Timing of testosterone discontinuation and assisted reproductive technology outcomes in transgender patients: a cohort study.

Objective: To determine if there is an association between the timing of testosterone discontinuation and assisted reproductive technology (ART) outcomes. Design: Retrospectivse cohort study. Setting: Single academic center. Patients: We included consecutive transgender patients seeking fertility preservation between October 2019 and April 2021. Patients who identified as transgender on androgens for >1 month on presentation were included. Interventions: None. Main outcome measures: A linear regression model was used to evaluate the effect of testosterone discontinuation duration on the number of mature oocytes retrieved. Results: Eighteen patients (mean age 27.7 [SD 5.2] years, mean body mass index 27.3 [SD 4.6] kg/m2, mean antimüllerian hormone 27.2 [SD 11.8], median antral follicle count 20 [interquartile range (IQR) 14-32]) were included in the analysis. No patient underwent transition-related surgery (eg, oophorectomy, hysterectomy). None of the patients were previously pregnant. Mean time o,n testosterone was 44 (SD 29.6) months. The median time off testosterone until the start of ovarian stimulation was 7.7 weeks (IQR 4.3-20.7). All patients underwent oocyte cryopreservation except one who had embryo cryopreservation. The median total number of oocytes was 11 (IQR 7-14). The median number of mature oocytes was 7.5 (IQR 5-12) oocytes. The univariate regression model evaluating the duration of time off testosterone before ART demonstrated no significant association with the outcome of mature oocytes (regression coefficient, 0.19; 95% confidence interval, -0.13 to 0.50). Conclusion: In a retrospective analysis of transgender patients recently on testosterone undergoing ART, no association was detected between the timing of testosterone cessation and the number of mature oocytes.

Efficacy and tolerability of metronomic chemotherapy in patients with metastatic breast cancer - an international experience in West Sweden and in the South of Ireland.

INTRODUCTION: Metronomic chemotherapy (MCT) is the continuous administration of low dose chemotherapy. It has significant clinical efficacy with minimal toxicity as compared to conventional chemotherapy regimens. Thus represents an attractive treatment modality in selected patients with advanced breast cancer. METHODS: Patients who received MCT in the form of Capecitabine/Cyclophosphamide for the treatment of advanced breast cancer between May 2014 and October 2018 in Sahlgrenska University Hospital in Sweden and in Cork University Hospital, University Hospital Kerry and the South Infirmary-Victoria University Hospital in Ireland were identified. Medical records were retrospectively reviewed to collect data. All survival analyses were described by Kaplan-Meier curves and analysed with log-rank tests. The primary end-point was time on treatment, used as a surrogate marker for efficacy. RESULTS: 148 patients were identified (84 - Sweden, 64 - Ireland), with a median age of 64.2 (range 31-89). The overall mean time on treatment for all patients in both countries is 9.05 months (range 0.36 - 67.21). In patients with bone only disease the mean time on treatment was 10.1 months (range 0.7 - 67.2), compared to patients with visceral disease of 8.91 months (range 0.36 - 39.77). Treatment was ended in the majority of patients because of progression of disease, representing 108 patients (72.9%). CONCLUSION: This is an observational, retrospective study demonstrating the real world effectiveness of MCT in the treatment of advanced breast cancer. In this cohort of unselected pre-treated patients, the efficacy of MCT was comparable with the survival outcomes of landmark clinical trials.

Expanding Urgent Oncofertility Services for Reproductive Age Women Remote from a Tertiary Level Fertility Centre by Use of Telemedicine and an On-site Nurse Navigator.

The objective of this study was to examine a 1-year pilot program aimed at increasing access to fertility preservation (FP) information and services for reproductive-age women newly diagnosed with cancer at a centre geographically remote from a tertiary fertility clinic. An oncofertility nurse navigator (ONN) position was created within the regional cancer centre with the goals of (1) improving local physician knowledge of FP and FP services and (2) improving patient access to FP counselling and services. The ONN identified all women diagnosed with cancer requiring treatment that could impact their fertility and discussed FP options with them and their physicians. As part of a comprehensive program aimed at facilitating access to FP services, the ONN arranged consultations with fertility specialists via telemedicine and coordinated satellite cycle monitoring with a local gynaecologist in order to minimize travel. Patients were surveyed about their reproductive plans, decision-making around FP and experiences with the program. Physicians were surveyed about their engagement with FP services, barriers to FP access and satisfaction with the program. Twenty-two women were eligible for FP during the year-long pilot program. All participated in the study. The most common diagnoses were breast and cervical cancer. At the time of diagnosis, 36.4% of women had no biological children and 68.2% did not desire (more) children. Four women had an FP consultation, and two proceeded with oocyte or embryo cryopreservation. At the end of the pilot program, more physician respondents often or always discussed FP with their patients, stated they frequently refer for FP consultations and stated their patients could obtain FP services in a timely fashion. An ONN within a cancer centre remote from tertiary fertility care can enable access to FP services with minimal need for travel by using local gynaecologic expertise and telemedicine.

