Pregnant and postpartum women's experiences of the indirect impacts of the COVID-19 pandemic in high-income countries: a qualitative evidence synthesis.

BACKGROUND: Pregnant and postpartum women's experiences of the COVID-19 pandemic, as well as the emotional and psychosocial impact of COVID-19 on perinatal health, has been well-documented across high-income countries. Increased anxiety and fear, isolation, as well as a disrupted pregnancy and postnatal period are widely described in many studies. The aim of this study was to explore, describe and synthesise studies that addressed the experiences of pregnant and postpartum women in high-income countries during the first two years of the pandemic. METHODS: A qualitative evidence synthesis of studies relating to women's experiences in high-income countries during the pandemic were included. Two reviewers extracted the data using a thematic synthesis approach and NVivo 20 software. The GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) was used to assess confidence in review findings. RESULTS: Sixty-eight studies were eligible and subjected to a sampling framework to ensure data richness. In total, 36 sampled studies contributed to the development of themes, sub-themes and review findings. There were six over-arching themes: (1) dealing with public health restrictions; (2) navigating changing health policies; (3) adapting to alternative ways of receiving social support; (4) dealing with impacts on their own mental health; (5) managing the new and changing information; and (6) being resilient and optimistic. Seventeen review findings were developed under these themes with high to moderate confidence according to the GRADE-CERQual assessment. CONCLUSIONS: The findings from this synthesis offer different strategies for practice and policy makers to better support women, babies and their families in future emergency responses. These strategies include optimising care delivery, enhancing communication, and supporting social and mental wellbeing.

The Problems with Online Health Product Sales: How can Regulations be Improved?

With the rapid proliferation of online businesses, national authorities are facing challenges managing the online supply of illegal health products due to the anonymity of the internet, increasing number of global syndicates, new technologies, and inability to enforce against overseas sellers. This paper describes these challenges and the Health Sciences Authority's regulatory approaches to tackle the online sales of illegal health products. These include partnering with platform administrators to remove illegal online postings, leveraging technological tools and relevant legislation, empowering consumers to make informed decisions, and fostering closer collaborations across different jurisdictions to combat online pharmaceutical crimes.

How do postnatal care guidelines in Australia compare to international standards? A scoping review and comparative analysis.

BACKGROUND: There is no single national guideline in Australia on the provision of postnatal care, which means there is potential for significant variation in the standard and quality of care. This review aimed to systematically identify, synthesise, and assess the quality of postnatal care guidelines produced for use in Australia. A second aim was to compare postnatal care recommendations in Australian guidelines to the National Institute for Health and Care Excellence's (NICE) and the World Health Organization's (WHO) postnatal care recommendations, to identify gaps and areas of disagreement. We focussed on recommendations regarding postnatal assessment of the woman or newborn, infant feeding, discharge planning, or community-based care. METHODS: A scoping review was undertaken informed by the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for scoping reviews. A database search and a manual search of state and national government health departments, professional associations and research institute websites was performed to identify relevant guidelines and recommendations. Guideline quality was assessed using the AGREE II tool. Guideline recommendations from Australia were mapped to 67 NICE/WHO recommendations. Recommendations that partially agreed, were modified, or in disagreement underwent further analysis. RESULTS: A total of 31 Australian postnatal guidelines were identified and overall, these were of moderate- to high-quality. Of the 67 NICE/WHO recommendations, most agreed with the recommendations contained in Australian guidelines. There were five NICE/WHO recommendations with which corresponding Australian recommendations disagreed. There were 12 NICE/WHO recommendations that were commonly modified within Australia's guidelines. There were three NICE/WHO recommendations that did not appear in any Australian guideline. CONCLUSIONS: Recommendations from postnatal guidelines in Australia have a high level of agreement with corresponding NICE/WHO recommendations. The few disagreements and modifications found in guideline recommendations - both across Australia's guidelines and between Australia's and the NICE/WHO guidelines - are worrying and warrant further examination, as they may result in different standards of care across Australia. Identified gaps in guidance should be prioritised for inclusion in new or updated guidelines where appropriate.

