A Surgical Framework for the Management of Incomplete Axillary Nerve Injuries.

BACKGROUND: Axillary nerve injury is the most common nerve injury affecting shoulder function. Nerve repair, grafting, and/or end-to-end nerve transfers are used to reconstruct complete neurotmetic axillary nerve injuries. While many incomplete axillary nerve injuries self-resolve, axonotmetic injuries are unpredictable, and incomplete recovery occurs. Similarly, recovery may be further inhibited by superimposed compression neuropathy at the quadrangular space. The current framework for managing incomplete axillary injuries typically does not include surgery. METHODS: This study is a retrospective analysis of 23 consecutive patients with incomplete axillary nerve palsy who underwent quadrangular space decompression with additional selective medial triceps to axillary end-to-side nerve transfers in 7 patients between 2015 and 2019. Primary outcome variables included the proportion of patients with shoulder abduction M3 or greater as measured on the Medical Research Council (MRC) scale, and shoulder pain measured on a Visual Analogue Scale (VAS). Secondary outcome variables included pre- and postoperative Disabilities of the Arm, Shoulder, and Hand Questionnaire (DASH) scores. RESULTS: A total of 23 patients met the inclusion criteria and underwent nerve surgery a mean 10.7 months after injury. Nineteen (83%) patients achieved MRC grade 3 shoulder abduction or greater after intervention, compared with only 4 (17%) patients preoperatively (p = 0.001). There was a significant decrease in VAS shoulder pain scores of 4.2 ± 2.5 preoperatively to 1.9 ± 2.4 postoperatively (p < 0.001). The DASH scores also decreased significantly from 48.8 ± 19.0 preoperatively to 30.7 ± 20.4 postoperatively (p < 0.001). Total follow-up was 17.3 ± 4.3 months. CONCLUSION: A surgical framework is presented for the appropriate diagnosis and surgical management of incomplete axillary nerve injury. Quadrangular space decompression with or without selective medial triceps to axillary end-to-side nerve transfers is associated with improvement in shoulder abduction strength, pain, and DASH scores in patients with incomplete axillary nerve palsy.

Gender Preferences of Patients When Selecting Orthopaedic Providers.

Background: Orthopaedic surgery is a male-dominated specialty associated with many stereotypes, despite the increased representation of females compared to 30 years ago. Numerous studies have examined medical student and resident perceptions regarding females in orthopaedic surgery to explain the disparity, but there are few studies that analyze whether patients have a gender preference in their orthopaedic surgeon. Our study sought to determine whether patients have a preference for the gender of their orthopaedic surgeon, and what traits in orthopaedic surgeons are important to their patients. Methods: A total of 191 new patients seen in the emergency department and orthopaedic urgent care clinic were administered a 22-question survey regarding preferences in their orthopaedic provider. Patients were asked questions regarding preferred gender of their provider, as well as preferences in characteristics exhibited. Results: The majority of patients did not have a preference for the gender of their orthopaedist (83.9%); however, 14.5% of patients preferred a female surgeon and 1.6% of patients preferred a male surgeon. Female patients had a preference for the same gender compared to male patients and preferred females (p=0.04). Of the patients that had a preference, 90% preferred a female provider. There were trends towards preference for gender that varied depending on subspecialty. There was a statistically insignificant trend towards preference for male providers in total joint replacements and spine surgery, and conversely a preference for female providers in hand surgery and pediatric orthopaedics. 48.6% of patients cited the single most important trait to be board certification, followed by years in practice (27.1%), then reputation or prestige (16.7%). Over one-third of patients found physical appearance, gender, racial background and age to be important traits. Conclusions: The majority of patients did not have a preference for the gender of their orthopaedic surgeon. 16.1% of patients had a preference, and the majority of these patients preferred female surgeons. Preferences for a specific gender were seen that varied based on the subspecialty. Efforts at increasing gender diversity in orthopaedics should continue to be a major goal.Level of Evidence: III.

Risk of Perforation Is High During Corrective Reaming of Retroverted Glenoids: A Computer Simulation Study.