Mycobacterium goodii pneumonia: An unusual presentation of nontuberculous mycobacterial infection requiring a novel multidisciplinary approach to management.

BACKGROUND: Mycobacterium goodii is a rapidly growing nontuberculous mycobacterium which has been associated with several infections including cellulitis, osteomyelitis, lymphadenitis, infected pacemakers and bursitis but it is a rare cause of respiratory infection. CASE PRESENTATION: In this case report we describe a 51-year-old woman who presented with a 6-week history of non-productive cough, pleuritic chest pain and weight loss. She had a history of gastric adenocarcinoma managed with a distal oesophagectomy and total gastrectomy and consequentially suffered severe post-operative gastric reflux. Initial cultures were negative but following a VATS lung biopsy Mycobacterium goodii was cultured and histology revealed an organising pneumonia. Treatment was with a prolonged course of steroids, amikacin and meropenem followed by oral ciprofloxacin and doxycycline. Ongoing gastric dysmotility and weight loss showed clinical improvement with a novel approach of a combination of prokinetics and somatostatin analogues controlling risk of repeat aspiration and improving symptom control. CONCLUSIONS: This is an unusual case of organising pneumonia related to Mycobacterium goodii infection and highlights the importance of mycobacterial culture in unusual and unresolving cases of organising pneumonia. The importance of controlling symptoms related to gastric dysmotility and aspiration is also addressed.

Fracture mechanics of shear crack propagation and dissection in the healthy bovine descending aortic media.

This experimental study adopts a fracture mechanics strategy to investigate the mechanical cause of aortic dissection. Inflation of excised healthy bovine aortic rings with a cut longitudinal notch that extends into the media from the intima suggests that an intimal tear may propagate a nearly circumferential-longitudinal rupture surface that is similar to the delamination that occurs in aortic dissection. Radial and 45°-from-radial cut notch orientations, as seen in the thickness surface, produce similar circumferential crack propagation morphologies. Partial cut notches, whose longitudinal length is half the width of the ring, measure the influence of longitudinal material on crack propagation. Such specimens also produce circumferential cracks from the notch root that are visible in the thickness circumferential-radial plane, and often propagate a secondary crack from the base of the notch, visible in the intimal circumferential-longitudinal plane. Inflation of rings with pairs of cut notches demonstrates that a second notch modifies the propagation created in a specimen with a single notch. The circumferential crack propagation is likely a consequence of the laminar medial structure. These fracture surfaces are probably due to non-uniform circumferential shear deformation in the heterogeneous media as the aortic wall expands. The qualitative deformation morphology around the root of the cut notch during inflation is evidence for such shear deformation. The shear apparently results from relative slip in the circumferential direction of collagen fibers. The slip may produce shear in the longitudinal-circumferential plane between medial layers or in the radial-circumferential plane within a medial lamina in an idealized model. Circumferential crack propagation in the media is then a shear mechanical process that might be facilitated by disease of the tissue. STATEMENT OF SIGNIFICANCE: An intimal tear of an apparently healthy aortic wall near the aortic arch is life-threatening because it may lead to full rupture or to wall dissection in which delamination of the medial layer extends around most of the aortic circumference. The mechanical events underlying dissection are not definitively established. This experimental fracture mechanics study provides evidence that shear rupture is the main mechanical process underlying aortic dissection. The commonly performed tensile strength tests of aortic tissue are not clinically useful to predict or describe aortic dissection. One implication of the study is that shear tests might produce more fruitful simple assessments of the aortic wall strength. A clinical implication is that when presented with an intimal tear, those who guide care might recommend steps to reduce the shear load on the aorta.

