Migration Of Head Research Articles

Nicotine-induced CHRNA5 activation modulates CES1 expression, impacting head and neck squamous cell carcinoma recurrence and metastasis via MEK/ERK pathway

The mucosal epithelium of the head and neck region (including the oral cavity, nasal cavity, pharynx, nasopharynx, and larynx) is the primary site exposed to tobacco smoke, and its presence of nicotinic acetylcholine receptors (nAChRs) has been observed in the mucosal epithelial cells of this area. It remains unclear whether HNSC cells can migrate and invade through nAChR signaling. A model of HNSC cells exposed to nicotine is established. Cell proliferation following nicotine exposure is assessed using the CCK-8 assay, while migration and invasion are evaluated through wound healing and Transwell assays. The effects of CHRNA5 knockdown and overexpression are also investigated. Immunofluorescence staining is used to analyze CHRNA5 expression and localization, and clonogenic assays are performed to measure colony proliferation after CHRNA5 knockdown and overexpression. The interaction between CHRNA5 and CES1 is examined using molecular docking, co-immunoprecipitation, and immunofluorescence. Differentially expressed genes are subjected to pathway enrichment analysis, and MEK/ERK protein expression and phosphorylation are validated via western blot. Tumor formation assays are performed in nude mice using sh-CHRNA5 Cal27 cells, followed by western blot and immunohistochemical staining. Additionally, laryngeal and hypopharyngeal cancer tissues are analyzed through immunohistochemistry. Nicotine significantly enhanced the proliferation, migration, and invasion capabilities of head and neck tumor cells, including Cal27, Fadu, HN6, and Tu686 cells, through the expression of CHRNA5. Knockdown of CHRNA5 can reduce cell migration, invasion, and proliferation, whereas nicotine exposure can reverse this trend. Additionally, the mRNA and protein expression of CES1 decreases with the knockdown of CHRNA5, indicating a regulatory relationship between the two. Transcriptomics revealed that the knockdown of CHRNA5 is associated with the MEK/ERK signaling pathway. Further cellular- and tissue-level evidence confirmed that the levels of p-MEK/MEK, p-ERK/ERK, and CES1 decreased following knockdown of CHRNA5, a trend that nicotine can reverse. Nicotine promotes the proliferation, migration, and invasion of HNSC by upregulating CHRNA5 expression. Knockdown of CHRNA5 reduces these effects, which can be reversed by nicotine. Nicotine exposure activates CHRNA5, regulating CES1 expression via the MEK/ERK pathway, contributing to the recurrence and metastasis of head and neck squamous carcinoma.

USP18 promotes the proliferation, invasion, and migration of head and neck squamous cell carcinoma by deubiquitinating PLK1

The ubiquitin specific peptidase 18 (USP18), a well-established deubiquitinase, has been extensively implicated in the malignant progression of various human tumors. However, its role in head and neck squamous cell carcinoma (HNSC) requires further investigation. Here, we revealed that USP18 was significantly upregulated in HNSC and knockdown of USP18 markedly suppressed tumor growth in vivo. Furthermore, silencing USP18 attenuated HNSC cell proliferation, invasion, and migration, while overexpression of USP18 exerted converse effects. Mechanistically, USP18 diminished K48-linked ubiquitination of polo-like kinase 1 (PLK1) to stabilize the protein through its deubiquitinase activity. Subsequently, we validated that USP18 modulated PLK1 to activate the mTORC1 pathway, thereby facilitating HNSC cell proliferation, invasion, and migration. In conclusion, our findings demonstrate that elevated expression of USP18 in HNSC cells promotes tumorigenesis by regulating the PLK1-mTORC1 pathway.

Long-term outcomes of acetabular impaction grafting with cemented cups and trabecular metal for revision hip arthroplasty: a follow-up study.

Revision hip arthroplasty in the presence of complex acetabular deficiencies is challenging. Cement, allograft, reconstruction rings and porous trabecular metal now provide versatile options for acetabular fixation and restoration of acetabular offset. We compare acetabular impaction bone grafting (AIBG) and trabecular metal (TM) cups at long-term follow-up. 53 patients who underwent revision hip arthroplasty were retrospectively reviewed from local joint registry data. 36 patients were revised using AIBG and 17 with TM. Median clinical follow-up was 9.57 (2.46-18.72) years and 9.65 (7.22-12.46) years, respectively. 82% of the TM group and 63% of the AIBG group were ⩾ Paprosky 2C. Re-revision was considered failure. Radiographs demonstrating 5 mm of femoral head migration and 5° of acetabular component inclination change were considered loose. Patients receiving AIBG were younger (68 vs. 74 years) with a longer interval from initial arthroplasty to revision (17 vs. 13 years). Revisions in both groups were indicated most commonly for failed cementing (AIBG 88.9% vs. TM 70.5%). No TM reconstructions underwent re-revision, with only 1 failing at 6.3 years, compared with 9 AIBG re-revisions. When revising for sepsis, 33% of AIBG revisions failed. AIBG demonstrated high failure rates at long-term follow-up when compared to TM constructs. We recommend the use of AIBG in small cavitary defects only. We strongly advise against its use in the setting of significant bony defects and for prosthetic joint infection.