NRG-GY012: Randomized phase 2 study comparing olaparib, cediranib, and the combination of cediranib/olaparib in women with recurrent, persistent, or metastatic endometrial cancer.

PURPOSE: This paper reports the efficacy of the poly (ADP-ribose) polymerase inhibitor olaparib alone and in combination with the antiangiogenesis agent cediranib compared with cediranib alone in patients with advanced endometrial cancer. METHODS: This was open-label, randomized, phase 2 trial (NCT03660826). Eligible patients had recurrent endometrial cancer, received at least one (<3) prior lines of chemotherapy, and were Eastern Cooperative Oncology Group performance status 0 to 2. Patients were randomly assigned (1:1:1), stratified by histology (serous vs. other) to receive cediranib alone (reference arm), olaparib, or olaparib and cediranib for 28-day cycles until progression or unacceptable toxicity. The primary end point was progression-free survival in the intention-to-treat population. Homologous repair deficiency was explored using the BROCA-GO sequencing panel. RESULTS: A total of 120 patients were enrolled and all were included in the intention-to-treat analysis. Median age was 66 (range, 41-86) years and 47 (39.2%) had serous histology. Median progression-free survival for cediranib was 3.8 months compared with 2.0 months for olaparib (hazard ratio, 1.45 [95% CI, 0.91-2.3] p = .935) and 5.5 months for olaparib/cediranib (hazard ratio, 0.7 [95% CI, 0.43-1.14] p = .064). Four patients receiving the combination had a durable response lasting more than 20 months. The most common grade 3/4 toxicities were hypertension in the cediranib (36%) and olaparib/cediranib (33%) arms, fatigue (20.5% olaparib/cediranib), and diarrhea (17.9% cediranib). The BROCA-GO panel results were not associated with response. CONCLUSION: The combination of cediranib and olaparib demonstrated modest clinical efficacy; however, the primary end point of the study was not met. The combination was safe without unexpected toxicity.

An evaluation of the introduction of telehealth for remote antenatal and postnatal contacts in Bangladesh and Lao People's Democratic Republic during the COVID-19 pandemic.

From 2020, COVID-19 spread rapidly around the globe and continues to have a major impact on health system functioning, with a disproportionate impact on low- and middle-income countries (LMIC). Reduced service utilisation and coverage of essential childbirth interventions is likely impacting maternal and newborn morbidity and mortality. Telehealth has been identified as an important tool in the continued provision of essential healthcare services. The aim of this study was to explore the experience and impact of implementing telehealth services for the provision of remote antenatal (ANC) and postnatal (PNC) contacts in regions of Bangladesh and Lao People's Democratic Republic through 100 semi-structured interviews with health service leaders and providers, and childbearing women who organised, provided, or were the recipients of ANC and PNC telehealth during the COVID-19 pandemic response. The findings showed that a sudden pivot from face-to-face to telehealth services posed both health system and provision of care challenges. Health systems lacked funding to support telehealth and the infrastructure needed for service changes; however, some were able to work with key maternal child health departments within Ministries of Health to find the resources to implement the services. Health providers found telehealth beneficial during the pandemic response but identified a lack of training, guidance, and support as a barrier to changing practice. Childbearing women reported being fearful of accessing care at health services due to COVID-19, and whilst they appreciated the telehealth contacts, many continued to prefer face-to-face delivery of ANC and PNC care. Telehealth, however, was a good alternative in a time when face-to-face care was not possible. Considerations for post-pandemic broader implementation or scale-up of telehealth for routine antenatal and postnatal maternity care provision include the need for further research on issues such as accessibility, acceptability, quality of care, and sustainability of service provision.

Challenges of being a maternity service leader during the COVID-19 pandemic: a descriptive analysis of the journey.

