Does the stemless reverse arthroplasty compare to a conventional stemmed implant? Clinical and radiographic evaluation at 2 years' minimum follow-up.

BACKGROUND: Reverse shoulder arthroplasty (RSA) is a well-recognized treatment for many shoulder conditions, including rotator cuff arthropathy, primary glenohumeral joint arthritis, and rheumatoid arthritis, and can be used in both trauma and revision settings. Over the past 10 years, its popularity in New Zealand has been increasing, with a 6%-7% annual growth rate during this period. Stemless RSA designs have the following proposed advantages: They can preserve humeral bone stock, they can limit periprosthetic fractures, and they can be indicated in patients with abnormal diaphyseal humeral anatomy. To date, only 1 study has evaluated the outcomes of the Lima SMR Stemless implant. We present our data with an aim to report how the stemless reverse arthroplasty compares to a conventional stemmed implant. METHODS: We performed a retrospective review of a consecutive series of patients treated at a single institution between 2015 and 2020. The endpoint was defined as final follow-up at a minimum of 2 years. Patients were excluded from the final analysis if they underwent revision. Thirty-three patients were identified as having undergone stemless RSA. Thirty patients had patient-reported outcome measures and radiographs at a minimum of 2 years' follow-up. Three patients had undergone revision within 2 years. The same sample size of stemmed RSAs (n = 33) was selected for comparison. RESULTS: A total of 60 patients were included in the final analysis, of whom 30 underwent stemless RSA and 30 underwent stemmed RSA. The demographic characteristics of the 2 groups were comparable except age at operation, which showed a statistically significant difference (P = .001): 77 years (stemmed) vs. 65 years (stemless). The mean Oxford Shoulder Score was 40.1 in the stemless group vs. 40 in the stemmed group. The mean American Shoulder and Elbow Surgeons score was 72.9 in the stemless group vs. 79 in the stemmed group. Patient-reported outcome measures, pain scores, and satisfaction ratings were not statistically significantly different between the 2 groups. In terms of radiographic data, subsidence was observed in 2 patients in the stemless RSA group but the patients had no clinical symptoms. Also in the stemless RSA group, 1 patient had an acromial stress fracture and 1 patient had a superficial wound infection successfully treated with oral antibiotics. In terms of revisions in the stemless RSA group, 1 patient underwent revision owing to chronic infection, 1 underwent revision as a result of a periprosthetic fracture after a fall, and 1 underwent revision for gross instability. CONCLUSIONS: The early results of sRSA are promising, and the stemless implant shows similar outcomes to a conventional stemmed implant.

HMGB1 neuroimmune signaling and REST-G9a gene repression contribute to ethanol-induced reversible suppression of the cholinergic neuron phenotype.

Adolescent binge drinking increases Toll-like receptor 4 (TLR4), receptor for advanced glycation end products (RAGE), the endogenous TLR4/RAGE agonist high-mobility group box 1 (HMGB1), and proinflammatory neuroimmune signaling in the adult basal forebrain in association with persistent reductions of basal forebrain cholinergic neurons (BFCNs). In vivo preclinical adolescent intermittent ethanol (AIE) studies find anti-inflammatory interventions post-AIE reverse HMGB1-TLR4/RAGE neuroimmune signaling and loss of BFCNs in adulthood, suggesting proinflammatory signaling causes epigenetic repression of the cholinergic neuron phenotype. Reversible loss of BFCN phenotype in vivo is linked to increased repressive histone 3 lysine 9 dimethylation (H3K9me2) occupancy at cholinergic gene promoters, and HMGB1-TLR4/RAGE proinflammatory signaling is linked to epigenetic repression of the cholinergic phenotype. Using an ex vivo basal forebrain slice culture (FSC) model, we report EtOH recapitulates the in vivo AIE-induced loss of ChAT+IR BFCNs, somal shrinkage of the remaining ChAT+ neurons, and reduction of BFCN phenotype genes. Targeted inhibition of EtOH-induced proinflammatory HMGB1 blocked ChAT+IR loss while disulfide HMBG1-TLR4 and fully reduced HMGB1-RAGE signaling decreased ChAT+IR BFCNs. EtOH increased expression of the transcriptional repressor RE1-silencing transcription factor (REST) and the H3K9 methyltransferase G9a that was accompanied by increased repressive H3K9me2 and REST occupancy at promoter regions of the BFCN phenotype genes Chat and Trka as well as the lineage transcription factor Lhx8. REST expression was similarly increased in the post-mortem human basal forebrain of individuals with alcohol use disorder, which is negatively correlated with ChAT expression. Administration of REST siRNA and the G9a inhibitor UNC0642 blocked and reversed the EtOH-induced loss of ChAT+IR BFCNs, directly linking REST-G9a transcriptional repression to suppression of the cholinergic neuron phenotype. These data suggest that EtOH induces a novel neuroplastic process involving neuroimmune signaling and transcriptional epigenetic gene repression resulting in the reversible suppression of the cholinergic neuron phenotype.

