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Background Limiting opioid use in perioperative pain management is currently an important focus in orthopedic surgery. The ability of acetaminophen to reduce postoperative opioid consumption while providing acceptable pain management has not been thoroughly investigated in patients undergoing rotator cuff repair (RCR). Methods Patients undergoing primary arthroscopic RCR were prospectively randomized to 1 of 3 treatment groups: Group 1 (control) received both 5 mg of oxycodone every 6 hours as needed and 1000 mg of acetaminophen orally every 6 hours as needed after surgery and had the option to take either medication or both. Group 2 (control) received only 5 mg of oxycodone every 6 hours as needed without any additional acetaminophen after surgery. Group 3 received 1000 mg of acetaminophen orally every 6 hours for 1 day prior to and after surgery, which was subsequently decreased to administration every 8 hours during postoperative days 2-5. Group 3 patients were also allowed to take 5 mg of oxycodone every 6 hours as needed after surgery. All patients received interscalene blocks with liposomal bupivacaine (Exparel). Opioid use, pain scores, side effects, and overall satisfaction were assessed daily for the first week after surgery. Results A total of 57 patients (mean age, 57.8 ± 9.55 years) were included in this study. Baseline demographic characteristics including age, sex, and body mass index were similar between the groups (P > .05). Patients in group 3 took significantly fewer narcotics overall (P = .017) and took significantly fewer pills each day compared with group 2. Group 3 also reported significantly better overall pain control compared with the other groups (P = .040). There were no significant differences in overall patient satisfaction between the groups (P > .05). Additionally, there were no significant differences between groups regarding postoperative medication-associated side effects (P > .05). Conclusion Perioperative acetaminophen represents an important component of multimodal analgesia in appropriately selected patients undergoing shoulder surgery. In this study, the use of perioperative acetaminophen significantly decreased opioid consumption and improved overall pain control after primary arthroscopic RCR.

BACKGROUND Despite the routine use of plain radiographs to stratify the severity of glenohumeral osteoarthritis, little is known about the relationship between radiographic measures and patient-perceived pain and function. QUESTIONS/PURPOSES (1) What radiographic findings are associated with worse pain and function in patients with glenohumeral osteoarthritis? (2) What demographic factors are associated with worse pain and function in patients with glenohumeral osteoarthritis? METHODS This retrospective study included patients presenting for an initial office visit for primary glenohumeral osteoarthritis. Patients with other concurrent shoulder pathologic findings, prior surgery, lack of pain and functional scores, recent injection, or inadequate radiographs were excluded. Between January 2017 and January 2019, 3133 patients were eligible based on these inclusion criteria; 59% (1860) had outcome assessments and 48% (893) of those had radiographs. An additional 42% (378) of those with radiographs were excluded because of other shoulder findings, recent injection, prior surgery, or inadequate radiographs, leaving 16% (515 of 3133) who were fully analyzed in this study. A radiographic review included the joint space width, posterior humeral head subluxation, inferior humeral head osteophyte size, cystic change, and head asphericity. Additionally, radiographic arthritis was classified according to the Walch, Samilson-Prieto, and Kellgren-Lawrence classifications by two separate reviewers. Radiographic and demographic criteria as well as the presence of psychologic or mental illness were correlated with VAS Pain (range 1-10; minimal clinically important difference [MCID] 1.6), American Shoulder and Elbow Surgeons (ASES; range 0-100; MCID 13.6), Single Assessment Numeric Evaluation (SANE; range 0-100; MCID 14), and Simple Shoulder Test (SST; range 0-12; MCID 1.5) scores using univariate and multivariable regression analyses. RESULTS After accounting for age, gender, and psychologic illness in the multivariable analysis, we found that patients with Samilson-Prieto Grade 4 arthrosis had lower VAS Pain scores (β = -1.9; p = 0.02) than those with Grade 0 or 1 did; however, no clinically important associations were found between Samilson-Prieto Grade 4 and ASES (β = 7; p = 0.25), SANE (β = 4; p = 0.63), or SST (β = 0.5; p = 0.62) scores. No clinically important associations were found between Kellgren-Lawrence Grade 3 and VAS Pain (β = 1.4; p = 0.10), ASES (β = -8; p = 0.22), SANE (β = -13; p = 0.11), or SST scores (β = 0.4; p = 0.66). Radiographic joint space and posterior subluxation also did not have any clinically important associations with VAS Pain or functional scores. In assessing Walch glenoid type, there was no clinically important association between glenoid type and VAS Pain (F = 3.1; p < 0.01), ASES (F = 1.9; p = 0.15), SANE (F = 0.45; p = 0.66), or SST scores (F = 0.76; p = 0.71). Men had higher SST scores than women did (β = 2.0; p < 0.01), but there were no clinically important differences in VAS Pain (β = -0.4; p = 0.04), ASES (β = 6; p < 0.01), or SANE (β = 4; p = 0.07) scores. No clinically important association was found between age or the presence of any psychologic illness and VAS Pain or functional scores. CONCLUSION In patients with glenohumeral arthritis, no consistent clinically important differences in pain or function were discovered with respect to radiographic or demographic factors. Surgeons should understand that the pain levels of patients with glenohumeral arthritis may not parallel radiographic severity. Future studies can build on these findings by examining other non-radiographic or demographic factors that affect pain in patients with shoulder arthritis, such as psychological factors. LEVEL OF EVIDENCE Level III, prognostic study.

