Multiple External Cervical Resorption Lesions in Patient with Graft versus Host Disease Treated with Systemic Bleomycin: A Case Report.

The phenomenon of multiple external cervical root resorption (ECRR) lesions in a single patient is rare but may have a link with the chemotherapeutic agent bleomycin. This case details an adult male with multiple ECRR lesions that developed following chemotherapy. His treatment regimen for Hodgkin's lymphoma included the chemotherapeutic antibiotic bleomycin, which has previously been linked with development of multiple ECRR lesions. The patient developed graft versus host disease following an allogeneic stem cell transplant, which could have a significant role in the development and promotion of the ECRR lesions. In total, 8 teeth developed ECRR, and all the known causative factors were excluded when examined. To our knowledge, this is only the second reported case in the literature to link bleomycin to multiple ECRR lesions. This case report aims to bring the reader's attention to the fact that multiple cervical resorption lesions can develop simultaneously. These lesions can be difficult to diagnose and treat and are often misdiagnosed as caries. Finally, the reader should consider the possible role of bleomycin and graft versus host disease in development of multiple lesions of ECRR.

Gluteal Tendinopathy Is Associated With Lower Patient-Reported Outcome Measures in Total Hip Arthroplasty With a Posterior Approach: A Prospective Cohort Study of 1,538 Patients.

BACKGROUND: Gluteal tendinopathy (GT) is found in 20 to 25% of patients undergoing total hip arthroplasty (THA). Despite this, there is a scarcity of literature assessing the association between GT and THA outcomes. The aim of this study was to evaluate whether intraoperative diagnosis of GT negatively affected postoperative outcomes. METHODS: Consecutive patients undergoing primary THA for osteoarthritis via a posterior approach over 5 years were recruited in a prospective study. Gluteal tendinopathy was assessed and graded at the time of surgery, but not repaired. A total of 1,538 (93%) completed the patient-reported outcome measures (PROMs) at 1 year after surgery and were included in the analysis. The PROMs included the Oxford Hip Score (OHS), Hip Disability and Osteoarthritis Outcome Score Joint Replacement (HOOS JR), and EuroQol 5-Dimension, and were collected preoperatively and one year after THA. RESULTS: The gluteal tendons were graded as 4 distinct grades: normal (n = 1,023, 66%), tendinopathy but no tear (n = 337, 22%), partial thickness tear (n = 131, 9%), and full thickness tear (n = 47, 3%). The occurrence of GT was associated with age, body mass index, and sex. There was no significant difference in baseline OHS or HOOS JR scores according to GT grade. As GT grade increased, lower median 1-year OHS (P = .001) and HOOS JR (P = .016) were observed. This association was confirmed by linear regression analysis with 1-year OHS (B = 0.5, 95% CI = -0.9 to -0.1, P = .011) when controlled for age and sex. CONCLUSIONS: Gluteal tendinopathy was commonly observed and was associated with inferior 1-year PROMs in patients undergoing THA via posterior approach. Increasing degree of tendinopathy was a negative prognostic factor for outcomes and patient satisfaction. LEVEL OF EVIDENCE: Level 2 (High quality prospective cohort study).

The biportal transorbital approach: quantitative comparison of the anterior subfrontal craniotomy, bilateral transorbital endoscopic, and microscopic approaches.

