Discovery of N-benzylbenzamide-based allosteric inhibitors of Aurora kinase A.

Aurora kinases (AurkA/B/C) regulate the assembly of bipolar mitotic spindles and the fidelity of chromosome segregation during mitosis, and are attractive therapeutic targets for cancers. Numerous ATP-competitive AurkA inhibitors have been developed as potential anti-cancer agents. Recently, a few allosteric inhibitors have been reported that bind to the allosteric Y-pocket within AurkA kinase domain and disrupt the interaction between AurkA and its activator TPX2. Herein we report a novel allosteric AurkA inhibitor (6h) of N-benzylbenzamide backbone. Compound 6h suppressed the both catalytic activity and non-catalytic functions of AurkA. The inhibitory activity of 6h against AurkA (IC50 = 6.50 µM) was comparable to that of the most potent allosteric AurkA inhibitor AurkinA. Docking analysis against the Y-pocket revealed important pharmacophores and interactions that were coherent with structure-activity relationship. In addition, 6h suppressed DNA replication in G1-S phase, which is a feature of allosteric inhibition of AurA. Our current study may provide a useful insight in designing potent allosteric AurkA inhibitors.

Arthroscopic cuff repair: footprint remnant preserving versus debriding rotator cuff repair of transtendinous rotator cuff tears with remnant cuff.

BACKGROUND: In transtendinous full thickness rotator cuff tears (FTRCT) with remnant cuff, conventionally, cuff remnant of the greater tuberosity (GT) is debrided for better tendon to bone healing. However, larger cuff defect caused overtension on the repaired tendon. The purpose of this study was to compare the clinical outcomes and tendon integrity between remnant preserving and remnant debriding cuff repairs in the transtendinous FTRCT with remnant cuff. METHODS: From March, 2012 to October, 2017, a total of 127 patients who had the transtendinous FTRCT with remnant cuff were enrolled in this study. Rotator cuff tears were repaired arthroscopically, with patients divided into two groups: group I (n = 63), where rotator cuff remnants were preserved during the repair, and group II (n = 64), where the remnants were debrided during the repair. Clinical outcomes were assessed at the last follow-up (minimum 2 years) using the UCLA score, ASES score, SST score, Constant Shoulder score, and range of motion (ROM). The analysis of structural integrity and tendon quality was performed using the Sugaya classification on postoperative MRI scans at 8 months after surgery. RESULTS: At the final follow-up, UCLA, ASES, SST, and CS scores significantly improved from preoperative values to postoperative (all p < 0.05): UCLA (I: 19.6 ± 6.0 to 31.7 ± 3.2, II: 18.0 ± 5.7 to 31.5 ± 3.2), ASES (I: 54.3 ± 10.7 to 86.5 ± 12.5, II: 18.0 ± 5.7 to 85.8 ± 12.4), SST (I: 5.6 ± 2.8 to 10.2 ± 2.0, II: 5.0 ± 2.9 to 10.1 ± 2.5), CS (I: 74.0 ± 17.2 to 87.8 ± 9.7, II: 62.0 ± 19.2 to 88.3 ± 6.2). However, there were no significant differences between the two groups (p > 0.05). Also, remnant preserving cuff repair yielded significantly better tendon quality on postoperative MRI (p < 0.05). The incidence of re-tear (Sugaya's Type IV and V) was not significantly different between the two groups (I:17% vs. II:19%; p = 0.053). CONCLUSIONS: Remnant preserving rotator cuff repairs, which facilitate tendon-to-tendon healing, are superior in terms of tendon quality and are the preferred option for transtendinous FTRCT. TRIAL REGISTRATION: Retrospectively registered.

Expression of Wild-Type and Mutant Human TDP-43 in Yeast Inhibits TOROID (TORC1 Organized in Inhibited Domain) Formation and Autophagy Proportionally to the Levels of TDP-43 Toxicity.