Background: Impaired healing after rotator cuff repair is a major concern, with retear rates as high as 94%. A method to predict whether patients are likely to experience poor surgical outcomes would change clinical practice. While various patient factors, such as age and tear size, have been linked to poor functional outcomes, it is currently very challenging to predict outcomes before surgery. Purpose: To evaluate gene expression differences in tissue collected during surgery between patients who ultimately went on to have good outcomes and those who experienced a retear, in an effort to determine if surgical outcomes can be predicted. Study Design: Case-control study; Level of evidence, 3. Methods: Rotator cuff tissue was collected at the time of surgery from 140 patients. Patients were tracked for a minimum of 6 months to identify those with good or poor outcomes, using clinical functional scores and follow-up magnetic resonance imaging to confirm failure to heal or retear. Gene expression differences between 8 patients with poor outcomes and 28 patients with good outcomes were assessed using a multiplex gene expression analysis via NanoString and a custom-curated panel of 145 genes related to various stages of rotator cuff healing. Results: Although significant differences in the expression of individual genes were not observed, gene set enrichment analysis highlighted major differences in gene sets. Patients who had poor healing outcomes showed greater expression of gene sets related to extracellular matrix production ( P < .0001) and cellular biosynthetic pathways ( P < .001), while patients who had good healing outcomes showed greater expression of genes associated with the proinflammatory (M1) macrophage phenotype ( P < .05). Conclusion: These results suggest that a more proinflammatory, fibrotic environment before repair may play a role in poor healing outcome. With validation in a larger cohort, these results may ultimately lead to diagnostic methods to preoperatively predict those at risk for poor surgical outcomes.

Cutibacterium acnes is a lipophilic, anaerobic, gram-positive bacillus that mainly colonizes the pilosebaceous glands of human skin. It has been implicated as the leading cause of prosthetic joint infection (PJI) after shoulder arthroplasty. However, PJI caused by C acnes rarely manifests as overt clinical, laboratory, or imaging features. In fact, more than 40% of shoulders undergoing revision arthroplasty are likely to be culture positive. However, rates of infection following a positive culture can be as low as 5%. The purpose of this review was to put forth alternative explanations for this discordance between positive cultures and infection. We describe C acnes roles as a commensal, bystander, and/or contaminant organism; the role of cultures in diagnosis and other methods that may be more accurate; its existence in a shoulder microbiome; and the variable virulence of C acnes. C acnes is an important cause of shoulder PJI in some patients. However, there is a large body of literature that suggests other functions that need to be considered. Further research is needed to define the role of C acnes that is logically explained by all of the literature and not only some.