Indomethacin restores loss of hippocampal neurogenesis and cholinergic innervation and reduces innate immune expression and reversal learning deficits in adult male and female rats following adolescent ethanol exposure.

BACKGROUND: Adolescent intermittent ethanol (AIE) exposure causes long-term changes in the brain and behavior of adult male rodents, including persistent induction of innate immune pathways, reductions in hippocampal neurogenic and forebrain cholinergic neuronal markers, and reversal learning deficits. The current study tests the hypothesis that proinflammatory induction mediates AIE-induced (1) loss of adult neurogenesis (i.e., doublecortin (DCX) expressing immature neurons), (2) reductions in forebrain and hippocampal cholinergic markers, and (3) reversal learning deficits. METHODS: Male and female rats underwent AIE (5.0 g/kg/day ethanol or water, i.g., 2 day-on/2 day-off from postnatal day (PND) 25-54), followed by a 2-week regimen of the anti-inflammatory compound indomethacin (4.0 g/kg/day, PND 56-69) or vehicle, after which one cohort was euthanized for immunohistochemical markers (PND 70) and the second underwent the Morris water maze to assess reversal learning. RESULTS: AIE reduced adult (PND 70) DCX+ immunoreactivity (IR) and increased hippocampal expression of the innate immune signal's high-mobility group box protein 1 (HMGB1 + IR) and cyclooxygenase-2 (COX-2 + IR) in adult male and female rats. AIE also reduced choline acetyltransferase (ChAT+IR) in the basal forebrain and co-labeling of hippocampal vesicular acetylcholine transporter (VAChT+) cholinergic terminals on DCX + IR neurons. Indomethacin treatment after AIE restored molecular endpoints to control levels and rescued AIE-induced reversal learning deficits in the Morris water maze in both sexes. Of note, indomethacin produced several adverse effects selectively in control conditions, highlighting the uniquely beneficial effect of indomethacin in AIE rats. CONCLUSIONS: These data suggest that in males and females, (1) AIE persistent neuroimmune induction mediates both the loss of adult hippocampal DCX and loss of basal forebrain cholinergic neurons and their innervation to hippocampal targets, and (2) anti-inflammatory indomethacin treatment following AIE that restores these persistent molecular pathologies also restores spatial reversal learning deficits.

Loss of Basal Forebrain Cholinergic Neurons Following Adolescent Binge Ethanol Exposure: Recovery With the Cholinesterase Inhibitor Galantamine.

Binge drinking and alcohol abuse are common during adolescence and cause both cognitive deficits and lasting cholinergic pathology in the adult basal forebrain. Acetylcholine is anti-inflammatory and studies using the preclinical adolescent intermittent ethanol (AIE; 5.0 g/kg, i.g., 2 day on/2 day off from postnatal day [P]25 to P54) model of human adolescent binge drinking report decreased basal forebrain cholinergic neurons (BFCNs) and induction of proinflammatory genes that persist long into adulthood. Recent studies link AIE-induced neuroimmune activation to cholinergic pathology, but the underlying mechanisms contributing to the persistent loss of BFCNs are unknown. We report that treatment with the cholinesterase inhibitor galantamine (4.0 mg/kg, i.p.) administered during AIE (i.e., P25-P54) or following the conclusion of AIE (i.e., P57-P72) recovered the persistent loss of cholinergic neuron phenotype markers (i.e., ChAT, TrkA, and p75NTR) and somal shrinkage of residual ChAT + neurons known to persist in AIE-exposed adults. Galantamine treatment also recovered the AIE-increased expression of the proinflammatory receptors TLR4 and RAGE, the endogenous TLR4/RAGE agonist HMGB1, and the transcription activation marker pNF-κB p65. Interestingly, we find BFCNs express TLR4 and RAGE, and that AIE treatment increased pNF-κB p65 expression in adult ChAT + IR neurons, consistent with intracellular HMGB1-TLR4/RAGE signaling within BFCNs. AIE increased epigenetic transcription silencing markers (i.e., H3K9me2 and H3K9me3) in the adult basal forebrain and H3K9me2 occupancy at cholinergic phenotype gene promoters (i.e., ChAT and TrkA). The finding of no AIE-induced changes in total basal forebrain NeuN + neurons with galantamine reversal of AIE-induced ChAT + neuron loss, TLR4/RAGE-pNF-κB p65 signals, and epigenetic transcription silencing markers suggests that AIE does not cause cell death, but rather the loss of the cholinergic phenotype. Together, these data suggest that AIE induces HMGB1-TLR4/RAGE-pNF-κB p65 signals, causing the loss of cholinergic phenotype (i.e., ChAT, TrkA, and p75NTR) through epigenetic histone transcription silencing that result in the loss of the BFCN phenotype that can be prevented and restored by galantamine.