TDP-43 forms aggregates in the neurons of patients with several neurodegenerative diseases. Human TDP-43 also aggregates and is toxic in yeast. Here, we used a yeast model to investigate (1) the nature of TDP-43 aggregates and (2) the mechanism of TDP-43 toxicity. Thioflavin T, which stains amyloid but not wild-type TDP-43 aggregates, also did not stain mutant TDP-43 aggregates made from TDP-43 with intragenic mutations that increase or decrease its toxicity. However, 1,6-hexanediol, which dissolves liquid droplets, dissolved wild-type or mutant TDP-43 aggregates. To investigate the mechanism of TDP-43 toxicity, the effects of TDP-43 mutations on the autophagy of the GFP-ATG8 reporter were examined. Mutations in TDP-43 that enhance its toxicity, but not mutations that reduce its toxicity, caused a larger reduction in autophagy. TOROID formation, which enhances autophagy, was scored as GFP-TOR1 aggregation. TDP-43 inhibited TOROID formation. TORC1 bound to both toxic and non-toxic TDP-43, and to TDP-43, with reduced toxicity due to pbp1Δ. However, extragenic modifiers and TDP-43 mutants that reduced TDP-43 toxicity, but not TDP-43 mutants that enhanced toxicity, restored TOROID formation. This is consistent with the hypothesis that TDP-43 is toxic in yeast because it reduces TOROID formation, causing the inhibition of autophagy. Whether TDP-43 exerts a similar effect in higher cells remains to be determined.

Tri-component hydrocolloid as egg white replacement in meringues: gellan gum with soy protein isolate and maltodextrin.

BACKGROUND: In the quest for sustainable food ingredients, the present study delves into the potential of a tri-component hydrocolloid blend, comprising gellan gum (GG), soy protein isolate (SPI) and maltodextrin (MD), as a replacement for egg white in meringue production. The research aims to elucidate the intricate physical properties of meringue containing this tri-component structure, focusing on foaming dynamics, rheological behavior and the textural properties of the resulting meringue cookies. RESULTS: Experiments were conducted with various hydrocolloids (k-carrageenan, GG, and locust bean gum) and GG was identified as optimal for improving foaming capacity and foaming stability. Rheological evaluations showed a positive correlation between increased GG concentration within the tri-component matrix and an increase in both storage modulus (G') and loss modulus (G"), indicating improved structural integrity. Furthermore, a comparative analysis of the texture profiles of cookies prepared with this blend highlighted the ability of higher GG concentrations to satisfactorily replicate the tactile and visual qualities of traditional egg white-based meringues. This result was particularly evident compared to formulations utilizing solely SPI or the combined SPI-MD configuration. CONCLUSION: Conclusively, the results of the present study highlight the significant potential of the GG-SPI-MD tri-component structure to closely mimic the critical properties of egg white, thus offering a promising plant-based alternative for meringue production. © 2024 Society of Chemical Industry.

Comparison between arthroscopic suture anchor fixation and open plate fixation in the greater tuberosity fracture of the proximal humerus.

INTRODUCTION: The purpose of this study is to compare the clinical and radiological outcomes of patients undergoing open reduction and internal fixation (OR/IF) using a plate or patients undergoing an arthroscopic suture anchor fixation for the greater tuberosity (GT) fracture of the proximal humerus. The purpose of this study is to compare the clinical and radiological outcomes of patients undergoing OR/IF or an arthroscopic suture anchor fixation for the GT fracture. MATERIALS AND METHODS: Between January, 2010 and December, 2020, 122 patients with GT fracture underwent operative fixation. Either OR/IF using proximal humeral locking plate (50 patients) or arthroscopic suture anchor (72 patients) fixation was performed. Fourteen patients were lost to follow-up and finally, 108 patients were enrolled in this study. We divided these patients into two groups: (1) OR/IF group (Group I: 44 patients) and arthroscopic anchor fixation group (Group II: 64 patients). The primary outcome was subjective shoulder function (shoulder functional scale). Secondary outcomes were range of motion, and complications including GT fixation failure, fracture migration, or neurologic complication. Also, age, sex, BMI, operation time, shoulder dislocation, fracture comminution, AP (anteroposterior), SI (superoinferior) size and displacement were evaluated and compared between two groups. RESULTS: Both groups showed satisfactory clinical and radiological outcomes at mid-term follow-up. Between 2 groups, there were no significant differences in age, sex, BMI, presence of shoulder dislocation or comminution. Group II showed higher clinical scores except VAS score (p < 0.05) and longer surgical times (95.3 vs. 61.5 min). Largest fracture displacement (Group I vs. II: SI displacement: 40 vs. 13 mm, and AP displacement: 49 vs. 11 mm) and higher complication rate (p = 0.049) was found in Group I. CONCLUSIONS: Both arthroscopic anchor fixation and open plate fixation methods showed satisfactory outcomes at mid-term follow-up. Among them, OR/IF is preferred for larger fracture displacement (> 5 mm) and shorter operation time However, arthroscopic anchor fixation group showed better clinical outcomes and less complications than the OR/IF group. LEVEL OF EVIDENCE: Level 4, Case series with subgroup analysis.