The primary aim of this study was to characterize opioid consumption in the first 30 days after shoulder surgery. Secondary aims were to assess patient expectations, pain tolerance, risk factors fo...

Cutibacterium acnes is the most prevalent cause of joint infection after shoulder surgery. Current methods for decolonizing this bacterium from the shoulder region have proved ineffective owing to its unique niche within dermal sebaceous glands and hair follicles. When we are making decisions to decolonize the skin of C acnes, the risks associated with decolonization must be balanced by the potential benefits of reduced deep tissue inoculation. The purpose of this review was to describe currently available methods of decolonization and their efficacy.

Variable neck-shaft angle (NSA) stemmed humeral components have been incorporated into certain implant designs to better re-create normal anatomy in total shoulder arthroplasty (TSA). The purpose of this study was to determine if premorbid glenohumeral joint anatomy is better restored with a fixed- vs. variable-NSA prosthesis.A randomized controlled trial was performed including 50 patients with osteoarthritis indicated for primary anatomic TSA. Patients were randomized preoperatively to receive either a variable- (n = 26) or fixed-NSA (n = 24) prosthesis. Humeral neck cut in the variable-NSA group matched the patient's anatomic neck, with prosthetic NSA of 127.5°, 132.5°, and 137.5° available. Fixed-NSA cuts were made with an intramedullary guide of 132.5°. Preoperative and postoperative radiographs were evaluated for specific radiographic anatomic variables: NSA, head thickness, tuberosity-to-head height, head offset, articular arc, greater tuberosity offset, and center of rotation (COR). Postoperative radiographic criteria were compared between groups.No differences were found between groups in demographics or preoperative radiographic measures. When comparing average difference in preoperative and postoperative measurements in the fixed-NSA group, the humeral head offset from the humeral shaft axis significantly decreased by 1.4 mm (P = .046), and the COR moved superiorly (3.0 mm, P = .002) without significant medialization or lateralization. In the variable angle group, humeral head offset decreased but did not reach significance (1.2 mm, P = .091), and the COR also moved superiorly (2.9 mm, P .001) without significant medialization or lateralization. All remaining radiographic parameters did not significantly change from pre- to postoperative imaging. In comparing the fixed- and variable-NSA groups' net change from the premorbid measurements, no significant differences were found in tuberosity-to-head height, head offset, or COR position in both the horizontal and vertical planes.Both fixed- and variable-NSA anatomic TSA humeral components demonstrate adequate restoration of premorbid anatomy radiographically.

Aging can lead to rectoanal incontinence due to internal anal sphincter (IAS) dysfunction, which is characterized by a decrease in IAS tone and contractility and an increase in nonadrenergic noncholinergic (NANC) relaxation. We aimed to determine whether brain-derived neurotropic factor (BDNF) rescues this aging-associated IAS dysfunction (AAID). To do so, we studied the effects of BDNF on the basal and G protein-coupled receptors (GPCR)-stimulated IAS smooth muscle tone and on NANC relaxation in Fischer 344 rats representing different age groups [26-mo-old (aging) vs. 6-mo-old (young)], before and after tyrosine kinase receptor B (TrkB) antagonist K252a. We also used isolated smooth muscle cells (SMCs) to determine the effects of BDNF before and after different agonists. For some studies, we monitored NO release using smooth muscle perfusates. BDNF reversed AAID by rescuing the basal IAS tone and agonists [thromboxane A(2) analog (U46619) and angiotensin II (ANG II)]-induced contractility, and NANC relaxation. These rescue effects of BDNF were selective as K252a attenuated the changes in the IAS without modifying the effects of K(+)depolarization. Because of the direct association between the basal and GPCR-stimulated IAS tone and RhoA/ROCK activation, we speculate that this pathway in the rescue effects of BDNF. Conversely, our data suggest that aging-associated increased NANC relaxation is reversed by decreased release of NO and decrease in the sensitivity of the released inhibitory neurotransmitter. In summary, BDNF rescue of AAID involves RhoA/ROCK and inhibitory neurotransmission. These data have direct implications for the role of BDNF in the pathophysiology and therapeutic targeting of aging-associated rectoanal motility disorders. NEW & NOTEWORTHY These studies demonstrate that brain-derived neurotropic factor (BDNF) rescues the aging-associated internal anal sphincter (IAS) dysfunction, characterized by a decrease in IAS tone, and increase in non-adrenergic noncholinergic relaxation. We determined the effects of BDNF on the basal and GPCR (TXA(2) and ANG II)-stimulated IAS tone, and on NANC relaxation, before and after TrkB inhibitor K252a. BDNF may have an important role in the pathophysiology and therapeutic targeting of certain rectoanal motility disorders.