No. 356-Egg Freezing for Age-Related Fertility Decline.

OBJECTIVE: To provide a comprehensive review and evidence based recommendations for Canadian fertility centres that offer social egg freezing. OUTCOMES: In social egg freezing cycles we evaluated thawed oocyte survival rates, fertilization rates, embryo quality, pregnancy rates, and live birth rates. We also review how these outcomes are impacted by age, ovarian reserve, and the number of eggs cryopreserved. Finally, we discuss the risks of social egg freezing, the alternatives, the critical elements for counselling and informed consent, and future reporting of egg freezing outcome data. EVIDENCE: Published literature was reviewed through searches of MEDLINE and CINAHL using appropriate vocabulary and using key words ("oocyte cryopreservation," "egg freezing," "egg vitrification," "social egg freezing," and "elective egg freezing"). Results included systematic reviews, randomized controlled trials, controlled clinical trials, and observational studies. Expert opinion based on clinical experience, descriptive studies, or reports of expert committees was also included to discuss aspects of egg freezing not currently rigorously studied. VALUES: The evidence obtained was reviewed and evaluated by the Clinical Practice Guideline (CPG) Committees of the Canadian Fertility and Andrology Society (CFAS) under the leadership of the principal authors. BENEFITS, HARMS, AND COSTS: Implementation of this guideline should assist the clinician to develop an optimal approach in providing counselling for egg freezing while minimizing harm and improving patient outcomes during treatment. VALIDATION: These guidelines have been reviewed and approved by the membership of the CFAS and by the CPG Committees of CFAS and The Society of Obstetricians and Gynaecologists of Canada (SOGC). SPONSORS: CFAS and SOGC.

ßhCG-secreting osteosarcoma.

A 35-year-old woman presented to our institution with tender, right knee swelling. Radiological and pathological work-up revealed metastatic osteosarcoma. Prior to the initiation of chemotherapy, she underwent a routine urine pregnancy test and was surprised with a positive result. Serum beta human chorionic gonadotropin (ßhCG) levels were also consistently positive and rising. No gestational sac was seen at transvaginal ultrasound. The paraneoplastic ectopic secretion of ßhCG has been well described in gestational trophoblastic and gonadal tumours but has very rarely been associated with other tumour types. This patient's ßhCG level was reflective of osteosarcoma activity and normalised with response to chemotherapy. The prognostic implications of ßhCG expression in more diverse tumours is unclear; however, where raised, it can be used to monitor disease activity.

Progressive multifocal leukoencephalopathy secondary to rituximab-induced immunosuppression and the presence of John Cunningham virus: a case report and literature review.

We present the case of a 60-year-old man who developed subacute neurologic changes, in the setting of stage III non-Hodgkin's follicular lymphoma, and was treated with induction chemotherapy, followed by a year of maintenance rituximab. Magnetic resonance imaging of the brain with gadolinium was pathognomonic for progressive multifocal leukoencephalopathy (PML). He was treated with sequential plasmapheresis and intravenous immunoglobulin with clinical improvement. A literature review of the diagnostic workup of rituximab-induced PML was undertaken. This case and the literature review demonstrate the important role of magnetic resonance imaging of the brain in diagnosis and follow-up of rituximab-induced PML. Specific radiologic features in combination with cerebrospinal fluid can be diagnostic and avoid the morbidity and mortality of a diagnostic brain biopsy. Plasmapheresis and intravenous immunoglobulin have a therapeutic role and demonstrate symptom improvement and disease control. Follow-up imaging in combination with clinical response is important in demonstrating a treatment response.

Automated Three-Dimensional Reconstruction of the Left Ventricle From Multiple-Axis Echocardiography.

Two-dimensional echocardiography (echo) is the method of choice for noninvasive evaluation of the left ventricle (LV) function owing to its low cost, fast acquisition time, and high temporal resolution. However, it only provides the LV boundaries in discrete 2D planes, and the 3D LV geometry needs to be reconstructed from those planes to quantify LV wall motion, acceleration, and strain, or to carry out flow simulations. An automated method is developed for the reconstruction of the 3D LV endocardial surface using echo from a few standard cross sections, in contrast with the previous work that has used a series of 2D scans in a linear or rotational manner for 3D reconstruction. The concept is based on a generalized approach so that the number or type (long-axis (LA) or short-axis (SA)) of sectional data is not constrained. The location of the cross sections is optimized to minimize the difference between the reconstructed and measured cross sections, and the reconstructed LV surface is meshed in a standard format. Temporal smoothing is implemented to smooth the motion of the LV and the flow rate. This software tool can be used with existing clinical 2D echo systems to reconstruct the 3D LV geometry and motion to quantify the regional akinesis/dyskinesis, 3D strain, acceleration, and velocities, or to be used in ventricular flow simulations.

