Multimodality Minimally Invasive Treatment of Large Joint Osteoarthritis: A Pilot Trial of Stromal Vascular Fraction from Autologous Fat Combined with Platelet-Rich Plasma

Osteoarthritis (OA) is a degenerative joint disease that can cause severe pain in those affected. Currently, there are no therapeutic drugs available to treat osteoarthritis. While total joint arthroplasties (TJA) allow for improved function, there are no less invasive, yet effective procedures that can be done for patients unwilling or unable to undergo major surgery. Platelet-rich plasma (PRP) has been shown to reduce the symptoms of OA when injected into the affected joint. Patients treated by this method alone have improved self-reported pain (at least a 50% reduction from original value) as well as lower extremity function. While the effects of PRP treatment on OA have been positive, treatment with SVF offers additional benefits that PRP alone cannot. SVF contains a significant amount of mesenchymal stem cells (MSC), which have great potential in the field of regenerative medicine. The potential to generate new cartilage in osteoarthritic joints goes beyond treatment of the symptoms offering a reversal of the harmful pathology. Considering the positive results seen from both SVF and PRP treatment, the reduced risk of surgical complication when compared to TJA, and the possibility for equal or greater pain improvement and joint functionality compared to TJA, we believed it would be advantageous to investigate a combined PRP and SVF therapy for relief of both mild and advanced stage O

Accuracy of Risk Estimation for Surgeons Versus Risk Calculators in Emergency General Surgery

IntroductionSurgical risk calculators have expanded in both number and sophistication of their predictive approach. These calculators are gaining popularity as validated tools to help surgeons estimate mortality and complications following emergency general surgery (EGS). However, the accuracy of risk estimates generated by these calculators compared to risk estimation by practicing surgeons has not been explored.MethodsAcute care surgeons at a quaternary care center prospectively estimated 30-d mortality and complications for adult EGS patients (2019-2021). Surgeon predictions were compared to Predictive OpTimal Trees in Emergency Surgery Risk (POTTER) and NSQIP estimates. Observed-to-expected (O:E) ratios of median aggregate estimates were calculated. C-statistics for surgeon and calculator estimations were utilized to quantify predictive accuracy.ResultsAmong 150 patients (median 61 y, 45% male), 30-d mortality was 15% (n = 23). Observed rates of prolonged mechanical ventilation and acute renal failures were 30% and 10%, respectively. Overall, surgeon predictions were similar to risk calculator estimates for mortality (c-statistics 0.843 [surgeon] versus 0.848 [POTTER] and 0.815 [NSQIP]) and need for prolonged ventilation (c-statistics 0.801 versus 0.722 and 0.689, respectively). Surgeons tended to overestimate complication risks. Surgeon experience was not significantly associated with mortality prediction in an adjusted model.ConclusionsAcute care surgeons at a quaternary care center predicted postoperative mortality and complications with similar discrimination when compared to surgical risk calculators. Surgeon expertise should be utilized in conjunction with risk calculators when counseling EGS patients regarding anticipated postoperative outcomes. Surgeons should be cognizant of patterns in overestimation or underestimation of complications

Evaluation of critical care burden following traumatic injury from two randomized controlled trials

Abstract Trauma resuscitation practices have continued to improve with new advances targeting prehospital interventions. The critical care burden associated with severely injured patients at risk of hemorrhage has been poorly characterized. We aim to describe the individual and additive effects of multiorgan failure (MOF) and nosocomial infection (NI) on delayed mortality and resource utilization. A secondary analysis of harmonized data from two large prehospital randomized controlled trials (Prehospital Air Medical Plasma (PAMPer) Trial and Study of Tranexamic Acid during Air and Ground Medical Prehospital Transport (STAAMP) Trial) was conducted. Only those patients who survived beyond the first 24 hours post-injury and spent at least one day in the ICU were included. Patients were stratified by development of MOF only, NI only, both, or neither and diagnosis of early (≤ 3 days) versus late MOF (> 3 days). Risk factors of NI and MOF, time course of these ICU complications, associated mortality, and hospital resource utilization were evaluated. Of the 869 patients who were enrolled in PAMPer and STAAMP and who met study criteria, 27.4% developed MOF only (n = 238), 10.9% developed NI only (n = 95), and 15.3% were diagnosed with both MOF and NI (n = 133). Patients developing NI and/or MOF compared to those who had an uncomplicated ICU course had greater injury severity, lower GCS, and greater shock indexes. Early MOF occurred in isolation, while late MOF more often followed NI. MOF was associated with 65% higher independent risk of 30-day mortality when adjusting for cofounders (OR 1.65; 95% CI 1.04–2.6; p = 0.03), however NI did not significantly affect odds of mortality. NI was individually associated with longer mechanical ventilation, ICU stay, hospital stay, and rehabilitation requirements, and the addition of MOF further increased the burden of inpatient and post-discharge care. MOF and NI remain common complications for those who survive traumatic injury. MOF is a robust independent predictor of mortality following injury in this cohort, and NI is associated with higher resource utilization. Timing of these ICU complications may reveal differences in pathophysiology and offer targets for continued advancements in treatment

