Distal Biceps Tendon Repair Using a Double Intracortical Button Anatomical Footprint Repair Technique.

INTRODUCTION: Distal biceps tendon repair is usually performed via a double-incision or single-incision bicortical drilling technique. However, these techniques are associated with specific complications and usually do not allow for anatomical footprint restoration. It was the aim of this study to report the clinical results of a double intracortical button anatomical footprint repair technique for distal biceps tendon tears. We hypothesized that this technique would result in supination strength comparable to the uninjured side with a low re-rupture rate and minimal bony or neurological complications. MATERIAL AND METHODS: This was a retrospective, single-surgeon cohort study of a consecutive series of 22 patients with a mean (SD) age of 50.7 (9.4) years and at least 1-year follow-up after distal biceps tendon repair. At final follow-up, complications, range of motion (ROM), the Patient-rated Elbow Evaluation (PREE), Mayo Elbow Performance Score (MEPS), Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, visual analog scale (VAS) for pain, patient satisfaction and supination strength in neutral as well as 60° of supination were analyzed. Radiographic evaluation was performed on a CT scan. RESULTS: One patient (4.5%) experienced slight paresthesia in the area of the lateral antebrachial cutaneous nerve. Heterotopic ossification was seen in one patient (4.5%). All patients recovered full ROM except for one who had 10° of loss of flexion and extension. Median PREE score was 4.6 (0-39.6), median MEP was 100 (70-100) and median DASH was 1.4 (0-16.7). All but one patient were very satisfied with the outcome. The affected arm had a mean of 98% (± 13) of neutral supination strength (p=0.633) and 94% (± 12) of supination strength in 60° (p=0.054) compared to the contralateral, unaffected side. There were four cases (18.2%) of cortical thinning due to at least one button and one case of button pull-out (4.5%). CONCLUSIONS: The double intracortical button anatomical footprint repair technique seems to provide reliable restoration of supination strength, excellent patient satisfaction while minimizing complications, particularly nerve damage and heterotopic ossification.

Current Evidence Regarding Shoulder Instability in the Paediatric and Adolescent Population.

Paediatric and adolescent shoulder instability is caused by a unique combination of traumatic factors, ligamentous laxity, and pattern of muscle contractility. The multifactorial nature of its aetiology makes interpretation of the literature difficult as nomenclature is also highly variable. The purpose of this review is to summarize the existing literature and shed light on the nuances of paediatric and adolescent shoulder instability. The epidemiology, clinical features, imaging, and management of all forms of paediatric shoulder instability are presented. The main findings of this review are that structural abnormalities following a dislocation are uncommon in pre-pubertal paediatric patients. Young post-pubertal adolescents are at the highest risk of failure of non-operative management in the setting of traumatic instability with structural abnormality, and early stabilisation should be considered for these patients. Remplissage and the Latarjet procedure are safe treatment options for adolescents at high risk of recurrence, but the side-effect profile should be carefully considered. Patients who suffer from instability due to generalized ligamentous laxity benefit from a structured, long-term physiotherapy regimen, with surgery in the form of arthroscopic plication as a viable last resort. Those who suffer from a predominantly muscle patterning pathology do not benefit from surgery and require focus on regaining neuromuscular control.

Clinical Outcomes Following Surgical Management of Post-Traumatic Elbow Contractures in the Pediatric Age Group: A Meta-Analysis and Systematic Review.

PURPOSE: Post-traumatic elbow stiffness is a common occurrence resulting in potentially substantial functional limitations in both daily activities and recreational endeavors. In children, this can be particularly difficult given the early stages of childhood and development and the challenges of rehabilitation. Several studies have reported favorable results of elbow contracture releases in children, resulting in improvements in outcomes. This meta-analysis aimed to determine the efficacy and safety of elbow contracture releases in the pediatric population (<18 years), along with subgroup analyses comparing age groups, operative approach, and post-traumatic versus nontraumatic etiologies. METHODS: Meta-analysis was performed with a multidatabase search (PubMed, OVID, EMBASE, and Medline) according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines on September 25, 2020. Data from all published literature meeting inclusion criteria were extracted and analyzed. RESULTS: Seven studies were included, comprising 114 post-traumatic elbow contractures. Mean age was 13.7 years. Contracture releases of the elbow led to improvements in flexion-extension arc of motion by 48º, and pronosupination arc of motion by 22º. Subgroup analysis comparing age groups of <10, 10-14 and 15-18 years showed greater improvements in flexion-extension arc in the older age group, whereas subgroup analysis comparing injury patterns revealed a larger improvement in pronosupination motion for radial head fractures. Comparing open and arthroscopic procedures, open releases had greater improvement in both flexion-extension and pronosupination motion by 18º and 21º, respectively, although there were limited patients in the arthroscopy group. CONCLUSION: Operative management of pediatric elbow contractures is effective. Older children, children with radial head fractures, and those receiving open contracture releases may be more likely to have greater improvements. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Natural History of Quantitative Fatty Infiltration and 3D Muscle Volume After Nonoperative Treatment of Symptomatic Rotator Cuff Tears: A Prospective MRI Study of 79 Patients.

