GLP-1, GIP, glicentin, FGF-21, and C-peptide were increased after glucose compared with the other meals. The neurotensin and bile acids responses were greater after fat, while the glucagon and CCK responses were greater after protein ingestion. Furthermore, compared with control subjects, RYGB subjects had greater responses of total PYY after glucose, glucagon after glucose and fat, glicentin after glucose and protein, and GLP-1 and neurotensin after all meals, while GIP and CCK responses were lower after fat. Ghrelin responses did not differ between meals or between groups. Orlistat reduced all hormone responses to fat ingestion, except for ghrelin in the RYGB group. In conclusion, after RYGB glucose is a more potent stimulator of most gut hormones, especially for the marked increased secretion of GLP-1 compared with fat and protein.NEW & NOTEWORTHY We investigated the impact of glucose, protein, and fat meals on intestinal and pancreatic hormones, bile acid, and fibroblast growth factor 21 (FGF-21) secretion in gastric bypass-operated patients compared with matched nonoperated individuals. The fat meal was administered with and without a pancreas lipase inhibitor. We found that the impact of the different meals on gut hormones, bile, and FGF 21 secretion differ and was different from the responses observed in nonoperated control subjects.

Diet change affects intestinal microbiota restoration and improves vertical sleeve gastrectomy outcome in diet-induced obese rats

PurposeObesity, a worldwide health problem, is linked to an abnormal gut microbiota and is currently most effectively treated by bariatric surgery. Our aim was to characterize the microbiota of high-fat fed Sprague–Dawley rats when subjected to bariatric surgery (i.e., vertical sleeve gastrectomy) and posterior refeeding with either a high-fat or control diet. We hypothesized that bariatric surgery followed by the control diet was more effective in reverting the microbiota modifications caused by the high-fat diet when compared to either of the two factors alone.MethodsUsing next-generation sequencing of ribosomal RNA amplicons, we analyzed and compared the composition of the cecal microbiota after vertical sleeve gastrectomy with control groups representing non-operated rats, control fed, high-fat fed, and post-operative diet-switched animals. Rats were fed either a high-fat or control low-fat diet and were separated into three comparison groups after eight weeks comprising no surgery, sham surgery, and vertical sleeve gastrectomy. Half of the rats were then moved from the HFD to the control diet. Using next-generation sequencing of ribosomal RNA amplicons, we analyzed the composition of the cecal microbiota of rats allocated to the vertical sleeve gastrectomy group and compared it to that of the non-surgical, control fed, high-fat fed, and post-operative diet-switched groups. Additionally, we correlated different biological parameters with the genera exhibiting the highest variation in abundance between the groups.ResultsThe high-fat diet was the strongest driver of altered taxonomic composition, relative microbial abundance, and diversity in the cecum. These effects were partially reversed in the diet-switched cohort, especially when combined with sleeve gastrectomy, resulting in increased diversity and shifting relative abundances. Several highly-affected genera were correlated with obesity-related parameters.ConclusionsThe dysbiotic state caused by high-fat diet was improved by the change to the lower fat, higher fiber control diet. Bariatric surgery contributed significantly and additively to the diet in restoring microbiome diversity and complexity. These results highlight the importance of dietary intervention following bariatric surgery for improved restoration of cecal diversity, as neither surgery nor change of diet alone had the same effects as when combined.

Comparison of bowel dysfunction between colorectal cancer survivors and a non-operative non-cancer control group.