BACKGROUND: In Australia, maternity care services provide care for pregnant and postpartum women and their newborns. The COVID-19 pandemic forced these services to quickly adapt and develop policies and procedures for dealing with transmission in health care facilities, as well as work under public health measures to counter its spread within the community. Despite well-documented responses and adaptations by healthcare systems, no studies have examined the experiences of maternity service leaders through the pandemic. This study aimed to explore the experiences of maternity service leaders, to understand their perspectives on what happened in health services and what was required of a leader during the COVID-19 pandemic in one Australian state. METHODS: A longitudinal qualitative study collected data from 11 maternity care leaders during the pandemic in the state of Victoria. Leaders participated in a series of interviews over the 16-month study period, with a total of 57 interviews conducted. An inductive approach to developing codes allowed for semantic coding of the data, then a thematic analysis was conducted to explore patterned meaning across the dataset. RESULTS: One overarching theme, 'challenges of being a maternity service leader during the pandemic', encompassed participant's experiences. Four sub-themes described the experiences of these leaders: (1) needing to be a rapid decision-maker, (2) needing to adapt and alter services, (3) needing to filter and translate information, and (4) the need to support people. At the beginning of the pandemic, the challenges were most acute with slow guideline development, rapid communications from the government and an urgent need to keep patients and staff safe. Over time, with knowledge and experience, leaders were able to quickly adjust and respond to policy change. CONCLUSION: Maternity service leaders played an important role in preparing and adapting services in accordance with government directives and guidelines while also developing strategies tailored to their own health service requirements. These experiences will be invaluable in designing high quality and responsive systems for maternity care in future crises.

GOG 244 - The Lymphedema and Gynecologic cancer (LeG) study: The impact of lower-extremity lymphedema on quality of life, psychological adjustment, physical disability, and function.

OBJECTIVE: To assess quality of life (QOL) in patients who developed lower-extremity lymphedema (LLE) after radical gynecologic cancer surgery on prospective clinical trial GOG 244. METHODS: The prospective, national, cooperative group trial GOG-0244 determined the incidence of LLE and risk factors for LLE development, as well as associated impacts on QOL, in newly diagnosed patients undergoing surgery for endometrial, cervical, or vulvar cancer from 6/4/2012-11/17/2014. Patient-reported outcome (PRO) measures of QOL (by the Functional Assessment of Cancer Therapy [FACT]), body image, sexual and vaginal function, limb function, and cancer distress were recorded at baseline (within 14 days before surgery), and at 6, 12, 18, and 24 months after surgery. Assessments of LLE symptoms and disability were completed at the time of lower limb volume measurement. A linear mixed model was applied to examine the association of PROs/QOL with a Gynecologic Cancer Lymphedema Questionnaire (GCLQ) total score incremental change ≥4 (indicative of increased LLE symptoms) from baseline, a formal diagnosis of LLE (per the GCLQ), and limb volume change (LVC) ≥10%. RESULTS: In 768 evaluable patients, those with a GCLQ score change ≥4 from baseline had significantly worse QOL (p < 0.001), body image (p < 0.001), sexual and vaginal function (p < 0.001), limb function (p < 0.001), and cancer distress (p < 0.001). There were no significant differences in sexual activity rates between those with and without LLE symptoms. CONCLUSIONS: LLE is significantly detrimental to QOL, daily function, and body image. Clinical intervention trials to prevent and manage this chronic condition after gynecologic cancer surgery are needed.

Promoting hospital and primary care collaboration for timely and effective care for chronic hepatitis B in western Melbourne.