Design, synthesis, and study of novel phenethyl-based antitumor phospholipids downregulating p38 mitogen-activated protein kinase.

Phenethyl-based edelfosine-analogs with saturated, monounsaturated, or polyunsaturated alkoxy substituents on phenyl ring were designed as novel antitumor lipids modulating p38 MAPK. Evaluation of the synthesised compounds against nine panels of diverse cancer cells presented saturated and monounsaturated alkoxy-substituted derivatives as the most active than other derivatives. In addition, ortho-substituted compounds were more active than meta- or ortho-substituted compounds. They were potential anticancer agents against blood, lung, colon, CNS, ovary, renal, and prostate cancers but not against skin nor breast cancers. Compounds, 1b and 1a emerged as the most potential anticancer agents. Assessment of compound 1b impact on p38 MAPK and AKT confirmed it as an inhibitor of p38 MAPK but not AKT. In silico study suggested compounds 1b and 1a as possible binders to the lipid binding pocket of p38 MAPK. Overall, compounds 1b and 1a as novel broad spectrum antitumor lipids modulating activity of p38 MAPK for further development.

Mid-term comparative study between the glenoid and humerus lateralization designs for reverse total shoulder arthroplasty: which lateralization design is better?

INTRODUCTION: The complications of the conventional medialized design for reverse total shoulder arthroplasty (RSA) are increased scapular notching, and decreased external rotation and deltoid wrapping. Currently, lateralization design RSA, which avoid scapular notching and improve impingement-free range of motion, is commonly used. Especially, humeral lateralization design was most commonly used and glenoid lateralization design was preferred for glenoid abnormities. We compared mid-term clinical and radiologic outcomes of glenoid and humeral lateralization RSA in an Asian population in this study. MATERIALS AND METHODS: We enrolled 124 shoulders of 122 consecutive patients (mean age 73.8 ± 6.8 years) who received glenoid or humeral lateralization RSA from May, 2012 to March, 2019. We divided these patients into two groups according to RSA using either glenoid or humeral lateralization design. These different designs were introduced consecutively in Korea. The clinical and radiological results of 60 glenoid lateralization RSA (Group I, 60 patients) and 64 humeral lateralization RSA (Group II, 62 patients) were retrospectively evaluated and also were compared between the two groups. All patients were followed for mean 3 years. RESULTS: The clinical and radiologic outcomes of the two groups did not differ significantly, including scapular notching (p = 0.134). However, humeral lateralization RSA showed a larger glenoid-tuberosity (GT) distance (p = 0.000) and less distalization shoulder angle (DSA) (p = 0.035). The complication rate did not differ significantly either. But, revision surgery was performed for 2 humeral loosening in the Group II. CONCLUSION: The clinical and radiologic outcomes of the two groups did not differ significantly, including scapular notching at mid-term follow-up. However, humeral lateralization design showed larger GT distance and less DSA. Humeral lateralization design RSA could preserve the normal shoulder contour due to a larger GT distance (more lateralization) and provide less deltoid tension due to less DSA (less distalization of COR).

Comparisons between treatment of isolated posterosuperior paralabral cysts and simultaneous treatment of cysts combined with associated shoulder pathologies: arthroscopic treatment of posterosuperior paralabral cysts.