OBJECTIVE: The aim of this study was to assess the surgical use and applicability of a biportal bitransorbital approach. Single-portal transorbital and combined transorbital transnasal approaches have been used in clinical practice, but no study has assessed the surgical use and applicability of a biportal bitransorbital approach. METHODS: Ten cadaver specimens underwent midline anterior subfrontal (ASub), bilateral transorbital microsurgery (bTMS), and bilateral transorbital neuroendoscopic surgery (bTONES) approaches. Morphometric analyses included the length of the bilateral cranial nerves I and II, the optic tract, and A1; the area of exposure of the anterior cranial fossa floor; craniocaudal and mediolateral angles of attack (AOAs); and volume of surgical freedom (VSF; maximal available working volume for a specific surgical corridor and surgical target structure normalized to a height of 10 mm) of the bilateral paraclinoid internal carotid arteries (ICAs), bilateral terminal ICAs, and anterior communicating artery (ACoA). Analyses were conducted to determine whether the biportal approach was associated with greater instrument freedom. RESULTS: The bTMS and bTONES approaches provided limited access to the bilateral A1 segments and the ACoA, which were inaccessible in 30% (bTMS) and 60% (bTONES) of exposures. The average total frontal lobe area of exposure (AOE) was 1648.4 mm2 (range 1516.6-1958.8 mm2) for ASub, 1658.9 mm2 (1274.6-1988.2 mm2) for bTMS, and 1914.9 mm2 (1834.2-2014.2 mm2) for bTONES exposures, with no statistically significant superiority between any of the 3 approaches (p = 0.28). The bTMS and bTONES approaches were significantly associated with decreases of 8.7 mm3 normalized volume (p = 0.005) and 14.3 mm3 normalized volume (p < 0.001) for VSF of the right paraclinoid ICA compared with the ASub approach. No statistically significant difference in surgical freedom was noted between all 3 approaches when targeting the bilateral terminal ICA. The bTONES approach was significantly associated with a decrease of 105% in the (log) VSF of the ACoA compared with the ASub (p = 0.009). CONCLUSIONS: Although the biportal approach is intended to improve maneuverability within these minimally invasive approaches, these results illustrate the pertinent issue of surgical corridor crowding and the importance of surgical trajectory planning. A biportal transorbital approach provides improved visualization but does not improve surgical freedom. Furthermore, although it affords impressive anterior cranial fossa AOE, it is unsuitable for addressing midline lesions because the preserved orbital rim restricts lateral movement. Further comparative studies will elucidate whether a combined transorbital transnasal route is preferable to minimize skull base destruction and maximize instrument access.

Quantification of basal stem cell elongation and stress fiber accumulation in the pseudostratified airway epithelium during the unjamming transition.

Under homeostatic conditions, epithelial cells remain non-migratory. However, during embryonic development and pathological conditions, they become migratory. The mechanism underlying the transition of the epithelial layer between non-migratory and migratory phases is a fundamental question in biology. Using well-differentiated primary human bronchial epithelial cells that form a pseudostratified epithelium, we have previously identified that a confluent epithelial layer can transition from a non-migratory to migratory phase through an unjamming transition (UJT). We previously defined collective cellular migration and apical cell elongation as hallmarks of UJT. However, other cell-type-specific changes have not been previously studied in the pseudostratified airway epithelium, which consists of multiple cell types. Here, we focused on the quantifying morphological changes in basal stem cells during the UJT. Our data demonstrate that during the UJT, airway basal stem cells elongated and enlarged, and their stress fibers elongated and aligned. These morphological changes observed in basal stem cells correlated to the previously defined hallmarks of the UJT. Moreover, basal cell and stress fiber elongation were observed prior to apical cell elongation. Together, these morphological changes indicate that basal stem cells in pseudostratified airway epithelium are actively remodeling, presumably through accumulation of stress fibers during the UJT.

Effect of reduced-calcium and high-calcium cheddar cheese consumption on the excretion of faecal fat: a 2-week cross-over dietary intervention study.

PURPOSE: Studies show that dairy fat consumed in the form of cheese reduce LDL-cholesterol concentration (LDL-c) compared to butter and mechanistic suggestions include the calcium content of cheese leading to enhanced faecal fat excretion. The aim of this study was to test the effect of varying the calcium content within a cheese, on faecal fat excretion as a primary outcome, and blood lipid markers, fasting glucose and calcium excretion as secondary outcomes. METHODS: 7 healthy males (BMI 18-25) participated in this randomized, cross-over control intervention, of 3 × 2 week periods. Diets contained 240 g/day cheese; a High Calcium Cheese (HCC) diet, a Reduced Calcium Cheese (RCC) diet, and a control arm: Reduced Calcium Cheese + CaCO3 Supplement (RCC + Supp) diet. Diets differed in calcium content and form but were otherwise controlled for energy and key macronutrients. Blood and 5-day faecal samples were collected. RESULTS: There was no significant difference in faecal fat excretion (g/day) between the diets (P = 0.066). Percent fat of faecel excretion was higher after RCC + Supp (P = 0.016). None of the individual fatty acids were different. Fasting LDL-c was significantly lower following the HCC diet vs. the other arms (P = 0.002). Faecal Ca was different across all diets (P = 0.001), lowest after RCC, and greatest after RCC + Supp. No differences were observed for fasting blood parameters or changes in anthropometry. CONCLUSION: Varying the calcium content within a cheese matrix significantly affected fasting LDL-c values. Results did not support higher faecal fat excretion as an underlying mechanism, but the high attrition rate was a limitation. Trial registerer Trial Registered at ISRCTN.org, registration number ISRCTN11663659 on 12.07.2022. Retrospectively registered.