BACKGROUND: The severity of fatty infiltration (FI) predicts the treatment outcome of rotator cuff tears. The purpose of this investigation was to quantitatively analyze supraspinatus (SSP) muscle FI and volume at the initial presentation and after a 3-month minimum of conservative management. We hypothesized that progression of FI could be predicted with initial tear size, FI, and muscle volume. METHODS: Seventy-nine shoulders with rotator cuff tears were prospectively enrolled, and 2 magnetic resonance imaging (MRI) scans with 6-point Dixon sequences were acquired. The fat fraction within the SSP muscle was measured on 3 sagittal slices, and the arithmetic mean was calculated (FI SSP ). Advanced FI SSP was defined as ≥8%, pathological FI SSP was defined as ≥13.5%, and relevant progression was defined as a ≥4.5% increase in FI SSP . Furthermore, muscle volume, tear location, size, and Goutallier grade were evaluated. RESULTS: Fifty-seven shoulders (72.2%) had normal FI SSP , 13 (16.5%) had advanced FI SSP , and 9 (11.4%) had pathological FI SSP at the initial MRI scan. Eleven shoulders (13.9%) showed a ≥4.5% increase in FI SSP at 19.5 ± 14.7 months, and 17 shoulders (21.5%) showed a ≥5-mm 3 loss of volume at 17.8 ± 15.3 months. Five tears (7.1%) with initially normal or advanced FI SSP turned pathological. These tears, compared with tears that were not pathological, had significantly higher initial mediolateral tear size (24.8 compared with 14.3 mm; p = 0.05), less volume (23.5 compared with 34.2 mm 3 ; p = 0.024), more FI SSP (9.6% compared with 5.6%; p = 0.026), and increased progression of FI SSP (8.6% compared with 0.5%; p < 0.001). An initial mediolateral tear size of ≥20 mm yielded a relevant FI SSP progression rate of 81.8% (odds ratio [OR], 19.0; p < 0.001). Progression rates of 72.7% were found for both initial FI SSP of ≥9.9% (OR, 17.5; p < 0.001) and an initial anteroposterior tear size of ≥17 mm (OR, 8.0; p = 0.003). Combining these parameters in a logistic regression analysis led to an area under the receiver operating characteristic curve (AUC) of 0.913. The correlation between FI SSP progression and the time between MRI scans was weak positive (ρ = 0.31). CONCLUSIONS: Three risk factors for relevant FI progression, quantifiable on the initial MRI, were identified: ≥20-mm mediolateral tear size, ≥9.9% FI SSP , and ≥17-mm anteroposterior tear size. These thresholds were associated with a higher risk of tear progression: 19 times higher for ≥20-mm mediolateral tear size, 17.5 times higher for ≥9.9% FI SSP , and 8 times higher for ≥17-mm anteroposterior tear size. The presence of all 3 yielded a 91% chance of ≥4.5% progression of FI SSP within a mean of 19.5 months. LEVEL OF EVIDENCE: Diagnostic Level II . See Instructions for Authors for a complete description of levels of evidence.

1,4-dihydroxy quininib activates ferroptosis pathways in metastatic uveal melanoma and reveals a novel prognostic biomarker signature.

