Direct thrombin inhibitors fail to reverse the negative effects of heparin on lung growth and function after murine left pneumonectomy.

Neonates with congenital diaphragmatic hernia (CDH) frequently require cardiopulmonary bypass and systemic anticoagulation. We previously demonstrated that even subtherapeutic heparin impairs lung growth and function in a murine model of compensatory lung growth (CLG). The direct thrombin inhibitors (DTIs) bivalirudin and argatroban preserved growth in this model. Although DTIs are increasingly used for systemic anticoagulation clinically, patients with CDH may still receive heparin. In this experiment, lung endothelial cell proliferation was assessed following treatment with heparin-alone or mixed with increasing concentrations of bivalirudin or argatroban. The effects of subtherapeutic heparin with or without DTIs in the CLG model were also investigated. C57BL/6J mice underwent left pneumonectomy and subcutaneous implantation of osmotic pumps. Pumps were preloaded with normal saline, bivalirudin, or argatroban; treated animals received daily intraperitoneal low-dose heparin. In vitro, heparin-alone decreased endothelial cell proliferation and increased apoptosis. The effect of heparin on proliferation, but not apoptosis, was reversed by the addition of bivalirudin and argatroban. In vivo, low-dose heparin decreased lung volume compared with saline-treated controls. All three groups that received heparin demonstrated decreased lung function on pulmonary function testing and impaired exercise performance on treadmill tolerance testing. These findings correlated with decreases in alveolarization, vascularization, angiogenic signaling, and gene expression in the heparin-exposed groups. Together, these data suggest that bivalirudin and argatroban fail to reverse the inhibitory effects of subtherapeutic heparin on lung growth and function. Clinical studies on the impact of low-dose heparin with DTIs on CDH outcomes are warranted.NEW & NOTEWORTHY Infants with pulmonary hypoplasia frequently require cardiopulmonary bypass and systemic anticoagulation. We investigate the effects of simultaneous exposure to heparin and direct thrombin inhibitors (DTIs) on lung growth and pulmonary function in a murine model of compensatory lung growth (CGL). Our data suggest that DTIs fail to reverse the inhibitory effects of subtherapeutic heparin on lung growth and function. Clinical studies on the impact of heparin with DTIs on clinical outcomes are thus warranted.

PTEN-restoration abrogates brain colonisation and perivascular niche invasion by melanoma cells.

BACKGROUND: Melanoma brain metastases (MBM) continue to be a significant clinical problem with limited treatment options. Highly invasive melanoma cells migrate along the vasculature and perivascular cells may contribute to residual disease and recurrence. PTEN loss and hyperactivation of AKT occur in MBM; however, a role for PTEN/AKT in perivascular invasion has not been described. METHODS: We used in vivo intracranial injections of murine melanoma and bulk RNA sequencing of melanoma cells co-cultured with brain endothelial cells (brECs) to investigate brain colonisation and perivascular invasion. RESULTS: We found that PTEN-null melanoma cells were highly efficient at colonising the perivascular niche relative to PTEN-expressing counterparts. PTEN re-expression (PTEN-RE) in melanoma cells significantly reduced brain colonisation and migration along the vasculature. We hypothesised this phenotype was mediated through vascular-induced TGFß secretion, which drives AKT phosphorylation. Disabling TGFß signalling in melanoma cells reduced colonisation and perivascular invasion; however, the introduction of constitutively active myristolated-AKT (myrAKT) restored overall tumour size but not perivascular invasion. CONCLUSIONS: PTEN loss facilitates perivascular brain colonisation and invasion of melanoma. TGFß-AKT signalling partially contributes to this phenotype, but further studies are needed to determine the complementary mechanisms that enable melanoma cells to both survive and spread along the brain vasculature.

Age-related increase in live-birth rates of first frozen thaw embryo versus first fresh transfer in initial assisted reproductive technology cycles without PGT.