Objective The aims of this study were to: (1) identify the characteristics of patients with chronic hepatitis B (CHB) who do not attend their hospital liver clinic appointments; and (2) raise awareness among general practitioners (GP) of alternative pathways to care for CHB in order to prevent long-term complications of CHB (liver cancer and cirrhosis). Methods This prospective study was conducted between May 2018 and January 2019 at one site of a tertiary referral hospital in western Melbourne. Patients with minimal liver complications who did not attend their first two initial appointments were included in the study, in addition to referring GPs of new CHB patients to the liver clinic who had minimal liver complications (characterised by minimal fibrosis (<7kPa)) and no liver comorbidities (including cirrhosis and/or hepatocellular carcinoma). GPs of patients who failed to attend the liver clinic as a new patient were sent an alternative discharge letter that included information on alternative pathways to care in the community for their patients. A follow-up survey to referring GPs was conducted afterwards for feedback. Demographic data was also collected for included patients. Results Thirty patients with non-complicated CHB were included in the study (median age 32.5 years). Patients were from 11 different countries and six regions. The mean wait time from referral to clinic date was 424 days (SD 218.9). Only four GPs responded to the letter, with non-responding GPs surveyed primarily not participating due to having over 1 year of no contact from the patient or hospital. Conclusion This study showed that there were long waiting lists for CHB referrals and alerting GPs to alternative pathways after patients failed to attend appointments was ineffective. There needs to be improved coordination between tertiary and primary services to provide timely and effective care for patients with CHB. What is known about this topic? There are 239000 Australians living with CHB: most recent estimates indicate that only 62% have been diagnosed, 15% are being monitored and 6% of those requiring treatment are receiving antiviral therapy. The complications of CHB (liver cancer and cirrhosis) can be averted by routine monitoring and timely commencement of highly effective oral antiviral therapy. In Australia, both GPs and specialists in gastroenterology and infectious diseases are involved in the management of CHB patients, but most prescribing occurs in specialist services. The current specialist-centred model of CHB care has been described as neither practical nor sustainable given the limited resources and capacity of specialist services, and the challenges for people with CHB to access public hospitals for routine care. What does this paper add? Non-attending patients were a primarily young population. The median wait time for a clinic appointment in this hospital setting was 424 days, with some patients waiting ≥800 days for an appointment. This extensive wait time for a largely asymptomatic condition may have affected attendance rates. Although this particular intervention to engage GPs in collaborative care had limited results, it is clear that management of CHB by GPs, transparency in wait lists and adequate resourcing of specialist services would help alleviate the referral burden on hospitals. What are the implications for practitioners? GPs should be aware that waiting lists for liver clinic appointments can be extensive in public hospital settings due to the high referral burden and limited resources of these services. Alternative pathways to care, such as GPs trained to prescribe Schedule 100 drugs, are an effective means of alleviating this burden while also ensuring CHB patients are seen in a timely manner and receive routine monitoring.

GOG 244-The lymphedema and gynecologic cancer (LEG) study: Incidence and risk factors in newly diagnosed patients.

OBJECTIVES: To evaluate the incidence and risk factors for lymphedema associated with surgery for gynecologic malignancies on GOG study 244. METHODS: Women undergoing a lymph node dissection for endometrial, cervical, or vulvar cancer were eligible for enrollment. Leg volume was calculated from measurements at 10-cm intervals starting 10 cm above the bottom of the heel to the inguinal crease. Measurements were obtained preoperatively and postoperatively at 4-6 weeks, and at 3-, 6-, 9-, 12-, 18-, and 24- months. Lymphedema was defined as a limb volume change (LVC) ≥10% from baseline and categorized as mild: 10-19% LVC; moderate: 20-40% LVC; or severe: >40% LVC. Risk factors associated with lymphedema were also analyzed. RESULTS: Of 1054 women enrolled on study, 140 were inevaluable due to inadequate measurements or eligibility criteria. This left 734 endometrial, 138 cervical, and 42 vulvar patients evaluable for LVC assessment. Median age was 61 years (range, 28-91) in the endometrial, 44 years (range, 25-83) in the cervical, and 58 years (range, 35-88) in the vulvar group. The incidence of LVC ≥10% was 34% (n = 247), 35% (n = 48), and 43% (n = 18), respectively. The peak incidence of lymphedema was at the 4-6 week assessment. Logistic regression analysis showed a decreased risk with advanced age (p = 0.0467). An exploratory analysis in the endometrial cohort showed an increased risk with a node count >8 (p = 0.033). CONCLUSIONS: For a gynecologic cancer, LVC decreased with age greater than 65, but increased with a lymph node count greater than 8 in the endometrial cohort. There was no association with radiation or other risk factors.

GOG 244 - The LymphEdema and Gynecologic cancer (LEG) study: The association between the gynecologic cancer lymphedema questionnaire (GCLQ) and lymphedema of the lower extremity (LLE).