Comparative clinical and radiographic results of three fixation systems for transverse subcapital osteotomy in treating hallux valgus

Objective: Compare three fixation models for Bosch osteotomy both clinically and radiographically.Methods: A retrospective comparative study was conducted on patients surgically treated for hallux valgus using Bosch osteotomywith three different fixation systems. The first group was treated with a temporary pin for three weeks; the second, received thesame pin plus a screw; and the third, used two screws without a pin. Radiographic analysis included the intermetatarsal angle,metatarsophalangeal angle, percentage of lateral shifting of the metatarsal head, dorsal or plantar migration of the metatarsal head,and consolidation time. Clinical evaluation was performed using the American Orthopaedic Foot and Ankle Society (AOFAS) scale.Complications during follow-up were recorded.Results: Twenty hallux valgus were included in each group. No significant differences were found in radiographic evaluations amonggroups in the preoperative and final follow-up, except that the third group showed less loss of correction. There were no significantdifferences in consolidation times. Clinical improvements were observed in all three fixation systems, with no significant differencesamong them according to the AOFAS scale.Conclusion: No significant clinical or radiographic differences were observed among the three fixation systems, except that the groupusing two screws showed less loss of correction. Level of evidence IV; Therapeutic studies; Case series.

Superior Capsular Reconstruction using the Long Head of Biceps Tendon: A Biomechanical Assessment of Tenodesis Location and Angle of Fixation

BackgroundMassive irreparable rotator cuff tears (MIRCT) treated with superior capsular reconstruction (SCR) using the long head of the biceps tendon have shown satisfactory early results. Different techniques and positions for biceps tenodesis have been described. This study aimed to evaluate the effect of tenodesis location and glenohumeral fixation angle for graft tensioning on the biomechanics of a SCR using a single strand biceps technique. MethodsEight cadaveric shoulders were mounted to a custom biomechanical simulator which employed static tone loads to the deltoid and rotator cuff muscles. All cadavers were first tested in the intact condition, and then in the simulated MIRCT condition by sectioning the tendinous insertions of the supraspinatus and upper border of the infraspinatus. SCR using the long head of the biceps tendon was then evaluated. Three biceps tenodesis locations relative to the greater tuberosity (anterior, middle, and posterior) and two glenohumeral fixation angles (0° and 30°) for graft tensioning were tested. An optical tracking system was used to quantify superior-inferior (SI) and anterior-posterior (AP) humeral head translation relative to the glenoid, while the functional abduction force was quantified using a load sensor. All tests were conducted at 0°, 30° and 60° of glenohumeral abduction in a randomized fashion. ResultsWhen assessing isolated superior humeral head migration, all biceps tenodesis locations were effective at decreasing superior migration, with no tenodesis location significantly better than the other (P=0.213). However, biceps grafts tensioned at 30° of glenohumeral abduction were significantly better at reducing proximal humeral migration as compared to graft tensioning at 0° abduction (P=0.008).Posterior humeral head translation observed in the MIRCT condition was significantly reduced when tensioning the biceps tendon at 30° of glenohumeral abduction compared to 0° for all tenodesis locations (P≤0.043). Tenodesis location also significantly influenced posterior humeral head translation (P=0.001), with middle and posterior positions restoring near normal humeral head position when fixed at 30° glenohumeral abduction. All SCR techniques using the biceps tendon improved the functional abduction force relative to the MIRCT condition, although no statistically significant differences were observed relative to the intact condition (P≥0.448). DiscussionSCR using the long head biceps tendon is biomechanically effective in reducing posterosuperior translation of the humeral head in the setting of a MIRCT. Graft tensioning and fixation at 30° of glenohumeral abduction combined with either a middle or posterior tenodesis location on the greater tuberosity most effectively restores near normal time-zero humeral head kinematics.

Fatigue-related changes in intermuscular electromyographic coherence across rotator cuff and deltoid muscles in individuals with and without subacromial pain.