INTRODUCTION: The purpose of this study is to report the radiologic and clinical outcomes of arthroscopic intervention for isolated posterosuperior paralabral cysts and simultaneous treatment of cysts combined with associated shoulder pathologies. MATERIALS AND METHODS: From March 2008 through December 2016, 70 cases (48 males and 22 females) operated on for symptomatic posterosuperior paralabral cysts were included. Mean age was 45 (range 18-69). These patients were classified into two groups depending on if they had accompanying lesions: Group I (isolated group, 27 patients) and Group II (concomitant group, 43 patients). Arthroscopic cyst decompression with a labral repair or posterior capsulotomy for patients without labral tear were performed. All concomitant pathologies were also operated simultaneously. Follow-up MRI were performed at postoperative 6 months and clinical outcomes were evaluated during the follow-up. RESULTS: Arthroscopic all intra-articular cyst decompression and labral repair was performed on 67 patients. In three patients, posterior capsulotomy without labral repair was performed for cyst removal. For 43 patients with concomitant lesions, 31 rotator cuff repairs, three SLAP repairs along with biceps tenodesis, two distal clavicle resections due to A-C joint arthritis, one calcific deposit removal, four Bankart repairs, and two acromioplasties were performed. The follow-up MRI showed complete cyst resorption except for two patients. The mean VAS, ASES, UCLA, SST and CS scores significantly improved at the last follow-up. Although both groups showed significantly improved range of motion after the surgery, improvement of ROM in Group II lagged at early periods of the rehabilitation. CONCLUSIONS: Arthroscopic labral repair with all intra-articular cysts decompression or simple posterior capsulotomy were both effective treatment modalities. If paralabral cysts were associated with other shoulder lesions, simultaneous treatment of combined lesions could be performed for the improved clinical outcomes at final follow-up with expected lag in the early rehabilitation period. LEVEL OF EVIDENCE: Level III, Retrospective Comparative Trial, Treatment Study.

Characteristics of plaque lipid-associated macrophages and their possible roles in the pathogenesis of atherosclerosis.

PURPOSE OF REVIEW: Recent findings from single-cell transcriptomic studies prompted us to revisit the role of plaque foamy macrophages in the pathogenesis of atherosclerosis. In this review, we compared the gene expression profile of plaque foamy macrophages with those of other disease-associated macrophages and discussed their functions in the pathogenesis of atherosclerosis. RECENT FINDINGS: To understand the phenotypes of macrophages in atherosclerotic aorta, many research groups performed single-cell RNA sequencing analysis and found that there are distinct phenotypic differences among intimal foamy, nonfoamy and adventitial macrophages. Especially, the plaque foamy macrophages express triggering receptor expressed on myeloid cells 2 (TREM2), a key common feature of disease-associated macrophages in Alzheimer's disease, obesity, cirrhosis and nonalcoholic steatohepatitis. These TREM2 + macrophages seem to be protective against chronic inflammation. SUMMARY: As the gene expression profile of plaque foamy macrophages is highly comparable to that of lipid-associated macrophages from obesity, we named the plaque foamy macrophages as plaque lipid-associated macrophages (PLAMs). PLAMs have a high level of gene expression related to phago/endocytosis, lysosome, lipid metabolism and oxidative phosphorylation. Considering the protective function of lipid-associated macrophages against adipose tissue inflammation, PLAMs may suppress atherosclerotic inflammation by removing modified lipids and cell debris in the plaque.

Calcium-responsive transactivator (CREST) toxicity is rescued by loss of PBP1/ATXN2 function in a novel yeast proteinopathy model and in transgenic flies.

Proteins associated with familial neurodegenerative disease often aggregate in patients' neurons. Several such proteins, e.g. TDP-43, aggregate and are toxic when expressed in yeast. Deletion of the ATXN2 ortholog, PBP1, reduces yeast TDP-43 toxicity, which led to identification of ATXN2 as an amyotrophic lateral sclerosis (ALS) risk factor and therapeutic target. Likewise, new yeast neurodegenerative disease models could facilitate identification of other risk factors and targets. Mutations in SS18L1, encoding the calcium-responsive transactivator (CREST) chromatin-remodeling protein, are associated with ALS. We show that CREST is toxic in yeast and forms nuclear and occasionally cytoplasmic foci that stain with Thioflavin-T, a dye indicative of amyloid-like protein. Like the yeast chromatin-remodeling factor SWI1, CREST inhibits silencing of FLO genes. Toxicity of CREST is enhanced by the [PIN+] prion and reduced by deletion of the HSP104 chaperone required for the propagation of many yeast prions. Likewise, deletion of PBP1 reduced CREST toxicity and aggregation. In accord with the yeast data, we show that the Drosophila ortholog of human ATXN2, dAtx2, is a potent enhancer of CREST toxicity. Downregulation of dAtx2 in flies overexpressing CREST in retinal ganglion cells was sufficient to largely rescue the severe degenerative phenotype induced by human CREST. Overexpression caused considerable co-localization of CREST and PBP1/ATXN2 in cytoplasmic foci in both yeast and mammalian cells. Thus, co-aggregation of CREST and PBP1/ATXN2 may serve as one of the mechanisms of PBP1/ATXN2-mediated toxicity. These results extend the spectrum of ALS associated proteins whose toxicity is regulated by PBP1/ATXN2, suggesting that therapies targeting ATXN2 may be effective for a wide range of neurodegenerative diseases.

