Postsurgical Day Research Articles

Use of Flavored Tablets of Gabapentin and Carprofen to Attenuate Postoperative Hypersensitivity in an Incisional Pain Model in Rats (Rattus norvegicus).

Providing postoperative analgesia to rats by oral administration, compared with injections, reduces stress from frequent handling and is technically easier for investigators. The purpose of this study was to investigate whether bacon-flavored tablets containing gabapentin, carprofen or a combination of both drugs effectively attenuates postoperative mechanical and thermal hypersensitivity in a rat model of incisional pain. Forty-eight Sprague-Dawley rats were randomly assigned to 1 of 5 treatment groups: placebo tablet; a single, subcutaneous injection of buprenorphine sustained release at 1.2 mg/kg; gabapentin 90 mg/tablet; carprofen 5 mg/tablet; gabapentin 90 mg and carprofen 5 mg/tablet (gabapentin/carprofen). Tablets were given to rats on days -3, -2, -1, 0 (surgery), 1, and 2. Rats were anesthetized using isoflurane. A 1 cm skin incision was made aseptically on the plantar surface of the left hindpaw and closed by using suture. Mechanical (von Frey monofilament) and thermal (Hargreaves method) hypersensitivity were tested daily, and analyzed on days -1, 1, 2, and 3. The amount of tablet consumed was recorded daily; postoperatively rats consumed 101 to 133 mg/kg of gabapentin, 5.5 to 5.8 mg/kg of carprofen, and 86-137/1.9-3 mg/kg of gabapentin/carprofen, respectively. Both the gabapentin and carprofen groups displayed attenuated mechanical hypersensitivity on all 3 postsurgical days and decreased thermal hypersensitivity on Day 3. The gabapentin/ carprofen group showed attenuated mechanical hypersensitivity on Day 2 and 3, but no significant reduction of thermal hypersensitivity. These data suggest that both gabapentin and carprofen, given orally by flavored tablet, effectively attenuate postoperative mechanical hypersensitivity for 3 d after surgery in a rat model of incisional pain.

Heterologous Bovine Tunica Albuginea Graft Conserved in Honey as Abdominal Wall Reinforcement in Rats

Complex abdominal wall defects might be challenging for human and veterinary surgeons worldwide. Defects from trauma or congenital causes may lead to hernias development. The introduction of meshes to reinforce hernia repairs has improved surgical outcomes and several synthetic and biologic materials have been used. In this context, biomaterial prosthesis seems to be a satisfactory solution when managing great abdominal wall defects. The aim of the current study is to evaluate the bovine tunica albuginea (BTA) preserved in honey as graft material for rats’ abdominal wall reinforcement in incisional herniorrhaphy surgery as well as its viability, cicatrization and integration into the host tissue. Wistar rats were assigned to two main groups: 1) animals (n = 20) underwent median longitudinal laparotomy followed by laparorraphy with suture of the bovine tunica albuginea (BTA) graft as abdominal wall reinforcement; and 2) animals (n = 20) underwent only laparotomy and subsequent laparorrhaphy. Rats were clinically evaluated until euthanasia at post-surgical day 7, 14, 21 and 28. Necropsy and histopathological analysis of abdominal wall fragments were performed to compare groups and subgroups findings. BTA promoted abundant fibrosis, providing resistance and low postoperative complication rates. Besides, animals did not show rejection signs to the implant. In conclusion, BTA preserved in honey is an affordable, easy collection and handling biomaterial for graft, demanding simple surgical implantation technique for abdominal wall repair in rats.

Bromfenac Ophthalmic Solution 0.07% Versus Nepafenac Ophthalmic Suspension 0.3% for Post-Cataract Surgery Inflammation: A Pilot Study of Identical Dosing Regimens with Pre-Surgical "Pulse" Dose.

