Stem cell, Granulocyte-Colony Stimulating Factor and/or Dihexa to promote limb function recovery in a rat sciatic nerve damage-repair model: Experimental animal studies.

BACKGROUND: Optimizing nerve regeneration and re-innervation of target muscle/s is the key for improved functional recovery following peripheral nerve damage. We investigated whether administration of mesenchymal stem cell (MSC), Granulocyte-Colony Stimulating Factor (G-CSF) and/or Dihexa can improve recovery of limb function following peripheral nerve damage in rat sciatic nerve transection-repair model. MATERIALS AND METHODS: There were 10 experimental groups (n = 6-8 rats/group). Bone marrow derived syngeneic MSCs (2 × 106; passage≤6), G-CSF (200-400 µg/kg b.wt.), Dihexa (2-4 mg/kg b.wt.) and/or Vehicle were administered to male Lewis rats locally via hydrogel at the site of nerve repair, systemically (i.v./i.p), and/or to gastrocnemius muscle. The limb sensory and motor functions were assessed at 1-2 week intervals post nerve repair until the study endpoint (16 weeks). RESULTS: The sensory function in all nerve boundaries (peroneal, tibial, sural) returned to nearly normal by 8 weeks (Grade 2.7 on a scale of Grade 0-3 [0 = No function; 3 = Normal function]) in all groups combined. The peroneal nerve function recovered quickly with return of function at one week (∼2.0) while sural nerve function recovered rather slowly at four weeks (∼1.0). Motor function at 8-16 weeks post-nerve repair as determined by walking foot print grades significantly (P < 0.05) improved with MSC + G-CSF or MSC + Dihexa administrations into gastrocnemius muscle and mitigated foot flexion contractures. CONCLUSIONS: These findings demonstrate MSC, G-CSF and Dihexa are promising candidates for adjunct therapies to promote limb functional recovery after surgical nerve repair, and have implications in peripheral nerve injury and limb transplantation. IACUC No.215064.

Focused Changes in Opioid Prescribing Yield Far-reaching Benefits Through Culture Change and Attention to Opioid Minimization.

OBJECTIVE: Standardization of prescriptions after specific procedures (laparoscopic appendectomy, cholecystectomy, inguinal/umbilical hernia repair) significantly reduces opioid prescriptions for these targeted procedures. We sought to determine the impact of increased attention to responsible opioid prescribing in the absence of protocolization. DESIGN: Prescription practices of Laparoscopic Sleeve Gastrectomies and Roux-en-y Gastric Bypasses at a tertiary medical center (October 1, 2016-September 30, 2018) were retrospectively reviewed. Patients were grouped into whether surgical intervention took place before or after institution of an unrelated opioid protocol in November 2017. Patients with chronic opioid use or extended hospital stay (>4 days) were excluded. Discharge prescriptions, oral morphine equivalents (OME), and need for repeat prescriptions were compared. SETTING: This study was set at Madigan Army Medical Center in Tacoma, Washington. PARTICIPANTS: All general surgery residents engaged in clinical duties at our institution during the dates of the study were included. RESULTS: Study population included 187 patients, with 91 patients undergoing surgery prior to the protocol and 88 post-protocol. Preprotocol patients were provided an average of 413 OME (SD 103) and 5.5% required repeat opioid prescriptions within 3 months of surgery. The most common opioid prescription was 300 mL of oxycodone elixir (450 OME, 88%). Postprotocol, opioid prescriptions fell 61% to an average of 161 OME (SD 71, p < 0.001). Repeat opioid requirements remained statistically unchanged (8.0%, p = 0.562). The most common opioid prescription postprotocol included 20 oxycodone tablets (150 OME, 76%). CONCLUSIONS: Opioid reduction efforts reap benefits beyond those procedures specifically targeted. Focus on responsible opioid prescribing through standardization, even when limited to certain procedures, may result in a hospital culture change with global opioid prescription reduction.

Validation of a novel partial resuscitative endovascular balloon occlusion of the aorta device in a swine hemorrhagic shock model: Fine tuning flow to optimize bleeding control and reperfusion injury.