Uveal melanoma (UM) is an ocular cancer, with propensity for lethal liver metastases. When metastatic UM (MUM) occurs, as few as 8% of patients survive beyond two years. Efficacious treatments for MUM are urgently needed. 1,4-dihydroxy quininib, a cysteinyl leukotriene receptor 1 (CysLT1) antagonist, alters UM cancer hallmarks in vitro, ex vivo and in vivo. Here, we investigated the 1,4-dihydroxy quininib mechanism of action and its translational potential in MUM. Proteomic profiling of OMM2.5 cells identified proteins differentially expressed after 1,4-dihydroxy quininib treatment. Glutathione peroxidase 4 (GPX4), glutamate-cysteine ligase modifier subunit (GCLM), heme oxygenase 1 (HO-1) and 4 hydroxynonenal (4-HNE) expression were assessed by immunoblots. Biliverdin, glutathione and lipid hydroperoxide were measured biochemically. Association between the expression of a specific ferroptosis signature and UM patient survival was performed using public databases. Our data revealed that 1,4-dihydroxy quininib modulates the expression of ferroptosis markers in OMM2.5 cells. Biochemical assays validated that GPX4, biliverdin, GCLM, glutathione and lipid hydroperoxide were significantly altered. HO-1 and 4-HNE levels were significantly increased in MUM tumor explants from orthotopic patient-derived xenografts (OPDX). Expression of genes inhibiting ferroptosis is significantly increased in UM patients with chromosome 3 monosomy. We identified IFerr, a novel ferroptosis signature correlating with UM patient survival. Altogether, we demontrated that in MUM cells and tissues, 1,4-dihydroxy quininib modulates key markers that induce ferroptosis, a relatively new type of cell death driven by iron-dependent peroxidation of phospholipids. Furthermore, we showed that high expression of specific genes inhibiting ferroptosis is associated with a worse UM prognosis, thus, the IFerr signature is a potential prognosticator for which patients develop MUM. All in all, ferroptosis has potential as a clinical biomarker and therapeutic target for MUM.

Hypoxia induces a glycolytic complex in intestinal epithelial cells independent of HIF-1-driven glycolytic gene expression.

The metabolic adaptation of eukaryotic cells to hypoxia involves increasing dependence upon glycolytic adenosine triphosphate (ATP) production, an event with consequences for cellular bioenergetics and cell fate. This response is regulated at the transcriptional level by the hypoxia-inducible factor-1(HIF-1)-dependent transcriptional upregulation of glycolytic enzymes (GEs) and glucose transporters. However, this transcriptional upregulation alone is unlikely to account fully for the levels of glycolytic ATP produced during hypoxia. Here, we investigated additional mechanisms regulating glycolysis in hypoxia. We observed that intestinal epithelial cells treated with inhibitors of transcription or translation and human platelets (which lack nuclei and the capacity for canonical transcriptional activity) maintained the capacity for hypoxia-induced glycolysis, a finding which suggests the involvement of a nontranscriptional component to the hypoxia-induced metabolic switch to a highly glycolytic phenotype. In our investigations into potential nontranscriptional mechanisms for glycolytic induction, we identified a hypoxia-sensitive formation of complexes comprising GEs and glucose transporters in intestinal epithelial cells. Surprisingly, the formation of such glycolytic complexes occurs independent of HIF-1-driven transcription. Finally, we provide evidence for the presence of HIF-1α in cytosolic fractions of hypoxic cells which physically interacts with the glucose transporter GLUT1 and the GEs in a hypoxia-sensitive manner. In conclusion, we provide insights into the nontranscriptional regulation of hypoxia-induced glycolysis in intestinal epithelial cells.

Medial Femoral Condyle Corticoperiosteal Flap for Failed Total Wrist Fusions.

Background Recalcitrant nonunion following total wrist arthrodesis is a rare but challenging problem. Most commonly, in the setting of failed fusion after multiple attempts of refixation and cancellous bone grafting, the underlying cause for the failure is invariably multifactorial and is often associated with a range of host issues in addition to poor local soft-tissue and bony vascularity. The vascularized medial femoral condyle corticoperiosteal (MFC-CP) flap has been shown to be a viable option in a variety of similar settings, which provides vascularity and rich osteogenic progenitor cells to a nonunion site, with relatively low morbidity. While its utility has been described for many other anatomical locations throughout the body, its use for the treatment of failed total wrist fusions has not been previously described in detail in the literature. Methods In this article, we outline in detail the surgical technique for MFC-CP flap for the management of recalcitrant aseptic nonunions following failed total wrist arthrodesis. We discuss indications and contraindications, pearls and pitfalls, and potential complications of this technique. Results Two illustrative cases are presented of patients with recalcitrant nonunions following multiple failed total wrist fusions. Conclusion When all avenues have been exhausted, a free vascularized corticoperiosteal flap from the MFC is a sound alternative solution to achieve union, especially when biological healing has been compromised. We have been able to achieve good clinical outcomes and reliable fusion in this difficult patient population.

Systematic discovery of gene fusions in pediatric cancer by integrating RNA-seq and WGS.