IntroductionThis small pilot study is the first direct comparison of the currently marketed formulations of bromfenac (0.07% solution) and nepafenac (0.3% suspension) using identical dosing regimens and including an extra pre-surgical “pulse” dose in patients undergoing cataract surgery.MethodsAdults scheduled for unilateral phacoemulsification with intraocular lens implantation were randomly assigned to bromfenac 0.07% or nepafenac 0.3%, each given once-daily 1 day prior to surgery, on the day of surgery plus an extra dose 1 h before surgery, and for 14 days after surgery. Assessments included summed ocular inflammation score (SOIS), visual acuity (VA), and retinal thickness measured via optical coherence tomography.ResultsThe study population included 49 patients (bromfenac, n = 24; nepafenac, n = 25). The percentage of patients with a SOIS = 0 (no cells or flare) at post-surgical day 15 (primary efficacy endpoint) was statistically similar between the bromfenac (57.1%) and nepafenac (50.0%) treatment groups (intent-to-treat with last observation carried forward) (P = 0.6318). The proportions of patients with an SOIS of 0 at days 3 and 8 were significantly (P < 0.05) higher in the bromfenac group (23.8 and 52.4%, respectively) versus the nepafenac group (0.0 and 20.8%, respectively). Visual acuity was similar between groups at each study visit, as were mean retinal thickness and change from baseline in retinal thickness. Rescue medication (typically difluprednate) was given on or before day 15 to 13 patients in each treatment group (bromfenac, 54.2%; nepafenac, 52.0%). There were no adverse events considered to be related to either treatment.ConclusionsThe results of this small pilot study suggest that once-daily bromfenac 0.07% produces similar benefits with regard to postsurgical inflammation, VA, and retinal thickness as once-daily nepafenac 0.3%, and possibly has a faster onset of anti-inflammatory action, when compared using identical dosing regimens.FundingBausch & Lomb Incorporated.Trial RegistrationNCT03886779.

Microencapsulated olfactory ensheathing cell transplantation reduces P2X4 receptor overexpression and inhibits neuropathic pain in rats

ObjectivesThe aim of this study was to determine the role of microencapsulated olfactory ensheathing cells (MC-OECs) transplantation in rats with sciatic nerve injury-induced neuropathic pain, and its relationship with P2X4 receptor expression in the L4-5 spinal cord segment. MethodsOlfactory bulb tissues of healthy Sprague Dawley (SD) rats were collected to culture olfactory ensheathing cells (OECs) using differential attachment methods. Seventy-two healthy SD rats were randomly assigned to four groups: the sham, chronic constriction injury (CCI), OECs, and MC-OECs groups. Mechanical paw withdrawal thresholds were measured on days 7, 14 and 21 after surgery. The expression of P2X4 receptor genes in the L4-5 spinal cord segment was detected by in situ hybridization, western blotting and RT-PCR. ResultsOn post-surgical days 7, 14 and 21. The mechanical paw withdrawal thresholds of rats from low to high were the CCI, OECs, MC-OECs and sham groups. The expression level of P2X4 receptor mRNA and protein from low to high were the sham, MC-OECs, OECs and CCI groups. Compared with the OECs group, the mechanical paw withdrawal thresholds of rats were increased, and the expression level of P2X4 receptor mRNA and protein were decreased in the MC-OECs group. In addition, the mechanical paw withdrawal thresholds of rats were higher and the expression level of P2X4 receptor were lower in the MC-OECs group on post-surgical days 21 than that on days 7 and 14. All differences between groups were statistically significant (P value < 0.05). ConclusionsOECs and MC-OECs transplantation can reduce the expression level of P2X4 receptor and relieve pain. The therapeutic efficacy was better in the MC-OECs group than in the OECs group. MC-OECs transplantation have the better effects of treatment with the increase of MC-OECs transplantation time.

Human Bone Marrow Mesenchymal Stem Cell Conditioned Medium Promotes Wound Healing in Deep Second-Degree Burns in Male Rats

Burn wound treatment is difficult and one of the most challenging problems in the clinic. Researchers have examined the applications of mesenchymal stem cells as a cell-based therapy for skin regeneration. But the role of human bone marrow mesenchymal stem cell conditioned medium (hBM-MSC-CM) in the treatment of burn injury remains unclear. This research aims at detecting whether hBM-MSC-CM can increase the wound healing of deep second-degree burns in male rats. In this study, 32 adult male rats per each time point were randomly divided into four groups: (1) control group, (2) sham group (DMEM), (3) common treatment group (CT), and (4) conditioned media group (CM). A 3 × 3 cm circular burn was created on the back of the rats. On postsurgical days 7, 15, and 28, the wound closure area of each wound was measured and then the skin samples were removed and analyzed using stereological methods. Wound closure area was significantly increased in the CM and CT groups on the 15th and the 28th day after burn injury compared to the control and DMEM groups. The stereological parameters and immunohistochemistry analysis of the wounds revealed significantly improved healing in the CM group compared to the control and other groups. It is concluded that these findings indicate that hBM-MSC-CM promotes skin wound healing by increasing cell proliferation, regulating collagen synthesis and collagen composition, and inducing angiogenesis at the injury site.