OBJECTIVES: Partial restoration of aortic flow during resuscitative endovascular balloon occlusion of the aorta (REBOA) is advocated by some to mitigate distal ischemia. Our laboratory has validated the mechanics and optimal partial REBOA (pREBOA) flow rates using a prototype device. We hypothesize that pREBOA will increase survival when compared with full REBOA (fREBOA) in prolonged nonoperative management of hemorrhagic shock. METHODS: Twenty swine underwent placement of aortic flow probes, zone 1 REBOA placement, and 20% blood volume hemorrhage. They were randomized to either solid organ or abdominal vascular injury. The pREBOA arm (10 swine) underwent full inflation for 10 minutes and then deflation to a flow rate of 0.5 L/min for 2 hours. The fREBOA arm (10 swine) underwent full inflation for 60 minutes, followed by deflation/resuscitation. The primary outcome is survival, and secondary outcomes are serologic/pathologic signs of ischemia-reperfusion injury and quantity of hemorrhage. RESULTS: Two of 10 swine survived in the fREBOA group (2/5 solid organ injury; 0/5 abdominal vascular injury), whereas 7 of 10 swine survived in the pREBOA group (3/5 solid organ injury, 4/5 abdominal vascular injury). Survival was increased (p = 0.03) and hemorrhage was higher in the pREBOA group (solid organ injury, 1.36 ± 0.25 kg vs. 0.70 ± 0.33 kg, p = 0.007; 0.86 ± 0.22 kg vs. 0.71 ± 0.28 kg, not significant). Serum evidence of ischemia was greater with fREBOA, but this was not significant (e.g., lactate, 16.91 ± 3.87 mg/dL vs. 12.96 ± 2.48 mg/dL at 120 minutes, not significant). Swine treated with pREBOA that survived demonstrated trends toward lower alanine aminotransferase, lower potassium, and higher calcium. The potassium was significantly lower in survivors at 60 minutes and 90 minutes time points (5.97 ± 0.60 vs. 7.53 ± 0.90, p = 0.011; 6.67 ± 0.66 vs. 8.15 ± 0.78, p = 0.029). Calcium was significantly higher at 30 minutes, 60 minutes, and 90 minutes (8.56 ± 0.66 vs. 7.50 ± 0.40, p = 0.034; 8.63 ± 0.62 vs. 7.15 ± 0.49, p = 0.019; 8.96 ± 0.64 vs. 7.00, p = 0.028). CONCLUSION: Prolonged pREBOA at a moderate distal flow rate provided adequate hemorrhage control, improved survival, and had evidence of decreased ischemic injury versus fREBOA. Prophylactic aggressive calcium supplementation may have utility before and during the reperfusion phase.

An Evaluation of a Novel Medical Device Versus Standard Interventions in the Treatment of Tension Pneumothorax in a Swine Model (Sus scrofa).

INTRODUCTION: Tension pneumothorax is a common cause of preventable death in trauma. Needle decompression is the traditional first-line intervention but has high failure rates. We sought to evaluate the effectiveness and expedience of needle thoracostomy, surgical tube thoracostomy, and Reactor™ thoracostomy - a novel spring-loaded trocar insertion device. MATERIALS AND METHODS: Yorkshire swine underwent controlled thoracic insufflation to create tension pneumothorax physiology for device comparison. Additional experiments were performed by increasing insufflation pressures to achieve pulseless electrical activity. Intervention was randomized to needle thoracostomy (14 gauge), tube thoracostomy (32Fr), or Reactor™ thoracostomy (36Fr). Air leak was simulated throughout intervention with 40-80 mL/kg/min insufflation. Intrathoracic pressure monitoring and hemodynamic parameters were obtained at 1 and 5 minutes. RESULTS: Tension physiology and tension-induced pulseless electrical activity were created in all iterations. Needle thoracostomy (n = 28) was faster at 7.04 ± 3.04 seconds than both Reactor thoracostomy (n = 32), 11.63 ± 5.30 (p < 0.05) and tube thoracostomy (n = 32), 27.06 ± 10.73 (p < 0.01); however, Reactor™ thoracostomy was faster than tube thoracostomy (p < 0.001). Physiological decompression was achieved in all patients treated with Reactor™ and tube thoracostomy, but only 14% of needle thoracostomy. Cardiac recovery to complete physiologic baseline occurred in only 21% (6/28) of those treated with needle thoracostomy whereas Reactor™ or tube thoracostomy demonstrated 88% (28/32) and 94% (30/32) response rates. When combined, needle thoracostomy successfully treated tension pneumothorax in only 4% (1/28) of subjects as compared to 88% (28/32) with Reactor™ thoracostomy and 94% (30/32) with tube thoracostomy (p < 0.01). CONCLUSIONS: Needle thoracostomy provides a rapid intervention for tension pneumothorax, but is associated with unacceptably high failure rates. Reactor™ thoracostomy was effective, expedient, and may provide a useful and technically simpler first-line treatment for tension pneumothorax or tension-induced pulseless electrical activity.