BACKGROUND: The landscape of assisted reproductive technology (ART) has seen a significant shift towards frozen-thawed embryo transfers (FET) over fresh transfers, driven by technological advancements and clinical considerations. This study aimed to compare live birth outcomes between primary FET and fresh transfers, focusing on cycles without preimplantation genetic testing (PGT), using United States national data from the SART CORS database spanning from 2014 to 2020. METHODS: We performed a retrospective cohort study of autologous first ART cycles without PGT comparing primary embryo transfer (frozen thaw vs. fresh) success rates from the 2014-2020 SARTCORS database. Live-birth rates (LBR) and cumulative live-birth rates (CLBR) were compared between first FET versus first fresh embryo transfer from an index retrieval. Multivariate logistic regression (MLR) determined association between live birth outcomes and method of transfer. In a subsequent sub-analysis, we compared these two embryo transfer methods among patients with either diminished ovarian reserve (DOR) or male factor infertility. RESULTS: 228,171 first ART cycles resulted in primary embryo transfer. 62,100 initial FETs and 166,071 fresh transfers were compared. Initial FETs demonstrated higher LBR and CLBR compared to fresh transfers (LBR 48.3% vs. 39.8%, p < 0.001; CLBR 74.0% vs. 60.0%, p < 0.0001). MLR indicated greater chances of live birth with FET across all age groups, with adjusted odds ratio (aOR) of live-birth incrementally increasing with advancing age groups. For DOR cycles, LBR and CLBR were significantly higher for FET compared to fresh (33.9% vs. 26.0%, p < 0.001, 44.5% vs. 37.6%, p < 0.0001), respectively. MF cycles also demonstrated higher LBR and CLBR with FET (52.3% vs. 44.2%, p < 0.001, 81.2% vs. 68.9%, p < 0.0001), respectively. MLR demonstrated that in DOR cycles, initial FET was associated with greater chance of live birth in age groups ≥ 35yo (p < 0.01), with aOR of live birth increasingly considerably for those > 42yo (aOR 2.63, p < 0.0001). CONCLUSIONS: Overall LBR and CLBR were greater for first FET than fresh transfers with incremental increases in odds of live birth with advancing age, suggesting the presence of a more favorable age-related change in endometrial receptivity present in frozen-thawed cycles. For both DOR and MF cycles, LBR and CLBR after primary transfer were greater for first FET than fresh. However, this was particularly evident in older ages for DOR cycles. This suggests that supraphysiologic stimulation in older DOR cycles may be detrimental to endometrial receptivity, which is in part corrected for in FET cycles.

Frailty is associated with increased risk of cirrhosis disease progression and death.

BACKGROUND AND AIMS: The Liver Frailty Index (LFI) is a well-studied tool that evaluates frailty in patients with cirrhosis. Consisting of grip strength, chair stands, and balance testing, the LFI has been associated with increased mortality in patients awaiting liver transplant. We aimed to extend our understanding of frailty in cirrhosis by exploring the relationship between the LFI and the risk of (1) cirrhosis progression, (2) mortality, and (3) unplanned hospitalizations, in both compensated and decompensated disease. APPROACH AND RESULTS: Adult patients with cirrhosis from four centers in North America and one in India were included. Frailty was measured at baseline using the LFI and categorized as robust (LFI < 3.2), prefrail (LFI 3.2-4.5), and frail (LFI > 4.5). Progression of cirrhosis was defined by an increase in clinical stage, ranging from 1 to 5, from baseline using the D'Amico classification. Factors associated with progression, mortality, and hospitalizations were evaluated using multivariate regression models, with transplant as a competing risk. In total, 822 patients with cirrhosis were included. Average Model for End-Stage Liver Disease (MELD) score was 15.5 ± 6.0. In patients with compensated cirrhosis, being frail versus robust was associated with increased risk of progression to the next cirrhosis stage or to death (HR, 2.45; 95% CI, 1.14-5.29) and with an increased risk of unplanned hospitalizations (2.32; 95% CI, 1.13-4.79), after adjusting for age, sex, and MELD score. Similar HRs were observed in patients with decompensated cirrhosis. CONCLUSIONS: Frailty was an independent predictor of cirrhosis progression or death and unplanned hospitalization across patients with compensated and decompensated cirrhosis. Future studies are needed to evaluate the possibility of slowing cirrhosis disease progression by reversing or preventing frailty.

Cumulative live birth rates with autologous oocytes plateau with fewer number of cycles for each year of age > 42.