Comparison of outcomes after different methods of fixation for extracapsular hip fractures: An observational study.

OBJECTIVE: Optimal management of intertrochanteric fractures using either sliding hip screws (SHS) or Intramedullary nail (IMN) fixation has long been disputed and the optimal length of a 'short nail' has yet to be clarified. Our aim was to investigate functional outcomes in patients who have undergone either sliding hip screw fixation or intramedullary fixation using varied lengths of nails to assess potential superiority. DESIGN: We retrospectively reviewed data from consecutive patients with trochanteric hip fractures between January 2010 - July 2019. Fracture fixation was performed with four different devices; SHS, 220mm and 175mm Targon PFT nails or 180mm Short Affixus Hip Fracture Nails. There was no significant difference in the patient demographics in each treatment group. MAIN OUTCOME MEASURES: Patients were followed up for 1 year post operatively to determine if there were differences in mobility and pain with the different fixation methods. RESULTS: There was no significant difference in the overall complication rate between methods of fixation. Overall Intramedullary nail fixation resulted in an improved mean pain score compared to SHS (mean difference 0.25, 95% CI 0.11 - 0.39, p=0.0005). On sub-analysis this was only statistically significant in 220mm Targon nails (mean difference 0.35, CI 0.19-0.57, p=0.0010) and not for the other two nails. In addition, there was a significant difference in mobility score (mean difference 0.38, CI 0.12-0.63, p=0.0036). On sub-analysis this was only statistically significant favouring the for 220 mm Targon nail (mean difference 0.57, CI 0.27-0.87, p=0.0002). CONCLUSION: We advise caution in interpreting the results of studies between different nails and SHS, as not all nails appear to be the same. Design features of modern nails such as length, proximal diameter, the use of a compression screw, lag screw interface within the nail and valgus inclination may all play a role in functional outcomes.

Mid-term outcomes of surgical management of complex, isolated radial head fractures: a multicentre collaboration.

OBJECTIVES: The available literature discussing optimal surgical management of Mason II and III radial head (RH) fractures without concomitant bone or ligamentous injuries is limited. We aim to help determine the appropriate management of these functionally significant injuries. DESIGN: We present our retrospective cohort study of outcomes of surgically managed isolated, displaced RH fractures SETTING: Study from three trauma centres. PATIENTS/PARTICIPANTS: Adults who underwent surgical treatment for isolated displaced RH fractures. INTERVENTION: RH open reduction internal fixation (ORIF), replacement or excision MAIN OUTCOME MEASUREMENTS: Elbow range of motion (ROM), pain and function using Oxford Elbow Score (OES), Mayo Elbow Performance Score (MEPS), Patient-Rated Elbow Evaluation (PREE) and QuickDASH (QD). RESULTS: Of 46 patients included (mean age 47 years and mean follow-up 48 months), 12 type II fractures were treated with ORIF and 34 type III injuries had ORIF (16), replacement (12) or resection (6). ROM was comparable in all groups, with mean arcs of flexion-extension of 131° and pronation-supination of 147°. Mean visual analogue score for pain was 1.3 in those treated with ORIF compared to 1.9 with arthroplasty and 2.5 with excision. Mean functional scores were 41, 92, 14 and 14 for OES, MEPS, PREE and QD, respectively. Complication rates were 39% for ORIF, 33% for arthroplasty and 33% for resection. Overall re-operation rate was 13%. CONCLUSIONS: Functional outcome is similar in all groups of surgically treated patients with isolated, displaced RH fractures. Complication rates are higher than that reported previously in the literature but with low re-operation rates. LEVEL OF EVIDENCE: IV.

Is there a survival advantage of incomplete resection of non-small-cell lung cancer that is found to be unresectable at thoracotomy?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: in patients with non-small-cell lung cancer that is found to be unresectable at thoracotomy, is incomplete resection superior for achieving survival advantage? Altogether more than 400 papers were found using the reported search, of which nine represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers were tabulated. In total, data from an estimated 1083 patients were analysed. Three-year survival rates varied from 0 to 22% in incomplete resection and from 0 to 10% in exploratory thoracotomy. Median survival ranged from 6.5 to 19.1 months in incomplete resection and from 5.3 to 17 months in exploratory thoracotomy. The majority of studies (8/9) found survival in incomplete resection to be superior. However, only 3/9 studies presented statistical analysis of results. The largest of these found superior postoperative survival in incomplete resection (including residual nodal disease), one study showed a significant survival difference for R1 but not R2 resection and another with small patient numbers (n = 29) found no significant difference. We conclude that the best evidence suggests that there may be a survival advantage from incomplete resection of non-small-cell lung cancer when there is microscopic (R1) or nodal residual disease, but not when macroscopic residual (R2) disease remains.