Advanced practice nurses: Improving access to fertility preservation for oncology patients.

Cancer therapies such as chemotherapy, radiation therapy and surgery may place the future fertility of both children and young adults at risk. Oncofertility is a rapidly evolving area that involves increasing access to fertility preservation (FP) information and services. This manuscript aims to: a) highlight the fertility risks associated with cancer therapy and its psychosocial impact, b) describe FP options, c) discuss the unique challenges of FP in distinct cancer populations, and d) illustrate the pivotal role of APNs in oncofertility counselling and education.

Crack Propagation and Its Shear Mechanisms in the Bovine Descending Aorta.

Aortic dissection and rupture may involve circumferential shear stress in the circumferential-longitudinal plane. Inflation of bovine descending aortic ring specimens provides evidence of such shear from the non-uniform circumferential distortion of radial lines drawn on the circumferential-radial ring face. Delamination without tensile peeling induces cracks that propagate nearly circumferentially in the circumferential-longitudinal plane from the root of a radial cut representing rupture initiation in a ring. Translational shear deformation tests of small rectangular aortic wall blocks in the circumferential and longitudinal direction measure the consequences of such shear on substructures in the aortic wall, in particular the collagen fibers. The two directions of shear deformation produce no statistical difference in the shear stress response of the wall. Possibly, the interfiber connections between collagen fibers are put into tension by either translational shear deformation so that the stress measured reflects the tensile response of these connections. Wall rupture may involve failure of these connections; such failure is supported by the voids parallel to the collagen fibers observed in a histological study after translational shear. Further, interstitial fluid is redistributed by shear as evidenced by the measured weight loss of a set of specimens during the translational shear of blocks. Because the mass changes, mathematical modeling of aortic tissue in vitro as incompressible is an approximation. These observations suggest that no simple modification of classical rupture theories, whether based on energy functions, stress or strain, suffices to predict the rupture of hydrated soft biological tissue that has complex substructures.

Acoustically active injection catheter guided by ultrasound: navigation tests in acutely ischemic porcine hearts.

Catheters are increasingly used therapeutically and investigatively. With complex usage comes a need for more accurate intracardiac localization than traditional guidance can provide. An injection catheter navigated by ultrasound was designed and then tested in an open-chest model of acute ischemia in eight pigs. The catheter is made "acoustically active" by a piezo-electric crystal near its tip, electronically controlled, vibrating in the audio frequency range and uniquely identifiable using pulsed-wave Doppler. Another "target" crystal was sutured to the epicardium within the ischemic region. Sonomicrometry was used to measure distances between the two crystals and then compared with measurements from 2-D echocardiographic images. Complete data were obtained from seven pigs, and the correlation between sonomicrometry and ultrasound measurements was excellent (p < 0.0001, ρ = 0.9820), as was the intraclass correlation coefficient (0.96) between two observers. These initial experimental results suggest high accuracy of ultrasound navigation of the acoustically active catheter prototype located inside the beating left ventricle.

Extrathymic Aire-expressing cells are a distinct bone marrow-derived population that induce functional inactivation of CD4⁺ T cells.

The autoimmune regulator (Aire) is essential for prevention of autoimmunity; its role is best understood in the thymus, where it promotes self-tolerance through tissue-specific antigen (TSA) expression. Recently, extrathymic Aire-expressing cells (eTACs) have been described in murine secondary lymphoid organs, but the identity of such cells and their role in immune tolerance remains unclear. Here we have shown that eTACs are a discrete major histocompatibility complex class II (MHC II)(hi), CD80(lo), CD86(lo), epithelial cell adhesion molecule (EpCAM)(hi), CD45(lo) bone marrow-derived peripheral antigen-presenting cell (APC) population. We also have demonstrated that eTACs can functionally inactivate CD4⁺ T cells through a mechanism that does not require regulatory T cells (Treg) and is resistant to innate inflammatory stimuli. Together, these findings further define eTACs as a distinct tolerogenic cell population in secondary lymphoid organs.