OBJECTIVE: To explore whether patient-reported lymphedema-related symptoms, as measured by the Gynecologic Cancer Lymphedema Questionnaire (GCLQ), are associated with a patient-reported diagnosis of lymphedema of the lower extremity (LLE) and limb volume change (LVC) in patients who have undergone radical surgery, including lymphadenectomy, for endometrial, cervical, or vulvar cancer on Gynecologic Oncology Group (GOG) study 244. METHODS: Patients completed the baseline and at least one post-surgery GCLQ and LVC assessment. The 20-item GCLQ measures seven symptom clusters-aching, heaviness, infection-related, numbness, physical functioning, general swelling, and limb swelling. LLE was defined as a patient self-reported LLE diagnosis on the GCLQ. LVC was measured by volume calculations based on circumferential measurements. A linear mixed model was fitted for change in symptom cluster scores and GCLQ total score and adjusted for disease sites and assessment time. RESULTS: Of 987 eligible patients, 894 were evaluable (endometrial, 719; cervical, 136; vulvar, 39). Of these, 14% reported an LLE diagnosis (endometrial, 11%; cervical, 18%; vulvar, 38%). Significantly more patients diagnosed versus not diagnosed with LLE reported ≥4-point increase from baseline on the GCLQ total score (p < 0.001). Changes from baseline were significantly larger on all GCLQ symptom cluster scores in patients with LLE compared to those without LLE. An LVC increment of >10% was significantly associated with reported general swelling (p < 0.001), heaviness (p = 0.005), infection-related symptoms (p = 0.002), and physical function (p = 0.006). CONCLUSIONS: Patient-reported symptoms, as measured by the GCLQ, discerned those with and without a patient-reported LLE diagnosis and demonstrated predictive value. The GCLQ combined with LVC may enhance our ability to identify LLE.

A mechanistic pan-cancer pathway model informed by multi-omics data interprets stochastic cell fate responses to drugs and mitogens.

Most cancer cells harbor multiple drivers whose epistasis and interactions with expression context clouds drug and drug combination sensitivity prediction. We constructed a mechanistic computational model that is context-tailored by omics data to capture regulation of stochastic proliferation and death by pan-cancer driver pathways. Simulations and experiments explore how the coordinated dynamics of RAF/MEK/ERK and PI-3K/AKT kinase activities in response to synergistic mitogen or drug combinations control cell fate in a specific cellular context. In this MCF10A cell context, simulations suggest that synergistic ERK and AKT inhibitor-induced death is likely mediated by BIM rather than BAD, which is supported by prior experimental studies. AKT dynamics explain S-phase entry synergy between EGF and insulin, but simulations suggest that stochastic ERK, and not AKT, dynamics seem to drive cell-to-cell proliferation variability, which in simulations is predictable from pre-stimulus fluctuations in C-Raf/B-Raf levels. Simulations suggest MEK alteration negligibly influences transformation, consistent with clinical data. Tailoring the model to an alternate cell expression and mutation context, a glioma cell line, allows prediction of increased sensitivity of cell death to AKT inhibition. Our model mechanistically interprets context-specific landscapes between driver pathways and cell fates, providing a framework for designing more rational cancer combination therapy.

The Gait Outcomes Assessment List (GOAL): validation of a new assessment of gait function for children with cerebral palsy.

AIM: We investigated the validity of the Gait Outcomes Assessment List (GOAL), as an assessment of gait function in children with cerebral palsy (CP). METHOD: We studied a prospective cohort of 105 children with CP (Gross Motor Function Classification System [GMFCS] levels I-III; 65 males, 40 females; mean [SD] age 11y 11mo [3y 5mo], range 6-20y), who attended gait assessment over a 10-month period. Parents completed the GOAL, Functional Mobility Scale (FMS), and Functional Assessment Questionnaire (FAQ) during their child's gait evaluation. Ninety children completed instrumented gait analysis (IGA). Total GOAL and domain scores, Gait Profile Score (GPS), and Gait Variable Scores were calculated. RESULTS: The total GOAL discriminated between GMFCS levels (mean [SD] GMFCS level I, 72.5 [12.7]; GMFCS level II, 61.4 [13.0]; GMFCS level III, 38.8 [10.6]; [F2,97 =42.4, p<0.001]). Moderate correlations were found between total GOAL and FMS (5m and 50m r=0.59; 500m r=0.66) and FAQ walking (r=0.77) and activities list (r=0.75, p<0.01). There was a moderate negative correlation between total GOAL and GPS (r=-0.59) and gait appearance domain and GPS (r=-0.52, p<0.01). INTERPRETATION: The GOAL is a valid assessment of gait function in ambulant children with CP. It has the potential to improve understanding of the child's and parents' priorities and thus, in conjunction with IGA, provide a more balanced assessment across the domains of the World Health Organization's International Classification of Functioning, Disability and Health. WHAT THIS PAPER ADDS: The Gait Outcomes Assessment List (GOAL) can discriminate between Gross Motor Function Classification System levels. The GOAL correlates with standard functional assessments and gait analysis. Used with gait analysis, the GOAL provides comprehensive assessment across all International Classification of Functioning, Disability and Health domains.