Stemming the Tide of Opioid Addiction-Dramatic Reductions in Postoperative Opioid Requirements Through Preoperative Education and a Standardized Analgesic Regimen.

INTRODUCTION: Surgery is a known gateway to opioid use that may result in long-term morbidity. Given the paucity of evidence regarding the appropriate amount of postoperative opioid analgesia and variable prescribing education, we investigated prescribing habits before and after institution of a multimodal postoperative pain management protocol. MATERIALS AND METHODS: Laparoscopic appendectomies, laparoscopic cholecystectomies, inguinal hernia repairs, and umbilical hernia repairs performed at a tertiary military medical center from 01 October 2016 until 30 September 2017 were examined. Prescriptions provided at discharge, oral morphine equivalents (OME), repeat prescriptions, and demographic data were obtained. A pain management regimen emphasizing nonopioid analgesics was then formulated and implemented with patient education about expected postoperative outcomes. After implementation, procedures performed from 01 November 2017 until 28 February 2018 were then examined and analyzed. Additionally, a patient satisfaction survey was provided focusing on efficacy of postoperative pain control. RESULTS: Preprotocol, 559 patients met inclusion criteria. About 97.5% were provided an opioid prescription, but prescriptions varied widely (256 OME, standard deviation [SD] 109). Acetaminophen was prescribed often (89.5%), but nonsteroidal anti-inflammatory drug (NSAID) prescriptions were rare (14.7%). About 6.1% of patients required repeat opioid prescriptions. After implementation, 181 patients met inclusion criteria. Initial opioid prescriptions decreased 69.8% (77 OME, SD 35; P < 0.001), while repeat opioid prescriptions remained statistically unchanged (2.79%; P = 0.122). Acetaminophen prescribing rose to 96.7% (P = 0.002), and NSAID utilization increased to 71.0% (P < 0.001). Postoperative survey data were obtained in 75 patients (41.9%). About 68% stated that they did not use all of the opioids prescribed and 81% endorsed excellent or good pain control throughout their postoperative course. CONCLUSIONS: Appropriate preoperative counseling and utilization of nonopioid analgesics can dramatically reduce opioid use while maintaining high patient satisfaction. Patient-reported data suggest that even greater reductions may be possible.

Preperitoneal balloon tamponade and resuscitative endovascular balloon occlusion of the aorta: Alternatives to open packing for pelvic fracture-associated hemorrhage.

BACKGROUND: The objective of this study was to compare the efficacy of preperitoneal balloon tamponade (PPB), resuscitative endovascular balloon occlusion of the orta (REBOA), and open preperitoneal packing (OP) in a realistic animal model of pelvic fracture-associated hemorrhage. METHODS: Thirty-nine swine underwent creation of open-book pelvic fracture and iliac vascular injury. Animals were randomized to no intervention (n = 7), OP (n = 10), PPB (n = 9), zone 1 REBOA (n = 7), and zone 3 REBOA (n = 6) at a mean arterial pressure less than 40 mm Hg from uncontrolled hemorrhage. Primary outcome was survival at 1 hour. Secondary outcomes included survival in the immediate 10 m following intervention reversal, peak preperitoneal pressure (PP), blood loss, bleed rate, and peak lactate. RESULTS: Prior to injury, no difference was measured between groups for weight, hemodynamics, lactate, and hematocrit (all p = NS). The injury was uniformly lethal without intervention, with survival time (mean) of 5 m, peak PP of 14 mm Hg, blood loss of 960 g, bleed rate of 450 g/m, and peak lactate of 2.6 mmol/L. Survival time (m) was extended to 44 with OP, 60 with PPB, and 60 with REBOA (p < 0.01). Peak PP (mm Hg) was 19 with OP, 23 with PPB, 10 with zone 1 REBOA, and 6 with zone 3 REBOA (p < 0.05). Blood loss (g) was 850 with OP, 930 with PPB, 610 with zone 1 REBOA, and 370 with zone 3 REBOA (p < 0.01). Peak lactate (mmol/L) was 3.3 with OP, 4.3 with PPB, 13.4 with zone 1 REBOA, and 5.3 with zone 3 REBOA (p < 0.01). Only 33% of zone 1 REBOA animals survived the initial 10 m after balloon deflation, compared to 60% for OP, 67% for PPB, and 100% for zone 3 REBOA (p < 0.01). CONCLUSION: Preperitoneal balloon tamponade and zone 3 REBOA are effective alternatives to OP in this animal model of lethal pelvic fracture-associated hemorrhage. Zone 1 REBOA extends survival time but with high mortality upon reversal.