Low anterior resection syndrome (LARS) detrimentally affects quality of life in colorectal cancer survivors. This study assessed the prevalence for LARS in colorectal cancer survivors and the same symptoms in a matched control group. Validated instruments, the LARS score and Short Form Survey 12, used to collect functional and quality of life outcomes from patients who had undergone distal colorectal resection at Auckland Hospital (2008-2015) or Dunedin Hospital (2008-2017). A matched non-operative control group was drawn from patients undergoing surveillance colonoscopy. The response rate was 79%. Cross-sectional prevalence of major LARS in rectal cancer patients was 52% at a median follow-up of 52months. Major LARS prevalence in the sigmoid cancer resection and non-cancer control groups was similar (25% vs 26%, P=0.6). On univariate analysis anastomotic height [risk ratio (RR) for low anterior resection4.6, P<0.001; ultralow anterior resection RR=15.5, P<0.001], radiotherapy (RR=2.6; P=0.009), stoma (RR=3.6; P=0.001) and J pouch reconstruction (vs straight anastomosis, RR=4.6; P=0.008) were associated with major LARS for rectal cancer patients. These factors were not significant when the analysis was stratified for anastomotic height. Despite correlation between LARS and Short Form Survey 12 outcomes (physical ρ=-0.2; mental ρ=-0.2) there was no difference in quality of life outcomes between the groups. Bowel dysfunction after low anterior resection affects the majority of rectal cancer patients. The high background rate of bowel dysfunction must be considered when assessing the prevalence of LARS.

Enhancement of Colonic Absorptive Function after the Massive Resection of the Small Intestine Based on the Creation of an Artificial Colonic Valve

The colon can have an absorptive function similar to that of the small intestine after the massive resection of the small bowel. To improve colonic absorptive function, we created a valve in the colon (artificial colonic valve, ACV). ACVs were created in 20 rats that had 80 percent of their small intestine resected, with an observation time of 30 weeks. The ACV rats were compared with those in the non-operated control group, the short bowel syndrome (SBS) group and the colon interposition (CI) group. The ACV rats were much heavier than those in the control group, SBS group and CI group. In terms of histology and the levels of α-amylase and the Na+-dependent bile salt transporter, the absorptive function of the colons before the valves resembled that of the small intestine. The colonic absorptive function was more obvious in ACV rats than in CI rats. An ACV can enhance colonic absorptive function after the massive resection of the small intestine. The colonic absorptive function of ACV rats was better than that of the rats in the CI group.

Multiple rib fractures: A novel and prognostic CT-based classification system

Background The accepted classification for multiple rib fractures is binary: flail chest or not. There is a wide spectrum of morphology with subsequent variation in the impact on chest wall mechanics and clinical outcomes. As the practice of surgical stabilisation of rib fractures evolves, there is a need for a better taxonomy. The aim of this study was to create a data-driven radiological classification system for multiple rib fractures, prognostic of both complications and surgical stabilisation of rib fracture. Methods The radiological pattern of injury was assessed for cases undergoing surgical stabilisation of rib fracture (n = 48) over a five-year period and a consecutive sample of non-operative controls (n = 48). Every rib fracture (n = 1032) was assessed on CT scans for location, displacement and comminution. An iterative classification system was developed and tested for inter-observer agreement and outcome prediction. Results The fractures occurred in a ‘series’ (≥3 consecutive ribs at a similar location) in 72% of cases: these were more likely to be displaced (p &lt; 0.001). Variables included in the classification were the anatomical pattern (presence, length and overlap of series) and degree of displacement. The classification was prognostic for complications (p &lt; 0.001), discriminated for fixation (C = 0.907) and had acceptable inter-observer agreement (k = 0.50). Conclusions The Sheffield Multiple Rib Fracture Classification derived categories of short/long series, and short/long flail chest, with sub-division according to the presence of displacement. It was prognostic for clinical outcomes and of surgical fixation. It may facilitate communication, comparison of outcomes and selection for management protocols.

Abdominal vagotomy reveals majority of small intestinal mucosal afferents labeled in nav 1.8cre-rosa26tdTomato mice are vagal in origin.

