Simplifying the Decision-Making Process in the Treatment of Kienböck's Disease.

Background In recent years, the classification and treatment algorithm for adult Kienböck's disease (KD) has expanded. However, the priority of the investigations done in determining its management has not been discussed, as not every patient with KD requires magnetic resonance imaging (MRI) or wrist arthroscopy. Materials and Methods We discuss the role of these investigations and emphasize the importance of computed tomography (CT) imaging in evaluating the cortical integrity of the lunate and its role in the decision-making process and management of KD. Results We put forward an investigative algorithm that places into context the investigative roles of MRI, arthroscopy, and CT. Conclusion KD is a rare condition, and there is a lack of comparative studies to help us choose the preferred treatment. The decision on the management options in adult KD may be made by determining the integrity of the lunate cortex and deciding whether the lunate is salvageable or not by CT scan. MRI may provide useful information on the vascular status if the lunate cortex is intact, and the lunate is salvageable. If the lunate is fragmented, it is not salvageable, and MRI does not provide useful information. Arthroscopy has a role in selective cases.

A Comparison of Rib Osteochondral Graft to Medial Femoral Trochlear Osteocartilaginous Graft for the Salvage of the Fragmented Scaphoid Proximal Pole: A Single-Center Experience with Minimum 2-Year Follow-Up.

Purpose Fragmented fractures of the proximal pole of the scaphoid that cannot be internally fixed may be salvaged by four-corner arthrodesis or proximal row carpectomy. Replacement of the proximal scaphoid with costal-osteochondral graft (COG) or the medial femoral trochlea (MFT) graft are two alternative solutions for this clinical presentation. The purpose of this study was to compare the clinical and radiographic results of the COG and the MFT graft with a minimum 2-year follow-up from a single centre. Methods A retrospective study was performed to investigate the outcome of COG and MFT with a minimum 2 year follow up. Demographic data and clinical assessment including wrist range of motion and grip strength measurements and Oxford Knee score were collected. Patients completed the outcome measures of Disabilities of Arm, Shoulder, and Hand (DASH), the Patient-Rated Wrist Evaluation (PRWE), and a ten-point visual analogue score for pain (VAS). Radiological examination was performed on all wrists at follow-up. Results The visual analogue score, DASH and PRWE were similar between the two groups. There was radiographic evidence of arthritis between the radial styloid and distal scaphoid in all patients that underwent COG but no evidence in those that underwent MFT graft reconstruction. There were different complications in each group. Thirty percent of patients that underwent MFT reconstruction had persistent knee pain at follow up. Conclusion Though there are notable differences in the follow-up period, patients undergoing MFT risk developing knee pain, while those undergoing COG risk radiographic progression of wrist arthritis. Level of Evidence III - Comparative study.

Infection prevention and control studies for care of patients with suspected or confirmed filovirus disease in healthcare settings, with focus on Ebola and Marburg: an integrative review.

Objective: To review evidence pertaining to methods for preventing healthcare-associated filovirus infections (including the survivability of filoviruses in clinical environments and the chlorine concentration required for effective disinfection), and to assess protocols for determining the risk of health worker (HW) exposures to filoviruses. Design: Integrative review. Data sources: PubMed, Embase, Google Scholar, internet-based sources of international health organisations (eg, WHO, CDC), references of the included literature and grey literature. Study selection: Laboratory science, clinical research and real-world observational studies identified through comprehensive search strings that pertained to Ebola disease and Marburg disease and the three research objectives. Methods: Using the framework of population, intervention or exposure, outcomes, study types and report characteristics, reviewers extracted data and critically appraised the evidence using predefined data extraction forms and summary tables. The extraction forms, summary tables and critical appraisals varied based on the included literature; we used both the QUIPS Risk-of-Bias tool when possible and an internally developed instrument to systematically extract and review the evidence from observational and experimental studies. Evidence was then synthesised and summarised to create summary recommendations. Results: Thirty-six studies (including duplicates across research questions) were included in our reviews. All studies that related to the review questions were either (1) descriptive, real-world studies (ie, environmental audits of various surfaces in operational Ebola Treatment Units) or (2) controlled, laboratory studies (ie, experimental studies on the survivability of ebolaviruses in controlled conditions), presenting a range of concerns pertaining to bias and external validity. Our reviews of viral survivability evidence revealed significant disconnections between laboratory-based and real-world findings. However, there is greater viral persistence in liquid than dried body fluids, with the possible exception of blood, and ebolaviruses can survive for significant periods of time in dried substrate. Evidence suggests that 0.5% hypochlorite solution should be used for disinfection activity. Spills should be cleaned with covering and soaking for 15 min. Existing literature suggests that within a well-resourced clinical environment with trained, foreign HWs and established protocols, transmission of ebolaviruses as an occupational risk is a rare event. Despite the high rates of HW infections within public African healthcare settings, no evidence with low risk of bias exists to assess the risk of various occupational exposures given that all high-quality studies were conducted on foreign Ebola clinicians who had low overall rates of infection. This review underscores the critical need for better-quality evidence to inform best practices to ensure HW safety during filovirus disease epidemics.