Neuromuscular fatigue induces superior migration of the humeral head in individuals with subacromial pain. This has been attributed to weakness of rotator cuff muscles and overactive deltoid muscles. Investigation of common inputs to motoneuron pools of the rotator cuff and deltoid muscles offers valuable insight into the underlying mechanisms of neuromuscular control deficits associated with subacromial pain. This study aims to investigate intermuscular coherence across the rotator cuff and deltoid muscles during a sustained submaximal isometric fatiguing contraction in individuals with and without subacromial pain. Twenty symptomatic and 18 asymptomatic young adults participated in this study. Surface electromyogram (EMG) was recorded from the middle deltoid (MD) and infraspinatus (IS). Intramuscular EMG was recorded with fine-wire electrodes in the supraspinatus (SS). Participants performed an isometric fatiguing contraction of 30° scaption at 25% maximum voluntary contraction (MVC) until endurance limit. Pooled coherence of muscle pairs (SS-IS, SS-MD, IS-MD) in the 2-5 Hz (delta), 5-15 Hz (alpha), and 15-35 Hz (beta) frequency bands during the initial and final 30 s of the fatigue task were compared. SS-IS and SS-MD delta-band coherence increased with fatigue in the asymptomatic group but not the symptomatic group. In the alpha and beta bands, SS-IS and SS-MD coherence increased with fatigue in both groups. IS-MD beta-band coherence was greater in the symptomatic than the asymptomatic group. Individuals with subacromial pain failed to increase common drive across rotator cuff and deltoid muscles and have altered control strategies during neuromuscular fatigue. This may contribute to glenohumeral joint instability and subacromial pain experienced by these individuals.NEW & NOTEWORTHY Through the computation of shared neural drive across glenohumeral muscles, this study reveals that individuals with subacromial pain were unable to increase shared neural drive within the rotator cuff and across the supraspinatus and deltoid muscles during neuromuscular fatigue induced by sustained isometric contraction. These deficits in common drive across the shoulder muscles likely contribute to the joint instability and pain experienced by these individuals.

COVID-19 pandemic intensity, migration status, and household financial vulnerability: evidence from India

ABSTRACT This paper employs COVID-19 as a quasi-natural experiment to conduct an analysis of the heterogeneous effects of the pandemic on households’ financial vulnerability across districts in India and investigates the role of migration and gender of the household head in moderating financial vulnerability. Using Indian panel household surveys and a difference-in-differences approach with coarsened exact matching, we provide causal evidence of a larger increase in the financial vulnerability index (FVI) of households in Indian districts with a higher incidence of COVID-19 cases per capita. A similar effect is observed when considering satellite-based night-time lights, a proxy for economic activity. Furthermore, during the pandemic, households with an out-migrant family member experienced relatively lower FVI, with a more pronounced effect for female-headed households, likely due to the financial help given by migrants. However, households that had an out-migrant in the pre-pandemic period, but not during the pandemic, were more financially vulnerable. This study provides a novel contribution to the literature through a better understanding of the varied effects of the pandemic-induced health and economic shocks on households’ financial vulnerability based on pandemic intensity, migration status, and gender.

Muscle and joint function in the rotator cuff deficient shoulder.

Full-thickness rotator cuff tears can lead to poor coaptation of the humeral head to the glenoid, disrupting muscle forces required for glenohumeral joint stability, ultimately leading to joint subluxation. The aim of this study was to evaluate muscle forces and glenohumeral joint translations during elevation in the presence of isolated and combined full-thickness rotator cuff tears. Eight fresh-frozen upper limbs were mounted to a computer-controlled testing apparatus that simulated joint motion by simulated muscle force application. Scapular-plane abduction was performed, and glenohumeral joint translations were measured using an optoelectronic system. Testing was performed in the native shoulder, a following an isolated tear to the supraspinatus, as well as combined tears involving the supraspinatus and subscapularis, as well as supraspinatus, infraspinatus, and teres minor. Rotator cuff tears significantly increased middle deltoid force at 30°, 60°, and 90° of abduction relative to that in the native shoulder (p < 0.05). Significantly greater superior translations were observed relative to the intact shoulder due to combined tears to the supraspinatus and infraspinatus at 30° of abduction (mean increase: 1.6 mm, p = 0.020) and 60° of abduction (mean increase: 4.8 mm, p = 0.040). This study illustrates the infraspinatus-teres minor complex as a major humeral head depressor and contributor to glenohumeral joint stability. An increase in deltoid force during abduction occurs in the presence of rotator cuff tears, which exacerbates superior migration of the humeral head. The findings may help in the development of clinical tests in rotator cuff tear diagnostics, in surgical planning of rotator cuff repair, and in planning of targeted rehabilitation.

Angiopoietin-like 4 is upregulated by amphiregulin and activates cell proliferation and migration through p38 kinase in head and neck squamous cell carcinoma.