Long non-coding RNA NEAT1_1 ameliorates TDP-43 toxicity in in vivo models of TDP-43 proteinopathy.

Pathological changes involving TDP-43 protein ('TDP-43 proteinopathy') are typical for several neurodegenerative diseases, including frontotemporal lobar degeneration (FTLD). FTLD-TDP cases are characterized by increased binding of TDP-43 to an abundant lncRNA, NEAT1, in the cortex. However it is unclear whether enhanced TDP-43-NEAT1 interaction represents a protective mechanism. We show that accumulation of human TDP-43 leads to upregulation of the constitutive NEAT1 isoform, NEAT1_1, in cultured cells and in the brains of transgenic mice. Further, we demonstrate that overexpression of NEAT1_1 ameliorates TDP-43 toxicity in Drosophila and yeast models of TDP-43 proteinopathy. Thus, NEAT1_1 upregulation may be protective in TDP-43 proteinopathies affecting the brain. Approaches to boost NEAT1_1 expression in the CNS may prove useful in the treatment of these conditions.

Evaluation of the Inhibitory Effects of Pyridylpyrazole Derivatives on LPS-Induced PGE2 Productions and Nitric Oxide in Murine RAW 264.7 Macrophages.

A series of thirteen triarylpyrazole analogs were investigated as inhibitors of lipopolysaccharide (LPS)-induced prostaglandin E2 (PGE2) and nitric oxide (NO) production in RAW 264.7 macrophages. The target compounds 1a-m have first been assessed for cytotoxicity against RAW 264.7 macrophages to determine their non-cytotoxic concentration(s) for anti-inflammatory testing to make sure that the inhibition of PGE2 and NO production would not be caused by cytotoxicity. It was found that compounds 1f and 1m were the most potent PGE2 inhibitors with IC50 values of 7.1 and 1.1 µM, respectively. In addition, these compounds also showed inhibitory effects of 11.6% and 37.19% on LPS-induced NO production, respectively. The western blots analysis of COX-2 and iNOS showed that the PGE2 and NO inhibitory effect of compound 1m are attributed to inhibition of COX-2 and iNOS protein expression through inactivation of p38.

Suture anchor fixation of comminuted inferior pole patella fracture-novel technique: suture bridge anchor fixation technique.

PURPOSE: Comminuted inferior pole fractures of the patella are notorious fractures where it is difficult to obtain rigid internal fixation by conventional tension band wiring. The purpose of this study is to evaluate the clinical and radiological outcomes of the suture bridge anchor fixation for these comminuted inferior pole fractures of the patella. METHODS: From March 2012 to December 2018, suture bridge anchor fixation for the inferior pole comminuted fracture of the patella was performed in 22 patients. There were 21 patients of inferior pole comminuted fracture and 1 patient of lower periosteal sleeve avulsion fracture. Clinical outcomes including SF-36 score, Knee injury and osteoarthritis outcome score (KOOS) and post-operative range of motion were evaluated. In all patients, suture bridge anchor fixation was performed and, tension band wiring with K wire was added for large fragment fixation in two patients. We evaluated bony union, the patellar height using Insall-Salvati ratio and its complications. RESULTS: Mean age was 46 ± 20 (15-82) years. Mean follow-up period was 25 ± 18 (11-74) months. In all patients, bony union was achieved at postoperative 4 months. At final follow-up, mean SF-36 score was 72 ± 15 (30-91) points and KOOS score was 66.7 ± 16 (43-97). The average range of motion was 134 ± 5 (125-140) degrees. As a complication, one patient developed a wound infection and subsequent osteomyelitis of inferior pole fracture fragment. Compared to the normal knee, the Insall-Salvati ratio of the injured knee averages 0.73 and this smaller ratio less than 0.8 meant patella baja. CONCLUSIONS: In the comminuted inferior pole fractures of the patella, suture bridge anchor fixation showed good bony union and satisfactory clinical outcomes at the short-term follow-up and could be a satisfactory alternative treatment option. Even though suture bridge anchor fixation in these fractures caused decreased Insall-Salvati ratio (patella height), any patellofemoral pain and limited range of motion was not developed. LEVEL OF EVIDENCE: Level IV.