Vagal afferents innervating the small intestinal mucosa regulate feeding, gastrointestinal (GI) digestive, and immune functions. Their anatomical-functional characterization has been impeded by the inability to selectively label and manipulate them. Nav 1.8-Cre-tdTomato mice label 80% of nodose and dorsal root ganglia neurons. Here, the origin of these neuron's terminals and their distribution in the small intestinal mucosa were examined by quantitatively comparing tdTomato-labeled innervation in nonoperated (control), subdiaphragmatic vagotomy (VAGX), and sham-operated mice. Control mice exhibited a large proximal-to-distal decrease and a moderate mesentery-to-antimesentery decrease in villus innervation. VAGX reduced this innervation to a greater degree proximally (91-93%) than distally (65-72%), resulting in flat proximal-distal distributions. Therefore, estimates of vagal villus afferent distributions (control minus VAGX) paralleled control distributions, but were slightly reduced in magnitude. Compared with villus afferents, crypt innervation exhibited a muted proximal-to-distal decrease in control mice and a smaller loss after VAGX (45-48%). Sham-operated mice exhibited similar distributions of villus and crypt afferents as control mice, suggesting surgery did not contribute to the effects of VAGX. Most crypt and villus afferent terminals along the entire proximal-distal small intestinal axis had similar morphology to those previously reported in the proximal duodenum, but the density of terminal branches varied. Our findings suggest the majority of small intestinal mucosal innervation labeled in Nav 1.8-Cre-tdTomato mice is vagal in origin. Therefore, these mice will be valuable for studying vagal mucosal afferent morphology, interactions with other GI elements, plasticity, and function.

Resting Energy Expenditure and Organ-Tissue Body Composition 5 Years After Bariatric Surgery.

Bariatric surgery-induced weight loss may reduce resting energy expenditure (REE) and fat-free mass (FFM) disproportionately thereby predisposing patients to weight regain and sarcopenia. We compared REE and body composition of African-American and Caucasian Roux-en-Y gastric bypass (RYGB) patients after surgery with a group of non-operated controls (CON). REE by indirect calorimetry; skeletal muscle (SM), trunk organs, and brain volumes by MRI; and FFM by DXA were measured at post-surgery visits and compared with CON (N = 84) using linear regression models that adjusted for relevant covariates. Ns in RYGB were 50, 42, and 30 for anthropometry and 39, 27, 17 for MRI body composition at years 1, 2, and 5 after surgery, respectively. Regression models adjusted for age, weight, height, ethnicity, and sex showed REE differences (RYGB minus CON; mean ± s.e.): year 1 (43.2 ± 34 kcal/day, p = 0.20); year 2 (- 27.9 ± 37.3 kcal/day, p = 0.46); year 5 (114.6 ± 42.3 kcal/day, p = 0.008). Analysis of FFM components showed that RYGB had greater trunk organ mass (~ 0.4 kg) and less SM (~ 1.34 kg) than CON at each visit. REE models adjusted for FFM, SM, trunk organs, and brain mass showed no between-group differences in REE (- 15.9 ± 54.8 kcal/day, p = 0.8; - 46.9 ± 64.9 kcal/day, p = 0.47; 47.7 ± 83.0 kcal/day, p = 0.57, at years 1, 2, and 5, respectively). Post bariatric surgery patients maintain a larger mass of high-metabolic rate trunk organs than non-operated controls of similar anthropometrics. Interpreting REE changes after weight loss requires an accurate understanding of fat-free mass composition at both the organ and tissue levels. Long-term Effects of Bariatric Surgery (LABS-2) NCT00465829.

Biopsying, fragmentation and autotransplantation of fresh ovarian cortical tissue in infertile women with diminished ovarian reserve.