The Triad of Childhood-Onset Schizophrenia, Autism Spectrum Disorder, and Catatonia: A Case Report.

Childhood-onset schizophrenia (COS) is a rare and severe form of schizophrenia with an estimated prevalence of 1/10,000. Schizophrenia and Autism spectrum disorder (ASD) have shared phenotypic features and shared genetic etiology. There is growing research surrounding the co-occurrence of psychomotor syndromes like catatonia with neurodevelopmental disorders like ASD or psychiatric disorders like schizophrenia. In 2013, Shorter and Wachtel described a phenomenon of the 'Iron Triangle' where COS, ASD, and catatonia often co-occur. The Iron Triangle theory is based on observation of historical case literature, which showed that all three diagnoses in the Iron Triangle were routinely assigned to children and adolescents. The pattern of this "Iron Triangle" suggests there may be a single underlying pathology resulting in a unique mixed form of catatonia, autism, and psychosis. We describe the case of a boy with sequential development of COS, ASD, and catatonia who also has syndromic facial and musculoskeletal features. This case highlights overlapping diagnostic features of these three disorders and can help us better understand how "hidden" features of catatonia may occur in patients with COS or ASD but go unrecognized, because they are grouped as features under autism/schizophrenia rather than a distinct diagnosis of catatonia. Further study is warranted to elucidate if this phenotypic pattern constitutes a new single diagnosis that is not well understood, an endophenotype of schizophrenia, or if this is the result of phenomenological overlap between catatonia, ASD, and COS.

Moderators, Mediators, and Prognostic Indicators of Treatment With Hip Arthroscopy or Physical Therapy for Femoroacetabular Impingement Syndrome: Secondary Analyses From the Australian FASHIoN Trial.

BACKGROUND: Although randomized controlled trials comparing hip arthroscopy with physical therapy for the treatment of femoroacetabular impingement (FAI) syndrome have emerged, no studies have investigated potential moderators or mediators of change in hip-related quality of life. PURPOSE: To explore potential moderators, mediators, and prognostic indicators of the effect of hip arthroscopy and physical therapy on change in 33-item international Hip Outcome Tool (iHOT-33) score for FAI syndrome. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Overall, 99 participants were recruited from the clinics of orthopaedic surgeons and randomly allocated to treatment with hip arthroscopy or physical therapy. Change in iHOT-33 score from baseline to 12 months was the dependent outcome for analyses of moderators, mediators, and prognostic indicators. Variables investigated as potential moderators/prognostic indicators were demographic variables, symptom duration, alpha angle, lateral center-edge angle (LCEA), Hip Osteoarthritis MRI Scoring System (HOAMS) for selected magnetic resonance imaging (MRI) features, and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) score. Potential mediators investigated were change in chosen bony morphology measures, HOAMS, and dGEMRIC score from baseline to 12 months. For hip arthroscopy, intraoperative procedures performed (femoral ostectomy ± acetabular ostectomy ± labral repair ± ligamentum teres debridement) and quality of surgery graded by a blinded surgical review panel were investigated for potential association with iHOT-33 change. For physical therapy, fidelity to the physical therapy program was investigated for potential association with iHOT-33 change. RESULTS: A total of 81 participants were included in the final moderator/prognostic indicator analysis and 85 participants in the final mediator analysis after exclusion of those with missing data. No significant moderators or mediators of change in iHOT-33 score from baseline to 12 months were identified. Patients with smaller baseline LCEA (ß = -0.82; P = .034), access to private health care (ß = 12.91; P = .013), and worse baseline iHOT-33 score (ß = -0.48; P < .001) had greater iHOT-33 improvement from baseline to 12 months, irrespective of treatment allocation, and thus were prognostic indicators of treatment response. Unsatisfactory treatment fidelity was associated with worse treatment response (ß = -24.27; P = .013) for physical therapy. The quality of surgery and procedures performed were not associated with iHOT-33 change for hip arthroscopy (P = .460-.665 and P = .096-.824, respectively). CONCLUSION: No moderators or mediators of change in hip-related quality of life were identified for treatment of FAI syndrome with hip arthroscopy or physical therapy in these exploratory analyses. Patients who accessed the Australian private health care system, had smaller LCEAs, and had worse baseline iHOT-33 scores, experienced greater iHOT-33 improvement, irrespective of treatment allocation.