OBJECTIVE: To disaggregate the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) age category of " > 42" and compare age-stratified cumulative live birth rates (CLBR) > 42 years old. DESIGN: Retrospective cohort study of autologous linked ART cycles. SETTING: United States (US) National ART Database. PATIENT(S): Women > 42 years old without a history of prior ART cycles who underwent ART between 2014-2020 as reported to the SART CORS database. INTERVENTION(S): Disaggregate the SART CORS age category of " > 42" into age-stratified cumulative live birth rates (CLBR). MAIN OUTCOME MEASURE(S): Age-stratified cumulative live birth rates (CLBR) for women ≥ 43 years old. RESULTS: Between 2014-2020, 24,650 women > 42 years old without history of prior ART underwent 58,132 cycles, resulting in 1,982 live births. Women ages 43, 44, 45, 46, 47, 48, 49, ≥ 50 achieved maximal CLBR of 9.7%, 8.6%, 5.0%, 3.6%, 2.5%, 1.5%, 2.7%, 1.3%, respectively. CLBR for women between 43-45 were significantly higher compared to those 46 and older (p < 0.05). Among women 46 and older, CLBR were not significantly different. Women ages 43 and 44 did not exhibit a significant increase in CLBR beyond the 5th cycle. Age 45 and 46 reached CLBR plateau by the 3rd cycle. Age ≥ 47 CLBR plateaued after the first cycle. After adjusting for age, race/ethnicity, BMI, nulliparity, etiology of infertility, number of oocytes retrieved, embryos transferred, blastocyst transfer, use of ICSI, PGT, and ART treatment cycle number, there was no association between markers of ovarian reserve (day 3 FSH and random AMH levels) and live birth for women > 42. CONCLUSIONS: While CLBR of autologous cycles from women 42 or younger generally plateau by cycle number 5, age-stratified cycles from women > 42 plateau after fewer cycles to maximize CLBR. Patient and physician expectations for maximum CLBR beyond 42 may be practically based on fewer planned cycles before reaching an age-specific CLBR plateau than may have been previously expected.

Adverse childhood experiences and the development of Down syndrome regression disorder.

Down syndrome regression disorder (DSRD) is a clinical symptom cluster of acute or subacute neurocognitive regression in otherwise health persons with Down syndrome. The objective of this study was to evaluate if adverse childhood experiences (ACEs) were more prevalent in children with DSRD than those with DS alone. A survey-based, cohort-based study was performed. Caregivers of individuals with DSRD with onset of symptoms between age 10 and 30 years and DS alone were administered the ACEs questionnaire via an online REDCap survey. A total of 159 responses were collected after excluding incomplete surveys and those not meeting criteria for DSRD. Individuals with DSRD were not more likely to experience ACEs (p = 0.18, 95% confidence interval [CI]: 0.43-1.17). In those with ACEs prior to the onset of symptoms, the median time prior was 7 months (interquartile range: 5-10). Individuals with DSRD were more likely to report three or more ACEs (52, 33%) compared to those with DS alone (39, 22%) (p = 0.02, 95% CI: 1.08-2.87). Exposure to ACEs were not predictive of response to particular therapeutic interventions although those with multiple ACEs 3 months prior to the onset of symptoms was associated with lower response rates to benzodiazepines and immunotherapy (p = 0.02, 95% CI: -3.64--1.13). This study provides preliminary data that individuals with DSRD experience ACEs at a similar rate to individuals with only DS alone, although three or more ACEs, often preceding the onset of symptoms, was more prevalent in individuals with DSRD.

Models and molecular mechanisms of blood vessel co-option by cancer cells.

Cancer cells have diverse mechanisms for utilizing the vasculature; they can initiate the formation of new blood vessels from preexisting ones (sprouting angiogenesis) or they can form cohesive interactions with the abluminal surface of preexisting vasculature in the absence of sprouting (co-option). The later process has received renewed attention due to the suggested role of blood vessel co-option in resistance to antiangiogenic therapies and the reported perivascular positioning and migratory patterns of cancer cells during tumor dormancy and invasion, respectively. However, only a few molecular mechanisms have been identified that contribute to the process of co-option and there has not been a formal survey of cell lines and laboratory models that can be used to study co-option in different organ microenvironments; thus, we have carried out a comprehensive literature review on this topic and have identified cell lines and described the laboratory models that are used to study blood vessel co-option in cancer. Put into practice, these models may help to shed new light on the molecular mechanisms that drive blood vessel co-option during tumor dormancy, invasion, and responses to different therapies.