Angiopoietin-like 4 is a molecular hallmark that correlates with the growth and metastasis of head and neck squamous cell carcinoma, one of the most prevalent cancers worldwide. However, the molecular mechanisms by which angiopoietin-like 4 promotes head and neck squamous cell carcinoma tumorigenesis are unclear. Using well-characterized cell lines of head and neck squamous cell carcinoma development, including human normal oral keratinocytes, dysplastic oral keratinocytes, oral leukoplakia-derived oral keratinocytes, and head and neck squamous cell carcinoma cell lines, HN13, HN6, HN4, HN12, and CAL27, we investigated the signaling pathways upstream and downstream of angiopoietin-like 4-induced head and neck squamous cell carcinoma tumorigenesis. We found that both epidermal growth factor receptor ligands, epithelial growth factor, and amphiregulin led to angiopoietin-like 4 upregulation in normal oral keratinocytes and dysplastic oral keratinocytes and cooperated with the activation of hypoxia-inducible factor-1 in this effect. Interestingly, amphiregulin and angiopoietin-like 4 were increased in dysplastic oral keratinocytes and head and neck squamous cell carcinoma cell lines, and amphiregulin-induced activation of cell proliferation was dependent on angiopoietin-like 4. Although both p38 mitogen-activated protein kinases (p38 MAPK) and protein kinase B (AKT) were activated by angiopoietin-like 4, only pharmacological inhibition of p38 MAPK was sufficient to prevent head and neck squamous cell carcinoma cell proliferation and migration. We further observed that angiopoietin-like 4 promoted the secretion of interleukin 11 (IL-11), interleukin 12 (IL-12), interleukin-1 alpha (IL-1α), vascular endothelial growth factor, platelet-derived growth factor (PDGF), and tumour necrosis factor alpha (TNF-α), cytokines and chemokines previously implicated in head and neck squamous cell carcinoma pathogenesis. Our results demonstrate that angiopoietin-like 4 is a downstream effector of amphiregulin and promotes head and neck squamous cell carcinoma development both through direct activation of p38 kinase as well as paracrine mechanisms.

Endophenotypes of Primary Osteoarthritis of the Hip Joint in the Bulgarian Population over 60 Years Old.

Aim. To identify subgroups of patients with primary osteoarthritis of the hip joint (pHOA) with similar imaging and laboratory findings, disease evolution, and response to conventional therapies. Methods. We performed further statistical analyses on patient data from two published, double-blind, randomized, and placebo-controlled studies (DB-RCTs), which examined the effects of intra-articular corticosteroids (ia-CSs), hyaluronic acid (ia-HA)-KИ-109-3-0008/14.01.2014, and intravenous bisphosphonates (iv-BPs) -KИ- 109-3-0009/14.01.2014 compared to the country's standard pHOA therapy. The data span an 8-year follow-up of 700 patients with pHOA, including: 1. Clinical parameters (WOMAC-A, B, C, and T; PtGA). 2. Laboratory markers (serum calcium and phosphate levels; 25-OH-D and PTH, markers for bone sCTX-I and cartilage uCTX-II turnover). 3. Radiological indicators: X-ray stage (Kellgren-Lawrence (K/L) and model (Bombelli/OOARSI), width (mJSW), speed (JSN mm/year), and zone of maximum narrowing of the joint space (max-JSN)-determining the type of femoral head migration (FHM). 4. DXA indicators: bone geometry (HAL; NSA; and MNW); changes in regional and total bone mineral density (TH-BMD, LS-BMD, and TB-BMD). 5. Therapeutic responses (OARSI/MCII; mJSW; JSNmm/yearly) to different drug regimens (iv-BP -zoledronic acid (ZA/-5 mg/yearly for 3 years)); ia-CS 40 mg methylprednisolone acetate, twice every 6 months; and ia-HA with intermediate molecular weight (20 mg/2 mL × 3 weekly applications, two courses every 6 months) were compared to standard of care therapy (Standard of Care/SC/), namely D3-supplementation according to serum levels (20-120 ng/mL; target level of 60 ng/mL), simple analgesics (paracetamol, up to 2.0 g/24 h), and physical exercises. The abovementioned data were integrated into a non-supervised hierarchical agglomerative clustering analysis (NHACA) using Ward's linkage method and the squared Euclidean distance to identify different endophenotypes (EFs). Univariate and multivariate multinomial logistic regression analyses were performed to determine the impact of sex and FHM on clinical and radiographic regression of pHOA. Results. A baseline cluster analysis using incoming (M0) patient data identified three EFs: hypertrophic H-HOA, atrophic A-HOA, and intermediate I-HOA. These EFs had characteristics that were similar to those of patients grouped by radiographic stage and pattern ('H'-RPs, 'I'-RPs, and 'A'-RPs), p < 0.05). The repeated cluster analysis of M36 data identified four EF pHOAs: 1. Hypertrophic (slow progressors, the influence of the type of femoral head migration (FHM) outweighing the influence of sex on progression), progressing to planned total hip replacement (THR) within 5 (K/LIII) to 10 (K/LII) years. 2. Intermediate (sex is more important than the FHM type for progression) with two subgroups: 2#: male-associated (slow progressors), THR within 4 (K/LIII) to 8 years. (K/LII). 2* Female-associated (rapid progressors), THR within 3 (K/LIII) to 5 (K/LII) years. 3. Atrophic (rapid progressors; the influence of FHM type outweighs that of sex), THR within 2 (K/LIII) to 4 (K/LII) years. Each EF, in addition to the patient's individual progression rate, was also associated with a different response to the aforementioned therapies. Conclusions. Clinical endophenotyping provides guidance for a personalized approach in patients with pHOA, simultaneously assisting the creation of homogeneous patient groups necessary for conducting modern genetic and therapeutic scientific studies.