Prosthetic femoral interposition arthroplasty with adult humeral implant, for children with cerebral palsy and symptomatic hips.

BACKGROUND: Immobile patients with cerebral palsy can suffer with painful dislocated hips. Decision-making and surgical management can prove challenging in this cohort of patients, with hips that cannot be reconstructed. METHODS: We conduced a retrospective chart review of all patients who underwent prosthetic femoral interposition arthroplasty (PFIA) by two surgeons from 2013 to 2021, for unreconstructable hips. We compared pain and range of motion in preoperative period to the postoperative period. Caregiver reported outcomes were used to assess satisfaction post operatively. During the follow up, radiographs of the PFIA were obtained to assess for proximal migration, heterotopic ossification and loosening of implants. RESULTS: Eleven index surgeries, which met the inclusion criteria, were included in this study. These were performed in eleven patients with an average follow up of 45 months. Regarding pain and range of motion post-operatively an excellent or good result was seen in nine cases. Two patients were classified as having a fair result with none having a poor result. Most caregivers reported being satisfied or very satisfied with the post-operative outcomes. CONCLUSION: A prescriptive operative solution to the painful dislocated hip in children with spastic cerebral palsy remains elusive. In this study, we have demonstrated both clinically and radiologically satisfactory results post proximal femoral interposition arthroplasty, for those patients with unreconstructable hips. Patient caregiver reported outcomes, show that the majority of caregivers were satisfied or very satisfied with the outcome of the surgery.

Clinical and radiological outcomes following surgical hip dislocation for paediatric hip pathologies, a prospective cohort study.

BACKGROUND: Surgical Hip Dislocation (SHD) is a powerful tool in the armamentarium of any surgeon treating conditions affecting the hips of children presenting with sequelae of a number of common conditions including Legg-CalvéPerthes disease (LCPD) and slipped capital femoral epiphysis (SCFE). Risks associated with the procedure are well described. We investigated to assess if SHD is associated with significant surgical risk and if it improved clinical outcomes for patients. METHODS: We conducted a prospective cohort study. We reviewed 18 (11 males and 7 females; mean age 13.7 years (6-17) with symptomatic hip pathology, secondary to femoroacetabular impingement (FAI) between 2017 and 2021. All patients underwent a surgical hip dislocation approach and femoral head-neck osteochondroplasty, Head Split osteotomy or both. Clinical improvement was assessed using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index. The minimum follow-up was 6 months (mean, 22 months; range, 6-42 months). RESULTS: WOMAC scores improved at final follow-up from 10 to 3 for pain, 33 to 10 for function, and 4 to 2 for the stiffness subscales. All radiographic measures improved significantly of the postoperative X-rays. No patients developed osteonecrosis, implant failure, deep infection, or nonunion. CONCLUSION: Surgical Hip Dislocation, in the short term, we found improvement in WOMAC scores and radiographic indices with a low complication rate.

Monogenic early-onset lymphoproliferation and autoimmunity: Natural history of STAT3 gain-of-function syndrome.

