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Plain balloon angioplasty is regarded as the mainstay of treatment for failing vascular access with high success rate, but the poor treatment durability creates significant workload and increases patient morbidity. The study aims to compare target lesion primary patency rate at 12 months between paclitaxel-coated balloon (DCB) versus plain old balloon angioplasty (POBA) for treatment of dysfunctional vascular access.

Study objective: To determine the pre-operative evaluation, surgical management and referral practices in patients with advanced stage endometriosis by Canadian gynaecologists.Design: A survey of obstetricians and gynaecologists.Setting: The survey was initiated and piloted at an academic centre by general gynaecologists and endometriosis specialists.Intervention: Electronically distributed to 733 individuals by the Society of Obstetricians and Gynaecologists of Canada. This included all members, irrespective of subspecialty and practice patterns.Measurement: Responses were collected using a web-based survey tool and analysed using Excel.Results: The response rate was 15.7% (115 respondents). Pre-operatively, 62.2% of respondents perform a transvaginal ultrasound on all of their patients, while magnetic resonance imaging is reserved for patients with physical exam findings suspicious for advanced endometriosis (26.7%) or in whom the surgeons suspect deep infiltrating endometriosis, bowel, bladder or uterosacral disease (54.4%). Most surgeons (81.4%) report encountering advanced disease that they did not suspect pre-operatively <10% of the time. Although 40% of respondents would refer their patients in whom they suspected deep infiltrating endometriosis, endometriomas, bowel, bladder or uterosacral ligament involvement to an endometriosis specialist prior to any attempted surgery, 54.4% would never refer without previously confirming the diagnosis at laparoscopy. In contrast, only 15% felt comfortable treating advanced endometriosis completely at time of laparoscopy (including deep infiltrating endometriosis, bladder and bowel disease). Post-operatively, 67.8% of respondents refer patients to an endometriosis specialist only if their disease was not appropriately treated surgically, while 23.3% do not refer any of their patients.Conclusion: Our study identified significant variability in the management of advanced endometriosis in Canada. Understanding these patterns will help us formulate a more universal investigation and management plan, which may improve the identification of patients pre-operatively with advanced stage endometriosis that could benefit from treatment by an endometriosis specialist.

The mTOR pathway integrates a diverse set of environmental cues, such as growth factor signals and nutritional status, to direct eukaryotic cell growth. Over the past two and a half decades, mapping of the mTOR signalling landscape has revealed that mTOR controls biomass accumulation and metabolism by modulating key cellular processes, including protein synthesis and autophagy. Given the pathway’s central role in maintaining cellular and physiological homeostasis, dysregulation of mTOR signalling has been implicated in metabolic disorders, neurodegeneration, cancer and ageing. In this Review, we highlight recent advances in our understanding of the complex regulation of the mTOR pathway and discuss its function in the context of physiology, human disease and pharmacological intervention.

A Patient Navigation (PN) model of care was introduced in a large metropolitan hospital in Ontario (Canada) to support transitions in care for older adults in 2019. The patient navigator is a community social worker or “community transitional lead” embedded in the hospital’s in care teams to assist with discharge planning and provide follow-up care to older adults, their families, and/or care partners for up to 90 days. Initially, the PN program supported acute care patients and has since expanded in the Emergency Department and Reactivation Care Centre. In this cohort retrospective observational study, we described the new PN model of care by analyzing the clinical notes collected by the patient navigator. This article provides preliminary insights for health leaders who are interested in implementing this novel PN model to improve transitions of care in a hospital setting. Funding was provided by the SLAIGHT Family Foundation.

Idiopathic pulmonary fibrosis (IPF) is a progressive, often fatal form of interstitial lung disease (ILD) characterized by the absence of a known cause and usual interstitial pneumonitis (UIP) pattern on chest CT imaging and/or histopathology. Distinguishing UIP/IPF from other ILD subtypes is essential given different treatments and prognosis. Lung biopsy is necessary when noninvasive data are insufficient to render a confident diagnosis.

To determine whether obstetrical patient outcomes have changed following the introduction of restricted resident work hours.

