Previous studies have demonstrated that pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, inhibits ischemia-induced brain injury. The present study was conducted to examine whether pioglitazone can reduce impairment of behavioral deficits mediated by inflammatory-induced brain white matter injury in neonatal rats. Intraperitoneal (i.p.) injection of lipopolysaccharide (LPS, 2 mg/kg) was administered to Sprague–Dawley rat pups on postnatal day 5 (P5), and i.p. administration of pioglitazone (20 mg/kg) or vehicle was performed 5 min after LPS injection. Sensorimotor behavioral tests were performed 24 h after LPS exposure, and changes in biochemistry of the brain was examined after these tests. The results show that systemic LPS exposure resulted in impaired sensorimotor behavioral performance, reduction of oligodendrocytes and mitochondrial activity, and increases in lipid peroxidation and brain inflammation, as indicated by the increment of interleukin-1β (IL-1β) levels and number of activated microglia in the neonatal rat brain. Pioglitazone treatment significantly improved LPS-induced neurobehavioral and physiological disturbances including the loss of body weight, hypothermia, righting reflex, wire-hanging maneuver, negative geotaxis, and hind-limb suspension in neonatal rats. The neuroprotective effect of pioglitazone against the loss of oligodendrocytes and mitochondrial activity was associated with attenuation of LPS-induced increment of thiobarbituric acid reactive substances (TBARS) content, IL-1β levels and number of activated microglia in neonatal rats. Our results show that pioglitazone prevents neurobehavioral disturbances induced by systemic LPS exposure in neonatal rats, and its neuroprotective effects are associated with its impact on microglial activation, IL-1β induction, lipid peroxidation, oligodendrocyte production and mitochondrial activity.

In the USA, spinal fusion surgery incurs the highest hospital cost. Despite the recent advances in the application of enhanced recovery after surgery (ERAS) protocols in these surgeries, the efficacy of these protocols in improving the perioperative outcomes remains unclear. We conducted a retrospective review as a quality improvement (QI) project to analyze the efficacy of the ERAS protocol with intraoperative modified thoracolumbar interfascial plane (mTLIP) block to determine whether these interventions reduce the length of stay (LOS) and opioid requirements during the postoperative period. Retrospective reviews of adult patients (>18 yrs) who underwent elective lumbar spinal fusion or laminectomy at our institute were reviewed. Patients were administered oral gabapentin and acetaminophen preoperatively. Prior to incision, an mTLIP block was performed using liposomal bupivacaine. Intraoperatively, ketamine, ketorolac, and tranexamic acid were administered. Postoperative, pain control was treated with scheduled acetaminophen, ketorolac, and low-dose ketamine infusion. Hydromorphone and oxycodone were administered for breakthrough pain. Patients who underwent a similar procedure without ERAS protocol were chosen as controls to assess the efficacy of ERAS protocol. Data pertaining to patient demographics, operative and perioperative use of analgesics, LOS, 90-day readmissions, and morbidity were collected. Patients who underwent laminectomy and spinal fusion surgery were analyzed separately A total of 65 patients were identified; laminectomy (n- 24), spinal fusion surgery (n-41). In the laminectomy patients, treatment group (n-12) and the control group (n-12). Treatment group receiving the ERAS protocol with the regional anesthesia via the mTLIP (n= 12) opioid requirement was reduced by 51.42% [P = 0.03], and LOS was reduced by 2.04 days [P = 0.01] [0.75 days vs. 2.79 days]). In the spinal fusion patients, treatment group (n-15) and control group (n-26). Treatment group receiving the ERAS protocol with the use of regional anesthesia via the mTLIP group (n= 15), opioid requirement was reduced by 38.33% [P = 0.04]. No difference in LOS was observed at 5.4 days vs. 4.88 days (P = 0.28). ERAS protocol in patients undergoing lumbar spinal surgery incorporated the use of regional anesthesia via the mTLIP block, we observed there is a statistically significant reduction in the LOS for lumbar laminectomy and a significant reduction in opioid administration for lumbar laminectomies and spinal fusion surgery.