Titrate to equilibrate and not exsanguinate! Characterization and validation of a novel partial resuscitative endovascular balloon occlusion of the aorta catheter in normal and hemorrhagic shock conditions.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a significant advancement in the control of noncompressible truncal hemorrhage. However, its ischemic burden and reperfusion injury following balloon deflation limits its utilization. Partial restoration of aortic flow during REBOA has the potential to balance hemorrhage control and ischemia. This study validates the mechanics, physiology, and optimal partial flow rates using a prototype partial REBOA (pREBOA) device. METHODS: Twenty-five swine underwent placement of aortic flow probes and zone 1 pREBOA. Experiment 1 (N = 5) animals were not injured and assessed the tested the catheters ability to titrate and control flow. Experiment 2 (N = 10) added 20% hemorrhage and either solid organ, or abdominal vascular injury to compare flow rate and rebleeding from injuries. Experiment 3 (N = 10) swine were similarly prepared, hemorrhaged, and underwent pREBOA at set partial flow rates for 2 hours followed by complete deflation for 30 minutes. RESULTS: Balloon volume at minimum flow (mean, 0.09 L/min) was 3.5 mL to 6.0 mL. Half maximal flow was achieved with 56.5% of maximum balloon inflation. Partial REBOA allowed very fine titration of flow rates. Rebleeding occurred at 0.45 L/min to 0.83 L/min. Distal flow of 0.7 L/min had 50% survival, 0.5 had 100% survival, and 0.3 L had 50% survival with mean end lactates of 9.6, 12.6, and 13.3, respectively. There was a trend toward hyperkalemia and hypocalcemia in nonsurvivors. CONCLUSION: The pREBOA device demonstrated a high level of titratability for restoration of aortic flow. An optimal partial flow of 0.5 L/min was effective at hemorrhage control while limiting the burden of ischemic injury, and extending the tolerable duration of zone 1 occlusion. Aggressive calcium supplementation prior to and during partial occlusion and reperfusion may be warranted to prevent hyperkalemic arrest.

Poor compliance despite equal access: Military experience with screening breast MRI in high risk women.

BACKGROUND: Using the military as a model for an equal-access, no-cost healthcare system, we sought to (1) describe screening breast MRI compliance rates and (2) identify patient-perceived barriers to screening. METHODS: In this retrospective cohort study of a prospectively maintained database at a tertiary level center, we compared compliance among women at ≥20% risk of developing breast cancer (Tyrer-Cuzick) and conducted structured phone interviews with women at ≥30% risk. RESULTS: From 2015 to 2016, 1,052 women met criteria for screening MRI. Of these, only 251 (24%) underwent MRI screening. Compliance among women with a 20-24%, 25-29%, 30-39%, and ≥40% risk was 16%, 24%, 37%, and 51%, respectively (p < 0.02). 37 of 128 unique patients (29%) with ≥30% risk agreed to interview. 43% cited time/inconvenience as the key barrier to screening; 22% cited questions regarding screening recommendations; and only 3% cited fear/concerns as the key barrier. CONCLUSIONS: Even in an equal-access system, there is poor compliance in patients who are at high risk for developing breast cancer. Patients cited time/inconvenience and questions regarding screening as key barriers to screening.

Sage wisdom or anecdotal dictum? Equivalent opioid use after open, laparoscopic, and robotic inguinal hernia repair.