Aspartate β-Hydroxylase Is Upregulated in Head and Neck Squamous Cell Carcinoma and Regulates Invasiveness in Cancer Cell Models.

Aspartate β-hydroxylase (ASPH) is a protein associated with malignancy in a wide range of tumors. We hypothesize that inhibition of ASPH activity could have anti-tumor properties in patients with head and neck cancer. In this study, we screened tumor tissues of 155 head and neck squamous cell carcinoma (HNSCC) patients for the expression of ASPH using immunohistochemistry. We used an ASPH inhibitor, MO-I-1151, known to inhibit the catalytic activity of ASPH in the endoplasmic reticulum, to show its inhibitory effect on the migration of SCC35 head and neck cancer cells in cell monolayers and in matrix-embedded spheroid co-cultures with primary cancer-associated fibroblast (CAF) CAF 61137 of head and neck origin. We also studied a combined effect of MO-I-1151 and HfFucCS, an inhibitor of invasion-blocking heparan 6-O-endosulfatase activity. We found ASPH was upregulated in HNSCC tumors compared to the adjacent normal tissues. ASPH was uniformly high in expression, irrespective of tumor stage. High expression of ASPH in tumors led us to consider it as a therapeutic target in cell line models. ASPH inhibitor MO-I-1151 had significant effects on reducing migration and invasion of head and neck cancer cells, both in monolayers and matrix-embedded spheroids. The combination of the two enzyme inhibitors showed an additive effect on restricting invasion in the HNSCC cell monolayers and in the CAF-containing co-culture spheroids. We identify ASPH as an abundant protein in HNSCC tumors. Targeting ASPH with inhibitor MO-I-1151 effectively reduces CAF-mediated cellular invasion in cancer cell models. We propose that the additive effect of MO-I-1151 with HfFucCS, an inhibitor of heparan 6-O-endosulfatases, on HNSCC cells could improve interventions and needs to be further explored.

Double Row Rotator Cuff Repair for Massive Reparable Rotator Cuff Tear

Background: Massive rotator cuff tears, defined as those that involved 2 or more tendons or where the length of the greatest diameter is greater than 5 cm, present a unique surgical challenge as there can be significant scarring, retraction, and poor tissue quality. Furthermore, healing of these tears is less reliable. This video presents our technique for anatomic, double row repair of a massive reparable rotator cuff tear. Indications: Indications for operative intervention include acute traumatic tears, as well as patients with pain and weakness who have failed to respond to conservative management, including physical therapy with confirmed large full thickness rotator cuff tear on advanced imaging. Of note, findings such as glenohumeral osteoarthritis, advanced muscle atrophy (Goutalier III/IV), superior migration of the humeral head &gt;7 mm, and tears larger than 40 mm in length and width are concerning for irreparable tears, and may represent contraindications to surgical repair. Technique Description: The patient is placed in the lateral decubitus position. After diagnostic arthroscopy is performed, a subacromial bursectomy is performed. A radiofrequency probe and arthroscopic shaver are used to perform releases in the subacromial space as well as superior to the glenoid. Preparation of the footprint of the humeral head is then performed to create a good healing surface. The rotator cuff is grasped to confirm tension free mobilization. The medial row anchors are then placed. Once placed, the sutures are incorporated into 2 lateral row anchors in sequential fashion. Subacromial decompression is then performed. Results: Reduced pain and improved shoulder function are the goals of treatment, with sling immobilization lasting for roughly 6 weeks postoperatively prior to initiating strengthening and range of motion protocols. Discussion/Conclusion: Arthroscopic double row repair produces an anatomic and stable reduction of reparable massive rotator cuff tears for patients that have failed conservative management. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Inferior subscapularis and hypertrophic teres minor contribute to preventing superior migration of humeral head

Inferior subscapularis and hypertrophic teres minor contribute to preventing superior migration of humeral head