N-terminal methionine excision of proteins creates tertiary destabilizing N-degrons of the Arg/N-end rule pathway.

All organisms begin protein synthesis with methionine (Met). The resulting initiator Met of nascent proteins is irreversibly processed by Met aminopeptidases (MetAPs). N-terminal (Nt) Met excision (NME) is an evolutionarily conserved and essential process operating on up to two-thirds of proteins. However, the universal function of NME remains largely unknown. MetAPs have a well-known processing preference for Nt-Met with Ala, Ser, Gly, Thr, Cys, Pro, or Val at position 2, but using CHX-chase assays to assess protein degradation in yeast cells, as well as protein-binding and RT-qPCR assays, we demonstrate here that NME also occurs on nascent proteins bearing Met-Asn or Met-Gln at their N termini. We found that the NME at these termini exposes the tertiary destabilizing Nt residues (Asn or Gln) of the Arg/N-end rule pathway, which degrades proteins according to the composition of their Nt residues. We also identified a yeast DNA repair protein, MQ-Rad16, bearing a Met-Gln N terminus, as well as a human tropomyosin-receptor kinase-fused gene (TFG) protein, MN-TFG, bearing a Met-Asn N terminus as physiological, MetAP-processed Arg/N-end rule substrates. Furthermore, we show that the loss of the components of the Arg/N-end rule pathway substantially suppresses the growth defects of naa20Δ yeast cells lacking the catalytic subunit of NatB Nt acetylase at 37 °C. Collectively, the results of our study reveal that NME is a key upstream step for the creation of the Arg/N-end rule substrates bearing tertiary destabilizing residues in vivo.

Trans-tendon suture bridge rotator cuff repair with tenotomized pathologic biceps tendon augmentation in high-grade PASTA lesions.

PURPOSE: The purpose of this study was to evaluate whether trans-tendon suture bridge repair with tenotomized pathologic biceps tendon augmentation improves mid-term clinical outcomes for high-grade partial articular-sided supraspinatus tendon avulsion (PASTA) lesions or not. METHODS: A retrospective review of a consecutive series of arthroscopic trans-tendon suture bridge repair with tenotomized pathologic biceps tendon augmentation was conducted. Total 115 patients (44 men and 71 women) with minimum 2 years follow-up were enrolled in our study. Their mean age was 59.7 ± 7.6 (38-77) years and mean follow-up were 6.9 ± 2.5 (2 ~ 10) years. Clinical assessment and radiological outcomes using post-operative MRI were evaluated at last follow-up. RESULTS: All these tears were high-grade PASTA lesions in which mean cuff tear size (exposed footprint) was anteroposterior length 15.7 ± 6.3 mm (5-25 mm) and mediolateral width 10.1 ± 3.6 mm 6.4 mm (5-16 mm). At last follow-up, mean pain VAS, ASES, UCLA, and SST scores were improved from pre-operative values of 5, 59, 21, and 7 to post-operative values of 1, 84.4, 29.5, and 9.4, respectively (p value < 0.001). ROM such as forward flexion, abduction, and internal rotation to the back were improved from a pre-operative mean of 148° (±24), 144° (±24), L2 (Buttock-T7) to a post-operative mean of 161° (±10), 160.0° (±12), and T12 (L3-T5), respectively (p value < 0.001). Follow-up MRI showed Sugaya classification type I in 24 patients (20.9%), type II in 78 patients (67.8%), type III in 11 patients (9.6%) and type 4 in 2 patients (1.7%) were found. As complications, shoulder stiffness was found in five patients, Popeye deformity in two patients and retear in two patients. Revision surgery of the retear was performed in 2 patients. At the last follow-up, 17% (20/115 patients) reported occasional discomfort at the extremes of range of motion during a heavy work or sports activities. CONCLUSIONS: In high-grade PASTA lesions, arthroscopic trans-tendon suture bridge repair with tenotomized pathologic biceps tendon augmentation could be a useful treatment modality capable of preserving rotator cuff footprint, providing simultaneous biceps tenodesis, inducing better tendon healing and possibly preventing tendon buckling and residual pain of the conventional trans-tendon repair methods. These specific methods showed satisfactory outcomes and decreased residual shoulder discomfort (17%) at mid-term follow-up. LEVEL OF EVIDENCE: Level IV, Retrospective case study.

