Paw placement during walking is altered by analgesic doses of opioids and post-surgical injury in mice

Hind paw-directed assays are commonly used to study the analgesic effects of opioids in mice. However, opioid-induced hyper-locomotion can obscure results of such assays. We aimed to overcome this potential confound by using gait analysis to observe hind paw usage during walking in mice. We measured changes in paw print area following induction of post-surgical pain (using the paw incision model) and treatment with oxycodone. Paw incision surgery reduced the paw print area of the injured hind paw as the mice avoided placing the incised section of the paw on the floor. Surprisingly, oxycodone caused a tiptoe-like gait in mice, resulting in a reduced paw print area in both hind paws. Further investigation of this opioid-induced phenotype revealed that analgesic doses of oxycodone or morphine dose-dependently reduced hind paw print area in uninjured mice. The gait changes were not dependent on opioid-induced increases in locomotor activity; speed and paw print area had no correlation in opioid-treated mice, and other analgesic compounds that alter locomotor activity did not affect paw print area. Unfortunately, the opioid-induced 'tiptoe' gait phenotype prevented gait analysis from being a viable metric for demonstrating opioid analgesia in injured mice. However, this work reveals an important, previously uncharacterized effect of treatment with analgesic doses of opioids on paw placement. Our characterization of how opioids affect gait has important implications for the use of mice to study opioid pharmacology and suggests that scientists should use caution when using hind paw-directed nociceptive assays to test opioid analgesia in mice.

Hyperactivation of dormant primordial follicles in ovarian endometrioma patients

Serum anti-Müllerian hormone (AMH) levels decrease after surgical treatment of ovarian endometrioma. This is the main reason that surgery for ovarian endometrioma endometriosis is not recommended before in vitro fertilization, unless the patient has severe pain or suspected malignant cysts. Furthermore, it has been suggested that ovarian endometrioma itself damages ovarian reserve. This raises two important challenges: (1) determining how to prevent surgical damage to the ovarian reserve in women with ovarian endometrioma and severe pain requiring surgical treatment and (2) deciding the best treatment for women with ovarian endometrioma without pain, who do not wish to conceive immediately. The mechanisms underlying the decline in ovarian reserve are potentially induced by both ovarian endometrioma and surgical injury but the relative contribution of each process has not been determined. Data obtained from various animal models and human studies suggest that hyperactivation of dormant primordial follicles caused by the local microenvironment of ovarian endometrioma (mechanical and/or chemical cues) is the main factor responsible for the decreased primordial follicle numbers in women with ovarian endometrioma. However, surgical injury also induces hyperactivation of dormant primordial follicles, which may further reduce ovarian reserve after removal of the endometriosis. Although further studies are required to elucidate the mechanisms underlying diminished ovarian reserve in women with ovarian endometrioma, the available data strongly suggests the need to prevent/minimize hyperactivation of dormant primordial follicles, regardless of whether surgery is performed, for better clinical management of ovarian endometrioma.

The case of the multistage treatment of acute pancreatitis using a variety of minimally invasive techniques

Treatment of acute pancreatitis and infectious complications is a complex multidisciplinary task. The use of traditional surgical procedures for the rehabilitation of foci of pancreatogenic infection often aggravates the course of the disease, leads to the development of postoperative complications, does not improve the results of treatment. On the contrary, the use of minimally invasive techniques avoids additional surgical injury. The case of stage treatment of acute pancreatitis and its purulent-septic complications with the use of minimally invasive technologies is presented to the readers.

Mice Fed an Obesogenic Western Diet, Administered Antibiotics, and Subjected to a Sterile Surgical Procedure Develop Lethal Septicemia with Multidrug-Resistant Pathobionts