MRI assessment of ischemic liver after intraportal islet transplantation.

BACKGROUND: There is a recent focus on embolization of the portal vein by transplanted islets as a major cause of early graft loss. The resultant ischemia causes necrosis or apoptosis of cells within the liver. Thus, noninvasive assessment of the liver receiving the islet transplant is important to evaluate the status islet grafts. METHODS: This study used noninvasive magnetic resonance imaging (MRI) for assessment of the posttransplant ischemic liver. Syngeneic islets in streprozotocin-induced diabetic mice were used. MRI and morphological liver assessments were performed at 0, 2, and 28 days after transplantation. Histologic assessment of insulin, hypoxia induced factor 1-alpha, and apoptosis were undertaken at similar time points. RESULTS: Ischemic/necrotic regions in the liver were detected by MRI at 2 days but not at 28 days after transplantation and were confirmed histologically. Liver injury was quantified from high intensity areas on T2-weighted images. Insulin release peaked 2 days after transplantation. CONCLUSION: Onset and reversal of liver ischemia due to intraportal islet transplantation are detectable using T2-weighted MRI. These changes coincide with periods of maximum insulin release likely due to partial islet destruction. We propose that MRI, as a noninvasive monitor of graft-related ischemia, may be useful in assessment of liver and islet engraftment after intraportal islet transplantation in a clinical setting.

In vivo imaging demonstrates a time-line for new vessel formation in islet transplantation.

Vascularization of transplanted islets must be maintained to provide long-term graft function. In vivo assessment of new vessel formation in islet grafts has been poorly documented. The purpose of this study was to investigate whether neovascularization was detectable in vivo in a Feridex-labeled murine syngeneic subcapsular islet mass using DCE MRI over 180 days. Subcapsular transplants could be visualized at post-transplant days three, seven, 14, and 28 using T2-weighted MRI and at post-transplant day 180 by immunohistochemistry. Injection of the contrast agent gadolinium (Gd)-DTPA for DCE at three, seven, and 14 days showed increased signal in the transplant area consistent with new vessel formation. Areas under contrast enhancement curves suggested peak angiogenesis at 14 days. At 180 days, there was no observable change in signal intensity after contrast injection suggesting established vascularization or islet mass reduction. Immunohistochemistry confirmed MRI and DCE findings. These data suggest that islet angiogenesis occurs early after transplantation and is likely established after one month of transplantation. This study provides an in vivo time-line of neovascularization in subcapsular islet grafts. We anticipate that contrast extravasation captured by MRI may provide useful monitoring of graft angiogenesis if reproduced in a clinically relevant intraportal model.

The use of sodium hyaluronate-carboxymethylcellulose (HA-CMC) barrier in gynecologic malignancies: a retrospective review of outcomes.