BACKGROUND: Gene fusions are important cancer drivers in pediatric cancer and their accurate detection is essential for diagnosis and treatment. Clinical decision-making requires high confidence and precision of detection. Recent developments show RNA sequencing (RNA-seq) is promising for genome-wide detection of fusion products but hindered by many false positives that require extensive manual curation and impede discovery of pathogenic fusions. METHODS: We developed Fusion-sq to overcome existing disadvantages of detecting gene fusions. Fusion-sq integrates and "fuses" evidence from RNA-seq and whole genome sequencing (WGS) using intron-exon gene structure to identify tumor-specific protein coding gene fusions. Fusion-sq was then applied to the data generated from a pediatric pan-cancer cohort of 128 patients by WGS and RNA sequencing. RESULTS: In a pediatric pan-cancer cohort of 128 patients, we identified 155 high confidence tumor-specific gene fusions and their underlying structural variants (SVs). This includes all clinically relevant fusions known to be present in this cohort (30 patients). Fusion-sq distinguishes healthy-occurring from tumor-specific fusions and resolves fusions in amplified regions and copy number unstable genomes. A high gene fusion burden is associated with copy number instability. We identified 27 potentially pathogenic fusions involving oncogenes or tumor-suppressor genes characterized by underlying SVs, in some cases leading to expression changes indicative of activating or disruptive effects. CONCLUSIONS: Our results indicate how clinically relevant and potentially pathogenic gene fusions can be identified and their functional effects investigated by combining WGS and RNA-seq. Integrating RNA fusion predictions with underlying SVs advances fusion detection beyond extensive manual filtering. Taken together, we developed a method for identifying candidate gene fusions that is suitable for precision oncology applications. Our method provides multi-omics evidence for assessing the pathogenicity of tumor-specific gene fusions for future clinical decision making.

Stereotactic Body Radiation Therapy With or Without Transarterial Chemoembolization Versus Transarterial Chemoembolization Alone in Early-Stage Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

PURPOSE: This study aims to review the current evidence on the utility of stereotactic body radiation therapy (SBRT), with or without transarterial chemoembolization (TACE), for early-stage hepatocellular carcinoma (ESHCC) patients not amenable to standard curative treatment options. METHODS: Literature search was conducted using PubMed, ScienceDirect, and Google Scholar. Comparative studies reporting oncologic outcomes were included in the review. RESULTS: Five studies (one phase II randomized controlled trial, one prospective cohort, three retrospective studies) compared SBRT versus TACE. Pooled analysis showed an overall survival (OS) benefit after 3 years (OR 1.65, 95% CI 1.17-2.34, p = 0.005) which persisted in the 5-year data (OR 1.53, 95% CI 1.06-2.22, p = 0.02) in favor of SBRT. RFS benefit with SBRT was also seen at 3 years (OR 2.06, 95% CI 1.03-4.11, p = 0.04) which continued after 5 years (OR 2.35, 95% CI 1.47-3.75, p = 0.0004). Pooled 2-year local control (LC) favored SBRT over TACE (OR 2.96, 95% CI 1.89-4.63, p < 0.00001). Two retrospective studies compared TACE + SBRT versus TACE alone. Pooled analysis showed significantly improved 3-year OS (OR 5.47; 95% CI 2.47-12.11, p < 0.0001) and LC (OR: 21.05; 95% CI 5.01-88.39, p ≤ 0.0001) in favor of the TACE + SBRT group. A phase III study showed significantly improved LC and PFS with SBRT after failed TACE/TAE versus further TACE/TAE. CONCLUSIONS: Taking into account the limitations of the included studies, our review suggests significantly improved clinical outcomes in all groups having SBRT as a component of treatment versus TACE alone or further TACE. Larger prospective studies are warranted to further define the role of SBRT and TACE for ESHCC.

Teleconsultation Perceptions of Medical and Radiation Oncologists in the COVID-19 and Post-COVID-19 Era: A National Survey in the Philippines.

PURPOSE: The study reports on the current perception of medical and radiation oncologists regarding teleconsultation in the Philippines. Before the COVID-19 pandemic, the adoption of telemedicine was not widespread. With movement restrictions imposed during the pandemic, physicians were compelled to use telemedicine. It is uncertain whether physicians will still adopt its use in practice in the post-COVID-19 era. This study gives insight into the possible adaptation of this mode of consultation in the future, especially in areas with limited health care resources. MATERIALS AND METHODS: We conducted a national survey among medical oncologists and radiation oncologists in the Philippines. A 43-item online survey was developed, validated, and administered to the oncologists. The demographics and data from categorical questions were reported as frequencies and percentages. RESULTS: A total of 142 responses were gathered from 82 medical oncologists and 60 radiation oncologists. There was agreement among participants that, during the pandemic, teleconsultation could be used for the first visit, diagnostic workup request, treatment explanation, follow-up care, and chronic disease management. There was disagreement whether cancer diagnosis disclosure and cancer prognosis revelation could be performed via teleconsultation, and there was agreement that emergency consultation and physical examination would warrant a face-to-face consultation. After the COVID-19 pandemic, 78.7% intend to continue using teleconsultation except for emergency consultations, first visits, physical examination, diagnosis disclosure, and cancer prognosis revelation. CONCLUSION: Teleconsultation was perceived by oncologists as an acceptable method of providing cancer care during and after the COVID-19 pandemic. Oncologists also intend to use teleconsultation in the post-COVID-19 era in certain aspects of patient care.