To evaluate the utility and side effect profile of subcutaneous repository corticotropin gel (RCI) in ocular sarcoidosis.Retrospective chart review.Among six identified patients on RCI therapy, 4 had uveitis, one had optic neuritis and one had uveitis and optic neuritis secondary to sarcoidosis. The average follow-up was 43.5 months. RCI therapy was continuous in 4 patients (average 7.7 months) and intermittent in 2 patients (24 and 12 months). Five of the 6 patients continued with local and/or systemic corticosteroids for ocular inflammation control while on RCI therapy. Two-thirds of patients experienced adverse effects including hyperpigmentation, alopecia, and severe hypertension. RCI therapy was discontinued in 5 of the 6 patients due to continued inflammation and side/adverse effects (4 patients) and loss of follow-up (1 patient).In this small cohort, the majority of patients failed to achieve adequate steroid-sparing ocular inflammation control and experienced side effects while on RCI therapy. Additional studies are needed to elucidate the role of RCI in ocular inflammation.

The benefit of rotator cuff repair (RCR) in patients with concurrent osteoarthritic changes remains unclear. RCR has the theoretical potential to increase the compressive force across the glenohumeral joint, further exacerbating osteoarthritis pain. The purpose of this study is to investigate pain relief and patient-reported outcomes of patients undergoing simultaneous RCR and microfracture of focal glenohumeral osteoarthritis.Thirty-four patients undergoing simultaneous RCR and microfracture were retrospectively reviewed at a minimum 1-year follow-up. Patient demographics, preoperative range of motion, functional outcomes (visual analog scale [VAS], Single Assessment Numeric Evaluation [SANE], American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form [ASES], and Simple Shoulder Test [SST]), and operative metrics were recorded. The patients were then contacted to obtain postoperative functional outcome scores (VAS, SANE, ASES, and SST).Twenty-seven patients (11 male/16 female [79%]) were evaluated at a mean follow-up of 25.8 months (range, 12-46). The average age at surgery was 64.9 years (range, 56-78). Chronic tears were more common than acute tears (57.7% vs. 42.3%). The majority of patients had a full rotator cuff tear (89%) involving a mean 1.7 ± 0.8 tendons (range, 1-3). Eighty-eight percent of the humeral lesions were Outerbridge 4 compared with 84% on the glenoid. The mean estimated involvement between the 2 groups with 38.4% ± 18.4% of the humeral head involved and 34.6% ± 18.4% of the glenoid involved. PRO scores improved postoperatively with a reduction in mean VAS (6.6-2.0, P.01), SANE (33.8-79.8, P.01), ASES (38.0-80.9, P.01), and SST (3.07-9.70, P.01) scores. Cumulatively, only 52% (14/27) of the patients improved, however, by the MCID for all collected PROs.Our results demonstrate modest improvements in postoperative pain and functional scores at a minimum of 1-year follow-up in a cohort of patients who have undergone RCR and glenohumeral microfracture. In cases of small focal lesions of full-thickness cartilage loss, RCR with microfracture is a reasonable treatment option; however, patients should be counseled on expectations accordingly.