Can ovarian biopsying per se and/or autotransplantation of fragmented ovarian cortical tissue activate dormant follicles and increase the number of recruitable follicles for IVF/ICSI in women with diminished ovarian reserve (DOR)? Ovarian biopsying followed by immediate autotransplantation of fragmented cortical tissue failed to increase the number of recruitable follicles for IVF/ICSI 10weeks after the procedure either at the graft site or in the biopsied ovary, but 12 of the 20 women subsequently had a clinical pregnancy during the 1-year follow-up. Infertile women with DOR constitute a group of patients with poor reproductive outcome mainly due to the low number of mature oocytes available for IVF/ICSI. Recent studies have shown that in vitro activation of residual dormant follicles by both chemical treatment and tissue fragmentation has resulted in return of menstrual cycles and pregnancies in a fraction of amenorrhoeic women with premature ovarian insufficiency. This is a prospective clinical cohort study including 20 women with DOR treated at the fertility clinic, Rigshospitalet, Denmark, during April 2016-December 2017. Non-pregnant patients were on average followed for 280days (range 118-408), while women who conceived were followed until delivery. Study follow-up of non-pregnant patients ended in September 2018. The study included infertile women aged 30-39years with preserved menstrual cycles, indication for IVF/ICSI and repeated serum measurements of anti-Müllerian hormone (AMH) ≤ 5pmol/L. Patients were randomized to have four biopsies taken from either the left or the right ovary by laparoscopy followed by fragmentation of the cortical tissue to an approximate size of 1mm3 and autotransplanted to a peritoneal pocket. The other ovary served as a control. Patients were followed weekly for 10weeks with recording of hormone profile, antral follicle count (AFC), ovarian volume and assessment for ectopic follicle growth. After 10weeks, an IVF/ICSI-cycle with maximal ovarian stimulation was initiated. No difference in the number of mature follicles after ovarian stimulation 10weeks after the procedure in the biopsied versus the control ovaries was observed (1.0 vs. 0.7 follicles, P= 0.35). In only three patients, growth of four follicles was detected at the graft site 24-268days after the procedure. From one of these follicles, a metaphase II (MII) oocyte was retrieved and fertilized, but embryonic development failed. Overall AMH levels did not change significantly after the procedure (P= 0.2). The AFC increased by 0.14 (95% CI: 0.06;0.21) per week (P< 0.005), and the biopsied ovary had on average 0.6 (95% CI: 0.3;-0.88) follicles fewer than the control ovary (P= 0.01). Serum levels of androstenedione and testosterone increased significantly by 0.63nmol/L (95% CI: 0.21;1.04) and 0.11nmol/L (95% CI: 0.01;0.21) 1week after the procedure, respectively, and testosterone increased consecutively over the 10weeks by 0.0095nmol/L (95% CI: 0.0002;0.0188) per week (P= 0.045). In 7 of the 20 patients, there was a serum AMH elevation 5 to 8weeks after the procedure. In this group, mean AMH increased from 2.08pmol/L (range 1.74-2.34) to 3.94pmol/L (range 3.66-4.29) from Weeks 1-4 to Weeks 5-8. A clinical pregnancy was obtained in 12 of the 20 (60%) patients with and without medically assisted reproduction (MAR) treatments. We report a cumulated live birth rate per started IVF/ICSI cycle of 18.4%. Limitations of the study were the number of patients included and the lack of a non-operated control group. Moreover, 9 of the 20 women had no male partner at inclusion and were treated with donor sperm, but each of these women had an average of 6.8 (range 4-9) unsuccessful MAR treatments with donor sperm prior to inclusion. Although 12 out of 20 patients became pregnant during the follow-up period, the current study does not indicate that biopsying, fragmenting and autotransplanting of ovarian cortical tissue increase the number of recruitable follicles for IVF/ICSI after 10weeks. However, a proportion of the patients may have a follicular response in Weeks 5-8 after the procedure. It could therefore be relevant to perform a future study on the possible effects of biopsying per se that includes stimulation for IVF/ICSI earlier than week 10. This study is part of the ReproUnion collaborative study, co-financed by the European Union, Interreg V ÖKS. The funders had no role in the study design, data collection and interpretation, or decision to submit the work for publication. None of the authors have a conflict of interest. NCT02792569.

Early Alterations of Subchondral Bone in the Rat Anterior Cruciate Ligament Transection Model of Osteoarthritis.

Advances in research have shown that the subchondral bone plays an important role in the propagation of cartilage loss and progression of osteoarthritis (OA), but whether the subchondral bone changes precede or lead to articular cartilage loss remains debatable. In order to elucidate the subchondral bone and cartilage changes that occur in early OA, an experiment using anterior cruciate ligament transection (ACLT) induced posttraumatic OA model of the rat knee was conducted. Forty-two Sprague Dawley rats were divided into 2 groups: the ACLT group and the nonoperated control group. Surgery was conducted on the ACLT group, and subsequently rats from both groups were sacrificed at 1, 2, and 3 weeks postsurgery. Subchondral bone was evaluated using a high-resolution peripheral quantitative computed tomography scanner, while cartilage was histologically evaluated and scored. A significant reduction in the subchondral trabecular bone thickness and spacing was found as early as 1 week postsurgery in ACLT rats compared with the nonoperated control. This was subsequently followed by a reduction in bone mineral density and bone fractional volume at week 2, and finally a decrease in the trabecular number at week 3. These changes occurred together with cartilage degeneration as reflected by an increasing Mankin score over all 3 weeks. Significant changes in subchondral bone occur very early in OA concurrent with surface articular cartilage degenerative change suggest that factors affecting bone remodeling and resorption together with cartilage matrix degradation occur very early in the disease.