Narrow locking compression plate vs long philos plate for minimally invasive plate osteosynthesis of spiral humerus shaft fractures.

BACKGROUND: Our hypothesis was that minimally invasive plate osteosynthesis (MIPO) using long philos plate (LPP) would show better clinical and radiological outcomes and less complications than narrow locking compression plate (NLCP) for spiral humerus shaft fractures with or without metaphyseal fracture extension. METHODS: From January 2009 to May 2016, we retrospectively studied 35 patients who underwent MIPO for spiral humerus shaft fractures with or without metaphyseal fracture extension (AO classification 12 A, B, C except A3). Eighteen patients underwent MIPO with a 4.5 mm NLCP (group I) in the early period of this study, while 17 patients underwent MIPO with LPP (group II) in the later period. Range of motion (ROM), pre- and post-operative anteroposterior (AP) and lateral angulation of the fracture, operation time, amount of bleeding, and functional outcomes including American Shoulder and Elbow Surgeons score, University of California at Los Angeles score, and Simple Shoulder Test score were analyzed at the final follow up. RESULTS: All patients had complete bony union and achieved satisfactory functional outcomes except 2 patients. In LPP group, better outcomes in postoperative fracture angulation on X-ray and operation time (p < 0.05) were shown. But, two revision surgery with NLCP and bone graft was performed owing to 2 metal failures. CONCLUSIONS: In spiral humeral shaft fractures, LPP group showed better fracture reduction on X-ray and shorter operation time except metal failure owing to weak fixation. Even though MIPO technique using LPP is easier and more accurate reduction method, rigid fixation should be considered.

Non-fracture stem vs fracture stem of reverse total shoulder arthroplasty in complex proximal humeral fracture of asian elderly.

PURPOSE: Fracture stem of the reverse total shoulder arthroplasty (RTSA) was designed for better tuberosity bone healing for the proximal bone defect of complex proximal humeral fractures (PHF). Our purpose was to compare the clinical and radiological outcomes of patients using fracture stem vs non-fracture (conventional) stem of RTSA in complex PHF of elderly patients. METHODS: Between 2008 March and 2017 June, 48 patients who had undergone an RTSA with non-fracture or fracture stem for complex PHF with a minimum 18 months of follow-up were evaluated. Finally, total 45 patients with a mean age of 80 ± 7 years (65-92 years) were enrolled because three patients were excluded due to age related mortality. We divided them into two groups: 25 patients using non-fracture stem (non-fracture stem group) in the early period of this study, and consecutive 20 patients using fracture stem (fracture stem group) in the later period. Between two groups, we compared clinical and radiologic outcomes such as tuberosity failure, heterotopic ossification (HO), dislocation, acromion fracture, notching, loosening and periprosthetic fracture. RESULTS: In all patients, clinical outcomes were improved significantly and tuberosity failure was found in 62% (28/45). Between two groups, there were no statistically significant differences on clinical outcomes and radiologic outcomes except UCLA score. As complications, two humeral stem revision was performed due to tuberosity failure related HO and stem loosening with subsequent periprosthetic fracture in non-fracture stem group. CONCLUSIONS: Compared to non-fracture stem, fracture stem usage of RTSA in complex PHF of elderly patients has no significant different impact on clinical and radiological outcomes. However, tuberosity failure related secondary HO of non-fracture stem might be responsible for stem loosening and periprosthetic fracture in the RTSA for complex PHF of elderly patients. LEVEL OF EVIDENCE: Level IV, case series study.

A nationwide study of the incidence rate of herb-induced liver injury in Korea.

