Presence of Additional Pathology in Low-Grade Acromioclavicular Joint Injuries.

OBJECTIVE: To determine if additional pathology is present in low-grade acromioclavicular (AC) joint injuries. DESIGN: Prospective case series. SETTING: Patients were assessed by primary care sports medicine physicians at a single institution between 2019 and 2023. PATIENTS: Patients aged 18 to 65 years diagnosed with a type I to III AC injury based on clinical and radiographic evaluation. INTERVENTION: Consenting patients underwent magnetic resonance imaging (MRI) evaluation within 21 days of injury. All injuries were treated nonoperatively. MAIN OUTCOME MEASURES: Additional pathologies identified on MRI were reported in a standardized fashion by fellowship-trained musculoskeletal radiologists. RESULTS: Twenty-nine patients (26 men/3 women) were consented with a mean (±SD) age of 28.6 ± 9.5 years. The mean time from injury to MRI was 8.1 ± 5.9 days. Twenty-three injuries were sport related, and 6 were accidental traumas. Based on MRI, injury type was reclassified in 16 of 29 patients, and 13 remained unchanged. Additional pathologies identified included 14 muscle injuries, 5 rotator cuff tears, 5 labral tears, 1 nondisplaced fracture, and 1 intra-articular body. CONCLUSION: MRI evidence suggests that most AC joint injuries are more severe than clinically diagnosed. Identifying additional pathology may alter diagnostic and treatment guidelines for type I to III AC joint injuries.

miR-200 family expression during normal and abnormal lung development due to congenital diaphragmatic hernia at the later embryonic stage in the nitrofen rat model.

INTRODUCTION: Congenital diaphragmatic hernia (CDH) is a life-threatening disease associated with pulmonary hypoplasia. CDH occurs approximately 1 in every 2000-3000 live births, and the pathophysiology is unknown. MicroRNAs are short, non-coding RNAs that control gene expression through post-transcriptional regulation. Based on our previous work, we hypothesized that the miR-200 family is differentially expressed in normal and abnormal lung development. We aimed to examine the expression of the miR-200 family during normal and hypoplastic lung development due to CDH. METHODS: We performed reverse transcriptase polymerase chain reaction (RT-qPCR) and fluorescent in situ hybridization (FISH) to study the expression levels and distribution of the miR-200 family members on embryonic day 21 (E21) rat control and nitrofen-induced hypoplastic CDH lungs. RESULTS: RT-qPCR showed up-regulation of miR-200a in hypoplastic CDH lungs. FISH showed contrasting expression patterns for miR- 200a, miR-200c, and miR-429 between control and hypoplastic CDH lungs, while we could not detect miR-141 in control and hypoplastic CDH lungs. CONCLUSION: We demonstrate a specific expression pattern of miR-200 family members in hypoplastic CDH lungs different from control lungs. This study suggests that disruption of miR-200 family expression plays a role in the pathogenesis of pulmonary hypoplasia associated with CDH.

Prenatal microRNA miR-200b Therapy Improves Nitrofen-induced Pulmonary Hypoplasia Associated With Congenital Diaphragmatic Hernia.

OBJECTIVE: We aimed to evaluate the use of miR-200b as a prenatal transplacental therapy in the nitrofen rat model of abnormal lung development and congenital diaphragmatic hernia (CDH). BACKGROUND: Pulmonary hypoplasia (PH) and pulmonary hypertension determine mortality and morbidity in CDH babies. There is no safe medical prenatal treatment available. We previously discovered that higher miR-200b is associated with better survival in CDH babies. Here, we investigate the role of miR-200b in the nitrofen rat model of PH and CDH and evaluate its use as an in vivo prenatal therapy. METHODS: We profiled miR-200b expression during nitrofen-induced PH using RT-qPCR and in situ hybridization in the nitrofen rat model of PH and CDH. The effects of nitrofen on downstream miR-200b targets were studied in bronchial lung epithelial cells using a SMAD luciferase assay, Western blotting and Immunohistochemistry. We evaluated miR-200b as a lung growth promoting therapy ex vivo and in vivo using lung explant culture and transplacental prenatal therapy in the nitrofen rat model. RESULTS: We show that late lung hypoplasia in CDH is associated with (compensatory) upregulation of miR-200b in less hypoplastic lungs. Increasing miR-200b abundance with mimics early after nitrofen treatment decreases SMAD-driven TGF-ß signaling and rescues lung hypoplasia both in vitro and in vivo. Also, prenatal miR-200b therapy decreases the observed incidence of CDH. CONCLUSIONS: Our data indicate that miR-200b improves PH and decreases the incidence of CDH. Future studies will further exploit this newly discovered prenatal therapy for lung hypoplasia and CDH.

