Comparing Outcomes of Acute Versus Gradual Surgical Correction in Brachymetatarsia.

Brachymetatarsia consists of a shortened metatarsal resulting in a shorter toe. Pain with shoe wear and cosmetic concerns are the main reasons for surgical intervention. Surgical techniques to increase metatarsal length include acute lengthening with interpositional bone grafting or gradual lengthening with callus distraction. We performed a retrospective cohort study for 1 surgeon's patients at 1 institution over 10 years. Twenty-nine feet in 22 patients met inclusion criteria for acute correction; 16 feet in 11 patients were included for gradual correction. Mean ages were 26.3 ± 12.1 and 27 ± 10.8 in the acute and gradual groups, respectively (p = .79). Most patients were female: 95.4% of acute cases and 90.1% of gradual cases. Most involved lengthening the fourth metatarsal: 86.7% and 100% of acute and gradual groups, respectively (p = .54). Correction obtained amounted to 14.4 ± 2.97 mm (range, 10-22 mm) in acute cases and 14.8 ± 2.39 mm (range, 10-20 mm) in gradual cases (p = .81). The mean percent increase in metatarsal length was 21.1 ± 14% for acute and 22.6 ± 12.4% for gradual (p = .72). Mean consolidation was 8.9 ± 2.51 weeks for acute and 21.4 ± 10.8 weeks for gradual (p = <.001). Nonunions were most common in the gradual group (37.5%) with need for more revisional surgery (43.5%) compared with the acute group; both were statistically significant. We conclude that acute brachymetatarsia correction can obtain correction similar to the gradual technique with fewer postoperative complications and less osseous consolidation time.

Isolation and genome sequence annotation of SallyK, a newly discovered cluster EG bacteriophage infecting Microbacterium.

Discovered from soil in a flower planter in Pocatello, Idaho and using Microbacterium foliorum, SallyK is a lytic bacteriophage with a siphovirus morphology. It has a 62,883 bp-long genome with 103 putative genes. Based on gene content similarity to actinobacteriophages, SallyK is assigned to cluster EG.

Isolation and genome sequence annotation of KillerTomato, a newly discovered cluster EE bacteriophage infecting Microbacterium.

Discovered in Pocatello, Idaho, soil near a tomato garden, siphovirus KillerTomato infects Microbacterium foliorum NRRL B-24224. KillerTomato is a lytic cluster EE phage with a 17,442-bp genome and 68.6% GC content. Of 25 genes, 20 were assigned putative functions, including a putative tail assembly chaperone protein with a programmed frameshift and an endolysin.

Women's preferences for a new contraceptive under development: an exploratory study.

Objective: Currently available contraceptive methods do not meet the needs of all users. We sought to explore preferences of potential end-users regarding an on-demand, non-hormonal female contraceptive currently under development, using a web-based survey. Study design: We recruited respondents for an exploratory survey via web link on Amazon Mechanical Turk (MTurk). Individuals were eligible if they were 18-44 years of age, identified as cis-gender female, were English-speaking, not pregnant, and had used barrier contraception previously. Respondents provided demographic characteristics and a basic reproductive history. We then provided a brief description of the potential contraceptive. Respondents were asked about their interest in the proposed contraceptive and preferences for method attributes. Results: A total of 500 respondents completed the survey. Three-quarters of respondents were <35 years of age and 48.2% were currently using a barrier contraceptive method. Three-fourths of respondents (73.8%) expressed interest in using the contraceptive under development. The majority wanted the method to be small (≤2 inches), rod-shaped, and low cost (<$5 per use). More than half (59.4%) said it was important to be able to use the method without partners' knowledge. The most reported potential concerns were vaginal irritation (51.6%) and lack of effectiveness (46.4%). Sixty percent of respondents were confident they could use the method correctly. Discussion: Available contraceptive methods lack attributes preferred by some users. Development of new contraceptives frequently does not involve end-user input early in the development process. Individuals in this sample displayed interest in the proposed contraceptive and expressed preferences that can inform the further development of this method.

Comparison of Minimally Invasive and Open Approaches for Midfoot Charcot Neuroarthropathy Reconstruction.

Charcot neuroarthropathy (CNA) is a progressive disease affecting the bones and joints of the foot that can lead to instability, breakdown, and collapse. Minimally invasive surgery (MIS) techniques are becoming a popular option within musculoskeletal surgery of the foot and ankle and may be an alternative to aggressive dissection seen during corrective surgery. An MIS approach minimizes vascular disruption, provides structural stability at an osteotomy or arthrodesis site, and encourages early mobilization if indicated. This retrospective study compares 17 patients who underwent an open approach for midfoot CNA reconstruction with 17 patients who underwent an MIS approach for midfoot CNA reconstruction. Preoperative and postoperative radiographic parameters were measured: lateral talus-first metatarsal, anteroposterior (AP) talus-first metatarsal, calcaneal pitch, and cuboid height. Difficulties that occurred during treatment were gathered and sorted into postoperative problems (stage I), obstacles (stage II), and complications (stage III). Changes from preoperative to postoperative radiographic lateral talus-first metatarsal and AP talus-first metatarsal angles were statistically significant (p < .001) for both the MIS and open approach. No true postoperative complications (stage III) were observed at last follow-up. The most common difficulty encountered was pin-site infection (stage I; in 23.5% of patients) in the MIS group. In the open group, the most common complications were wound development (stage I; 23.5%) and nonunions (stage II; 23.5%). Our findings suggest that midfoot CNA reconstruction with MIS methods offers similar outcomes to the open approach.