Motion analysis of right ventricular dysfunction under mild or moderate pressure overload caused by acute pulmonary embolism.

Acute pulmonary embolism (APE) is the third most common cause of death in the United States. Appearing as a sudden blockage in a major pulmonary artery, APE may cause mild, moderate or severe right ventricular (RV) overload. Although severe RV overload produces diagnostically obvious RV mechanical failure, little progress has been made in gaining a clinical and biophysical understanding of moderate and mild acute RV overload and its impact on RV functionality. In the research described here, we conducted a pilot study in pigs using echocardiography and observed the following abnormalities in RV functionality under acute mild or moderate RV overload: (i) occurrence of paradoxical septal motion with "waving" dynamics; (ii) decrease in local curvature of the septum (p < 0.01); (iii) lower positive correlation between movement of the RV free wall and movement of the septum (p < 0.05); (iv) slower rate of RV fractional area change (p < 0.05); and (v) decrease in movement stability, particularly in the middle of the septum (p < 0.05).

Left ventricular flow analysis: recent advances in numerical methods and applications in cardiac ultrasound.

The left ventricle (LV) pumps oxygenated blood from the lungs to the rest of the body through systemic circulation. The efficiency of such a pumping function is dependent on blood flow within the LV chamber. It is therefore crucial to accurately characterize LV hemodynamics. Improved understanding of LV hemodynamics is expected to provide important clinical diagnostic and prognostic information. We review the recent advances in numerical and experimental methods for characterizing LV flows and focus on analysis of intraventricular flow fields by echocardiographic particle image velocimetry (echo-PIV), due to its potential for broad and practical utility. Future research directions to advance patient-specific LV simulations include development of methods capable of resolving heart valves, higher temporal resolution, automated generation of three-dimensional (3D) geometry, and incorporating actual flow measurements into the numerical solution of the 3D cardiovascular fluid dynamics.

Abbreviated exposure to cuprizone is sufficient to induce demyelination and oligodendrocyte loss.

Cuprizone intoxication is one of several animal models used to study demyelination and remyelination. Early treatment protocols exposed mice to cuprizone for 6 weeks to induce demyelination; however, more recent reports have varied exposure times from 4 to 5 weeks. The goal of this study was to determine the minimal exposure of cuprizone in C57BL/6 mice that would induce a pathology of robust demyelination and gliosis similar to that described for a 5- or 6-week treatment. We found that an abbreviated insult of only 2 weeks of exposure to cuprizone induced significant demyelination 3 weeks later (5-week time point) but was somewhat variable. Three weeks of exposure to cuprizone produced extensive demyelination by week 5, equivalent to that observed with 5 weeks of exposure. The depletion of mature oligodendrocytes, as well as microglia and astrocyte accumulation, showed trends similar to those with 5-week exposure to cuprizone. Once mature oligodendrocytes are perturbed after a 3-week treatment, the progression to demyelination occurs without requiring further exposure. Furthermore, the early removal of cuprizone did not accelerate remyelination, suggesting that other sequences of events must follow before repair can occur. Thus, a short, "hit and run" CNS insult triggers a cascade of events leading to demyelination 2-3 weeks later.

Detection of progressive myocardial tissue injury by ultrasonic integrated backscatter immediately after coronary reperfusion.

Myocardial reperfusion following ischemia may paradoxically cause additional injury, including microvascular damage and edema. These structural alterations augment tissue echogenicity, which is measurable by ultrasonic integrated backscatter (IB). We sought to characterize alterations in myocardial IB in an ischemic and reperfused region of the rat heart. Myocardial IB of the regions of interest in 12 adult male Sprague-Dawley rats was studied at baseline, during ischemia, and chronologically after coronary reopening, using an ultrasound frequency of 8 MHz. IB did not significantly change between baseline and ischemia. However, within 1 min of reperfusion, IB significantly increased and continued to increase until 10 min of reperfusion, when a plateau was reached. Areas of high echogenicity were comparable to infarcted areas on gross pathologic slices and had edema with extravasation of red blood cells. Myocardial reperfusion following ischemia significantly augments tissue echogenicity. A continuing increase of IB suggests a rapid progression of reperfusion injury.