MicroRNA 200b is upregulated in the lungs of fetal rabbits with surgically induced diaphragmatic hernia.

OBJECTIVE: Profiling of miR-200b expression and its targets (transforming growth factor [TGF]-ß2 and ZEB2) in the surgical rabbit congenital diaphragmatic hernia (DH) model before and after tracheal occlusion (TO). METHODS: Thirty-eight timed-pregnant rabbits had left DH creation on gestational day (GD) 23. On GD28, 17 randomly selected fetuses had TO. We harvested fetuses at GD23, GD28, or GD30. We calculated lung-to-body weight ratios, processed lungs for miR-200b in situ hybridization and real-time quantitative polymerase chain reaction, and evaluated effects on downstream targets TGF-ß2 or ZEB2. RESULTS: We obtained 16 DH fetuses (n = 7 GD28 and n = 9 GD30), 13 TO fetuses (GD30), and 38 control fetuses (n = 15 GD23, n = 11 GD28, and n = 12 GD30). Diaphragmatic hernia lungs were hypoplastic, and TO resulted in control lung-to-body weight ratio levels. Term miR-200b-3p levels were significantly upregulated in the hypoplastic compared with control ipsilateral lung (1.906 ± 0.90 vs 0.7429 ± 0.44) (P < .01). Fetal TO ipsilateral lungs displayed a variable miR-200b response on in situ hybridization and polymerase chain reaction, with levels similar to control and congenital DH lungs. The TGF-ß2 was unchanged in hypoplastic and TO lungs, and ZEB2 tended to be reduced in TO compared with DH lungs (1.79 [0.4-2.9] vs 0.73 [0.5-1.4]). CONCLUSIONS: Hypoplastic fetal rabbit lungs display upregulation of miR-200b expression although downstream targets are not different from controls. Following TO, fetal rabbit lungs display a variable miR-200b response.

Claudin 1 expression in basal-like breast cancer is related to patient age.

BACKGROUND: Defects in tight junctions, gate-keepers of the integrity of the epidermal barrier function, are known to contribute to cancer development. As such, enhancing our understanding of how the expression of proteins involved in these junctions is regulated in cancer, remains a priority. Although the expression of one of these proteins, claudin 1, is down regulated in most invasive human breast cancers (HBC), we have recently shown that high levels of claudin 1, characterized tumors belonging to the very aggressive basal-like breast cancer (BLBC) subtype. In these tumors, the claudin 1 protein, usually localized in the cell membrane, is often mislocalized to the cytoplasm. METHODS: To examine the clinical relevance of this observation, we have generated and analyzed an invasive HBC tissue microarray consisting of 151 breast tumor samples; 79 of which presented a basal-like phenotype (i.e. ER-ve, PR-ve HER2-ve, CK5/6 or EGFR+ve). We also interrogated the outcome of claudin 1 knockdown in a human BLBC cell line, BT-20. RESULTS: Immunohistochemical analysis of this patient cohort revealed a significant association between high claudin 1 expression and BLBCs in women 55 years of age and older. Interestingly, no significant association was found between claudin 1 and nodal involvement, tumor grade or tumor size. Regression analysis however, showed a significant positive association between claudin 1 and claudin 4, even though claudin 4 did not significantly correlate with patient age. Claudin 1 knockdown in BT-20 cells resulted in decreased cell migration. It also significantly altered the expression of several genes involved in epithelial-mesenchymal-transition (EMT); in particular, SERPINE 1 (PAI1) and SSP1 (osteopontin), known to inhibit EMT and cancer cell migration. Conversely, genes known to maintain EMT through their interaction, SNAIL2, TCF4 and FOXC2 were significantly down regulated. CONCLUSIONS: The association of high claudin 1 protein levels observed in tumors derived from older women with BLBC, suggests that claudin 1 has the potential to serve as a marker which can identify a specific subgroup of patients within the BLBC subtype and thus, further contribute to the characterization of these ill-defined breast cancers. More importantly, our studies strongly suggest that claudin 1 directly participates in promoting breast cancer progression, possibly through the alteration of expression of EMT genes.

Postoperative weight-bearing restrictions and rehabilitation protocols after hip arthroscopy for femoroacetabular impingement: a systematic review.