Prevalence, Patterns, and Predictors of SARS-CoV-2 RNA and Culturable Virus in Tears of a Case-Ascertained Household Cohort.

PURPOSE: To investigate the prevalence, patterns, and predictors of SARS-CoV-2 RNA and culturable virus in tears of a case-ascertained household cohort. DESIGN: Prospective, longitudinal case-ascertained household cohort identified through convenience sampling. METHODS: This analysis was restricted to individuals who were non-hospitalized, symptomatic, and tested positive for SARS-CoV-2 by nasal RT-PCR. Tears and anterior nasal biospecimens were serially collected throughout the acute period. Tears specimens were collected by the study staff using Schirmer test strips, and nasal specimens were self-collected. For both, SARS-CoV-2 RNA was quantified using qRT-PCR, and culturable virus was detected using presence of cytopathic effect (CPE) in tissue culture; positive CPE was confirmed by a qRT-PCR step. A series of cross-sectional unadjusted analyses were performed investigating the relationship between different sociodemographic determinants and biological factors associated with tears RNA positivity. RESULTS: Among the 83 SARS-CoV-2 infected participants, 10 (12%) had at least one RNA-positive tears specimen. Amongst these 10, 5 (50%) had concurrent presence of culturable virus, at a median of 7 days postsymptom onset (IQR: 4-7 days) (absolute range: 4-8 days). CONCLUSIONS: In this longitudinal cohort, we found evidence of culturable virus in the tears of a small proportion of nonhospitalized SARS-CoV-2 infected individuals. Current public health infection precautions do not account for transmission via tears, so these findings may improve our understanding of potential sources of SARS-CoV-2 transmission and contribute to developing future guidelines.

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.

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.

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.

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.

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.

Representations of an Ebola 'outbreak' through Story Technologies.

BACKGROUND: Attempts to understand biosocial phenomena using scientific methods are often presented as value-neutral and objective; however, when used to reduce the complexity of open systems such as epidemics, these forms of inquiry necessarily entail normative considerations and are therefore fashioned by political worldviews (ideologies). From the standpoint of poststructural theory, the character of these representations is at most limited and partial. In addition, these modes of representation (as stories) do work (as technologies) in the service of, or in resistance to, power. METHODS: We focus on a single Ebola case cluster from the 2013-2016 outbreak in West Africa and examine how different disciplinary forms of knowledge production (including outbreak forecasting, active epidemiological surveillance, post-outbreak serosurveys, political economic analyses, and ethnography) function as Story Technologies. We then explore how these technologies are used to curate 'data,' analysing the erasures, values, and imperatives evoked by each. RESULTS: We call attention to the instrumental-in addition to the descriptive-role Story Technologies play in ordering contingencies and establishing relationships in the wake of health crises. DISCUSSION: By connecting each type of knowledge production with the systems of power it reinforces or disrupts, we illustrate how Story Technologies do ideological work. These findings encourage research from pluriversal perspectives and advocacy for measures that promote more inclusive modes of knowledge production.

The impact of anthropogenic climate change on pediatric viral diseases.