Retinal microvascular changes in microvascular angina: Findings from the Australian Heart Eye Study.

OBJECTIVE: Microvascular changes in microvascular angina are poorly understood due to difficulties in imaging the coronary microcirculation in vivo. The retinal microvasculature may reflect changes in coronary microcirculation. We assessed microvascular changes in the retina in patients with microvascular angina and compared them with patients with angiographically proven coronary artery disease. METHODS: We performed retinal photography and coronary angiography on 915 patients. Retinal vessel calibers were measured using a validated computer-assisted method; coronary artery disease was graded from coronary angiograms. Microvascular angina was defined as angina with <25% stenosis in all coronary epicardial arteries. RESULTS: A total of 139 patients (15.2%) had microvascular angina, while 776 (84.8%) had coronary artery disease. Participants with microvascular angina and coronary artery disease had similar retinal arteriolar and venular calibers. After adjustment for age, ethnicity, mean arterial pressure, diabetes, current smoking, body mass index, and fellow vessel caliber, women with smaller venules were threefold more likely to have microvascular angina than women with larger venules (multivariable-adjusted odds ratio 3.54, 95% confidence interval 1.35 to 9.24, P < 0.01). This difference was not observed in men. CONCLUSIONS: Microvascular angina in women was associated with microvascular changes distinct from those in coronary artery disease.

Patient Experience with Rechargeable Implantable Pulse Generator Deep Brain Stimulation for Movement Disorders.

BACKGROUND/AIMS: Nonrechargeable deep brain stimulation implantable pulse generators (IPGs) for movement disorders require surgical replacement every few years due to battery depletion. Rechargeable IPGs reduce frequency of replacement surgeries and inherent risks of complications but require frequent recharging. Here, we evaluate patient experience with rechargeable IPGs and define predictive characteristics for higher satisfaction. METHODS: We contacted all patients implanted with rechargeable IPGs at a single center in a survey-based study. We analyzed patient satisfaction with respect to age, diagnosis, target, charging duration, and body mass index. We tabulated hardware-related adverse events. RESULTS: Dystonia patients had significantly higher satisfaction than Parkinson's disease patients in recharging, display, programmer, and training domains. Common positive responses were "fewer surgeries" and "small size." Common negative responses were "difficulty finding the right position to recharge" and "need to recharge every day." Hardware-related adverse events occurred in 21 of 59 participants. CONCLUSION: Patient experience with rechargeable IPGs was largely positive; however, frustrations with recharging and adverse events were common. Dystonia diagnosis was most predictive of high satisfaction across multiple categories, potentially related to expected long disease duration with need for numerous IPG replacements.

Retinal Vascular Geometry and the Prevalence of Atrial Fibrillation and Heart Failure in a Clinic-Based Sample.

BACKGROUND: We aimed to examine the cross-sectional association between a range of retinal vascular geometric variables and the prevalence of atrial fibrillation (AF) and heart failure. METHODS: The Australian Heart Eye Study (AHES) surveyed 1,680 participants presenting to a tertiary referral hospital for the evaluation of potential coronary artery disease by coronary angiography. Retinal vascular geometric variables (tortuosity, branching, and fractal dimension) were measured from retinal photographs using a computer-assisted program (Singapore I Vessel Assessment). Atrial fibrillation was determined based on a combination of: self-reported history of AF; self-reported use of rate-control and anti-arrhythmic medications; and/or screening electrocardiogram. Self-reported echocardiography-confirmed heart failure was also documented. RESULTS: A total of 1,169 participants had complete information on retinal vascular geometric variables and AF and of these 104 (8.9%) had AF. Participants in the second tertile of fractal dimension (Df) compared to those in the highest tertile (reference group), had 92% increased likelihood of having AF after multivariable adjustment. A threshold effect for Df was identified, and participants below versus those above a Df threshold value of 1.472, had greater odds of having AF: multivariable-adjusted OR 1.85 (95% CI 1.03-3.31). Measures of retinal tortuosity and branching were not associated with AF. Retinal vascular geometric variables were also not associated with prevalence of heart failure. CONCLUSIONS: A sparser retinal microvascular network (lower Df) was independently associated with greater likelihood of AF. Further studies are needed to investigate whether temporal changes to the retinal vascular geometry are predictive of AF in the longer term.