As theoretical underpinning is a priority for inter-professional teamwork, this scoping review examines theories for inter-professional teamwork in health care in the academic literature over the last 10 years. The review found 56 papers from 4 databases (CINAHL, Medline, Scholar's Portal and Web of Science) published in English. A content strategy approach was used to categorise the theories, interventions and outcomes. The literature revealed a trend moving away from single theories, into multifaceted theories. There were more papers on inter-professional education interventions, compared to interprofessional practice or organisation interventions. Many papers reported the importance of patient outcomes as the driving force for teamwork. However, there is a lack of evidence to support this notion. Further research is suggested on teamwork effectiveness, including measurement and evaluation of patient and system outcomes. Based on the scoping literature review, a conceptual model is developed to align interventions with theory to outcomes, which considers four broad theoretical perspectives highlighted herein (learning, social-psychological, organisation and system), interventions at various levels (patient, profession, micro, meso and macro) and measurement of outcomes. This framework identifies various theories, interventions and outcomes, which will help direct policy, practice and research in matching the right theory(ies) to intervention(s) and outcome(s).

Genetic alterations disrupting the transcription factor IKZF1 (encoding IKAROS) are associated with poor outcome in B lineage acute lymphoblastic leukemia (B-ALL) and occur in >70% of the high-risk BCR-ABL1+ (Ph+) and Ph-like disease subtypes. To examine IKAROS function in this context, we have developed novel mouse models allowing reversible RNAi-based control of Ikaros expression in established B-ALL in vivo. Notably, leukemias driven by combined BCR-ABL1 expression and Ikaros suppression rapidly regress when endogenous Ikaros is restored, causing sustained disease remission or ablation. Comparison of transcriptional profiles accompanying dynamic Ikaros perturbation in murine B-ALL in vivo with two independent human B-ALL cohorts identified nine evolutionarily conserved IKAROS-repressed genes. Notably, high expression of six of these genes is associated with inferior event–free survival in both patient cohorts. Among them are EMP1, which was recently implicated in B-ALL proliferation and prednisolone resistance, and the novel target CTNND1, encoding P120-catenin. We demonstrate that elevated Ctnnd1 expression contributes to maintenance of murine B-ALL cells with compromised Ikaros function. These results suggest that IKZF1 alterations in B-ALL leads to induction of multiple genes associated with proliferation and treatment resistance, identifying potential new therapeutic targets for high-risk disease.

B-lymphoid transcription factors, such as PAX5 and IKZF1, are critical for early B-cell development, yet lesions of the genes encoding these transcription factors occur in over 80% of cases of pre-B-cell acute lymphoblastic leukaemia (ALL). The importance of these lesions in ALL has, until now, remained unclear. Here, by combining studies using chromatin immunoprecipitation with sequencing and RNA sequencing, we identify a novel B-lymphoid program for transcriptional repression of glucose and energy supply. Our metabolic analyses revealed that PAX5 and IKZF1 enforce a state of chronic energy deprivation, resulting in constitutive activation of the energy-stress sensor AMPK. Dominant-negative mutants of PAX5 and IKZF1, however, relieved this glucose and energy restriction. In a transgenic pre-B ALL mouse model, the heterozygous deletion of Pax5 increased glucose uptake and ATP levels by more than 25-fold. Reconstitution of PAX5 and IKZF1 in samples from patients with pre-B ALL restored a non-permissive state and induced energy crisis and cell death. A CRISPR/Cas9-based screen of PAX5 and IKZF1 transcriptional targets identified the products of NR3C1 (encoding the glucocorticoid receptor), TXNIP (encoding a glucose-feedback sensor) and CNR2 (encoding a cannabinoid receptor) as central effectors of B-lymphoid restriction of glucose and energy supply. Notably, transport-independent lipophilic methyl-conjugates of pyruvate and tricarboxylic acid cycle metabolites bypassed the gatekeeper function of PAX5 and IKZF1 and readily enabled leukaemic transformation. Conversely, pharmacological TXNIP and CNR2 agonists and a small-molecule AMPK inhibitor strongly synergized with glucocorticoids, identifying TXNIP, CNR2 and AMPK as potential therapeutic targets. Furthermore, our results provide a mechanistic explanation for the empirical finding that glucocorticoids are effective in the treatment of B-lymphoid but not myeloid malignancies. Thus, B-lymphoid transcription factors function as metabolic gatekeepers by limiting the amount of cellular ATP to levels that are insufficient for malignant transformation.

