A synopsis of global frontiers in fertility preservation.

Since 2007, the Oncofertility Consortium Annual Conference has brought together a diverse network of individuals from a wide range of backgrounds and professional levels to disseminate emerging basic and clinical research findings in fertility preservation. This network also developed enduring educational materials to accelerate the pace and quality of field-wide scientific communication. Between 2007 and 2019, the Oncofertility Consortium Annual Conference was held as an in-person event in Chicago, IL. The conference attracted approximately 250 attendees each year representing 20 countries around the world. In 2020, however, the COVID-19 pandemic disrupted this paradigm and precluded an in-person meeting. Nevertheless, there remained an undeniable demand for the oncofertility community to convene. To maintain the momentum of the field, the Oncofertility Consortium hosted a day-long virtual meeting on March 5, 2021, with the theme of "Oncofertility Around the Globe" to highlight the diversity of clinical care and translational research that is ongoing around the world in this discipline. This virtual meeting was hosted using the vFairs ® conference platform and allowed over 700 people to participate, many of whom were first-time conference attendees. The agenda featured concurrent sessions from presenters in six continents which provided attendees a complete overview of the field and furthered our mission to create a global community of oncofertility practice. This paper provides a synopsis of talks delivered at this event and highlights the new advances and frontiers in the fields of oncofertility and fertility preservation around the globe from clinical practice and patient-centered efforts to translational research.

Installing oncofertility programs for breast cancer in limited versus optimum resource settings: Empirical data from 39 surveyed centers in Repro-Can-OPEN Study Part I & II.

PURPOSE: As a further step to elucidate the actual diverse spectrum of oncofertility practices for breast cancer around the globe, we present and discuss the comparisons of oncofertility practices for breast cancer in limited versus optimum resource settings based on data collected in the Repro-Can-OPEN Study Part I & II. METHODS: We surveyed 39 oncofertility centers including 14 in limited resource settings from Africa, Asia & Latin America (Repro-Can-OPEN Study Part I), and 25 in optimum resource settings from the United States, Europe, Australia and Japan (Repro-Can-OPEN Study Part II). Survey questions covered the availability of fertility preservation and restoration options offered to young female patients with breast cancer as well as the degree of utilization. RESULTS: In the Repro-Can-OPEN Study Part I & II, responses for breast cancer and calculated oncofertility scores showed the following characteristics: (1) higher oncofertility scores in optimum resource settings than in limited resource settings especially for established options, (2) frequent utilization of egg freezing, embryo freezing, ovarian tissue freezing, GnRH analogs, and fractionation of chemo- and radiotherapy, (3) promising utilization of oocyte in vitro maturation (IVM), (4) rare utilization of neoadjuvant cytoprotective pharmacotherapy, artificial ovary, and stem cells reproductive technology as they are still in preclinical or early clinical research settings, (5) recognition that technical and ethical concerns should be considered when offering advanced and innovative oncofertility options. CONCLUSIONS: We presented a plausible oncofertility best practice model to guide oncofertility teams in optimizing care for breast cancer patients in various resource settings.

Vulvar Aphthous Ulcer in an Adolescent With COVID-19.

BACKGROUND: Vulvar aphthous ulcers have been associated with various prodromal viral illnesses. We describe the case of an adolescent girl who developed vulvar aphthous ulcers during infection with Coronavirus, SARS-CoV-2. CASE: A 19-year-old girl presented to the emergency department with cough, sore throat, fevers, and rash, and tested positive for COVID-19. She re-presented 2 days later with vulvar pain and was found to have a vulvar aphthous ulcer. She was admitted for pain control and treated with oral steroids. Improvement in her vulvar pain was noted, along with resolution of fevers, cough, and rash. SUMMARY AND CONCLUSION: This case illustrates the novel association of COVID-19 with vulvar aphthous ulcers in adolescents. Use of oral steroids for symptomatic management of COVID-19 led to rapid clinical improvement.

National Trends and Outcomes of Patients Bridged to Transplant With Continuous Flow Left Ventricular Assist Devices.