Five cases of orbital extramedullary plasmacytoma: diagnosis and management of an aggressive malignancy.

Purpose: Multiple myeloma is an insidious haematological malignancy characterised by monoclonal proliferation of plasma cells in the bone marrow. Extramedullary plasmacytoma is a rare manifestation of multiple myeloma and usually occurs in the upper respiratory tract. Orbital involvement is particularly uncommon, but may be associated with devastating visual impairment and poor clinical outcomes. Therefore, this article aims to highlight the need for multidisciplinary management of orbital extramedullary plasmacytoma. Methods: This is a retrospective observational case series of five patients. All presented to the authors for management of orbital extramedullary plasmacytomas from 2004 to 2015 at Prince of Wales and Mater Hospitals in Sydney, Australia. Medical records were reviewed for pertinent information including demographics, disease features, management strategy, and clinical progress. The study met Medical Ethics Board standards and is in accordance with the Helsinki Agreements. Results: This case series of five patients underscores the poor prognosis of orbital extramedullary plasmacytoma. Despite aggressive multidisciplinary management, four of these five patients succumbed to their illness during the study period. However, multidisciplinary management did manage to minimise symptoms and preserve quality of life. Conclusions: On a case-by-case basis, patients may derive palliative benefit from orbital surgery in conjunction with radiotherapy and chemotherapy. Orbital surgeons are encouraged to work within a multidisciplinary framework of medical specialists, including haematologists and radiation oncologists, when determining the optimal management plan in cases of orbital extramedullary plasmacytoma.

When Fathers are Perceived to Share in the Maternal Decision to Breastfeed: Outcomes from the Infant Feeding Practices Study II.

Objectives The present study investigates the influence of joint feeding preferences of both the mother and father on initiation and duration of breastfeeding. Methods Data from the Infant Feeding Practices Study II was analyzed. Female participants in a national consumer opinion panel were followed from pregnancy through 1 year postpartum, and were asked about infant feeding practices. We examined the association between maternal prenatal perception of the expectant father's breastfeeding preferences and breastfeeding outcomes (initiation, duration of exclusive breastfeeding and any breastfeeding) and whether concordance between the parents' infant feeding preferences influenced breastfeeding. Results Mothers who perceived that the father preferred exclusive breastfeeding (vs. no preference) were more likely to initiate breastfeeding [adjusted odds ratio (aOR) = 1.9; 95% confidence interval (95% CI) 1.0-3.7], and they had a lower hazard of stopping exclusive and any breastfeeding at any given time [exclusive breastfeeding: adjusted hazard ratio (aHR) = 0.8; 95% CI 0.6-0.9; any breastfeeding: aHR = 0.6; 95% CI 0.5-0.7]. When both the mother and the father preferred exclusive breastfeeding, the hazard of breastfeeding cessation at any given time was lowest (exclusive breastfeeding: aHR = 0.4; 95% CI 0.3-0.5; any breastfeeding: aHR = 0.4; 95% CI 0.3-0.5). The risk of breastfeeding cessation remained lower even when only the father preferred exclusive breastfeeding. Conclusions for Practice Mothers tend to breastfeed for a longer duration when they perceive that the expectant father prefers exclusive breastfeeding and, even more so, when both parental preferences for exclusive breastfeeding concur. Efforts are needed to involve expectant fathers in breastfeeding decision-making and education to achieve breastfeeding success.

Gamma Oscillations in the Hyperkinetic State Detected with Chronic Human Brain Recordings in Parkinson's Disease.