The Omicron variant of the SARS-CoV-2 virus is described as more contagious than previous variants. We sought to assess risk to health care workers (HCWs) caring for patients with COVID-19 in surgical/obstetrical settings, and the perception of risk among this group.

To describe recent evidence regarding the surgical approach of strabismus in children with various forms of developmental delay.

Purpose:Recent literature reports that patients and parents of pediatric patients prefer their physician to wear a white coat and to address them informally. This study aims to characterize current practice patterns of pediatric ophthalmologists regarding their use of white coats and salutations during outpatient pediatric encounters.Methods:An eight-question survey was e-mailed to members of the American Academy of Pediatric Ophthalmology and Strabismus in 2012. The questions focused on clinical setting, use of white coats in out-patient encounters, and preferred language used to address the patient’s parents. Surveys not completed in full were excluded from data analysis.Results:Of approximately 1,266 members who received the survey, 606 completed the survey. Five hundred ninety-nine surveys were included in the data analysis. Sixty-three percent of attending physicians and 80% of fellows reported they did not routinely wear white coats while examining outpatient children. Forty-six percent of attending physicians and 48% of fellows addressed the patient’s parents as “mom” or “dad”. There was no significant association between wearing a white coat and type of practice setting, practice characteristics, or location in a children’s hospital for attending physicians or fellows.Conclusions:Contrary to preferences expressed by patients and their parents, a majority of pediatric ophthalmologists do not routinely wear white coats during pediatric outpatient examinations. Practice patterns appear to be in line with previously reported parental greeting preferences.[J Pediatr Ophthalmol Strabismus 2014;51(1):13–16.]

To compare the relative long-term effects on ovarian reserve of treating fibroids in reproductive-aged women with uterine artery embolization (UAE) versus laparoscopic myomectomy (LM), using sensitive measures including antral follicle count (AFC) and serum anti-Müllerian hormone (AMH).

To estimate the clinical and economic effect of using second-generation endometrial ablation devices compared to first-generation devices for treatment of menorrhagia in pre-menopausal women. The secondary objective was to compare the second-generation devices with one another.

To survey all gynaecologists in Canada to determine the number who perform or offer the laparoscopic myomectomy (LM) procedure, the barriers that deter gynaecologists from performing or offering LM, and to understand the perceptions and attitudes of Canadian gynaecologists with respect to LM.

Post hoc analyses evaluated the effect of infliximab upon concurrent perianal Crohn disease (CD) in a subpopulation of 31 patients from REACH, a randomized trial of 112 children with moderately to severely active luminal CD.

Post hoc analyses evaluated the effect of infliximab upon concurrent perianal Crohn disease (CD) in a subpopulation of 31 patients from REACH, a randomized trial of 112 children with moderately to severely active luminal CD. The Pediatric Crohn Disease Activity Index perirectal subscore was used to assess perianal symptom activity and therapeutic response. Patients with no symptoms or asymptomatic tags received a score of 0; those with “1–2 indolent fistula, scant drainage, no tenderness” received a score of 5; and those with “active fistula, drainage, tenderness or abscess” received a score of 10. Initial perirectal subscores of 10 or 5 decreasing to 0 were considered complete response. Subscores of 10 decreasing to 5 were considered partial response. All patients were followed for efficacy and safety through week 54. Twenty-two patients with baseline perianal disease were randomized at week 10 following a 3-dose infliximab induction regimen. At week 2, 40.9% (9/22) of patients with signs and symptoms of perianal disease at baseline attained response (4 partial and 5 complete). At week 54, 72.7% (16/22) of patients with signs and symptoms of perianal disease attained response (1 partial and 15 complete). Nine patients developed perianal signs and symptoms during treatment; 7 had complete response and 2 had no response at week 54. The incidence of adverse events for patients with perianal symptoms at baseline and for those in the overall REACH population was similar (95.7% vs 94.6%). Infliximab rapidly reduced concurrent perianal disease signs and symptoms in this REACH cohort.

We wished to determine prescribing practices of obstetricians in Canada regarding tocolytics, antenatal corticosteroids, and progesterone for women at increased risk of preterm labour and birth, and to determine whether these practices changed between 1997–98 and 2004.

Objective:To compare endometrial cancer treatment strategies and outcomes across the province of Ontario, Canada.