1936-P: Muscle Ischemia Impairs Insulin-Mediated Microvascular Recruitment

Diabetes predisposes patients to peripheral artery disease (PAD). Muscle microvasculature plays a critical role in maintaining muscle function and health by delivering oxygen, nutrients and hormones to myocytes. Insulin dilates precapillary arterioles to increase muscle perfusion. To define the impact of ischemia to muscle microvascular perfusion and microvascular response to insulin, adult male rats were subject to hind limb ischemic surgery. Total hind limb blood flow was determined using laser Doppler blood flowmetry and muscle microvascular blood volume (MBV) measured using contrast-enhanced ultrasound in both the ischemic (left) and control (right) hind limb. Ischemic to control limb (I/C) ratios were calculated. Hyperinsulinemic euglycemia clamps were performed to determine microvascular responses to insulin. Hind limb ischemic surgery decreased total limb blood flow by ∼70% immediately, from a pre-surgical I/C ratio of 1.10 ± 0.07 to 0.34 ± 0.06. The I/C ratios then progressively increased to 0.45 ± 0.08, 0.54 ± 0.06, 0.67 ± 0.11, and 0.74± 0.11 on postsurgical day 3, 7, 14 and 21 respectively. Similarly, ischemic surgery decreased MBV promptly from a pre-surgical I/C ratio of 1.01 ± 0.04 to 0.39 ± 0.06. MBV I/C ratios completely recovered on day 3 (1.11 ± 0.09) and remained stable afterwards. Insulin induced similar increases in muscle MBV in both legs before surgery (I/C ratio 1.14 ± 0.16) but the increase was much less in ischemic leg on day 3 (I/C ratio 0.63 ± 0.15). Microvascular insulin responses fully recovered on day 7 (I/C ratio 0.97± 0.25). We conclude that hind limb ischemia is associated with decreased total blood flow, muscle microvascular perfusion as well as microvascular responses to insulin. While the recovery in muscle microvascular perfusion precedes that of total limb blood flow, recovery in muscle microvascular response to insulin is delayed. These changes may contribute to muscle injury in patients with diabetes and the muscle microvasculature is potentially a therapeutic target for PAD. Disclosure N. Wang: None. Z. Liu: None. Funding American Diabetes Association (1-17-ICTS-059 to Z.L.); National Institutes of Health (R01DK102359)

Comparison of Once-Daily Bromfenac 0.07% Versus Once-Daily Nepafenac 0.3% in Patients Undergoing Phacoemulsification.

AimRandomized pilot study comparing clinical outcomes with bromfenac ophthalmic solution 0.07% versus nepafenac 0.3% ophthalmic suspension administered as identical dosing regimens in patients undergoing uncomplicated phacoemulsification with intraocular lens implantation.MethodsForty-nine subjects were treated with bromfenac (n = 25) or nepafenac (n = 24) once daily starting 3 days before cataract surgery, continued on the day of surgery, and for 21 days following surgery, in addition to standard of care. Subjects were followed at 1 day and 7, 21, and 42 days postoperatively. Assessments included best-corrected visual acuity [Early Treatment Diabetic Retinopathy Study (ETDRS)], summed ocular inflammation score (SOIS; anterior chamber cells plus flare grading), macular volume and thickness (spectral domain optical coherence tomography), intraocular pressure, and adverse events.ResultsTreatment groups were similar at baseline. Outcomes for mean letters read (p = 0.20), mean change in macular volume (p = 0.98), and retinal thickness (p = 0.93) were not statistically different between the groups at day 42. Mean SOIS dropped markedly and similarly from post-surgical day 1 to day 7 in both treatment groups and was statistically equivalent to baseline in both groups by day 21. At day 42, 87% of subjects in the bromfenac group and 82% of subjects in the nepafenac group demonstrated stable or improved visual acuity. The proportions of eyes with mean retinal thickness of 10 µm or less at days 7, 21, and 42 were similar for the bromfenac (95.8%, 78.3%, 73.9%, respectively) and nepafenac (91.7%, 87.5%, 66.7%) groups (all p = NS, bromfenac vs. nepafenac).ConclusionBoth bromfenac 0.07% and nepafenac 0.3% produced positive and similar clinical outcomes with regard to ETDRS visual acuity post-cataract surgery when dosed using identical regimens. Increases in mean retinal thickness and mean macular volume were small and similar between treatments.Trial Registration numberNCT01847638.FundingBausch & Lomb Incorporated.