The adverse effects of climate change on human health are unfolding in real time. Environmental fragmentation is amplifying spillover of viruses from wildlife to humans. Increasing temperatures are expanding mosquito and tick habitats, introducing vector-borne viruses into immunologically susceptible populations. More frequent flooding is spreading water-borne viral pathogens, while prolonged droughts reduce regional capacity to prevent and respond to disease outbreaks with adequate water, sanitation, and hygiene resources. Worsening air quality and altered transmission seasons due to an increasingly volatile climate may exacerbate the impacts of respiratory viruses. Furthermore, both extreme weather events and long-term climate variation are causing the destruction of health systems and large-scale migrations, reshaping health care delivery in the face of an evolving global burden of viral disease. Because of their immunological immaturity, differences in physiology (e.g., size), dependence on caregivers, and behavioral traits, children are particularly vulnerable to climate change. This investigation into the unique pediatric viral threats posed by an increasingly inhospitable world elucidates potential avenues of targeted programming and uncovers future research questions to effect equitable, actionable change. IMPACT: A review of the effects of climate change on viral threats to pediatric health, including zoonotic, vector-borne, water-borne, and respiratory viruses, as well as distal threats related to climate-induced migration and health systems. A unique focus on viruses offers a more in-depth look at the effect of climate change on vector competence, viral particle survival, co-morbidities, and host behavior. An examination of children as a particularly vulnerable population provokes programming tailored to their unique set of vulnerabilities and encourages reflection on equitable climate adaptation frameworks.

Integrated analysis of transcriptomic and proteomic alterations in mouse models of ALS/FTD identify early metabolic adaptions with similarities to mitochondrial dysfunction disorders.

OBJECTIVE: Sporadic and familial amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease that results in loss of motor neurons and, in some patients, associates with frontotemporal dementia (FTD). Apart from the accumulation of proteinaceous deposits, emerging literature indicates that aberrant mitochondrial bioenergetics may contribute to the onset and progression of ALS/FTD. Here we sought to investigate the pathophysiological signatures of mitochondrial dysfunction associated with ALS/FTD. METHODS: By means of label-free mass spectrometry (MS) and mRNA sequencing (mRNA-seq), we report pre-symptomatic changes in the cortices of TDP-43 and FUS mutant mouse models. Using tissues from transgenic mouse models of mitochondrial diseases as a reference, we performed comparative analyses and extracted unique and common mitochondrial signatures that revealed neuroprotective compensatory mechanisms in response to early damage. RESULTS: In this regard, upregulation of both Acyl-CoA Synthetase Long-Chain Family Member 3 (ACSL3) and mitochondrial tyrosyl-tRNA synthetase 2 (YARS2) were the most representative change in pre-symptomatic ALS/FTD tissues, suggesting that fatty acid beta-oxidation and mitochondrial protein translation are mechanisms of adaptation in response to ALS/FTD pathology. CONCLUSIONS: Together, our unbiased integrative analyses unveil novel molecular components that may influence mitochondrial homeostasis in the earliest phase of ALS.

The Influence of Glenoid Bone Loss and Graft Positioning on Graft and Cartilage Contact Pressures After the Latarjet Procedure.

BACKGROUND: Glenohumeral joint contact loading before and after glenoid bone grafting for recurrent anterior instability remains poorly understood. PURPOSE: To develop a computational model to evaluate the influence of glenoid bone loss and graft positioning on graft and cartilage contact pressures after the Latarjet procedure. STUDY DESIGN: Controlled laboratory study. METHODS: A finite element model of the shoulder was developed using kinematics, muscle and glenohumeral joint loading of 6 male participants. Muscle and joint forces at 90° of abduction and external rotation were calculated and employed in simulations of the native shoulder, as well as the shoulder with a Bankart lesion, 10% and 25% glenoid bone loss, and after the Latarjet procedure. RESULTS: A Bankart lesion as well as glenoid bone loss of 10% and 25% significantly increased glenoid and humeral cartilage contact pressures compared with the native shoulder (P < .05). The Latarjet procedure did not significantly increase glenoid cartilage contact pressure. With 25% glenoid bone loss, the Latarjet procedure with a graft flush with the glenoid and the humerus positioned at the glenoid half-width resulted in significantly increased humeral cartilage contact pressure compared with that preoperatively (P = .023). Under the same condition, medializing the graft by 1 mm resulted in humeral cartilage contact pressure comparable with that preoperatively (P = .097). Graft lateralization by 1 mm resulted in significantly increased humeral cartilage contact pressure in both glenoid bone loss conditions (P < .05). CONCLUSION: This modeling study showed that labral damage and greater glenoid bone loss significantly increased glenoid and humeral cartilage contact pressures in the shoulder. The Latarjet procedure may mitigate this to an extent, although glenoid and humeral contact loading was sensitive to graft placement. CLINICAL RELEVANCE: The Latarjet procedure with a correctly positioned graft should not lead to increased glenohumeral joint contact loading. The present study suggests that lateral graft overhang should be avoided, and in the situation of large glenoid bone defects, slight medialization (ie, 1 mm) of the graft may help to mitigate glenohumeral joint contact overloading.

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.