Minor and Major Amputation Rates Following Midfoot Charcot Reconstructive Surgery.

Charcot neuroarthropathy (CNA) is a progressive disease that affects the bones and joints of the foot. To prevent collapse and loss of stability within the pedal architecture, CNA should be diagnosed and managed early. The objective of this retrospective study was to review patients who underwent midfoot CNA reconstructive surgery and evaluate subsequent rates of minor and major amputations. Secondary objectives include identifying patients that underwent midfoot CAN with and without a subtalar joint (STJ) arthrodesis. Out of the 72 patients, 4 (5.6%) underwent minor (digital, ray) amputation, 2 (2.8%) underwent proximal amputations (either below or above the knee), and none underwent midfoot amputation (transmetatarsal, Lisfranc, Chopart). A Fisher's exact test was employed to compare the outcomes of minor and major amputation rates in our CNA cohort with those who underwent midfoot CNA reconstruction with STJ arthrodesis and found no statistical significance (p = .15). Overall, a total progression to amputation was 8.4% following midfoot CNA reconstruction, with 2.8% of patients undergoing major amputation (below knee or above knee). Despite no statistical significance, we recommend surgeons to consider including an STJ arthrodesis in addition to midfoot CNA reconstruction to establish a stable and plantigrade foot.

Progression to Hindfoot Charcot Neuroarthropathy After Midfoot Charcot Correction in Patients With and Without Subtalar Joint Arthrodesis.

Charcot neuroarthropathy (CNA) is a disabling and progressive disease that affects the bones and joints of the foot. Successful Charcot reconstruction focuses on restoring anatomic alignment, obtaining multiple joint arthrodesis, selecting stable fixation, preserving foot length, and creating a foot suitable for community ambulation in supportive shoegear. Intramedullary fixation arthrodesis of the medial and lateral columns has been previously reported to produce improvement in midfoot Charcot reconstruction. More recently, a growing trend of stabilization of the subtalar joint (STJ) has been incorporated alongside the medial and lateral column fusion. Our objectives were to retrospectively review patients who underwent midfoot Charcot reconstructive surgery, whether with or without accompanying STJ arthrodesis, and establish which patients progressed to ankle CNA. Of the 72 patients who underwent midfoot Charcot reconstruction, 28 (38.9%) underwent STJ arthrodesis, and 22 converted to ankle CNA (30.6%). Fourteen (63.6%) of 22 ankle CNA cases had not undergone STJ arthrodesis; 8 patients (36.4%) had it. A Fisher exact test was performed to identify the relationship between those without STJ arthrodesis and those progressing to ankle CNA; it revealed statistical significance (p = .001). Performing an STJ arthrodesis with midfoot Charcot reconstructive surgery may be beneficial to aiding in hindfoot stability, establishing a plantigrade foot, and providing further insight into the management of midfoot Charcot.

The Prevalence of Bunions in the Setting of Brachymetatarsia.

Brachymetatarsia is caused by premature closure of the physis and is characterized by a short metatarsal. Additional foot conditions may exist in patients presenting with brachymetatarsia, such as hallux valgus (HV). A retrospective study was performed to evaluate the prevalence of HV and brachymetatarsia in the ipsilateral foot. Ninety-seven feet with congenital brachymetatarsia were reviewed in a multi-study cohort of 66 patients who underwent surgical correction between January 2005 and August 2020 at a single institution. The group was comprised of 61 females and 5 males, with a mean age of 27 years. HV deformities were verified with standardized anteroposterior radiographs. HV was present in 29 of 97 feet for a prevalence of 30% in the feet with brachymetatarsia. Our results demonstrate a 30% prevalence of HV associated with brachymetatarsia. This information is helpful for foot and ankle surgeons managing brachymetatarsia to determine appropriate conservative or surgical management of this condition.

The Role of the Shortened Proximal Phalanx in the Setting of Brachymetatarsia.

Brachymetatarsia is a condition in which a metatarsal bone does not grow out to full length. This is caused by premature physeal closure. The proximal phalanx associated with the shortened metatarsal helps achieve the natural parabola of the foot. A hypoplastic proximal phalanx is a common finding in patients with brachymetatarsia. The goal of this study was to determine the length of the proximal phalanx in the setting of brachymetatarsia, and how much the shortening is attributed to the clinically smaller toe. We performed a retrospective study to evaluate the length of the proximal phalanx in the shortened ray. After the metatarsal was brought out to the desired length of correction, the proximal phalanx was measured on radiographs. Ninety-seven feet with congenital brachymetatarsia were reviewed in a cohort of 66 patients who underwent surgical correction between January 2005 and February 2020 at a single institution. The group was comprised of 61 females and 5 males, with a mean age of 27.5 years. The average length of the proximal phalanx associated with the affected metatarsal was noted to be 18.9 ± 3.83 mm for males and 15.6 ± 4.02 mm for females. Our results indicate the shortened proximal phalanx is 5 mm shorter when compared to normal population and is a contributing factor to the shortened clinical appearance of the digit in brachymetatarsia. Treating surgeons should be aware of this to better educate patients on the influence of the digit on the overall shortening seen in cases of brachymetatarsia.