Background Data on the neuromodulatory effects of brain-derived neurotrophic factor (BDNF) in the gastrointestinal tract were recently reported, but there are still no data on the presence, distribution, and release of BDNF in the gastrointestinal tract, including the internal anal sphincter (IAS). Methods We examined the presence and distribution of BDNF and its receptor TrkB in the different IAS structures (neuronal and non-neuronal) via immunohistochemical and immunocytochemical analyses. We also monitored the release of BDNF in an IAS muscle bath (consisting of smooth muscle cells [SMCs], myenteric plexus, and submucosal plexus) before and after different agonists, and electrical field stimulation in the absence and presence of neurotoxin tetrodotoxin. Key results BDNF/TrkB was found to be present in all layers of the IAS, especially the smooth muscle, mucosa, myenteric plexus, and submucosal plexus. Detailed analyses revealed a significant colocalization between BDNF and TrkB in different structures, especially in the smooth muscle, the SMCs, and both plexuses. Data further showed higher levels of BDNF in the cytosol and that of TrkB toward the periphery of the SMCs. Conclusions & inferences These studies showed that BDNF/TrkB was present not only in the enteric nervous system (ENS), but also in the SMCs. For the neuromodulatory effects, BDNF is released locally from the ENS ((myenteric (10.01 ± 0.23 pg/ml) and submucosal plexus (9.05 ± 0.51 pg/ml)) and the SMCs (18.63 ± 1.63 pg/ml). Collectively, these findings have pathophysiological and therapeutic implications regarding the role of BDNF/TrkB in the IAS-associated rectoanal motility disorders.

Presently, there are no studies examining the neuromodulatory effects of brain-derived neurotropic factor (BDNF) on the basal internal anal sphincter (IAS) tone and nonadrenergic noncholinergic (NANC) relaxation. To examine this, we determined the neuromuscular effects of BDNF on basal IAS smooth muscle tone and the smooth muscle cells (SMCs) and the effects of NANC nerve stimulation before and after high-affinity receptor tyrosine kinase receptor B (TrkB) antagonist K252a. We also investigated the mechanisms underlying BDNF-augmented increase in the IAS tone and NANC relaxation. We found that BDNF-increased IAS tone and SMC contractility were TTX resistant and attenuated by K252a. TrkB-specific agonist 7,8-dihydroxyflavone, similar to BDNF, also produced a concentration-dependent increase in the basal tone, whereas TrkB inhibitors K252a and ANA-12 produced a decrease in the tone. In addition, BDNF produced leftward shifts in the concentration-response curves with U46619 and ANG II (but not with bethanechol and K+ depolarization), and these shifts were reversed by K252a. Effects of Y27632 and Western blot data indicated that the BDNF-induced increase in IAS tone was mediated via RhoA/ROCK. BDNF-augmented NANC relaxation by electrical field stimulation was found to be mediated via the nitric oxide (NO)/soluble guanylate cyclase (sGC) pathway rather than via increased sensitivity to NO. In conclusion, the net effect of BDNF was that it caused an increase in the basal IAS tone via RhoA/ROCK signaling. BDNF also augmented NANC relaxation via NO/sGC. These findings may have relevance to the role of BDNF in the pathophysiology and therapeutic targeting of the IAS-associated rectoanal motility disorders. NEW & NOTEWORTHY These studies for the first time to our knowledge demonstrate that increased levels of brain-derived neurotrophic factor (BDNF; conceivably released from smooth muscle cells and/or the enteric neurons) has two major effects. First, BDNF augments the internal anal sphincter (IAS) tone via tyrosine kinase receptor B/thromboxane A2-receptor, angiotensin II receptor type 1/RhoA/ROCK signaling; and second, it increases nonadrenergic noncholinergic relaxation via nitric oxide/soluble guanylate cyclase. These studies may have relevance in therapeutic targeting in the anorectal motility disorders associated with the IAS.