BACKGROUND: In 2014, germline signal transducer and activator of transcription (STAT) 3 gain-of-function (GOF) mutations were first described to cause a novel multisystem disease of early-onset lymphoproliferation and autoimmunity. OBJECTIVE: This pivotal cohort study defines the scope, natural history, treatment, and overall survival of a large global cohort of patients with pathogenic STAT3 GOF variants. METHODS: We identified 191 patients from 33 countries with 72 unique mutations. Inclusion criteria included symptoms of immune dysregulation and a biochemically confirmed germline heterozygous GOF variant in STAT3. RESULTS: Overall survival was 88%, median age at onset of symptoms was 2.3 years, and median age at diagnosis was 12 years. Immune dysregulatory features were present in all patients: lymphoproliferation was the most common manifestation (73%); increased frequencies of double-negative (CD4-CD8-) T cells were found in 83% of patients tested. Autoimmune cytopenias were the second most common clinical manifestation (67%), followed by growth delay, enteropathy, skin disease, pulmonary disease, endocrinopathy, arthritis, autoimmune hepatitis, neurologic disease, vasculopathy, renal disease, and malignancy. Infections were reported in 72% of the cohort. A cellular and humoral immunodeficiency was observed in 37% and 51% of patients, respectively. Clinical symptoms dramatically improved in patients treated with JAK inhibitors, while a variety of other immunomodulatory treatment modalities were less efficacious. Thus far, 23 patients have undergone bone marrow transplantation, with a 62% survival rate. CONCLUSION: STAT3 GOF patients present with a wide array of immune-mediated disease including lymphoproliferation, autoimmune cytopenias, and multisystem autoimmunity. Patient care tends to be siloed, without a clear treatment strategy. Thus, early identification and prompt treatment implementation are lifesaving for STAT3 GOF syndrome.

Does a relationship exist between preoperative expectations and overall satisfaction in spine surgery patients?-a prospective cohort study.

Background: The role of preoperative patient expectation in spine surgery is not completely understood, but could be essential in predicting patient outcomes. The purpose of this study was to create a standard means to assess patient preoperative expectations and its effect on postoperative satisfaction in the midterm follow-up period. Methods: This is a prospective cohort study design. Forty-five patients undergoing elective cervical or lumbar spine surgery were asked to participate in the study. Using a 10 cm visual analog scale (VAS) score, patients were asked to rate their preoperative pain along with what they expect it to be after surgery. Pre- and postoperative Oswestry Disability Index (ODI) and Neck Disability Index (NDI) were recorded. Overall satisfaction with surgery was recorded along with if they would have surgery again. The patients' preoperative expectations were compared to their postoperative ODI/NDI scores at terminal follow-up around 1 year. Postoperative satisfaction was also correlated as to whether they would have surgery again. Results: Patients who would have surgery again had an average expected decrease in their disability by 37 (±23) compared to 26 (±19) in patients who would not (P=0.201). For patients who would have surgery again, their postoperative pain more closely matched their preoperative expectations. Conclusions: In conclusion, the authors found that patients who were satisfied with their spine surgery improved functionally to a much greater degree from baseline, tended to have higher expectations with regards to level of disability improvement, and had lower expectations with regards to improvement in neck/back pain.

STAT3 gain-of-function mutations connect leukemia with autoimmune disease by pathological NKG2Dhi CD8+ T cell dysregulation and accumulation.

The association between cancer and autoimmune disease is unexplained, exemplified by T cell large granular lymphocytic leukemia (T-LGL) where gain-of-function (GOF) somatic STAT3 mutations correlate with co-existing autoimmunity. To investigate whether these mutations are the cause or consequence of CD8+ T cell clonal expansions and autoimmunity, we analyzed patients and mice with germline STAT3 GOF mutations. STAT3 GOF mutations drove the accumulation of effector CD8+ T cell clones highly expressing NKG2D, the receptor for stress-induced MHC-class-I-related molecules. This subset also expressed genes for granzymes, perforin, interferon-γ, and Ccl5/Rantes and required NKG2D and the IL-15/IL-2 receptor IL2RB for maximal accumulation. Leukocyte-restricted STAT3 GOF was sufficient and CD8+ T cells were essential for lethal pathology in mice. These results demonstrate that STAT3 GOF mutations cause effector CD8+ T cell oligoclonal accumulation and that these rogue cells contribute to autoimmune pathology, supporting the hypothesis that somatic mutations in leukemia/lymphoma driver genes contribute to autoimmune disease.

Opioid use and patient outcomes in an Australian hip and knee arthroplasty cohort.