UNLABELLED: Hyperkinetic states are common in human movement disorders, but their neural basis remains uncertain. One such condition is dyskinesia, a serious adverse effect of medical and surgical treatment for Parkinson's disease (PD). To study this, we used a novel, totally implanted, bidirectional neural interface to obtain multisite long-term recordings. We focus our analysis on two patients with PD who experienced frequent dyskinesia and studied them both at rest and during voluntary movement. We show that dyskinesia is associated with a narrowband gamma oscillation in motor cortex between 60 and 90 Hz, a similar, though weaker, oscillation in subthalamic nucleus, and strong phase coherence between the two. Dyskinesia-related oscillations are minimally affected by voluntary movement. When dyskinesia persists during therapeutic deep brain stimulation (DBS), the peak frequency of this signal shifts to half the stimulation frequency. These findings suggest a circuit-level mechanism for the generation of dyskinesia as well as a promising control signal for closed-loop DBS. SIGNIFICANCE STATEMENT: Oscillations in brain networks link functionally related brain areas to accomplish thought and action, but this mechanism may be altered or exaggerated by disease states. Invasive recording using implanted electrodes provides a degree of spatial and temporal resolution that is ideal for analysis of network oscillations. Here we used a novel, totally implanted, bidirectional neural interface for chronic multisite brain recordings in humans with Parkinson's disease. We characterized an oscillation between cortex and subcortical modulators that is associated with a serious adverse effect of therapy for Parkinson's disease: dyskinesia. The work shows how a perturbation in oscillatory dynamics might lead to a state of excessive movement and also suggests a possible biomarker for feedback-controlled neurostimulation to treat hyperkinetic disorders.

Comparison between intraocular pressure spikes with water loading and postural change.

BACKGROUND: To compare the agreement between peak intraocular pressures measured through the water drinking test and the supine test, in patients with primary open angle glaucoma. DESIGN: Consecutive, prospective, blinded. PARTICIPANTS: Twenty-one patients from the Glaucoma Unit, Prince of Wales Hospital, Sydney, Australia. METHODS: For the supine test, intraocular pressure was recorded immediately after the patient had lain down and at 20 and 40 min. At the second evaluation, intraocular pressure was measured in each patient after drinking 10 mL/kg body weight of water for the water drinking test. Again, all patients had their intraocular pressure measured at 20 and 40 min (t = 20 and t = 40, respectively). Patients were excluded from the study if they had pre-existing cardiac, renal or pulmonary complications or had concurrent ocular disease or an anatomical abnormality (including angle recession, peripheral anterior synechiae and developmental anomalies of the angle) that may have influenced intraocular pressure. MAIN OUTCOME MEASURE: Bland-Altman analysis. RESULTS: Bland-Altman analysis indicated an overall excellent agreement in terms of mean difference between methods (1.0, -1.0 and -0.90 mmHg, at 0, 20 and 40 min, respectively). Further, with the exception of t = 40, all measured time points had 95% confidence intervals within 6.5 mmHg of their mean difference on the Bland-Altman plot. CONCLUSIONS: There was close agreement between the intraocular pressure values of the supine test and water drinking test. However, as the water drinking test may be uncomfortable and potentially hazardous, there is potential that the supine test may be a safer and more comfortable alternative.

Materials in the vitreous during cataract surgery: nature and incidence, with two cases of histological confirmation.

BACKGROUND: To identify and classify materials in the vitreous observed during phacoemulsification cataract surgery (phaco). DESIGN: Prospective, consecutive, observational case series at one ophthalmic day surgery in Sydney, Australia. PARTICIPANTS: A total of 767 consecutive phaco cases. Cases were excluded if there was posterior capsule rupture or vitreous loss intraoperatively. METHODS: For each patient, age, gender, baseline corrected distance visual acuity, presence of pseudoexfoliation, nuclear sclerosis grade and phacoemulsification ultrasound time were recorded. The relationship between these variables and materials in the vitreous was evaluated with regression analysis. Two patients with materials in the vitreous developed an acute intraoperative rock-hard eye syndrome. In these two patients, pars plana needle aspiration of retrolenticular fluid was performed to re-establish normal intraocular pressure. Histology was undertaken to compare this fluid with known lens material retrieved from the Fluid Management System bags in two unrelated cases. MAIN OUTCOME MEASUREMENTS: Presence of materials in the vitreous during phaco. RESULTS: Materials in the vitreous were observed in either Berger's space or the anterior vitreous in 386 eyes (50.3% of cases); the majority was putatively lens material (46.5% of all cases). Pigment and ophthalmic viscoelastic device were seen in the anterior vitreous in 9.8% and 1.7% of cases, respectively. Logistic regression analysis demonstrated that higher nuclear sclerosis grade (P = 0.025), male gender (P = 0.003) and greater age (P = 0.016) were predictive of the presence of materials in the vitreous. Histological assessment with light microscopy and birefringence techniques identified the materials in the vitreous as lens material. CONCLUSION: Materials in the vitreous were seen in 50.3% of phaco cases. It has been histologically demonstrated that lens materials can be introduced into the anterior vitreous during phaco.