BACKGROUND: Continuous flow left ventricular assist devices (CF-LVAD) are widely used as a bridge to transplantation (BTT) among patients with advanced heart failure. The primary outcome of the current study was to study the incidence of waitlist mortality and morbidity of CF-LVAD patients bridged to heart transplantation in the current BTT era and to determine the factors that increased their risk of delisting. METHODS: Patients who were bridged to heart transplant with a CF-LVAD between April 2008 and September 2015 were identified from the United Network for Organ Sharing heart transplant registry. They were then categorized based on the development of complications. Cox proportional hazards and Kaplan-Meier survival curves were used for time-to-event analysis for the primary outcome. RESULTS: Out of 7070 patients who were bridged to heart transplant, 2510 (36%) developed device-related complications. The primary outcome was present in 1631 of 7070 patients (23%). Independent predictors of primary outcome were age, ABO blood group, etiology of cardiomyopathy, and history of diabetes mellitus. Developing one device-related complication was associated with a hazard ratio (HR) of 2.59 of having the primary outcome. The HR increased to 3.45 when ≥2 of the defined complications occurred. In patients who developed the primary outcome, they most likely had a device infection (odds ratio 2.51). CONCLUSION: Findings from the current study add to the existing literature about the incidence of morbidity and mortality in the current BTT era. Development of one device-related complication increases the risk of death or delisting among patients on the heart transplant waitlist; however, this risk almost doubles when 2 or more complications occur.

Renal health after long-term exposure to tenofovir disoproxil fumarate (TDF) in HIV/HBV positive adults in Ghana.

OBJECTIVES: The study assessed markers of renal health in HIV/HBV co-infected patients receiving TDF-containing antiretroviral therapy in Ghana. METHODS: Urinary protein-to-creatinine ratio (uPCR) and albumin-to-protein ratio (uAPR) were measured cross-sectionally after a median of four years of TDF. At this time, alongside extensive laboratory testing, patients underwent evaluation of liver stiffness and blood pressure. The estimated glomerular filtration rate (eGFR) was measured longitudinally before and during TDF therapy. RESULTS: Among 101 participants (66% women, median age 44 years, median CD4 count 572 cells/mm3) 21% and 17% had detectable HIV-1 RNA and HBV DNA, respectively. Overall 35% showed hypertension, 6% diabetes, 7% liver stiffness indicative of cirrhosis, and 18% urinary excretion of Schistosoma antigen. Tubular proteinuria occurred in 16% of patients and was independently predicted by female gender and hypertension. The eGFR declined by median 1.8 ml/min/year during TDF exposure (IQR -4.4, -0.0); more pronounced declines (≥ 5 ml/min/year) occurred in 22% of patients and were associated with receiving ritonavir-boosted lopinavir rather than efavirenz. HBV DNA, HBeAg, transaminases, and liver stiffness were not predictive of renal function abnormalities. CONCLUSIONS: The findings mandate improved diagnosis and management of hypertension and suggest targeted laboratory monitoring of patients receiving TDF alongside a booster in sub-Saharan Africa.

Antibody screening tests variably overestimate the prevalence of hepatitis C virus infection among HIV-infected adults in Ghana.

HIV coinfection with HCV has been poorly studied in sub-Saharan Africa, and the reliability of available seroprevalence estimates remains uncertain. The study aim was to determine HCV RNA prevalence in HIV-infected subjects receiving care in Kumasi, Ghana, and relate the findings to HCV antibody detection. From a population of 1520 HIV-infected adults, all HBsAg-positive subjects (n = 236) and a random subset of HBsAg-negative subject (n = 172) were screened for HCV RNA using pooled plasma; positive samples were genotyped by core and NS5B sequencing. HCV antibodies were detected by three commercial screening assays and confirmed by the line immunoassay. HCV RNA was detected in 4/408 subjects (1.0%, 95% confidence interval 0.0-1.9%), comprising 3/236 (1.3%; 0.0-2.8%) HBsAg-positive and 1/172 (0.6%; 0.0-1.8%) HBsAg-negative subjects. HCV RNA-positive subjects showed reactivity in all three antibody screening assays. Among HCV RNA-negative subjects, 5/67 (7.5%), 5/67 (7.5%) and 19/67 (28.4%) showed antibody reactivity by each screening assay, respectively, including two (3.0%) with reactivity by all three assays. Only one sample (1.5%) had confirmed antibody reactivity by line immunoassay indicating past HCV infection. HCV-positive subjects (three males, two females) were aged 30-46 years, by questionnaire-based interview reported surgical procedures and blood transfusion as risk factors for infection. HCV genotypes were 2 (subtypes 2j, 2l, 2k/unassigned) and 1 (subtype unassigned). Without further testing, HCV antibody screening assays variably overestimated HCV prevalence among HIV-infected subjects in Ghana. These findings inform the interpretation of previous seroprevalence estimates based upon screening assays alone.