BACKGROUND: Corrective anterior reaming is an accepted method for addressing retroversion in a biconcave retroverted (Walch classification, type B2) glenoid in anatomic total shoulder arthroplasty. However, concern still exists regarding early glenoid component failure in the setting of severe retroversion, which may be related to loss of component containment and/or violation of subchondral bone resulting from reaming. The goal of this study was to determine what characteristics of B2 glenoids are less amenable to corrective reaming by virtually implanting anatomic glenoid components. QUESTIONS/PURPOSES: (1) How much medial reaming is required to correct the version of a B2 glenoid to an acceptable position? (2) Are glenoids with more severe retroversion (> 25°) at higher risk of component perforation than less retroverted glenoids? (3) Is correcting to 10° of retroversion associated with greater risk as compared with reaming to 15°? (4) How does corrective reaming affect the underlying bone density on the glenoid face of B2 glenoids? METHODS: A series of 71 patients with B2 glenoids (posterior subluxation of the humeral head with posterior bone loss) with CT scans who were indicated for shoulder arthroplasty were reviewed. Forty-four of 71 glenoids (62.5%) had < 25° of native retroversion. Anatomic glenoid implants were then virtually implanted using three-dimensional CT software that allows for preoperative shoulder arthroplasty planning to correct native retroversion to 15° or 10° of retroversion using both a central peg with an inverted triangle peg configuration or a keel. The amount of reaming of the anterior glenoid required to correct retroversion, perforation of peripheral pegs, or keel was compared. Additionally, assessment of the surface area of the glenoid that had poor bone density (defined as cancellous bone under the subchondral plate) was analyzed by the software after correction. RESULTS: Correction to 15° of retroversion required 5 ± 3 mm of reaming, and correction to 10° of retroversion required 8 ± 3 mm of reaming to obtain at least 80% seating. Peripheral peg perforation with correction to 15° occurred in 15 of 27 (56%) glenoids with > 25° of retroversion compared with 10 of 44 (23%) of glenoids with < 25° of retroversion (relative risk [RR], 2.4; 95% confidence interval [CI], 1.3-4.6; p = 0.006). There was no difference in perforation with keeled components. Increased correction to 10° did not increase the risk of component perforation. When correction to 15°, glenoids with higher native version (> 25°) had a greater risk of poor bone quality support (10 of 27 [37%]) when compared with glenoids with less version (four of 44 [9%]; RR, 4.1; 95% CI, 1.5-12.8; p = 0.006). Increased correction resulted in 13 of 27 (48%) glenoids with version > 25° having poor bone density versus 10 of 44 (23%) with ≤ 25° of version (RR, 2.1; 95% CI, 1.1-4.1; p = 0.028). CONCLUSIONS: There is a high risk of vault perforation after corrective reaming. Glenoid retroversions > 25° are at a higher risk of having poor bone quality supporting the component. CLINICAL RELEVANCE: When contemplating options for patients with severe retroversion, surgeons should consider alternatives other than corrective reaming if achieving normal glenoid version is desired.

Interleukin-6 regulation of direct lung ischemia reperfusion injury.

BACKGROUND: Lung ischemia reperfusion injury continues to adversely affect patient and graft survival after transplantation. While the role of interleukin-6 has been studied in ischemia-reperfusion models of intestine, liver, and heart, its participation in lung reperfusion injury has not been characterized. METHODS: We administered recombinant interleukin-6 to rat lungs through the intratracheal route before inducing left lung ischemia and reperfusion. Multiple in-vivo indicators of left lung injury were studied, as were transactivation patterns for nuclear factor kappa B and signal transduction and activators of transcription-3. Downstream effects on the elaboration of proinflammatory chemokines and cytokines were also studied. RESULTS: Recombinant interleukin-6 reduced endothelial disruption and neutrophil sequestration in left lung and alveolar spaces, resulting in improved oxygenation after ischemia and 4 hours of reperfusion. This protection was associated with decreased nuclear factor kappa B and signal transduction and activators of transcription-3 nuclear translocation early in reperfusion, and diminished proinflammatory mediator secretion late in reperfusion. CONCLUSIONS: Further studies focusing on the effects of recombinant interleukin-6 in large animal models are warranted, as this may be a novel strategy to improve outcomes after lung transplantation. Intratracheal administration may focus its efficacy on the lung while reducing effects on other organ systems during organ procurement.

Poly (ADP) ribose polymerase inhibition improves rat cardiac allograft survival.