ABSTRACT Despite antibiotics and sterile technique, postoperative infections remain a real and present danger to patients. Recent estimates suggest that 50% of the pathogens associated with postoperative infections have become resistant to the standard antibiotics used for prophylaxis. Risk factors identified in such cases include obesity and antibiotic exposure. To study the combined effect of obesity and antibiotic exposure on postoperative infection, mice were allowed to gain weight on an obesogenic Western-type diet (WD), administered antibiotics and then subjected to an otherwise recoverable sterile surgical injury (30% hepatectomy). The feeding of a WD alone resulted in a major imbalance of the cecal microbiota characterized by a decrease in diversity, loss of Bacteroidetes, a bloom in Proteobacteria, and the emergence of antibiotic-resistant organisms among the cecal microbiota. When WD-fed mice were administered antibiotics and subjected to 30% liver resection, lethal sepsis, characterized by multiple-organ damage, developed. Notable was the emergence and systemic dissemination of multidrug-resistant (MDR) pathobionts, including carbapenem-resistant, extended-spectrum β-lactamase-producing Serratia marcescens, which expressed a virulent and immunosuppressive phenotype. Analysis of the distribution of exact sequence variants belonging to the genus Serratia suggested that these strains originated from the cecal mucosa. No mortality or MDR pathogens were observed in identically treated mice fed a standard chow diet. Taken together, these results suggest that consumption of a Western diet and exposure to certain antibiotics may predispose to life-threating postoperative infection associated with MDR organisms present among the gut microbiota. IMPORTANCE Obesity remains a prevalent and independent risk factor for life-threatening infection following major surgery. Here, we demonstrate that when mice are fed an obesogenic Western diet (WD), they become susceptible to lethal sepsis with multiple organ damage after exposure to antibiotics and an otherwise-recoverable surgical injury. Analysis of the gut microbiota in this model demonstrates that WD alone leads to loss of Bacteroidetes, a bloom of Proteobacteria, and evidence of antibiotic resistance development even before antibiotics are administered. After antibiotics and surgery, lethal sepsis with organ damage developed in in mice fed a WD with the appearance of multidrug-resistant pathogens in the liver, spleen, and blood. The importance of these findings lies in exposing how the selective pressures of diet, antibiotic exposure, and surgical injury can converge on the microbiome, resulting in lethal sepsis and organ damage without the introduction of an exogenous pathogen.

Towards a Physiological Scale of Vocal Fold Agent-Based Models of Surgical Injury and Repair: Sensitivity Analysis, Calibration and Verification

Agent based models (ABM) were developed to numerically simulate the biological response to surgical vocal fold injury and repair at the physiological level. This study aimed to improve the representation of existing ABM through a combination of empirical and computational experiments. Empirical data of vocal fold cell populations including neutrophils, macrophages and fibroblasts were obtained using flow cytometry up to four weeks following surgical injury. Random Forests were used as a sensitivity analysis method to identify model parameters that were most influential to ABM outputs. Statistical Parameter Optimization Tool for Python was used to calibrate those parameter values to match the ABM-simulation data with the corresponding empirical data from Day 1 to Day 5 following surgery. Model performance was evaluated by verifying if the empirical data fell within the 95% confidence intervals of ABM outputs of cell quantities at Day 7, Week 2 and Week 4. For Day 7, all empirical data were within the ABM output ranges. The trends of ABM-simulated cell populations were also qualitatively comparable to those of the empirical data beyond Day 7. Exact values, however, fell outside of the 95% statistical confidence intervals. Parameters related to fibroblast proliferation were indicative to the ABM-simulation of fibroblast dynamics in final stages of wound healing.

The Associations of Early Sport Specialization and Training Volume with Injury Rates in NCAA Division I Athletes