The profile of risk factors and in-patient outcomes of stroke in Kumasi, Ghana.

BACKGROUND: Stroke is an emerging public health challenge in Ghana requiring urgent attention for its control. Because some of the risk factors for stroke are modifiable, characterisation of these risk factors in the Ghanaian population as well as outcomes of stroke are urgently needed to guide policy for non-communicable diseases. We therefore conducted this study to evaluate the frequencies of the traditional risk factors and outcomes of stroke at the main tertiary referral centre in the middle belt of Ghana in a prospective observational study. METHODS AND RESULTS: Patients with a clinical diagnosis of stroke were consecutively recruited and vascular risk factors were assessed as well as markers of severity of stroke and in-patient treatment outcomes. 265 patients were recruited, 56.6% were females and mean ± SD age of 64.6 ± 14.54 years. 85%, 73% and 58% of patients had systemic arterial hypertension, physical inactivity and obesity respectively as common risk factors. We identified that patients with stroke had a median of 3 traditional risk factors, were unaware of the presence of these risk factors or were poorly controlled if known. Stroke was associated with a high in-patient case fatality rate of 43% principally among patients with haemorrhagic stroke. CONCLUSIONS: Our findings indicate that urgent concerted efforts are required to improve public awareness and management of the prevailing risk factors of stroke in Ghana.

Outcomes of starting first-line antiretroviral therapy in hepatitis B virus/HIV-coinfected patients in Ghana.

OBJECTIVES: HIV/hepatitis B virus (HBV) coinfection is common in Ghana, where first-line antiretroviral therapy (ART) comprises lamivudine with zidovudine or stavudine and nevirapine or efavirenz. Little is known about ART outcomes in the context of coinfection. This study evaluated outcomes of ART among HIV/HBV-coinfected Ghanaians, focusing on locally available parameters. PATIENTS AND METHODS: An observational study comparing clinical and virological outcomes in HIV-infected individuals who were either hepatitis B surface antigen (HBsAg) positive or HBsAg negative was conducted over 36 months. Clinical events, hepatic transaminases, CD4 count and body mass index (BMI) were evaluated among 143 HBsAg-positive and 228 HBsAg-negative patients. In a random subset of HBsAg-positive patients, HBV-DNA levels and polymerase sequences were analysed. RESULTS: Comparing HBsAg-positive and HBsAg-negative patients, 44/143 (30.8%) and 83/228 (36.4%) defaulted follow-up, 15/143 (10.5%) and 30/228 (13.2%) experienced a new clinical event, and 8/143 (5.6%) and 11/228 (4.8%) discontinued their initial regimen, respectively. Transaminase levels were higher in HBsAg-positive patients, although elevations were low grade. HBV coinfection was associated with an adjusted 2.04 (95% CI 0.59-3.49) cells/mm(3)/month smaller CD4 cell increase; there was no significant effect on BMI changes. After a median of 9 months of ART, 64/66 (97.0%) patients showed detectable HBV-DNA (median 3.3 log(10) IU/mL; IQR 2.6-6.2); 12/53 (22.6%) of these showed lamivudine-associated resistance mutations. CONCLUSIONS: HIV/HBV-coinfected Ghanaians tolerated first-line ART well, but experienced blunted CD4 cell responses. There was evidence of ongoing HBV replication, mild but persistent transaminase elevations and emerging lamivudine resistance in a proportion of treated patients, indicating the potential for progressive liver damage.