BACKGROUND: Purported benefits of minimally-invasive inguinal hernia repair techniques include less postoperative pain, but objective data is lacking. We analyzed prescribing habits and opiate requirements to provide an objective comparison. METHODOLOGY: Inguinal hernia repairs performed on patients aged 18-65 from October 2016 through February 2018 were examined. Patients with prior opiate use or complicated operative courses were excluded. Discharge prescriptions, morphine milligram equivalents(MME), and additional prescriptions within three months were evaluated. RESULTS: 173 patients met criteria including 90 open(OMR), 34 laparoscopic(TEP), and 49 robotic(RTAPP) repairs. There was no difference in age or gender. There was no difference in average opiate prescriptions(OMR 230 MME, TEP 229 MME, RTAP 208 MME; p = 0.581), percentage prescribed acetaminophen(OMR 96.7%, TEP 97.1%, RTAPP 98.0%; p = 0.910), or percentage prescribed NSAIDs(OMR 43.3%, TEP 44.1%, RTAP 46.9%; p = 0.919). On follow up, there was no difference in repeat opiate prescriptions(OMR 10.0%, TEP 8.8%, RTAPP 8.2%; p = 0.934). CONCLUSIONS: Patients undergoing open, laparoscopic, and robotic inguinal hernia repairs showed no evidence of differing pain medication requirements. The implication that minimally-invasive techniques cause less pain may be inaccurate.

Is bigger better? Twenty-year institutional experience of atypical ductal hyperplasia discovered by core needle biopsy.

OBJECTIVES: The increasing accuracy of large-bore (11- or 8-gauge) vacuum-assisted core needle biopsies (VACNB) has challenged the commonly-accepted practice that surgery is needed for definitive diagnosis when atypical ductal hyperplasia (ADH) is found on VACNB. This study seeks to demonstrate the impact of increased VACNB caliber on the pathologic upgrade rate of ADH. METHODS: Patients diagnosed with isolated ADH by VACNB who subsequently underwent surgical excision at our tertiary medical center were retrospectively studied. Demographics, needle gauge, number of needle passes, and pathology results were analyzed. RESULTS: From June 1996 to June 2016, approximately 3740 VACNBs were performed. 139 patients were diagnosed with isolated ADH on VACNB and underwent surgical excision. 30 patients (22%) were upgraded to ductal carcinoma in-situ or invasive cancer; 17 upgrades (21%) from 11-gauge CNB vs. 13 upgrades (23%) from 8-gauge CNB (p = 0.67). CONCLUSION: Increasing core needle biopsy size from 11 g to 8 g does not decrease the rate of pathologic upstaging at the time of surgical excision. Surgical excision of ADH is still required for complete diagnosis.

Minimally invasive preperitoneal balloon tamponade and abdominal aortic junctional tourniquet versus open packing for pelvic fracture-associated hemorrhage: Not all extrinsic compression is equal.

BACKGROUND: Minimally invasive preperitoneal balloon tamponade (PPB) and abdominal aortic junctional tourniquets (AAJT) have been proposed as alternatives to open preperitoneal packing (OP) for the management of pelvic fracture-associated hemorrhage. We hypothesized that the PPB (SpaceMaker Pro) and AAJT would result in similar rates of survival and blood loss versus OP. METHODS: Thirty-two swine underwent creation of a combined open-book pelvic fracture and major iliac vascular injuries. Animals were randomized to no intervention (n = 7), OP (n = 10), PPB (n = 9), or AAJT (n = 6) at a mean arterial pressure <40 mm Hg following initiation of uncontrolled hemorrhage. Survival (up to 60 minutes + 10 minutes after intervention reversal), hemodynamics, extraperitoneal pressures, blood loss, and associated complications were compared between groups. RESULTS: Prior to injury, no difference was measured between groups for weight, hemodynamics, lactate, and hematocrit (all p > 0.05). The injury was uniformly lethal without intervention, with survival time (mean) of 5 minutes, peak preperitoneal pressure (PP) of 14 mm Hg, blood loss of 960 g, and peak lactate of 2.6 mmol/L. Survival time was 44 minutes with OP versus 60 minutes with PPB and AAJT (p < 0.01). Peak PP (mm Hg) was 19 with OP, 23 with PPB, and 23 with AAJT (p > 0.05). Blood loss (g) was 850 with OP, 930 with PPB, and 600 with AAJT (p > 0.05). Peak lactate (mmol/L) was 3.3 with OP, 4.3 with PPB, and 6.3 with AAJT (p < 0.01). Only 33% of AAJT animals survived intervention reversal versus 60% for OP and 67% for PPB (p < 0.01). Necropsy revealed bowel/bladder injury in 50% of AAJT subjects versus 0% in all other arms (p < 0.01). CONCLUSION: Preperitoneal balloon tamponade is a safe and potentially effective alternative to OP for the management of lethal pelvic fracture-associated hemorrhage. Abdominal aortic junctional tourniquet offers a similar survival benefit to PPB but has concerning rates of ischemia-reperfusion and compressive abdominal organ injury.