Objectives: Sixty million United States youth ages 6-18 participate in organized athletics, with large increases in both sport participation and specialization in the past two decades. This study seeks to determine whether early specialization in a single sport and high training volume is associated with an increased risk of injury and surgery in NCAA Division I athletes. A secondary aim is to assess whether sport specialization and high training volume is associated with elite athletic status (i.e. being recruited and/or receiving athletic scholarships). Methods: All NCAA Division I athletes at a single institution were sent a voluntary survey by email. Athletes were surveyed regarding demographics, scholarship status, reasons for sport specialization, age of specialization, training volume, and injury/surgical history. A total of 232 out of 652 athletes completed some portion of the survey. 30 surveys were excluded due to incomplete or incorrect survey completion, leaving 202 surveys available for analysis. Injuries were defined as those which precluded sport participation for > 1 week. Early sport specialization was defined as narrowing participation to one primary sport prior to age 14. High training volume was defined as greater than 28 hours per week during pre-high school years. Exclusion criteria included incomplete surveys and individuals less than age 18. Chi-square, Fisher’s Exact, and Mann-Whitney U tests were performed to establish significant differences. Results: Individuals who specialized in their varsity sport prior to age 14 were more likely to report a history of injury (86.9 vs. 74.0%, X = 4.7, p = .03), multiple injuries (64.6 vs. 49.4%, X = 4.2, p = .04), multiple college injuries (17.2 vs. 6.5%, X = 4.5, p = .03), total injuries (2 vs. 1, U = 3035, p = .02), and total time out for injury (15.2 vs. 7.0 weeks, U = 3150, p = .05). Early specializers were more likely to be recruited (92.9 vs. 83.1%, X = 4.1, p = .04) and receive a scholarship in their varsity sport (82.8 vs. 67.5%, X = 5.6, p =.02). Full scholarship athletes were more likely to report multiple surgical injuries (11.7 vs. 3.5%, X = 5.0, p =.03). Those with a scholarships greater than 50% were more likely to report a surgical injury (34.1 vs. 18.3%, X = 6.5, p = .01). Individuals who trained for greater than 28 hours per week in their varsity sport prior to high school were more likely to report multiple injuries (90.0 vs. 56.7%, X = 4.3, p = .04) multiple college injuries (40.0% vs. 14.0%, p = .05), a surgical injury (60.0 vs. 21.7%, p = .01), multiple surgical injuries (30.0 vs. 4.5%, p = .02), and greater total time out for injury (36.5 vs. 11.0 weeks, U = 424, p = .02). Individuals with a pre-high school training volume greater than 28 hours/week in their varsity sport were not more likely to be recruited (90.0 vs. 89.8%, p = 1.0) or receive a scholarship (80.0 vs. 74.5%, p = 1.0). Those in non-contact varsity sports were more likely to report multiple college injuries than those in limited and full contact sports, respectively (20.4 vs. 6.4 vs. 8.8%, X = 7.0, p = .03). Those in individual sports were more likely to report a college injury (55.3 vs. 38.9%, X = 5.1, p = .02) and multiple college injuries (25.0 vs. 7.1%, X = 12.7, p &lt .001). Conclusion: NCAA Division I athletes who specialized in their varsity sport prior to age 14 were more likely to be recruited and receive an athletic scholarship. However, these individuals, as well as those with high training volume prior to high school, had increased rates of injury and injuries requiring surgery.

Surgical quality in organ procurement during day and night: an analysis of quality forms

ObjectivesTo analyse a potential association between surgical quality and time of day.DesignA retrospective analysis of complete sets of quality forms filled out by the procuring and accepting surgeon on organs from deceased donors.SettingProcurement procedures in the Netherlands are organised per region. All procedures are performed by an independent, dedicated procurement team that is associated with an academic medical centre in the region.ParticipantsIn 18 months’ time, 771 organs were accepted and procured in The Netherlands. Of these, 17 organs were declined before transport and therefore excluded. For the remaining 754 organs, 591 (78%) sets of forms were completed (procurement and transplantation). Baseline characteristics were comparable in both daytime and evening/night-time with the exception of height (p=0.003).Primary outcome measureAll complete sets of quality forms were retrospectively analysed for the primary outcome, procurement-related surgical injury. Organs were categorised based on the starting time of the procurement in either daytime (8:00–17:00) or evening/night-time (17:00–8:00).ResultsOut of 591 procured organs, 129 organs (22%) were procured during daytime and 462 organs (78%) during evening/night-time. The incidence of surgical injury was significantly lower during daytime; 22 organs (17%) compared with 126 organs (27%) procured during evening/night-time (p=0.016). This association persists when adjusted for confounders.ConclusionsThis study shows an increased incidence of procurement-related surgical injury in evening/night-time procedures as compared with daytime. Time of day might (in)directly influence surgical performance and should be considered a potential risk factor for injury in organ procurement procedures.