Guanine nucleotide exchange factors in the Dbl family activate Rho GTPases by accelerating dissociation of bound GDP, promoting acquisition of the GTP-bound state. Dbl proteins possess a ∼200 residue catalytic Dbl-homology (DH) domain, that is arranged in tandem with a C-terminal pleckstrin homology (PH) domain in nearly all cases. Here we report the solution structure of the DH domain of human PAK-interacting exchange protein (βPIX). The domain is composed of 11 α-helices that form a flattened, elongated bundle. The structure explains a large body of mutagenesis data, which, along with sequence comparisons, identify the GTPase interaction site as a surface formed by three conserved helices near the center of one face of the domain. Proximity of the site to the DH C-terminus suggests a means by which PH-ligand interactions may be coupled to DH-GTPase interactions to regulate signaling through the Dbl proteins in vivo.

An antidiarrhea mixture containing attapulgite and citrus pectin was studied for its potential effect on the absorption of promazine from the human gastrointestinal tract. Test conditions were established so that results would have maximum applicability to the clinical use situation. Drug and adsorbent were not equilibrated prior to administration. Under these conditions, the antidiarrhea mixture decreased the rate and extent of absorption of the test drug. An in vitroadsorption study established that the antidiarrhea mixture had a strong affinity for the test drug. Results are in general agreement with the previous report in this series.

B cell and plasma cell fates are controlled by different transcriptional networks, as exemplified by the mutually exclusive expression and cross-antagonism of the B cell identity factor Pax5 and the plasma cell regulator Blimp1. It has been postulated that repression of Pax5 by Blimp1 is essential for plasma cell development. Here, we challenged this hypothesis by analyzing the IghPax5/+ mouse, which expressed a Pax5 minigene from the immunoglobulin heavy-chain locus. Despite high Pax5 expression, plasma cells efficiently developed in young IghPax5/+ mice at steady state and upon immunization, while their number moderately declined in older mice. Although Pax5 significantly deregulated the plasma cell expression program, key plasma cell regulators were normally expressed in IghPax5/+ plasma cells. While IgM and IgA secretion by IghPax5/+ plasma cells was normal, IgG secretion was modestly decreased. Hence, Pax5 repression is not essential for robust plasma cell development and antibody secretion, although it is required for optimal IgG production and accumulation of long-lived plasma cells.

The purpose of this video is to provide an overview of the guidelines and indications for laparoscopy in pregnancy as well as to review preoperative, intraoperative and postoperative considerations in this unique patient population. In this video, we review topics such as patient positioning, surgical techniques to aid with visualization, recommendations for venous thromboembolism prophylaxis and monitoring for preterm labor, among others. Although historically contraindicated in pregnancy, laparoscopy is now the preferred treatment approach to surgical conditions in pregnancy. We aim to provide an approach to laparoscopy in pregnancy through this educational video.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

To determine whether DNA methylation patterns in genes coding for selected T-lymphocyte proteins are associated with perinatal psychiatric distress or with complications of pregnancy.

Dielectric constants of water–ethanol–sucrose and water–ethanol–sorbitol systems have been experimentally determined. Dielectric constant values in these systems were generally found to be a complex function of composition expressed as weight per cent. Data are presented which will allow generation of dielectric constant—composition relationships over a dielectric constant range between 40 and 70.

Tumors are composed of phenotypically heterogeneous cancer cells that often resemble various differentiation states of their lineage of origin. Within this hierarchy, it is thought that an immature subpopulation of tumor-propagating cancer stem cells (CSCs) differentiates into non-tumorigenic progeny, providing a rationale for therapeutic strategies that specifically eradicate CSCs or induce their differentiation. The clinical success of these approaches depends on CSC differentiation being unidirectional rather than reversible, yet this question remains unresolved even in prototypically hierarchical malignancies, such as acute myeloid leukemia (AML). Here, we show in murine and human models of AML that, upon perturbation of endogenous expression of the lineage-determining transcription factor PU.1 or withdrawal of established differentiation therapies, some mature leukemia cells can de-differentiate and reacquire clonogenic and leukemogenic properties. Our results reveal plasticity of CSC maturation in AML, highlighting the need to therapeutically eradicate cancer cells across a range of differentiation states.