Environmental enrichment and amantadine confer individual but nonadditive enhancements in motor and spatial learning after controlled cortical impact injury

Environmental enrichment (EE) and amantadine (AMT) enhance motor and cognitive outcome after experimental traumatic brain injury (TBI). However, there are no data on the effects of combining these two therapies. Hence, the aim of the current study was to combine EE and AMT after TBI to determine if their net effect further enhances motor and cognitive performance. Anesthetized adult male rats received either a cortical impact of moderate severity or sham injury and then were randomly assigned to EE or standard (STD) housing and once daily administration of AMT (20 mg/kg; i.p.) or saline vehicle (VEH, 1 mL/kg; i.p.) beginning 24 h after injury for 19 days. Motor and cognitive function were assessed on post-surgical days 1–5 and 14–19, respectively. Cortical lesion volume was quantified on day 21. There were no statistical differences among the sham groups regardless of therapy, so the data were pooled. EE, AMT, and their combination (EE + AMT) improved beam-balance, but only EE and EE + AMT enhanced beam-walking. All three treatment paradigms improved spatial learning and memory relative to the VEH-treated STD controls (p < 0.05). No differences were revealed between the EE groups, regardless of treatment, but both were better than the AMT-treated STD group on beam-walking and spatial learning (p < 0.05). Both EE groups equally reduced cortical lesion volume relative to the STD-housed AMT and VEH groups (p < 0.05). The results indicate that although beneficial on their own, EE + AMT do not provide additional benefits after TBI. It is important to note that the lack of additive effects using the current treatment and behavioral protocols does not detract from the benefits of each individual therapy. The findings provide insight for future combination studies.

Effects of microencapsulated olfactory ensheathing cell transplantation on neuropathic pain and P2X7 receptor expression in the L4-5 spinal cord segment

ObjectivesThe aim of this study was to determine the role of microencapsulated olfactory ensheathing cell (MC-OEC) transplantation in rats with sciatic nerve injury-induced pain, and its relationship with P2 × 7 receptor expression in the L4-5 spinal cord segment. MethodsOlfactory bulb tissues of healthy Sprague Dawley (SD) rats were collected to culture olfactory ensheathing cells using differential attachment methods. Forty-eight healthy SD rats were randomly assigned to four groups: the sham, chronic constriction injury (CCI), olfactory ensheathing cell (OEC), and MC-OEC groups. Mechanical paw withdrawal thresholds were measured on days 7 and 14 after surgery. The expression of P2 × 7 receptor genes in the L4-5 spinal segment was detected by in situ hybridization and western blotting. ResultsOn post-surgical days 7 and 14, the mechanical paw withdrawal thresholds of rats in the MC-OEC, OEC and CCI were lower than that in the sham group. The mechanical paw withdrawal thresholds of rats in the MC-OEC and OEC were higher than that in the CCI group, compared with the OEC group. The mechanical paw withdrawal thresholds of rats in the MC-OEC were increased. The expression levels of P2 × 7 receptors in the L4-5 spinal cord segment in the CCI, OEC and MC-OEC were higher than that in the sham group, the expression levels of P2 × 7 receptors in the MC-OEC and OEC group were lower than that in the CCI group, compared with the OEC group, the expression levels of P2 × 7 receptors in the MC-OEC were decreased. All differences between groups were statistically significant (P value <0.05). ConclusionsOEC and MC-OEC transplantation can relieve pain and reduce the expression level of P2 × 7 receptors in the L4-5 spinal cord segment. The therapeutic efficacy was better in the MC-OEC group than in the OEC group.