Anterior Cruciate Ligament Reconstruction with Hamstring Tendons Has no Deleterious Effect on Hip Extension Strength.

Hamstring tendons are secondary hip extensors. Their harvest for graft in anterior cruciate ligament (ACL) reconstruction may create deleterious effect on hip extension strength. This is of particular importance in sports that need powerful hip extension force like climbing and sprinting. Due to scarcity of a comprehensive study in this area, we designed this prospective study to evaluate hip extension strength following ACL reconstruction using different types of grafts. Fifty eight patients were enrolled in this prospective non-randomized case control study to compare isokinetic hip extension strength following ACL reconstruction with different graft types. Twenty patients in group A (both Semitendinosus and Gracilis tendons autograft (ST-G)), 14 patients in group B (Tibialis Posterior tendon allograft (Allograft)), 12 patients in group C (bone-patellar tendon-bone autograft (BPTB)) and 12 patients in group D (only semitendinosus autograft (ST)) were studied. Hip extension strength was tested post-operatively at three- and six-month periods using a Biodex isokinetic testing machine at a speed of 30 degree per second in operated (cases) and non-operated (controls) limbs. There was a significant increase in hip extension force between three and six month intervals in all four groups and in both operated (case) and non-operated (control) limbs (P<0.05, 95% CI). However, there was more increase in case limbs in comparison to control limbs. There was no significant difference in hip extension strength among all four groups (both in case and control limbs) in the third- and the sixth-month post-operative tests. Graft type had no effect on hip extension strength following ACL reconstruction, and the harvest of one or both hamstrings had no deleterious effect on hip extension force. III.

Effects of tendon injury on uninjured regional tendons in the distal limb: An in-vivo study using an ovine tendinopathy model.

Following injury to a tendon little is known about potential for pathology to develop in other regional tendons from overloading or altered function. The aim of this study was to investigate the gene expression and histopathological changes that occur 1) within the deep digital flexor tendon (DDFT) after injury to the superficial digital flexor tendon (SDFT) and 2) within the flexor tendons (SDFT and DDFT) after injury to the extensor tendons. Merino wethers [Ovis aries] (n = 18) were divided into three equal groups and underwent either partial transection of the SDFT, complete transection of the extensor tendons or were left as non-operated controls. Tendons were harvested and sampled regionally for gene expression (real time PCR) and histologic analysis eight weeks after surgery. Transection of the SDFT resulted in increased expression of collagen III, versican, biglycan, lumican and MMP1 (P<0.026 for all genes) within the DDFT. There was no effect of transecting the extensor tendons on the expression of any gene tested in either the SDFT or the DDFT. The DDFT had elevated histopathology scores induced by transection of the SDFT, eight weeks previously. There were minimal histological differences in either the SDFT or DDFT after transection of the extensor tendons. Transection of the SDFT results in a mild, subclinical tendinopathy within the DDFT with potential implications on treatment and rehabilitation of SDFT injuries. Injury to the extensor tendons has minimal measured effect on the SDFT or DDFT.

Early varicocelectomy by percutaneous scleroembolization improves seminiferous tubules spermatozoa release in the adolescent phase of testicular growth.

Varicocele is a rather common andrological condition in adolescents, which can adversely affect testicular growth and seminal parameters, leading to infertility in about 20% of adults. The aim of this study was to investigate if treating varicocele before the age of 18 is a beneficial option to improve testicular hypotrophy and seminal parameters and if minimally invasive techniques could be an appropriate treatment choice for adolescent varicocele associated with spermatic vein reflux. A percutaneous scleroembolization was performed in sixty-four consecutive young patients (13-19years old) with left varicocele, preceded by a fluoroscopy. In thirty-four of them, semen samples were also collected. We examined semen samples and testicles dimensions before and after percutaneous varicocelectomy, compared to a nonoperated control group, with a six-month follow-up. Total sperm count and sperm morphology were significantly increased in the intervention group. Left testicular volume significantly increased in both groups, while only correction of varicocele improved spermatozoa release per unit of testis volume. We conclude that early varicocelectomy by percutaneous scleroembolization significantly ameliorates seminiferous tubules activity in the critical adolescent phase of testicular growth. It is suggested that adolescents should be; offered varicocele repair as soon as possible in order to improve reproductive potential.