Biomechanical Comparison of Distal Biceps Tendon Repair Techniques: Extracortical Single-Button Inlay Fixation Versus Intracortical Double-Button Onlay Anatomic Footprint Fixation.

BACKGROUND: Extracortical single-button (SB) inlay repair is a commonly used distal biceps tendon technique. However, complications (eg, neurovascular injury) and nonanatomic repairs have led to the development of intracortical fixation techniques. PURPOSE: To compare the biomechanical stability of extracortical SB repair with an anatomic intracortical double-button (DB) repair technique. STUDY DESIGN: Controlled laboratory study. METHODS: The distal biceps tendon was transected in 18 cadaveric elbows from 9 donors. One elbow of each donor was randomly assigned to the extracortical SB or anatomic DB group. Both groups were cyclically loaded with 60 N over 1000 cycles between 90° of flexion and full extension. The elbow was then fixed in 90° of flexion and the repair construct loaded to failure. Gap formation and construct stiffness during cyclic loading and ultimate load to failure were analyzed. RESULTS: When compared with the extracortical SB technique after 1000 cycles, the anatomic DB technique showed significantly less gap formation (mean ± SD, 2.7 ± 0.8 vs 1.5 ± 0.9 mm; P = .017) and significantly more construct stiffness (87.4 ± 32.7 vs 119.9 ± 31.6 N/mm; P = .023). Ultimate load to failure was not significantly different between the groups (277 ± 93 vs 285 ± 135 N; P = .859). The failure mode in the anatomic DB group was significantly different from that of the extracortical SB technique (P = .002) and was due to fracture avulsion of the cortical button in 7 of 9 specimens (vs none in the SB group). CONCLUSION: Our study shows that the intracortical DB technique produces equivalent or superior biomechanical performance to that of the SB technique. The DB technique may offer a clinically viable alternative to the SB repair technique. CLINICAL RELEVANCE: This study suggests, at worst, an equivalent and, at best, a superior biomechanical performance of intracortical anatomic DB footprint repair at the time of surgery. However, the mode of failure suggests that this technique should not be used in patients with poor bone quality.

Technical details and clinical outcomes after high-dose-rate intracavitary brachytherapy for squamous cell carcinoma of external auditory canal and external beam radiotherapy for nodal coverage: A case report.

Purpose: To report technical details and 15-month outcomes of a patient with node-positive external auditory canal (EAC) squamous cell carcinoma (SCC) treated with definitive intracavitary high-dose-rate (HDR) brachytherapy to primary tumor, and external beam radiotherapy (EBRT) to draining lymphatics. Material and methods: A 21-year-old male was diagnosed with SCC of the right EAC. The patient underwent definitive HDR intracavitary brachytherapy, 340 cGy/fraction for 14 twice-daily fractions, followed by EBRT using intensity-modulated radiation therapy (IMRT) to cover the grossly enlarged pre-auricular node, ipsilateral intra-parotid, and cervical lymph node levels II and III. Results: The approved brachytherapy plan had an average high-risk clinical tumor volume (CTV-HR) D90 of 341 cGy with a total dose of 47.7 Gy (BED, 80.3 Gy, EQD2, 66.6 Gy). For the approved IMRT plan, the prescription to the involved right pre-auricular node was 66 Gy in 33 fractions, and more than 95% of the target received at least 62.7 Gy. High-risk nodal regions were simultaneously prescribed: 59.4 Gy in 1.8 Gy fractions, and more than 95% received at least 56.4 Gy. Organs at risk (OARs) were kept below their dose constraints.The patient tolerated both the procedures with no grade ≥ 2 treatment-related adverse events. Grade 1 dermatitis in the right pre-auricular and cervical areas during the course of EBRT was experienced. Fifteen months post-RT, the patient has no evidence of disease, and was noted to have EAC stenosis, which translated to moderate conductive hearing loss of the right ear. Thyroid function was normal at 15 months after EBRT. Conclusions: This case report illustrates that the delivered definitive radiotherapy is technically feasible, effective, and well-tolerated in patients with SCC of EAC.