Perioperative systemic magnesium sulphate to minimize acute and chronic post-thoracotomy pain: a prospective observational study.

Thoracotomy leads to acute and chronic post-thoracotomy pain (CPTP). The purpose of this study was to investigate the effect of magnesium sulphate (MgSO4) administered perioperatively on acute postoperative and CPTP syndrome. One hundred patients were enrolled in this prospective, observational study. Analgesic medication was provided according to the World Health Organization pain relief ladder (control group). The study group received additionally MgSO4 (40 mg/kg over 10 minutes) during induction of anesthesia followed by an infusion over 24 hours (10 mg/kg/h). The presence and severity of pain were assessed before surgery, on postsurgical days 1-8, 30 and 90, respectively. The Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) was used pre- and postoperatively for documentation of neuropathic pain. The incidence and severity of CPTP were assessed by a telephone survey 30 and 90 days after surgery. Numerical rating scale (NRS) pain scores at rest were significantly lower in the study group receiving MgSO4 at days 1 to 8 (P<0.05). Thirty days after surgery, 2.1% of the MgSO4-patients had a LANSS score ≥12 compared to 14.3% in the control group (P=0.031). No patient had a LANSS score ≥12 in the study group compared to the control group (0% vs. 12.2%, P<0.05) 90 days following surgery. MgSO4 administration reduces postoperative pain at rest according to the NRS pain scores and is effective in preventing chronic neuropathic post-thoracotomy pain measured by LANSS score. Prospective-randomized trials are needed to confirm the results of the present study.

Mechanical Loading Promotes the Expansion of Primitive Osteoprogenitors and Organizes Matrix and Vascular Morphology in Long Bone Defects.

Elucidating the effects of mechanical stimulation on bone repair is crucial for optimization of the healing process. Specifically, the regulatory role that mechanical loading exerts on the osteogenic stem cell pool and vascular morphology during healing is incompletely understood. Because dynamic loading has been shown to enhance osteogenesis and repair, we hypothesized that loading induces the expansion of the osteoprogenitor cell population within a healing bone defect, leading to an increased presence of osteogenic cells. We further hypothesized that loading during the repair process regulates vascular and collagen matrix morphology and spatial interactions between vessels and osteogenic cells. To address these hypotheses, we used a mechanobiological bone repair model, which produces a consistent and reproducible intramembranous repair response confined in time and space. Bilateral tibial defects were created in adult C57BL/6 mice, which were subjected to axial compressive dynamic loading either during the early cellular invasion phase on postsurgical days (PSDs) 2 to 5 or during the matrix deposition phase on PSD 5 to 8. Confocal and two-photon microscopy was used to generate high-resolution three-dimensional (3D) renderings of longitudinal thick sections of the defect on PSD 10. Endomucin (EMCN)-positive vessels, Paired related homeobox 1 (Prrx1+) stem cell antigen-1 positive (Sca-1+) primitive osteoprogenitors (OPCs), and osterix positive (Osx+) preosteoblasts were visualized and quantified using deep tissue immunohistochemistry. New bone matrix was visualized with second harmonic generation autofluorescence of collagen fibers. We found that mechanical loading during the matrix deposition phase (PSD 5 to 8) increased vessel volume and number, and aligned vessels and collagen fibers to the load-bearing direction of bone. Furthermore, loading led to a significant increase in the proliferation and number of Prrx1+ Sca-1+ primitive OPCs, but not Osx+ preosteoblasts within the defect. Together, these data illustrate the adaptation of both collagen matrix and vascular morphology to better withstand mechanical load during bone repair, and that the mechanoresponsive cell population consists of the primitive osteogenic progenitors. © 2019 American Society for Bone and Mineral Research.

Role of anxiety in young children's pain memory development after surgery.