The H2S-Releasing Naproxen Derivative ATB-346 and the Slow-Release H2S Donor GYY4137 Reduce Intestinal Inflammation and Restore Transit in Postoperative Ileus.

Objective: Intestinal inflammation triggers postoperative ileus (POI), commonly seen after abdominal surgery and characterized by impaired gastrointestinal transit; when prolonged, this leads to increased morbidity. Hydrogen sulfide (H2S) is recognized as an important mediator of many (patho)physiological processes, including inflammation, and is now investigated for anti-inflammatory application. Therefore, the aim of this study was to investigate the effect of the H2S-releasing naproxen derivative ATB-346, developed to reduce gastrointestinal injury by naproxen, and the slow-release H2S donor GYY4137 on intestinal inflammation and delayed gastrointestinal transit in murine POI.Methods: C57Bl6J mice were fasted for 6 h, anesthetized and after laparotomy, POI was induced by compressing the small intestine with two cotton applicators for 5 min (intestinal manipulation; IM). GYY4137 (50 mg/kg, intraperitoneally), ATB-346 (16 mg/kg, intragastrically) or naproxen (10 mg/kg, intragastrically) were administered 1 h before IM. At 24 h postoperatively, gastrointestinal transit was assessed via fluorescent imaging, and mucosa-free muscularis segments were prepared for later analysis. Inflammatory parameters and activity of inducible nitric oxide synthase (iNOS) and cyclo-oxygenase (COX)-2 were measured. Histological examination of whole tissue sections was done on hematoxylin-eosin stained slides.Results: Pre-treatment with GYY4137 (geometric center; GC: 7.6 ± 0.5) and ATB-346 (GC: 8.4 ± 0.3) prevented the delayed transit induced by IM (GC: 3.6 ± 0.5 vs. 9.0 ± 0.4 in non-operated controls) while naproxen only partially did (GC: 5.9 ± 0.5; n = 8 for all groups). GYY4137 and ATB-346 significantly reduced the IM-induced increase in muscular myeloperoxidase (MPO) activity and protein levels of interleukin (IL)-6, IL-1β and monocyte chemotactic protein 1; the reduction by naproxen was less pronounced and only reached significance for MPO activity and IL-6 levels. All treatments significantly reduced the increase in COX-2 activity caused by IM, whereas only GYY4137 significantly reduced the increase in iNOS activity. Naproxen treatment caused significant histological damage of intestinal villi. Conclusion: The study shows that naproxen partially prevents POI, probably through its inhibitory effect on COX-2 activity. Both ATB-346 and GYY4137 were more effective, the result with GYY4137 showing that H2S per se can prevent POI.

Biomimetic proteoglycans can molecularly engineer early osteoarthritic cartilage in vivo.

Biomimetic proteoglycans (BPGs) have the potential to treat osteoarthritis (OA) given that these molecules mimic the structure and properties of natural proteoglycans, which are significantly reduced in OA. We examined the effects of BPGs injected into the intra-articular space in an in vivo OA rabbit knee model and evaluated the effect on histological response, joint friction, and BPG distribution and retention. Rabbits underwent ACL transection to create an arthritic state after 5 weeks. OA rabbits were treated with BPGs or Euflexxa® (hyaluronic acid) intra-articular injections. Non-OA rabbits were injected similarly with BPGs; contralateral joints served as controls. The progression of OA and response to injections were evaluated using Mankin and gross grading systems indicating that mild OA was achieved in operated joints. The coefficient of friction (COF) of the intact knee joints were measured using a custom pendulum friction apparatus, showing that OA joints and OA + Euflexxa® joints demonstrated increased COF than non-operated controls, while BPG-injected non-OA and OA + BPGs were not significantly different from non-OA controls. Injected fluorescently labeled BPGs demonstrated that BPGs diffused into cartilage with localization in the pericellular region. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:403-411, 2019.