BACKGROUND: To determine the prevalence of opioid use in Australian hip (THA) or knee (TKA) cohort, and its association with outcomes. METHODS: About 837 primary THA or TKA subjects prospectively completed Oxford Scores, and Knee or Hip Osteoarthritis Outcomes Score(KOOS/HOOS) and opioid use in the previous week before arthroplasty. Subjects repeated the baseline survey at 6 months, with additional questions regarding satisfaction. RESULTS: Opioid use was reported by 19% preoperatively and 7% at 6 months. Opioid use was 46% at 6 weeks and 10% at 6 months after TKR, and 16% at 6 weeks and 4% at 6 months after THR. Preoperative opioid use was associated with back pain(OR 2.2, P = 0.006), anxiety or depression(OR 1.8, P = 0.001) and Oxford knee scores <30(OR 5.6, P = 0.021) in TKA subjects, and females in THA subjects(OR 1.7, P = 0.04). There was no difference between preoperative opioid users and non-users for satisfaction, or KOOS or HOOS scores at 6 months. 77% of patients taking opioids before surgery had ceased by 6 months, and 3% of preoperative non users reported opioid use at 6 months. Opioid use at 6 months was associated with preoperative use (OR 6.6-14.7, P < 0.001), and lower 6 month oxford scores (OR 4.4-83.6, P < 0.01). CONCLUSION: One in five used opioids before arthroplasty. Pre-operative opioid use was the strongest risk factor for opioid use at 6 months, increasing odds 7-15 times. Prolonged opioid use was rarely observed in the opioid naïve (<5% TKA and 1% THA). Preoperative opioid use was not associated with inferior outcomes or satisfaction.

A Novel Targeted Amplicon Next-Generation Sequencing Gene Panel for the Diagnosis of Common Variable Immunodeficiency Has a High Diagnostic Yield: Results from the Perth CVID Cohort Study.

With the advent of next-generation sequencing (NGS), monogenic forms of common variable immunodeficiency (CVID) have been increasingly described. Our study aimed to identify disease-causing variants in a Western Australian CVID cohort using a novel targeted NGS panel. Targeted amplicon NGS was performed on 22 unrelated subjects who met the formal European Society for Immunodeficiencies-Pan-American Group for Immunodeficiency diagnostic criteria for CVID and had at least one of the following additional criteria: disease onset at age <18 years, autoimmunity, low memory B lymphocytes, family history, and/or history of lymphoproliferation. Candidate variants were assessed by in silico predictions of deleteriousness, comparison to the literature, and classified according to the American College of Medical Genetics and Genomics-Association for Molecular Pathology criteria. All detected genetic variants were verified independently by an external laboratory, and additional functional studies were performed if required. Pathogenic or likely pathogenic variants were detected in 6 of 22 (27%) patients. Monoallelic variants of uncertain significance were also identified in a further 4 of 22 patients (18%). Pathogenic variants, likely pathogenic variants, or variants of uncertain significance were found in TNFRSF13B, TNFRSF13C, ICOS, AICDA, IL21R, NFKB2, and CD40LG, including novel variants and variants with unexpected inheritance pattern. Targeted amplicon NGS is an effective tool to identify monogenic disease-causing variants in CVID, and is comparable or superior to other NGS methods. Moreover, targeted amplicon NGS identified patients who may benefit from targeted therapeutic strategies and had important implications for family members.

Collagenase and the Treatment of Dupuytren Contracture: Efficacy of Treatment and Patient Satisfaction.

Background: Collagenase clostridium histolyticum has become a widely used treatment in the management of Dupuytren disease. The aims of this study are to assess the immediate success of treatment of Dupuytren contracture with collagenase injection, to measure long-term patient-rated outcomes, to determine whether the risk factors for the disease impacted outcomes and to report complications of collagenase treatment. Methods: A prospective study was performed in a tertiary referral centre. Measurements were recorded pre-treatment, day 1 and day 90. Patient-rated outcome scores were measured using Disability of the Arm, Shoulder and Hand questionnaire (DASH) and the Michigan Hand Questionnaire (MHQ) at minimum 36 months post-injection. Results: The study included 45 patients with 53 hands with a mean age of 65.7 years. The treatment was successful in 62% of patients with the greatest improvement in the metacarpal-phalangeal joint of the little finger. Diabetes, epilepsy, gender, alcohol intake and positive family history had no statistically significant predictive value on successful outcomes. Patient satisfaction at 41 months was high with mean MHQ score of 97.3. Conclusions: Collagenase is effective in the treatment of Dupuytren contracture, with disease involving the little finger showing the greatest benefit. Risk factors for development of Dupuytren disease had no effect on successful outcome and long-term satisfaction rates are high. Level of Evidence: Level III (Therapeutic).