Despite recent increased interest in hip arthroscopy for the management of femoroacetabular impingement (FAI), there is little evidence to guide weight-bearing recommendations and rehabilitation postoperatively. The primary objective of this study was to determine if sufficient evidence exists to recommend specific weight-bearing restrictions postoperatively. This study was registered with PROSPERO (CRD42021247741). PubMed, MEDLINE and Embase were searched on 3 March 2023 for Level I-IV studies including patients over the age of 18 years, with a minimum 1-year follow-up and reporting of a weight-bearing status, a patient-reported outcome measure (PROM) and a clinical outcome. Meta-analysis was precluded due to heterogeneity in the included studies, and a descriptive analysis was undertaken. Methodological quality and risk of bias were assessed with the methodological index for non-randomized studies (MINORS). Twenty-four studies including 2231 patients who underwent hip arthroscopy for treatment of FAI were included (follow-up interval 33.2 ± 24.7 months). Most articles (62.5%) were case series. There were seven terms describing weight-bearing recommendations, with 83% being some variation of 'partial weight-bearing'. Eight PROMs were reported, with 83% using the modified Harris Hip Score and 87.5% of studies reporting reoperation rates. Only 75% of studies reported rehabilitation protocols. The average MINORS score was 11.07 ± 1.10 out of 16 for non-comparative studies and 18.22 ± 1.48 out of 24 for comparative studies. The reporting of weight-bearing status, clinical outcomes, PROMs and rehabilitation parameters remains poor. At present, sufficient comparative evidence does not exist to make specific weight-bearing recommendation postoperatively.

Characterising methamphetamine use to inform health and social policies in Manitoba, Canada: a protocol for a retrospective cohort study using linked administrative data.

INTRODUCTION: Rising use of methamphetamine is causing significant public health concern in Canada. The biological and behavioural effects of methamphetamine range from wakefulness, vigour and euphoria to adverse physical health outcomes like myocardial infarction, haemorrhagic stroke, arrhythmia and seizure. It can also cause severe psychological complications such as psychosis. National survey data point to increasing rates of methamphetamine use, as well as increasing ease of access and serious methamphetamine-related harms. There is an urgent need for evidence to address knowledge gaps, provide direction to harm reduction and treatment efforts and inform health and social policies for people using methamphetamine. This protocol describes a study that aims to address this need for evidence. METHODS: The study will use linked, whole population, de-identified administrative data from the Manitoba Population Research Data Repository. The cohort will include individuals in the city of Winnipeg, Manitoba, who came into contact with the health system for reasons related to methamphetamine use from 2013 to 2021 and a comparison group matched on age, sex and geography. We will describe the cohort's sociodemographic characteristics, calculate incidence and prevalence of mental disorders associated with methamphetamine use and examine rates of health and social service use. We will evaluate the use of olanzapine pharmacotherapy in reducing adverse emergency department outcomes. In partnership with Indigenous co-investigators, outcomes will be stratified by First Nations and Métis identity. ETHICS AND DISSEMINATION: The study was approved by the University of Manitoba Health Research Ethics Board, and access datasets have been granted by all data providers. We also received approval from the First Nations Health and Social Secretariat of Manitoba's Health Information Research Governance Committee and the Manitoba Métis Federation. Dissemination will be guided by an 'Evidence 2 Action' group of public rightsholders, service providers and knowledge users who will ensure that the analyses address the critical issues.

Intraoperative Dexamethasone Intravitreal Implant (Ozurdex) in Vitrectomy Surgery for Epiretinal Membrane.

Objective: To study the effectiveness and safety of the intravitreal dexamethasone implant 0.7 mg (Ozurdex®) in vitrectomy surgery for epiretinal membrane.Methods: This is a prospective, multicenter, pilot study. Inclusion criteria included visually significant (<20/50) idiopathic epiretinal membrane. All patients underwent 23-gauge pars plana vitrectomy with membrane peeling and Ozurdex implant injection. The primary outcome measure was best corrected visual acuity (BCVA) change at 3 months. Secondary outcomes included BCVA at 6 months and changes in central retinal thickness (CRT). Intraocular (IOP) changes were monitored and cataract progression in phakic patients was documented.Results: 15 patients were enrolled in the study, 12 eyes of 12 patients were included in the analysis. Mean preoperative BCVA was 50.67 ETDRS letters and improved significantly to 63.67 (+12.91 letters, p = .008) at 3 months. Mean CRT improved from 548 to 409 microns (p = .002) at 3 months. The IOP showed mild elevation at months 1 and 2 and returned almost to baseline at month six. There were no complications related to the steroid implant injection procedure in an air-filled eye.Conclusions: Intra-operative injection of Ozurdex® at the conclusion of PPV can be done safely. The peak IOP and lowest CRT after 2 months strengthens the findings of prior studies demonstrating Ozurdex activity up to 3 months in vitrectomized eyes.