Spontaneous hyphaema secondary to bleeding from an iris vascular tuft in a patient with a supratherapeutic International normalised ratio: case report.

BACKGROUND: Iris vascular tufts are rare iris stromal vascular hamartomas. Patients with iris vascular tufts generally remain asymptomatic until presenting with a spontaneous hyphaema or with mild intraoperative pupil margin haemorrhage during anterior segment surgery. This is the first reported case of spontaneous hyphaema from iris vascular tuft related to a documented supratherapeutic International Normalised Ratio as a predisposing factor. At 86 years of age, this patient also represents the oldest documented first occurrence of bleeding from an iris vascular tuft. CASE PRESENTATION: An 86 year old Caucasian lady presented with sudden and persisting loss of vision in her right eye, ocular pain and vomiting. She had a supratherapeutic International Normalised Ratio of 3.9 related to Warfarin use. Her intraocular pressure in the right eye was raised at 55 mmHg, with a 1.6 mm hyphaema and multiple iris vascular tufts visible around the entire pupil. CONCLUSION: The present case highlights the risk of anticoagulation therapy as a predisposing factor for spontaneous hyphaema and adds to the management considerations for this condition. It also demonstrates the need for Ophthalmologists to be aware of iris vascular tufts as a cause for spontaneous hyphaema, independent of age and systemic associations.

Assessment of a Decade of Change in U.S. Assisted Reproductive Technology Cumulative Live-Birth Rates: 2004-2009 Compared With 2014-2020.

OBJECTIVE: To assess the effects of demographic shifts, changes in contemporaneous clinical practices, and technologic innovation on assisted reproductive technology (ART) success rates by conducting an analysis of cumulative live-birth rates across different time periods, age groups, and infertility diagnoses. METHODS: We conducted a retrospective cohort study of autologous linked cycles comparing cumulative live-birth rates over successive cycles from patients undergoing their first retrieval between 2014 and 2019 in the SART CORS (Society for Assisted Reproductive Technology Clinic Outcome Reporting System) database. All cycles reported for these individuals up to 2020 were included for analysis. We compared cumulative live-birth rates stratified by age and infertility cause with published data from the 2004-2009 SART CORS database. RESULTS: From 2014 to 2019, 447,042 patients underwent their first autologous index retrieval, resulting in 1,007,374 cycles and 252,215 live births over the period of 2014 to 2020. In contrast, between 2004 and 2008, 246,740 patients underwent 471,208 cycles, resulting in 140,859 births by 2009. Noteworthy shifts in demographics were observed, with an increase in people of color seeking reproductive technology (57.9% vs 51.7%, P <.001). There was also an increase in patients with diminished ovarian reserve and ovulatory disorders and a decrease in endometriosis, tubal, and male factor infertility ( P <.001). Previously associated with decreased odds of live birth, frozen embryo transfer and preimplantation genetic testing showed increased odds in 2014-2020. Preimplantation genetic testing rose from 3.4% to 36.0% and was associated with a lower cumulative live-birth rate for those younger than age 35 years ( P <.001) but a higher cumulative live-birth rate for those aged 35 years or older ( P <.001). Comparing 2014-2020 with 2004-2009 shows that the overall cumulative live-birth rate improved for patients aged 35 years or older and for all infertility diagnoses except ovulatory disorders ( P <.001). CONCLUSION: This analysis provides insights into the changing landscape of ART treatments in the United States over the past two decades. The observed shifts in demographics, clinical practices, and technology highlight the dynamic nature of an evolving field of reproductive medicine. These findings may offer insight for clinicians to consider in counseling patients and to inform future research endeavors in the field of ART.