PLAU promotes cell proliferation and migration of head and neck cancer via STAT3 signaling pathway

It was reported that within the head and neck cancer (HNC) cell line CAL21 the epithelial-mesenchymal transition (EMT) and cell proliferation were promoted by Urokinase-Type Plasminogen Activator (PLAU) proteinase through TNFRSF12A. Additionally, in this paper HNC cell lines refer to Fadu and Tu686. A novel PLAU-STAT3 axis was found to be involved in HNC cell line proliferation and metastasis. PLAU expression in HNC samples was upregulated, besides, the elevated expression of PLAU was linked to the lower overall survival (OS) and disease-free survival (DFS). Ectopic PLAU expression promoted cell proliferation and migration, while PLAU knockdown exhibited opposite results. RNA-seq data identified the JAK-STAT signaling pathway, confirmed by western blotting. A recovery assay using S3I-201, a selective inhibitor of signal transducer and activator of transcription 3 (STAT3), indicated that PLAU promoted HNC cell line progression via STAT3 signaling in vitro. The oncogenic role of PLAU in HNC tumor growth in vivo was confirmed using xenograft models. In summary, we identified the tumorigenic PLAU function in the HNC progress. PLAU may represent a potential prognostic biomarker of HNC and the PLAU-STAT3 pathway might be considered a therapeutic target of HNC.

Combined Anterior Latissimus Dorsi and Teres Major Tendon Transfer (aLDTM) for Irreparable Anterosuperior Rotator Cuff Tears.

Transfer of the anterior latissimus dorsi and teres major (LDTM) tendons has demonstrated favorable outcomes in patients with irreparable anterosuperior rotator cuff tears1. The objective of this procedure is to restore internal rotation strength, enhance active range of motion, and provide pain relief while preserving the glenohumeral joint. The incision extended from the coracoid to the inferior border of the pectoralis major tendon, following the deltopectoral interval located laterally to the coracoid. While preserving the pectoralis major tendon, the latissimus dorsi (LD) and teres major (TM) tendons are identified and detached from the humerus without separating the tendons. The LDTM tendons are grasped, and nonabsorbable sutures are placed in a continuous running-locking suture fashion. Traction is applied to the sutures while bluntly releasing the adhesions surrounding the LDTM muscles in order to enable further mobilization and excursion. With the patient's arm positioned in full internal rotation and at 45° of abduction for physiological tensioning, the LDTM tendons are attached 2 cm distal to the lateral edge of the greater tuberosity and lateral to the biceps groove with use of 1 medial anchor and 3 lateral anchors. Arthroscopic partial repair, superior capsular reconstruction, pectoralis major tendon transfer, and isolated LD tendon transfer are potential alternative treatments. In cases in which these options are not feasible or have been unsuccessful, reverse total shoulder arthroplasty can be considered as a treatment option. Arthroscopic partial repair can provide pain relief, but its effectiveness in improving range of motion and muscle strength is limited2,3. Additionally, there is a high risk of retear, with reported rates as high as 52%4. Superior capsular reconstruction is considered a viable treatment, but it is not recommended in cases involving irreparable subscapularis tears5-7. Pectoralis major transfer may lead to less favorable clinical outcomes in cases in which an irreparable subscapularis tear and an irreparable supraspinatus tear are simultaneously present8-10. In cases of irreparable anterosuperior rotator cuff tears, the transfer of the LD tendon alone may not fully restore the superior migration and anterior subluxation of the humeral head.11. Reverse total shoulder arthroplasty may be another option in these cases, but it does not preserve the glenohumeral joint. The procedure involves stabilizing the superior translation of the humeral head by rebalancing the force couple, as the TM tendon exhibits scapulohumeral kinematics similar to the subscapularis tendon. Additionally, the procedure effectively reduces anterior glenohumeral subluxation through the combined effect of the posterior line of pull from the combined LDTM tendons and the scapulohumeral kinematics of the teres minor tendon. Also, by fixing the transferred LDTM tendons just distal to the greater tuberosity, the vector becomes less vertical, thereby preventing axillary nerve impingement and achieving appropriate tendon tensioning. The use of this procedure is supported by a study of 30 patients who were followed for a minimum of 2 years1. Significant improvements were observed in various scoring systems, including the pain VAS (visual analogue scale), Constant, ASES (American Shoulder and Elbow Surgeons), UCLA (University of California-Los Angeles), SANE (Single Assessment Numeric Evaluation), and ADLIR (Activities of Daily Living requiring active Internal Rotation) scores. Importantly, there was no significant progression of cuff tear arthropathy observed during the final follow-up. Additionally, preoperative anterior glenohumeral subluxation (15 of 30 patients) was restored in all patients after LDTM tendon transfer. Careful attention should be paid to the anterior humeral circumflex vessels to prevent bleeding.The radial nerve, passing through the anteroinferior surface of the LDTM tendons, should be carefully identified and protected to avoid iatrogenic injury.To maintain physiologic tension, the patient's arm should be positioned in full internal rotation and 45° of abduction.To avoid axillary nerve impingement, the LDTM tendons should be fixed just distal to the greater tuberosity and lateral to the biceps groove. SCR = superior capsular reconstructionLDTM = latissimus dorsi combined with teres majorASRCTs = anterosuperior rotator cuff tearsA/S = arthroscopicROM = range of motionTM = teres majorTm = teres minorLD = latissimus dorsiSSC = subscapularisSSP = supraspinatusPM = Pectoralis majorPm = Pectoralis minorRSA = reverse total shoulder arthroplastyASES = American Shoulder and Elbow SurgeonsUCLA = University of California-Los AngelesADLIR = Activities of Daily Living requiring active Internal RotationGT = greater tuberosityACR = anterior capsular reconstructionFF = forward flexionER = external rotationIR = internal rotationAHD = acromiohumeral distanceMRI = magnetic resonance imagingISP = infraspinatusPEEK = polyetheretherketonePOD = postoperative dayEMG = electromyographySD = standard deviationBMI = body mass indexDM = diabetes mellitusHTN = hypertensionVAS = visual analogue scaleSANE = Single Assessment Numeric EvaluationaROM =active range of motion.