Biomechanical analysis of plating techniques for unstable lateral clavicle fractures with coracoclavicular ligament disruption (Neer type IIB).

BACKGROUND: Neer type IIB lateral clavicle fractures are inherently unstable fractures with associated disruption of the coracoclavicular (CC) ligaments. Because of the high rate of nonunion and malunion, surgical fixation is recommended; however, no consensus has been reached regarding the optimal fixation method. A new plating technique using a superior lateral locking plate with anteroposterior (AP) locking screws, resulting in orthogonal fixation in the lateral fragment, has been designed to enhance stability and reduce implant failure. The purpose of this study was to biomechanically compare 3 different clavicle plating constructs within a fresh frozen human cadaveric shoulder model. METHODS: Twenty-four fresh frozen cadaveric shoulders were randomized into 3 groups (n = 8 specimens): group 1, lateral locking plate only (Medartis Aptus Superior Lateral Plate); group 2, lateral locking plate with CC stabilization (No. 2 FiberWire); and group 3, lateral locking plate with 2 AP locking screws stabilizing the lateral fragment. All specimens were subject to cyclic loading of 70 N for 500 cycles. Data were analyzed for gap formation after cyclic loading, construct stiffness, and ultimate load to failure, defined by a marked decrease in the load displacement curve. RESULTS: After 500 cycles, there was no statistically significant difference between the 3 groups in gap formation (P = .179). No specimen (0/24) failed during cyclic loading. Ultimate load to failure was significantly higher in group 3 compared to group 1 (286 N vs. 167 N; P = .022), but not to group 2 (286 N vs. 246 N; P = .604). There were no statistically significant differences in stiffness (group 1: 504 N/mm; group 2: 564 N/mm; group 3: 512 N/mm; P = .712). Peri-implant fracture was the primary mode of failure for all 3 groups, with group 3 demonstrating the lowest rate of peri-implant fractures (group 1: 6/8; group 2: 7/8; group 3: 4/8; P = .243). CONCLUSION: Biomechanical evaluation of the clavicle plating techniques showed effective fixation across all specimens at 500 cycles. The lateral locking plate with orthogonal AP locking screw fixation in the lateral fragment demonstrated the greatest ultimate failure load, followed by the lateral locking plate with CC stabilization. This new plating technique showed compatible stiffness and gap formation when compared to conventional lateral locking plates as well as plates with CC fixation. The use of orthogonal screw fixation in the distal fragment may negate against the need for CC stabilization in these types of fractures, thus minimizing surgical dissection around the coracoid and potential complications.

Clinical outcomes of single application multi-fractionated CT-guided interstitial high-dose-rate brachytherapy for locally advanced cervical cancer: A multi-institution initial experience.

Purpose: The aim of the study was to evaluate the safety and clinical outcomes of single application multi-fractionated computed tomography (CT)-guided interstitial high-dose-rate brachytherapy given in four fractions in locally advanced cervical cancer. Material and methods: Patients with locally advanced cervical cancer stage IIB-IVA treated definitively with external radiation ± weekly cisplatin, followed by single application multi-fractionated CT-guided interstitial high-dose-rate brachytherapy in four fractions were included. Dosimetry data, clinical response, and toxicity records were reviewed. Results: Between January 2018 and December 2022, twenty-two patients were included. Clinical stage distribution was as follows: IIB - 13.6%, IIIB - 27.3%, IIIC - 22.7%, and IVA - 36.4%. Mean high-risk clinical target volume (HR-CTV) was 66.19 ±32.69 cm3, and HR-CTV D90 dose was 86.8 ±1.7 Gy. 2 cc doses to bladder, rectum, and sigmoid were 84.6 ±2.8 Gy, 71.5 ±2.4 Gy, and 65.6 ±4.0 Gy, respectively. Mean overall treatment time was 66 ±21 days. With a median follow-up of 11.5 months (range, 5-44 months), median survival and local control were not achieved. One-year local control rate, one-year progression-free survival, and one-year overall survival were 82%, 66%, and 78%, respectively. Univariate analysis showed overall treatment time to be the only variable associated with all oncologic outcomes. For acute toxicity, grade 3 toxicity in four patients and grade 4 toxicity of infection in one patient were observed. For late toxicity, grade 3 gastrointestinal toxicity was noted in two patients. Conclusions: Initial results suggest that single application multi-fractionated CT-guided interstitial brachytherapy given in four fractions in locally advanced cervical cancer seems to be feasible and safe, but additional evidence is needed to generate more validated conclusions.