Kudsi R, et al. J Periodontal Implant Sci. 2024 Dec;55:e5. https://doi.org/10.5051/jpis.2401320066

Study Design: Basic science. Objective: To compare the effects of a neuropeptide Y1 receptor antagonist (NPY-1RA) to estrogen on maintaining vertebral bone microarchitecture and disc height in a rat model of menopause. Methods: This study was an institutional animal care approved randomized control study with 104 ovariectomized rats and 32 intact control animals. Comparison of disc height, trabecular bone, body weights, circulating levels of NPY and estrogen, and distribution of Y1 receptors in the intervertebral disc in an established rodent osteoporotic model were made at baseline and after 2, 4, and 8 weeks after receiving either an implant containing estrogen or an antagonist to the neuropeptide Y1 receptor. Data was compared statistically using One-way analysis of variance. Results: Circulating levels of estrogen increased and NPY decreased following estrogen replacement, with values comparable to ovary-intact animals. NPY-1RA-treated animals had low estrogen and high NPY circulating levels and were similar to ovariectomized control rats. Both NPY-1RA and estrogen administration were able reduce, menopause associated weight gain. NPY-1RA appeared to restore bone formation and maintain disc height, while estrogen replacement prevented further bone loss. Conclusion: NPY-1RA in osteoporotic rats activates osteoblast production of bone and decreased marrow and body fat more effectively than estrogen replacement when delivered in similar concentrations. Annulus cells had NPY receptors, which may play a role in disc nutrition, extracellular matrix production, and pain signaling cascades.

Opioid sparing anesthesia and enhanced recovery after surgery protocols are not innovative ideas. However, the utilization of pancreaticoduodenectomy is limited. With the rise in awareness of the opioid epidemic in the United States, we have created a multimodal approach to anesthesia and postoperative care to limit adverse effects of opioids and curb the use of opioids postoperatively. We conducted a retrospective cohort study performed by chart review of an opioid-sparing anesthetic and enhanced recovery after surgery (ERAS) protocol initiated jointly by the anesthesiology departments and transplant surgery for pancreaticoduodenectomy from January 2017 to October 2019. Demographic data was found to be comparable between the control and protocol groups. Hospital length of stay, ICU length of stay, and opioid requirements significantly decreased in the protocol group. Hospital length of stay decreased from 8.92 to 5.72 days, ICU days decreased from 1.52 to 0.42 days, and narcotics for the first five hospital days were significantly decreased from 130.13 to 71.2 morphine milligram equivalents. Proper postoperative pain management can improve patient satisfaction and decrease complication rates. Pancreaticoduodenectomy is a complicated procedure with relatively limited data regarding enhanced recovery after surgery protocols. Likewise, there is limited data regarding opioid-sparing anesthesia techniques. Our protocol produced promising hospital length of stay and reduced opioid administration during the first five hospital days without increasing 30-day readmission rates.

Wound healing is a complex dynamic biomechanical process as the body attempts to restore the integrity of traumatized or devitalized tissues. There are four stages of wound of healing that begins with hemostasis followed by inflammation, proliferation and finally weeks later wound remodeling. Full thickness wounds usually are covered with a dressing material after hemostasis, which allows for controlled hydration. We investigated the potential of a visco-liquid hemostat, polyhedral oligomeric silsesquioxane (POSS), for providing hemostasis and to maintain a microenvironment in the wound bed that would maintain moisture content and promote early re-epithelialization. We hypothesized that the hemostatic agent POSS if left in the wound bed would maintain a protective barrier and accelerate wound healing similar to using saline to irrigate the wound to keep the wound moist. We compared the early phase of wound repair (3–7 days) in a porcine full thickness wound model to evaluate the efficacy of the material. Biopsies were taken after 3 and 7 days to determine the acute response of the POSS hemostat or saline on inflammation, cell migration, concentrations of metalloproteinase (MMPs), and tissue inhibitors of metalloproteinase (TIMPs). Accelerated healing was observed in POSS treated wounds by changes in wound contraction, keratinocyte migration, and development of granulation tissue in comparison to saline treated wounds. Increased concentrations at day 3 of MMP-2, MMP-3, and in MMP-1 at day 7 in POSS treated wounds compared to saline coincide with keratinocyte migration observed in the tissue histology and changes in wound contraction. Tissue concentrations of TIMP-1 and TIMP-2 in POSS treated wounds appear to coordinate the sequence of MMP events in the healing tissue. Matrix metalloproteinase-13, a marker for tissue remodeling, was not upregulated in the early wound healing cascade in either POSS or saline treated wounds at 3 or 7 days. Overall, the data suggests POSS treatment contributed to enhanced early cell migration and wound closure compared to saline treatment.