Long-gap peripheral nerve repair through sustained release of a neurotrophic factor in nonhuman primates.

Severe injuries to peripheral nerves are challenging to repair. Standard-of-care treatment for nerve gaps \u3e2 to 3 centimeters is autografting; however, autografting can result in neuroma formation, loss of sensory function at the donor site, and increased operative time. To address the need for a synthetic nerve conduit to treat large nerve gaps, we investigated a biodegradable poly(caprolactone) (PCL) conduit with embedded double-walled polymeric microspheres encapsulating glial cell line-derived neurotrophic factor (GDNF) capable of providing a sustained release of GDNF for \u3e50 days in a 5-centimeter nerve defect in a rhesus macaque model. The GDNF-eluting conduit (PCL/GDNF) was compared to a median nerve autograft and a PCL conduit containing empty microspheres (PCL/Empty). Functional testing demonstrated similar functional recovery between the PCL/GDNF-treated group (75.64 ± 10.28%) and the autograft-treated group (77.49 ± 19.28%); both groups were statistically improved compared to PCL/Empty-treated group (44.95 ± 26.94%). Nerve conduction velocity 1 year after surgery was increased in the PCL/GDNF-treated macaques (31.41 ± 15.34 meters/second) compared to autograft (25.45 ± 3.96 meters/second) and PCL/Empty (12.60 ± 3.89 meters/second) treatment. Histological analyses included assessment of Schwann cell presence, myelination of axons, nerve fiber density, an

Long-gap peripheral nerve repair through sustained release of a neurotrophic factor in nonhuman primates

Severe injuries to peripheral nerves are challenging to repair. Standard-of-care treatment for nerve gaps >2 to 3 centimeters is autografting; however, autografting can result in neuroma formation, loss of sensory function at the donor site, and increased operative time. To address the need for a synthetic nerve conduit to treat large nerve gaps, we investigated a biodegradable poly(caprolactone) (PCL) conduit with embedded double-walled polymeric microspheres encapsulating glial cell line-derived neurotrophic factor (GDNF) capable of providing a sustained release of GDNF for >50 days in a 5-centimeter nerve defect in a rhesus macaque model. The GDNF-eluting conduit (PCL/GDNF) was compared to a median nerve autograft and a PCL conduit containing empty microspheres (PCL/Empty). Functional testing demonstrated similar functional recovery between the PCL/GDNF-treated group (75.64 ± 10.28%) and the autograft-treated group (77.49 ± 19.28%); both groups were statistically improved compared to PCL/Empty-treated group (44.95 ± 26.94%). Nerve conduction velocity 1 year after surgery was increased in the PCL/GDNF-treated macaques (31.41 ± 15.34 meters/second) compared to autograft (25.45 ± 3.96 meters/second) and PCL/Empty (12.60 ± 3.89 meters/second) treatment. Histological analyses included assessment of Schwann cell presence, myelination of axons, nerve fiber density, and g-ratio. PCL/GDNF group exhibited a statistically greater average area occupied by individual Schwann cells at the distal nerve (11.60 ± 33.01 μm2) compared to autograft (4.62 ± 3.99 μm2) and PCL/Empty (4.52 ± 5.16 μm2) treatment groups. This study demonstrates the efficacious bridging of a long peripheral nerve gap in a nonhuman primate model using an acellular, biodegradable nerve conduit