Quality of life and clinical outcomes in severely involved cerebral palsy patients and spastic hips undergoing Castle surgery: a cross-sectional study.

As progressive hip dislocation causes pain in children with spastic cerebral palsy (CP) and spasticity needs surgical correction, we aimed to describe clinical and radiographic outcomes in CP patients with painful hip deformity treated with the Castle salvage procedure. We included all patients operated in the same hospital between 1989 and 2017 with painful spastic hips and femoral head deformity making joint reconstruction unfeasible. We collected clinical and functional data from medical records and evaluated radiographies to classify cases for femoral head shape and migration, type of deformity, spinal deformity, and heterotopic ossification. We investigated quality of life oneyear after surgery. We analyzed 41 patients (70 hips) with complete medical records. All had severe function compromise GMFCS V (Gross Motor Function Classification System) and heterotopic ossifications, all but one had scoliosis, and most had undergone other surgeries before Castle procedure. Patients were followed up for 77.1months (mean) after surgery. The mean initial migration index was 73%. Seven patients had complications, being three patients minor (two femur and one tibial fracture) and four majors (patients requiring surgical revision). Quality of life was considered improved by most of the carers (35 children; 85.3%) as level 4/5 according to CPCHILD instrument. No child was able to stand or walk, but moving in and out of bed, of vehicles, and to a chair, remaining seated, or visiting public places was "very easy." We considered most patients (37 patients-90%, 66 hips-94%) as having satisfactory outcomes because they had no or minor complications, absence of pain, free mobility of the lower limbs and were able to sit in a wheelchair.

Arthroscopic repair of large and massive rotator cuff tears-"sandwich augmentation" with the long head of the biceps tendon: a technical note.

For most shoulder surgeons, addressing massive rotator cuff tears that have retracted ends poses a significant challenge. This study introduces a technique, termed the "sandwich augmentation technique," which incorporates the long head of the biceps tendon (LHBT) into a single-row rotator cuff repair. The procedure, performed arthroscopically with the patient in the lateral decubitus position, involves attaching the LHBT and rotator cuff tissues together to the greater tuberosity. This effectively sandwiches them within the rotator cuff footprint. The goal of this technique is to enhance the thickness of the fully interposed cuff margin, thereby providing better support for the repair. The sandwich augmentation technique, which integrates the biceps into the rotator cuff repair, has demonstrated positive clinical outcomes and moderate anatomical results. It also prevents superior migration of the humeral head in cases of large or massive rotator cuff tears. Further research is required to assess the long-term effectiveness of this procedure.

Recurrent UBE3C-LRP5 translocations in head and neck cancer with therapeutic implications