Pediatric pain is common, and memory for it may be distressing and have long-lasting effects. Children who develop more negatively biased memories for pain (ie, recalled pain is higher than initial pain report) are at risk of worse future pain outcomes. In adolescent samples, higher child and parent catastrophic thinking about pain was associated with negatively biased memories for postsurgical pain. This study examined the influence of child and parent anxiety on the development of younger children's postsurgical pain memories. Seventy-eight children undergoing a tonsillectomy and one of their parents participated. Parents reported on their anxiety (state and trait) before surgery, and trained researchers observationally coded children's anxiety at anaesthesia induction. Children reported on their postsurgical pain intensity and pain-related fear for 3 days after discharge. One month after surgery, children recalled their pain intensity and pain-related fear using the same scales previously administered. Results revealed that higher levels of postsurgical pain and higher parent trait anxiety predicted more negatively biased memories for pain-related fear. Parent state anxiety and child preoperative anxiety were not associated with children's recall. Children who developed negatively biased pain memories had worse postsurgical pain several days after surgery. These findings underscore the importance of reducing parental anxiety and effective postsurgical pain management to potentially buffer against the development of negatively biased pain memories in young children.

Suberoylanilide Hydroxamic Acid Triggers Autophagy by Influencing the mTOR Pathway in the Spinal Dorsal Horn in a Rat Neuropathic Pain Model.

Histone acetylation levels can be upregulated by treating cells with histone deacetylase inhibitors (HDACIs), which can induce autophagy. Autophagy flux in the spinal cord of rats following the left fifth lumber spinal nerve ligation (SNL) is involved in the progression of neuropathic pain. Suberoylanilide hydroxamic acid (SAHA), one of the HDACIs can interfere with the epigenetic process of histone acetylation, which has been shown to ease neuropathic pain. Recent research suggest that SAHA can stimulate autophagy via the mammalian target of rapamycin (mTOR) pathway in some types of cancer cells. However, little is known about the role of SAHA and autophagy in neuropathic pain after nerve injury. In the present study, we aim to investigate autophagy flux and the role of the mTOR pathway on spinal cells autophagy activation in neuropathic pain induced by SNL in rats that received SAHA treatment. Autophagy-related proteins and mTOR or its active form were assessed by using western blot, immunohistochemistry, double immunofluorescence staining and transmission electron microscopy (TEM). We found that SAHA decreased the paw mechanical withdrawal threshold (PMWT) of the lower compared with SNL. Autophagy flux was mainly disrupted in the astrocytes and neuronal cells of the spinal cord dorsal horn on postsurgical day 28 and was reversed by daily intrathecal injection of SAHA (n = 100nmol/day or n = 200nmol/day). SAHA also decreased mTOR and phosphorylated mTOR (p-mTOR) expression, especially p-mTOR expression in astrocytes and neuronal cells of the spinal dorsal horn. These results suggest that SAHA attenuates neuropathic pain and contributes to autophagy flux in astrocytes and neuronal cells of the spinal dorsal horn via the mTOR signaling pathway.

Robot-assisted laparoscopic partial hepatic caudate lobectomy

Background: Hepatic caudate lobectomy is considered to be a technically difficult surgery because of the unique anatomy and deep location of the hepatic caudate lobe. Here, we assessed the technical feasibility and safety of robotic partial caudate lobectomy using the da Vinci® Surgical System and compared it with traditional open/laparoscopic surgery.Material and methods: Six patients diagnosed with liver cancer (primary liver cancer, 5; metastasis of breast cancer, 1) who underwent caudate lobectomy were prospectively enrolled. Two patients underwent robotic surgery, one underwent laparoscopic surgery, and three underwent traditional/open surgery. Surgical procedure, recovery, and characteristics of robotic surgery were noted and compared with other approaches.Results: All surgeries were successfully completed, and no serious postsurgical complications were observed. In the robotic group, the time taken to complete the surgery and the estimated intraoperative bleeding were 150 and 90 min and 50 and 100 ml in patient 1 and patient 2, respectively. The patients were able to tolerate fluid diet on the following postsurgical day. These two patients had no postsurgical complications and were discharged from the hospital on days 5 and 6 after recovery, respectively. Pathologically, the margins of specimens obtained from these two patients were tumor-free (R0 resection). Tumor size in the traditional/open group was larger than that in the robotic and laparoscopic groups. Blood loss in the laparoscopic case was 50 ml and was less than that in the traditional/open surgery cases (300, 2100, and 1500 ml).Conclusions: Robot-assisted partial hepatic caudate lobectomy is a technically feasible surgery. Our study illustrated an advantage of robotic hepatic caudate lobectomy over laparoscopic or traditional/open surgery and suggested that da Vinci® minimally invasive hepatectomy is applicable in even more technically challenging anatomic locations.