Molecular Characterization Reveals Subclasses of 1q Gain in Intermediate Risk Wilms Tumors.

Chromosomal alterations have recurrently been identified in Wilms tumors (WTs) and some are associated with poor prognosis. Gain of 1q (1q+) is of special interest given its high prevalence and is currently actively studied for its prognostic value. However, the underlying mutational mechanisms and functional effects remain unknown. In a national unbiased cohort of 30 primary WTs, we integrated somatic SNVs, CNs and SVs with expression data and distinguished four clusters characterized by affected biological processes: muscle differentiation, immune system, kidney development and proliferation. Combined genome-wide CN and SV profiles showed that tumors profoundly differ in both their types of 1q+ and genomic stability and can be grouped into WTs with co-occurring 1p-/1q+, multiple chromosomal gains or CN neutral tumors. We identified 1q+ in eight tumors that differ in mutational mechanisms, subsequent rearrangements and genomic contexts. Moreover, 1q+ tumors were present in all four expression clusters reflecting activation of various biological processes, and individual tumors overexpress different genes on 1q. In conclusion, by integrating CNs, SVs and gene expression, we identified subgroups of 1q+ tumors reflecting differences in the functional effect of 1q gain, indicating that expression data is likely needed for further risk stratification of 1q+ WTs.

Implementation of paediatric precision oncology into clinical practice: The Individualized Therapies for Children with cancer program 'iTHER'.

iTHER is a Dutch prospective national precision oncology program aiming to define tumour molecular profiles in children and adolescents with primary very high-risk, relapsed, or refractory paediatric tumours. Between April 2017 and April 2021, 302 samples from 253 patients were included. Comprehensive molecular profiling including low-coverage whole genome sequencing (lcWGS), whole exome sequencing (WES), RNA sequencing (RNA-seq), Affymetrix, and/or 850k methylation profiling was successfully performed for 226 samples with at least 20% tumour content. Germline pathogenic variants were identified in 16% of patients (35/219), of which 22 variants were judged causative for a cancer predisposition syndrome. At least one somatic alteration was detected in 204 (90.3%), and 185 (81.9%) were considered druggable, with clinical priority very high (6.1%), high (21.3%), moderate (26.0%), intermediate (36.1%), and borderline (10.5%) priority. iTHER led to revision or refinement of diagnosis in 8 patients (3.5%). Temporal heterogeneity was observed in paired samples of 15 patients, indicating the value of sequential analyses. Of 137 patients with follow-up beyond twelve months, 21 molecularly matched treatments were applied in 19 patients (13.9%), with clinical benefit in few. Most relevant barriers to not applying targeted therapies included poor performance status, as well as limited access to drugs within clinical trial. iTHER demonstrates the feasibility of comprehensive molecular profiling across all ages, tumour types and stages in paediatric cancers, informing of diagnostic, prognostic, and targetable alterations as well as reportable germline variants. Therefore, WES and RNA-seq is nowadays standard clinical care at the Princess Máxima Center for all children with cancer, including patients at primary diagnosis. Improved access to innovative treatments within biology-driven combination trials is required to ultimately improve survival.

Case Report: Midshaft clavicle fracture with concomitant high grade (Type V) acromioclavicular joint dislocation.

Introduction: Concomitant acromioclavicular joint dislocation and midshaft clavicle fracture are rare injuries, generally resulting from high energy trauma, with limited previous experience in management. Case: A 30 year old male presented following a pushbike accident. He had suffered a head on collision with another cyclist. Radiographic examination demonstrated a displaced midshaft clavicle fracture with a Rockwood Type V acromioclavicular joint dislocation. Operative management was undertaken using a dual plating technique. At six month follow up the patient demonstrated full range of motion and had no pain. Conclusion: Appropriate radiographic evaluation and careful intraoperative assessment are required using the principles of management for acromioclavicular joint injuries, along with stabilization of the mid-clavicular fracture to reduce the risk of non-union.

The role of elbow positioning on arthroscopic assessment of the long head of biceps tendon in the beach chair position.