Diabetic retinopathy in people with Type 2 diabetes and obesity treated by Roux-en-Y gastric bypass compared with non-operated controls: with focus on the role of diabetes remission in a cross-sectional and a 6-year follow-up study.

Whether or not Roux-en-Y gastric bypass (RYGB) and the derived metabolic improvements are beneficial to diabetic retinopathy is controversial. We aimed to determine the presence and development of retinopathy in individuals with obesity and Type 2 diabetes treated by RYGB compared with non-operated controls, and to determine the role of diabetes remission. We graded fundus photography using the Wisconsin Epidemiologic Study of Diabetic Retinopathy in 96 individuals with obesity and Type 2 diabetes treated by RYGB 6 years after surgery compared with 48 non-operated controls. In a subsample, we investigated the development of retinopathy over time. In the secondary analysis, we divided the RYGB group according to diabetes remission. RYGB surgery was not statistically associated with less retinopathy [relative risk (RR) 0.82, 95% CI 0.59 to 1.14], when adjusted for diabetes duration, sex, age and BMI. During 5.9years of follow-up, retinopathy grading in the RYGB group was unchanged, whereas the control group displayed worse grading by 0.69 steps (95% CI 0.18 to 1.19). The RYGB group with diabetes remission (52%) showed a trend towards less retinopathy [adjusted RR (aRR) 0.45; 95% CI 0.19 to 1.06] than controls, and less retinopathy (aRR 0.33; 95% CI 0.11 to 0.94) than the RYGB group without remission in the cross-sectional data. In a cross-sectional setting, individuals with Type 2 diabetes treated by RYGB showed a tendency towards less retinopathy than non-operated controls, in particular diabetes remission following RYGB was associated with less retinopathy. Moreover after 5.9years, retinopathy in the RYGB group had progressed less than in the control group. (Clinical Trial Registry No: NCT02625649).

Cartilage repair surgery prevents progression of knee degeneration.

To investigate, whether cartilage repair surgery for focal osteochondral defects at the knee results in less degenerative changes over 6years in a MR imaging follow-up than morphologically initially identical defects in non-operated control subjects from the osteoarthritis initiative (OAI). A total of 32 individuals received baseline and follow-up MRI. In n = 16 patients with cartilage repair [osteochondral autograft transfer system (OATS), n = 12; spongiosa-augmented matrix-associated autologous chondrocyte implantation (MACI), n = 4] MRI was performed preoperatively and after 5.7 ± 2.3year follow-up. Baseline MRIs of non-operated subjects from the OAI were screened for initially identical cartilage defects (n = 16). Morphological knee abnormalities were assessed using WORMS, AMADEUS and MOCART scores. A sagittal 2D MSME sequence was implemented for quantitative cartilage T2 relaxation time measurements in all (0, 2, 4, 6 and 8-years) follow-ups from the OAI and in the postoperative MRI protocol. For both groups, focal osteochondral defects were located at the femoral condyle in 8/16 cases (5 medial, 3 lateral) and at the patella in 8/16 cases. At baseline, the mean cartilage defect size ± SD was 1.4 ± 1.3cm2 for the control group and 1.3 ± 1.2cm2 for the cartilage repair group (n.s.). WORMS scores were not significantly different between the cartilage repair group and the control group at baseline [mean difference ± SEM (95%CI); 0.5 ± 2.5 (- 4.7, 5.7), n.s.]. During identical follow-up times, the progression of total WORMS scores [19.9 ± 2.3 (15.0, 24.9), P < 0.001] and of cartilage defects scores in the affected (P < 0.001) and in the opposing (P = 0.029) compartment was significantly more severe in non-operated individuals (P < 0.05). In non-operated subjects, T2 values increased continuously from baseline to the 8-year follow-up (P = 0.001). Patients with cartilage repair showed less progression of degenerative MRI changes at 6-year follow-up than a control cohort from the OAI with initially identical osteochondral defects. Patients with focal cartilage defects may profit from cartilage repair surgery since it may prevent progression of early osteoarthritis at the knee joint. Prognostic study, Level II.