Discrepant incidence has been reported regarding the incidence of herb-induced liver injury (HILI). To address the growing worldwide concern of HILI, we evaluated the risk of HILI in a nationwide prospective study. Between April 2013 and January 2016, 1001 inpatients (360 males and 641 females) from 10 tertiary hospitals throughout South Korea were treated with herbal drugs and had their liver enzymes periodically measured. A total of six patients met the criteria for HILI with RUCAM scores ranging from 4 to 7. All these participants were women and developed the hepatocellular type of HILI. One HILI participant met the criteria for Hy's law; however, none of six cases presented clinical symptoms related to liver injury. This is the first nationwide prospective study that estimated the extent of the incidence of HILI [total: 0.60%, 95% confidence interval (CI) 0.12-1.08; women: 0.95%, 95% CI 0.19-1.68] and described its features in hospitalized participants.

Clinical and radiologic outcomes of arthroscopic suture bridge repair for the greater tuberosity fractures of the proximal humerus.

PURPOSE: To report the clinical and radiological outcomes of arthroscopic suture bridge repair for the GT fractures of the shoulder joint. METHODS: From March 2008 to July 2013, we performed arthroscopic suture bridge repair of the GT fractures displaced more than 5 mm superiorly or posteriorly, but less than 2 cm in 40 cases [20 men, 20 women; mean age, 56 (27-80) years] with the average 32 (24-48) months follow-up. At the final follow-up, clinical (ASES, UCLA, SST, KSS score and range of motions) and radiological outcomes using post-operative MRI or CT scan were evaluated. Associated injuries occurred in 21 cases (52.5%): 8 rotator cuff tears; 7 SLAP lesions; 3 glenoid rim fractures; 3 Bankart lesions; 5 biceps tendon tears; 1 partial subscapularis tear; 1 combined subscapularis and biceps tendon tear, and 1 brachial plexus injury. RESULTS: At the final follow-up, the mean VAS score improved from 7 to 1; ASES, to 92; UCLA, to 32; KSS, to 90; and SST, to 10. Mean forward flexion, abduction, external rotation at the side, and internal rotation at the back were improved to 157°, 157°, 37° and T11, respectively. Mean residual superior and posterior displacement of the fracture was 0 (range -5 to 3.3) mm and 0.1 (-5.5 to 3.2) mm, respectively, compared to pre-operative displacement of 4.9 (0-14) mm and 4.5 (0-20) mm, respectively (p < 0.001). Complications included anchor protrusion in five cases. CONCLUSION: Arthroscopic suture bridge repair was useful for the treatment of displaced GT fractures with or without comminution and the management of the combined lesions. At the final follow-up, meaningful remodeling of the GT fracture and satisfactory clinical outcomes could be achieved.

The Safety of Using Proximal Anteromedial Portals in Elbow Arthroscopy With Prior Ulnar Nerve Transposition.

PURPOSE: To report the safety of using the proximal anteromedial portal, using a simplified ulnar nerve management strategy derived from an earlier study, in a series of patients with previously transposed ulnar nerves. METHODS: A retrospective review of all elbow arthroscopies performed by a single surgeon from 2009 to 2014 was performed. The following techniques were used if, by palpation, localization of the ulnar nerve was considered to be certain (group 1) or uncertain (group 2): In group 1 (certain) the proximal anteromedial portal was established in the normal antegrade fashion. In group 2 (uncertain) a 1- to 3-cm incision was made at the planned proximal anteromedial portal site, and blunt dissection down to the capsule was performed without identification of the nerve. The nerve was not visualized but sometimes was palpated through the wound to confirm its location anteriorly or posteriorly. If there was a disparity between the prior operative records and the physical examination findings, the nerve was explored through a 3- to 4-cm incision. RESULTS: We reviewed 394 elbow arthroscopy cases, 22 of which had a prior transposed ulnar nerve (21 subcutaneous and 1 submuscular) that required anterior-compartment arthroscopic surgery. Group 1 (certain location) consisted of 9 elbows (41%), whereas group 2 (uncertain location) consisted of 13 (59%). In 2 cases in group 2, the ulnar nerve was explored because of the disparity between the previous medical records and the physical examination findings. There were no operative ulnar nerve injuries related to the use of the proximal anteromedial portal. CONCLUSIONS: The proximal anteromedial portal was able to be used safely in patients with prior transposition of the ulnar nerve. This was achieved by using an algorithm based on the degree of certainty with which the nerve can be localized in the region of the planned portal by clinical palpation. LEVEL OF EVIDENCE: Level IV, therapeutic case series.