The Transition to Data-Driven Quality Metrics: Determining the Optimal Surveillance Period for Complications After Surgery

BackgroundThirty-day complications frequently serve in the surgical literature as a quality indicator. This metric is not meant to capture the full array of complication resulting from surgical intervention. However, this period is largely based on convention, with little evidence to support it. This study sought to determine the optimal surveillance period for postsurgical complications, defined as the shortest period that also encompassed the highest proportion of postsurgical adverse events. MethodsTRICARE data (2006-2014) were queried for adult (18-64 y) patients who underwent one of 11 surgical procedures. Patients were assessed for complications up to 90 d after surgery. Kaplan–Meier curves, linear spline regression models at each incremental postsurgical day, and adjusted R-squared values were used to identify critical time point cutoffs for the surveillance of complications. Optimal length of surveillance was defined as the postsurgical day on which the model demonstrated the highest R-squared value. A supplemental analysis considered these measures for orthopedic and general surgical procedures. ResultsOne lakh ninety-eight patients met the inclusion criteria. A total of 21.8% patients experienced at least one complication during the follow-up period, with 59% occurring within the first 15 d. Kaplan–Meier curves for complications showed a demonstrable inflection before 20 d and 14-15 d possessed the highest R-squared values. ConclusionsIn this analysis, the optimal surveillance period for postsurgical complications was 15 d. While the conventional 30-d period may still be appropriate for a variety of reasons, the shorter interval identified here may represent a superior quality measure specific to surgical practice.

Application of Fibrin Rich in Leukocytes and Platelets in the Reconstruction of Endoscopic Approaches to the Skull Base

The objective of this work is to report the feasibility and results of an institutional protocol for the application of an innovative biologically active hemoderivative autologous material, denominated leukocyte- and platelet-rich fibrin (L-PRF), in the reconstruction of endoscopic approaches to the sellar region. L-PRF membranes were produced from centrifuged autologous venous blood. They were used for the reconstruction of transsphenoidal endoscopic approaches to the sellar region in 12 patients. The trophism of the mucosa was monitored during the first 30 days by means of fiberoptic endoscopic controls on the second and seventh postoperative days. Follow-up was performed to rule out complications up to 30 postoperatively days. The product obtained bore the characteristics of the original descriptions of L-PRF. Standardized preparation of L-PRF membranes promoted early regeneration of the sphenoid sinus mucosa to close endoscopic approaches to the sellar region. No complications within the first 30 postsurgical days were reported. L-PRF membranes offer characteristics that are superior to other techniques and products, mainly because of their role as biological promoters of tissue regeneration, their low economic cost, and immediate availability. However, it would be necessary to confirm these results in studies involving more patients.

Effect of operative local anesthesia on postoperative pain outcomes of inflatable penile prosthesis: prospective comparison of two medications.

Few studies have examined the roles of dorsal penile nerve block (DPNB) and penile ring block (PRB) in surgery of inflatable penile prosthesis (IPP) placement. We sought to compare the postoperative pain outcomes of two different medications used in DPNB plus PRB. We thus carried out a prospective study of patients with erectile dysfunction who underwent "de novo" IPP placement between January 2013 and June 2013. Patients were divided to one of three groups: 1-DPNB plus PRB with bupivacaine injection; 2-DPNB plus PRB with ropivacaine injection and, 3-Control group without DPNB or PRB injection. Postoperative pain score and pain medication usage were recorded 2 h postoperatively, and every 24 h, for a week. The Visual Analog Scale (VAS) was used as pain scale measurement. A total of 131 patients were included in this study: 40 to bupivacaine, 47 to ropivacaine, and the rest were controls. Two hours postoperatively, mean VAS was significantly different (p < 0.0001) between medicated patients and the control group, however, no significant differences were observed between medication groups. Mean VAS was not significantly different among the groups from post-surgical day 2 thru 7. In conclusion, DPNB plus PRB during IPP provided effective analgesia in the immediate post-operative recovery.