Foot Pain is Common, But Frequently Improves 1 Year After Total Knee Arthroplasty.

BACKGROUND: Osteoarthritis frequently affects multiple joints through the lower limbs. This study sought to examine the incidence of foot pain in subjects undergoing total knee arthroplasty (TKA) and determine if foot symptoms improved following surgery. METHODS: Six hundred ten subjects undergoing TKA completed patient-reported outcome measures preoperatively, and at 6 and/or 12 months after surgery including the incidence and severity of foot or ankle pain, Knee Injury and Osteoarthritis Outcome Scores (KOOS) Joint Replacement, Oxford Knee Scores (OKS), EQ5D, and satisfaction. RESULTS: Foot or ankle pain was reported in 45% before, 32% at 6 months, and 36% at 12 months after TKA. Of those with preoperative foot pain, 42% at 6 months and 50% at 12 months reported no foot pain after TKA, and the Visual Analog Scale severity reduced from a mean of 4.0 before to 1.7 after surgery. Those with preoperative foot pain had lower baseline KOOS (P = .001), OKS (P = .001), and more depression/anxiety (P = .010), but experienced equivalent postoperative KOOS, OKS, and satisfaction with surgery, compared to those without foot pain. CONCLUSION: Foot or ankle pain was reported by nearly half of TKA subjects, but resolved after surgery in 50%. Those with preoperative foot pain experienced at least equivalent improvement in knee-related symptoms and mobility compared to those without foot pain. The presence of foot pain should not be a deterrent to TKA.

Mechanical Compression of Human Airway Epithelial Cells Induces Release of Extracellular Vesicles Containing Tenascin C.

Aberrant remodeling of the asthmatic airway is not well understood but is thought to be attributable in part to mechanical compression of airway epithelial cells. Here, we examine compression-induced expression and secretion of the extracellular matrix protein tenascin C (TNC) from well-differentiated primary human bronchial epithelial (HBE) cells grown in an air-liquid interface culture. We measured TNC mRNA expression using RT-qPCR and secreted TNC protein using Western blotting and ELISA. To determine intracellular signaling pathways, we used specific inhibitors for either ERK or TGF-ß receptor, and to assess the release of extracellular vesicles (EVs) we used a commercially available kit and Western blotting. At baseline, secreted TNC protein was significantly higher in asthmatic compared to non-asthmatic cells. In response to mechanical compression, both TNC mRNA expression and secreted TNC protein was significantly increased in both non-asthmatic and asthmatic cells. TNC production depended on both the ERK and TGF-ß receptor pathways. Moreover, mechanically compressed HBE cells released EVs that contain TNC. These data reveal a novel mechanism by which mechanical compression, as is caused by bronchospasm, is sufficient to induce the production of ECM protein in the airway and potentially contribute to airway remodeling.

Can a Hip Brace Improve Short-Term Hip-Related Quality of Life for People With Femoroacetabular Impingement and Acetabular Labral Tears: An Exploratory Randomized Trial.