BACKGROUND: Tendinopathy of the long head of biceps (LHB) tendon is a common cause of anterior shoulder pain and dysfunction. The extra-articular portion within the bicipital groove undergoes frequent load and friction during shoulder movements and pathology within this area is frequently missed during arthroscopic assessment. METHODS: We quantified the arthroscopically assessable length of tendon within the shoulder in 14 consecutive patients undergoing subpectoral biceps tenodesis. After biceps tenotomy at the superior labrum, the tagged tendon was maximally tensioned and marked at the biceps outlet with the elbow in extension and flexion. The distance in distance between the two were measured. RESULTS: Mean distance from the superior labral insertion of the biceps to the outlet was 16.4 ± 4.1 mm (range, 11-25). With tension on the biceps with elbow extension, the mean measurable distance was 31.3 ± 6.7 mm (range, 19-45). With elbow flexion, this increased to 39.5 ± 5.9 mm (range, 25-52). Mean increase in visible tendon length was 8.2 ± 4.3 mm (range, 5-21) (p = 0.002). CONCLUSION: Elbow flexion results in an average increase of 26.2% more extra-articular tendon visualized at arthroscopy. Therefore, we believe that elbow flexion is a useful adjunct, especially when performed in conjunction with techniques that pull the tendon into the joint, thus allowing for more complete arthroscopic assessment of the LHB, increasing detection of symptomatic biceps tendonitis. LEVEL OF EVIDENCE: Level IV.

Role of Tranexamic Acid in Arthroscopic Osteocapsular Release of the Elbow for Degenerative Arthritis.

Background: Minimizing intra-articular bleeding and swelling is crucial in preventing the development of stiffness around the elbow. Tranexamic acid (TXA) has been shown to be an effective adjunct in reducing perioperative bleeding after surgery. Purpose: To determine the effect of intravenous (IV) TXA on postoperative drain tube output in arthroscopic osteocapsular release of the elbow for primary degenerative arthritis. Study Design: Cohort study; Level of evidence, 3. Methods: The authors performed a retrospective cohort study of 83 consecutive patients with primary degenerative elbow arthritis who underwent an arthroscopic osteocapsular release between 2015 and 2018. They organized patients into a no-TXA group (control) and a group that was given 1.0 g of IV TXA before tourniquet release. The primary outcome measure was drain tube output, and secondary outcome measures included postoperative day 1 pain levels on a visual analog scale and early range of motion at 8 weeks. Differences between groups were analyzed using 1-way analysis of variance, the Mann-Whitney U test, or the Fisher exact test. Results: There were 43 patients in the no-TXA group and 40 patients in the TXA group. Administration of IV TXA resulted in a 51% decrease in mean intra-articular bleeding for the TXA group, as measured via drain tube output (88.8 ± 80.5 mL [no-TXA] vs 43.4 ± 52.4 mL [TXA]; P = .0016). In both groups, there were significant increases in elbow arc of motion when compared with preoperative measurements. There were no between-group differences in early range of motion (129.7° ± 12.4° [no-TXA] vs 131.7° ± 9.2° [TXA]; P = .549) or postoperative pain (1.9 ± 2.2 [no-TXA] vs 1.5 ± 1.7 [TXA]; P = .89). Conclusion: In this study, IV TXA significantly reduced postoperative intra-articular bleeding in patients who underwent arthroscopic osteocapsular release of the elbow for primary degenerative arthritis. However, there were no differences in postoperative range of motion or pain between patients who received TXA and controls.

Contamination Associated With Glove Changing Techniques in the Operating Theatre.

Background: Sterility of the operative field during surgery is imperative in reducing the risk of infection. Most commonly, double gloves are worn by surgeons. When contamination occurs, the top gloves are changed intra-operatively. No studies have investigated which glove changing technique is best. Therefore, in this study, we aim to identify which top glove changing technique causes the least surface contamination. Methods: Glitterbug™ (UV fluorescent powder) was applied to the top gloves of 3 individuals who changed their top gloves according to a randomised method - Method 1: 3 pairs worn, remove the outer pair; Method 2: 2 pairs worn, remove the top glove, replace unassisted; and Method 3: 2 pairs worn, remove the top glove, and replace assisted by a scrub nurse. A blinded investigator inspected for Glitterbug™ contamination under UV light. Results: Two hundred and ten trials were performed and two types of contamination were identified, namely, direct contact and airborne spread. For absolute contamination, Method 1 had 59/64 (92%) contaminated trials, Method 2 had 49/65 (75%) contaminated trials, and Method 3 had 64/81 (79%) contaminated trials. This was statistically significant (p = 0.031). For direct contamination only, Method 1 had 38/64 (59%) contaminated trials, Method 2 had 24/65 (37%) contaminated trials, and Method 3 had 20/81 (25%) contaminated trials. This was statistically significant (p < 0.0001). Conclusions: Method 2 had a statistically significant lower contamination rate overall, with Method 3 having the lowest direct contamination rate. We believe that wearing 2 gloves, removing the top glove and replacing it, either assisted or unassisted, could decrease surface contamination of the sterile field.