BACKGROUND: Heart transplantation is an accepted treatment modality for end-stage heart failure. However, acute cellular rejection (ACR) continues to be a morbid complication. Recently a novel mechanism of inflammatory allograft injury has been characterized which involves overactivation of the nuclear enzyme poly (ADP-ribose) polymerase (PARP). In the present studies, we compared the efficacy of INO-1001, a novel, potent PARP inhibitor, in limiting ACR with and without adjuvant low-dose cyclosporine (CSA). METHODS: Heterotopic heart transplantation was performed utilizing Brown-Norway strains as donors and Lewis rats as recipients. Groups received daily intraperitoneal injections of: vehicle, low-dose CSA, low-dose INO-1001, high-dose INO-1001, and low-dose CSA combined with high-dose INO-1001. Additional animals were sacrificed on postoperative Day 5 for histologic assessments of allograft inflammation, including immunohistochemistry for nitrotyrosine and poly (ADP-ribose) (the product of PARP) staining. RESULTS: PARP inhibition significantly prolonged allograft survival relative to vehicle controls. The combination of low-dose CSA and INO-1001 resulted in a marked increase in allograft survival and significant reductions in allograft rejection scores. This was associated with decreased nitrotyrosine and PAR staining in transplanted cardiac allografts. CONCLUSIONS: Pharmacologic inhibition of INO-1001 prolongs allograft survival in a dose-dependent fashion in a rodent model of heart transplantation. PARP inhibitors may permit reductions in the dose of CSA needed for adequate immunosuppression after heart transplantation.

The role of CC and CXC chemokines in cardiac allograft rejection in rats.

Acute cellular rejection is due in part to an upregulation of chemokine genes, resulting in eventual cell-mediated cytotoxicity. The role of chemokines in acute cardiac allograft rejection is not fully characterized presently. These studies compared the patterns of expression for multiple chemokines in rodent cardiac allograft rejection. Allogeneic transplants were performed from Brown-Norway donors to Lewis recipients. Survival studies utilized daily administration of neutralizing antisera to MCP-1, CINC, and MIP-1alpha. Patterns of mRNA and protein expression were determined by Northern blots and immunohistochemistry. Allogeneic controls rejected at mean of 6.5 days. Neutralization of MCP-1 (10.8 days, P<0.001) and MIP-1alpha (7.5 days, P=0.004) function, but not CINC (6.2 days, P>0.05), significantly prolonged allograft survival. Message expression for the beta chemokines studied were increased by day 2 and continued to increase until day 6 just before rejection, while CINC levels did not change as dramatically after day 2. Chemokine protein levels mirrored mRNA patterns by IHC analysis. MCP-1 and MIP-1alpha appear to play regulatory roles in cardiac allograft rejection, while CINC is expressed, but not functional, in injury development. Beta chemokine activity should be studied further in hope of developing more targeted immunosuppression, or identifying specific chemokines that may be useful for immunosurveillance purposes.

Cyclosporine modulates the response to hypoxia-reoxygenation in pulmonary artery endothelial cells.

BACKGROUND: Depletion of macrophages, neutrophils, or lymphocytes confers only partial protection against experimental lung reperfusion injury, suggesting that inflammatory responses in other cell types contribute to tissue injury. Endothelial cell activation has previously been shown to be critical to the development of ischemia-reperfusion injury in other vascular beds. Furthermore, cyclosporine (CSA) reduces in vivo lung reperfusion injury through attenuated secretion of proinflammatory mediators. These studies determined whether pulmonary artery endothelial cells (PAEC), subjected to hypoxia and reoxygenation, promote inflammation and whether CSA afforded any modulation of that response. METHODS: Isolated rat PAEC were subjected in vitro to 2 hours hypoxia followed by up to 4 hours reoxygenation. Cells were pretreated with CSA or a cremaphor vehicle. Differences in activation of signaling kinases and transcription factors were assessed, as was cytokine-chemokine protein secretion. RESULTS: There was significant signaling kinase (extracellular signal regulated kinase [ERK 1/2]) activation by 15 minutes reoxygenation, which was temporally associated with marked activation of the transcription factors nuclear factor kappa B (NFkappaB) and early growth response one (EGR-1). At 4 hours reoxygenation there were significant increases in chemokine protein secretion. The CSA decreased ERK 1/2 phosphorylation and significantly attenuated transcription factor transactivation at 15 minutes reoxygenation. The CSA was found to be selective in reducing cytokine-chemokine elaboration at 4 hours reoxygenation. CONCLUSIONS: Hypoxia-reoxygenation induces ERK 1/2 phosphorylation, as well as transactivation of the transcription factors NFkappaB and EGR-1 in PAEC. Cyclosporine selectively reduces proinflammatory mediator secretion, likely by transcriptional regulation through NFkappaB and EGR-1. This is the first demonstration of ERK 1/2 inhibition afforded by CSA.