OBJECTIVES: To examine whether a hip brace can improve hip health quality-of-life (QoL) and is well-tolerated in people with femoroacetabular impingement syndrome (FAIS) or symptomatic labral tears after 6 weeks of wear. DESIGN: Parallel, two-arm, exploratory randomized trial. SETTING: Hospital and private clinics of orthopaedic surgeons. PARTICIPANTS: Individuals >18 years with FAIS or labral tears. INTERVENTIONS: Usual conservative care versus usual conservative care plus a hip brace. MAIN OUTCOMES: Patient-reported outcomes were assessed with the International Hip Outcome Tool (iHOT-33), and Copenhagen Hip and Groin Outcome Scores (HAGOS). Brace acceptability was measured using the Quebec User Evaluation of Satisfaction with Assistive Technology survey. Independent t-tests assessed between-group differences. RESULTS: Thirty-eight participants were recruited, 19 each group, 60% women, mean age 39.3 ± 11.8 years, body mass index 25.3 ± 4.4 kg/m2, iHOT-33 36.6 ± 24.8. Three participants dropped out (one usual care, 2 braced). The mean between-group difference for iHOT-33 was 19.4 (95% confidence interval [CI] 1.68-37.06, P = 0.03) favoring the brace. There were improvements in most HAGOS subscale scores favoring the brace. Issues with brace tolerability for some participants were perceived comfort and effectiveness. Three brace-related adverse events were reported. CONCLUSION: Between-group differences favored the braced group for hip health QoL, pain, symptoms, and function. Although these were promising results, the CIs for the estimates were wide, the small sample size likely a contributing factor. Our results suggest that further investigation of the brace is warranted, we calculated sample sizes and made recommendations for the design of a future trial.

The utility of plasma circulating cell-free messenger RNA as a biomarker of glioma: a pilot study.

BACKGROUND: Research into the potential utility of plasma-derived circulating cell-free nucleic acids as non-invasive adjuncts to radiological imaging have been occasioned by the invasive nature of brain tumour biopsy. The objective of this study was to determine whether significant differences exist in the plasma transcriptomic profile of glioma patients relative to differences in their tumour characteristics, and also whether any observed differences were representative of synchronously obtained glioma samples and TCGA glioma-derived RNA. METHODS: Blood samples were collected from twenty glioma patients prior to tumour resection. Plasma ccfmRNAs and glioma-derived RNA were extracted and profiled. RESULTS: BCL2L1, GZMB, HLA-A, IRF1, MYD88, TLR2, and TP53 genes were significantly over-expressed in glioma patients (p < 0.001, versus control). GZMB and HLA-A genes were significantly over-expressed in high-grade glioma patients (p < 0.001, versus low-grade glioma patients). Moreover, the fold change of the BCL2L1 gene was observed to be higher in patients with high-grade glioma (p = 0.022, versus low-grade glioma patients). There was positive correlation between the magnitude of fold change of differentially expressed genes in plasma- and glioma-derived RNA (Spearman r = 0.6344, n = 14, p = 0.017), and with the mean FPKM in TCGA glioma-derived RNA samples (Spearman r = 0.4614, n = 19, p < 0.05). There was positive correlation between glioma radiographic tumour burden and the magnitude of fold change of the CSF3 gene (r = 0.9813, n = 20, p < 0.001). CONCLUSION: We identified significant differential expression of genes involved in cancer inflammation and immunity crosstalk among patients with different glioma grades, and there was positive correlation between their transcriptomic profile in plasma and tumour samples, and with TCGA glioma-derived RNA.

Electronic cigarette smoke reduces ribosomal protein gene expression to impair protein synthesis in primary human airway epithelial cells.

The widespread use of electronic cigarettes (e-cig) is a serious public health concern; however, mechanisms by which e-cig impair the function of airway epithelial cells-the direct target of e-cig smoke-are not fully understood. Here we report transcriptomic changes, including decreased expression of many ribosomal genes, in airway epithelial cells in response to e-cig exposure. Using RNA-seq we identify over 200 differentially expressed genes in air-liquid interface cultured primary normal human bronchial epithelial (NHBE) exposed to e-cig smoke solution from commercial e-cig cartridges. In particular, exposure to e-cig smoke solution inhibits biological pathways involving ribosomes and protein biogenesis in NHBE cells. Consistent with this effect, expression of corresponding ribosomal proteins and subsequent protein biogenesis are reduced in the cells exposed to e-cig. Gas chromatography/mass spectrometry (GC/MS) analysis identified the presence of five flavoring chemicals designated as 'high priority' in regard to respiratory health, and methylglyoxal in e-cig smoke solution. Together, our findings reveal the potential detrimental effect of e-cig smoke on ribosomes and the associated protein biogenesis in airway epithelium. Our study calls for further investigation into how these changes in the airway epithelium contribute to the current epidemic of lung injuries in e-cig users.