Stereological and molecular studies on the combined effects of photobiomodulation and human bone marrow mesenchymal stem cell conditioned medium on wound healing in diabetic rats

We investigated the effects of conditioned medium (CM) from human bone marrow mesenchymal stem cells (h BMMSC)s and pulse wave photobiomodulation (PW PBM), applied alone or in combination, on the stereological parameters and gene expression of some growth factors, during wound healing in a streptozotocin (STZ)-induced rat model of type one diabetes mellitus (T1DM).T1DM was induced in 72 rats and two incisions were made in each animal. The rats were assigned to one of four groups: a control (placebo) group, a Laser group (890 nm, 80 Hz, 0.2 J/cm2); a CM group, and a combined CM + Laser group. On post-surgical days 4, 7, and 15, skin samples were extracted for stereology and reverse transcription PCR (RT-PCR) analyses of gene expression of basic fibroblast growth factor (bFGF), hypoxia-inducible factor (HIF-1α), and stromal cell-derived factor-1α (SDF-1α).The stereological examinations of the proximal and distal wounds revealed significantly enhanced healing in all the treated groups, compared to the control group. The extent of healing was significantly greater in the CM + Laser group than in the other treatment groups. The RT-PCR results also indicated greater gene expression in the CM + Laser and Laser groups than in the CM and control groups.Application of CM and PW PBM, alone or in combination accelerated the process of wound healing in T1DM rats. The results of combined application of CM and PW PBM, indicated a synergistic effect, and the combination treatment was statistically more effective than single applications of CM or PW PBM.

Localized Intrathecal Delivery of Mesenchymal Stromal Cells Conditioned Medium Improves Functional Recovery in a Rat Model of Spinal Cord Injury.

It was recently shown that the conditioned medium (CM) of mesenchymal stem cells can enhance viability of neural and glial cell populations. In the present study, we have investigated a cell-free approach via CM from rat bone marrow stromal cells (MScCM) applied intrathecally (IT) for spinal cord injury (SCI) recovery in adult rats. Functional in vitro test on dorsal root ganglion (DRG) primary cultures confirmed biological properties of collected MScCM for production of neurosphere-like structures and axon outgrowth. Afterwards, rats underwent SCI and were treated with IT delivery of MScCM or vehicle at postsurgical Days 1, 5, 9, and 13, and left to survive 10 weeks. Rats that received MScCM showed significantly higher motor function recovery, increase in spared spinal cord tissue, enhanced GAP-43 expression and attenuated inflammation in comparison with vehicle-treated rats. Spared tissue around the lesion site was infiltrated with GAP-43-labeled axons at four weeks that gradually decreased at 10 weeks. Finally, a cytokine array performed on spinal cord extracts after MScCM treatment revealed decreased levels of IL-2, IL-6 and TNFα when compared to vehicle group. In conclusion, our results suggest that molecular cocktail found in MScCM is favorable for final neuroregeneration after SCI.

Plasticity of oral mucosal cell sheets for accelerated and scarless skin wound healing

ObjectivesWound healing is generally faster and associated with less scarring in the oral mucosa than in the skin. Although rarely studied, oral mucosa equivalents may contribute to rapid, scarless cutaneous wound healing. Therefore, we examined the potential utility of our newly developed oral mucosal cell sheet in skin wound healing. Materials and methodsOral mucosa and skin samples were obtained from surgical patients and Sprague-Dawley rats. Keratinocytes and fibroblasts were primarily cultured for in vitro cell expansion. Mucosa and skin equivalents were produced with a mixture of cultured fibroblasts and autologous fibrin from plasma and seeding keratinocytes. Mucosal and skin cell sheets were transplanted in full-thickness excisional wounds of rat skin with control wounds. Gross, histological, and molecular characteristics of wound healing according to different postsurgical days were compared in control and cell sheet-covered wounds. ResultsKeratinocytes and fibroblasts derived from the oral mucosa were cultured faster than those derived from the skin. The in vitro-engineered oral mucosa and skin equivalents were successfully produced using complete autologous mucosa or skin and plasma fibrin, showing similarity to the histological characteristics of the skin or mucosa. In the in vivo rat model, the oral mucosal and skin cell sheet promoted wound healing with early wound closure and less scarring. The cell sheet-treated wounds showed lower TGF-β1, α-smooth muscle actin, and fibronectin mRNA expression than the control wounds. ConclusionsThe oral mucosal cell sheet demonstrated in vivo tissue plasticity through good adaptation to skin wounds, contributing to accelerated and scarless healing.