Head and neck cancer is a major cause of morbidity and mortality worldwide. The identification of genetic alterations in head and neck cancer may improve diagnosis and treatment outcomes. In this study, we report the identification and functional characterization of UBE3C-LRP5 translocation in head and neck cancer. Our whole transcriptome sequencing and RT-PCR analysis of 151 head and neck cancer tumor samples identified the LRP5-UBE3C and UBE3C-LRP5 fusion transcripts in 5.3% of patients of Indian origin (n = 151), and UBE3C-LRP5 fusion transcripts in 1.2% of TCGA-HNSC patients (n = 502). Further, whole genome sequencing identified the breakpoint of UBE3C-LRP5 translocation. We demonstrate that UBE3C-LRP5 fusion is activating in vitro and in vivo, and promotes the proliferation, migration, and invasion of head and neck cancer cells. In contrast, depletion of UBE3C-LRP5 fusion suppresses the clonogenic, migratory, and invasive potential of the cells. The UBE3C-LRP5 fusion activates the Wnt/β-catenin signaling by promoting nuclear accumulation of β-catenin, leading to upregulation of Wnt/β-catenin target genes, MYC, CCND1, TCF4, and LEF1. Consistently, treatment with the FDA-approved drug, pyrvinium pamoate, significantly reduced the transforming ability of cells expressing the fusion protein and improved survival in mice bearing tumors of fusion-overexpressing cells. Interestingly, fusion-expressing cells upon knockdown of CTNNB1, or LEF1 show reduced proliferation, clonogenic abilities, and reduced sensitivity to pyrvinium pamoate. Overall, our study suggests that the UBE3C-LRP5 fusion is a promising therapeutic target for head and neck cancer and that pyrvinium pamoate may be a potential drug candidate for treating head and neck cancer harboring this translocation.

IL-8 activates fibroblasts to promote the invasion of HNSCC cells via STAT3-MMP1

Matrix metalloproteinase-1 (MMP1) has an aberrant expression relevant to various behaviors of cancers. As dominant components of the tumor stroma, fibroblasts constitute an important source of Matrix metalloproteinase (MMPs) including mainly MMP1. The impacts of MMP1 derived from fibroblasts in tumor microenvironment, however, is not well defined. In this study, we demonstrated a part of crosstalk between fibroblasts and cancer cells that enhanced the invasiveness of cancer cells, IL8-induced activation of STAT3 signaling pathway as a key promoter to elevated MMP1 level in fibroblasts that supports the migration and invasion of head and neck squamous cell carcinoma (HNSCC) cells by extracellular matrix degradation. Importantly, once exposed to the inhibitor of STAT3 phosphorylation (TPCA-1), the enhanced induction of HNSCC cells invasion triggered by fibroblasts was significantly impaired.

Anterior Latissimus Dorsi Transfer for Irreparable Subscapularis Tears Improves Shoulder Kinematics in a Dynamic Biomechanical Cadaveric Shoulder Model

Background: In young patients with irreparable subscapularis deficiency (SSC-D) and absence of severe osteoarthritis, anterior latissimus dorsi transfer (aLDT) has been proposed as a treatment option to restore the anteroposterior muscular force couple to regain sufficient shoulder function. However, evidence regarding the biomechanical effect of an aLDT on glenohumeral kinematics remains sparse. Purpose/Hypothesis: The purpose of this study was to investigate the effects of an aLDT on range of glenohumeral abduction motion, superior migration of the humeral head (SM), and cumulative deltoid force (cDF) in a simulated SSC-D model using a dynamic shoulder model. It was hypothesized that an aLDT would restore native shoulder kinematics by reestablishing the insufficient anteroposterior force couple. Study Design: Controlled laboratory study. Methods: Eight fresh-frozen cadaveric shoulders were tested using a validated shoulder simulator. Glenohumeral abduction angle (gAA), SM, and cDF were compared across 3 conditions: (1) native, (2) SSC-D, and (3) aLDT. gAA and SM were measured using 3-dimensional motion tracking, while cDF was recorded in real time during dynamic abduction motion by load cells connected to actuators. Results: The SSC-D significantly decreased gAA (Δ–9.8°; 95% CI, –14.1° to −5.5°; P < .001) and showed a significant increase in SM (Δ2.0 mm; 95% CI, 0.9 to 3.1 mm; P = .003), while cDF was similar (Δ7.8 N; 95% CI, –9.2 to 24.7 N; P = .586) when compared with the native state. Performing an aLDT resulted in a significantly increased gAA (Δ3.8°; 95% CI, 1.8° to 5.7°; P < .001), while cDF (Δ–36.1 N; 95% CI, –48.7 to −23.7 N; P < .001) was significantly reduced compared with the SSC-D. For the aLDT, no anterior subluxation was observed. However, the aLDT was not able to restore native gAA (Δ–6.1°; 95% CI, –8.9° to −3.2°; P < .001). Conclusion: In this cadaveric study, performing an aLDT for an irreparable subscapularis insufficiency restored the anteroposterior force couple and prevented superior and anterior humeral head migration, thus improving glenohumeral kinematics. Furthermore, compensatory deltoid forces were reduced by performing an aLDT. Clinical Relevance: Given the favorable effect of the aLDT on shoulder kinematics in this dynamic shoulder model, performing an aLDT may be considered as a treatment option in patients with irreparable SSC-D.