Concerns exist regarding the safety of sodium hyaluronate-carboxymethylcellulose (HA-CMC, Seprafilm) adhesion barrier in regard to cancer survival as a result of in vitro data demonstrating that hyaluronan, a component of HA-CMC, may promote tumor growth. We sought to determine whether use of HA-CMC is associated with duration of disease-free or overall survival and rates of immediate complication in patients with gynecologic malignancies. We identified 202 consecutive patients with epithelial ovarian, fallopian tube, and primary peritoneal cancer who underwent initial surgical staging or interval debulking at the University of Minnesota between January 2001 and December 2004. Information on patients' demographics, medical history, surgical procedures, postoperative complications, disease stage, histology, adjuvant therapy, and disease-free and overall survival was collected from medical records. Survival curves were compared between patients receiving or not receiving HA-CMC by stratified Cox regression models, log rank, and Wilcoxon tests. The level of significance was set to alpha = .05 for each test. Eighty patients received intraoperative placement of HA-CMC and 122 did not. Immediate postoperative complication rates were equivalent in both groups. Median follow-up was 2.1 years. There was no difference in disease-free survival (5-year estimate 23.6% vs. 33.3%, P = .80) or overall survival (5-year estimate 29.7% vs. 40.3%, P = .75) between those who received HA-CMC and those who did not. Our retrospective analysis suggests that HA-CMC adhesion barrier does not affect disease-free survival or overall survival; nor does it increase the immediate postoperative complication rates in patients undergoing abdominal surgery for ovarian, fallopian tube, and primary peritoneal carcinomas.

Monitoring neovascularization of intraportal islet grafts by dynamic contrast enhanced magnetic resonance imaging.

Fifteen thousand youths are diagnosed yearly with type 1 diabetes mellitus. Pancreatic islet transplantation has been shown clinically to provide short-term (~1 year) insulin independence. However, challenges associated with early vascularization of transplanted islet grafts and long-term islet survival remain. We utilized dynamic contrast enhanced magnetic resonance imaging (DCE MRI) to monitor neovascularization of islets transplanted into the right lobe of the liver in a syngeneic mouse model system. The left lobe received no islets and served as a control. DCE data were analyzed for temporal dynamics of contrast (gadolinium) extravasation and the results were fit to a Tofts two-compartment exchange model. We observed maximal right lobe enhancement at seven days post-transplantation. Histological examination up to 28 days was used to confirm imaging results. DCE-derived enhancement strongly correlated with immunohistochemical measures of neovascularization. To our knowledge, these results are the first to demonstrate using a FDA approved contrast agent that DCE MRI can effectively and non-invasively monitor the progression of angiogenesis in intraportal islet grafts.

Monitoring neovascularization of intraportal islet grafts by dynamic contrast enhanced magnetic resonance imaging.

Fifteen thousand youths are diagnosed yearly with type 1 diabetes mellitus. Pancreatic islet transplantation has been shown clinically to provide short-term (~1 year) insulin independence. However, challenges associated with early vascularization of transplanted islet grafts and long-term islet survival remain. We utilized dynamic contrast enhanced magnetic resonance imaging (DCE MRI) to monitor neovascularization of islets transplanted into the right lobe of the liver in a syngeneic mouse model. The left lobe received no islets and served as a control. DCE data were analyzed for temporal dynamics of contrast (gadolinium) extravasation and the results were fit to a Tofts two-compartment exchange model. We observed maximal right lobe enhancement at seven days post-transplantation. Histological examination up to 28 days was used to confirm imaging results. DCE-derived enhancement strongly correlated with immunohistochemical measures of neovascularization. To our knowledge these results are the first to demonstrate, using a FDA approved contrast agent, that DCE MRI can effectively and non-invasively monitor the progression of angiogenesis in intraportal islet grafts.

In vivo magnetic resonance imaging of vascularization in islet transplantation.

To evaluate changes in neovascularization of transplanted islets in vivo, dynamic contrast (gadolinium) enhanced magnetic resonance imaging (MRI) was used. Both iron (Feridex)-labeled and unlabeled syngeneic murine subcapsular islet grafts were studied. Differences in dynamic contrast enhancement of islet grafts were quantified after gadolinium injection at post-transplant days 3 and 14. Normalized contrast concentrations at day 14 in transplanted islets were increased relative with that on day 3. Time to peak contrast enhancement was faster by 12 min at day 14 compared to day 3 islets (while kidney and muscle peak times remained the same). Areas under the curve for contrast concentration versus time plots were larger in 14-day relative to 3-day islet grafts. In conclusion, noninvasive assessment of neovascularization is achievable. In vivo dynamic contrast-enhanced MRI can be used to detect and quantify changes in vascularization following islet transplantation. This technique may be useful in developing pro-angiogenic strategies to improve the transplantation outcome in experimental and clinical settings.