Annotation of the Complete Genome Sequences of Bacteriophages Sara and Birdfeeder.

Sara is a siphovirus with a linear 17,362bp genome containing 25 genes. Birdfeeder is a podovirus with a circularly permuted 53,897bp genome containing 52 genes. Sara and Birdfeeder were isolated from environmental samples in Plattsburgh, NY, USA and Forest Hill, MD, USA, respectively, using Microbacterium foliorum NRRL B-24224.

Continuation rates of two different-sized copper intrauterine devices among nulliparous women: Interim 12-month results of a single-blind, randomised, multicentre trial.

Background: The most widely used copper intrauterine device (IUD) in the world (the TCu380A), and the only product available in many countries, causes side effects and early removals for many users. These problems are exacerbated in nulliparous women, who have smaller uterine cavities compared to parous women. We compared first-year continuation rates and reasons/probabilities for early removal of the TCu380A versus a smaller Belgian copper IUD among nulliparous users. Methods: This 12-month interim report is derived from a pre-planned interim analysis of a sub population and focused on key secondary comparative endpoints. In this participant-blinded trial at 16 centres in the USA, we randomised participants aged 17-40 in a 4:1 ratio to the NT380-Mini or the TCu380A. In the first year, participants had follow-up visits at 6-weeks and 3, 6, and 12-months, and a phone contact at 9 months; we documented continued use, expulsions, and reasons for removal. Among participants with successful IUD placement, we compared probabilities of IUD continuation and specific reasons for discontinuation using log-rank tests. This trial is registered with ClinicalTrials.gov number NCT03124160 and is closed to recruitment. Findings: Between June 1, 2017, and February 25, 2019, we assigned 927 nulliparous women to either the NT380-Mini (n = 744) or the TCu380A (n = 183); the analysis population was 732 (NT380-Mini) and 176 (TCu380A). Participants using the NT380-Mini, compared to the TCu380A, had higher 12-month continuation rates (78·7% [95% CI: 72·9-84·5%] vs. 70·2% [95% CI: 59·7-80·7], p = 0·014), lower rates of removal for bleeding and/or pain (8·1% vs. 16·2%, p = 0·003) and lower IUD expulsion rates (4·8% vs. 8·9%, p = 0·023), respectively. Interpretation: The NT380-Mini offers important benefits for a nulliparous population compared to the TCu380A in the first twelve months, when pivotal experiences typically occur. Higher continuation rates with the NT380-Mini may avert disruptions in contraceptive use and help users avoid unintended pregnancy. Funding: Bill & Melinda Gates Foundation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Mona Lisa, N.V. (Belgium).

Sexual Satisfaction Results With the Vaginal pH Modulator From the Phase 3 AMPOWER Study.

BACKGROUND: The novel vaginal pH modulator (VPM; Phexxi) is a non-hormonal, woman-controlled, on-demand, water-based, surfactant-free contraceptive vaginal gel; VPM has also been cleared by the Food and Drug Administration for use as a personal lubricant. AIM: The aim of this study is to report on sexual satisfaction results from the phase 3 AMPOWER study. METHODS: AMPOWER was a single-arm, open-label, multicenter study to assess the safety and efficacy of VPM in preventing pregnancy. Women were enrolled who were healthy, age 18-35 years, and sexually active with regular cyclic menses. OUTCOMES: Women's satisfaction (including sexual satisfaction) was an exploratory endpoint measured at Baseline and Visits 3-5; sexual satisfaction-related patient reported outcomes (PROs) were assessed via 3 different questions: (i) a question related to the impact on a woman's sex life; (ii) a question from the Sexual Function Questionnaire (SFQ) related to the frequency of ten sexual problems; and (iii) a question from the Female Sexual Function Index (FSFI) related to lubrication. RESULTS: For sexual satisfaction-related PRO measures with baseline assessments, the majority of women reported the same or improved scores at Visit 5 (ranging from 85.8% to 98.4%). The percentage of women who reported that their sex life was improved and/or maintained was higher in Visit 3, 4, and 5 (95.4%, 95.1%, and 93.6%, respectively) compared to Baseline (87.6%). The mean impact on sex life score significantly improved at Visit 5 compared to Baseline (P < .001). In the SFQ, the mean score significantly improved (P < .005) at Visit 5 vs Baseline in 7 of the 10 variables measured (vaginal dryness, lack of sexual interest and/or desire, vaginal tightness, pain, anxiety, unable to orgasm, and vaginal bleeding or irritation). In women who reported sexual activity in the last 4 weeks, the mean FSFI score also significantly improved from Baseline to Visit 5 (P = .037). CLINICAL IMPLICATIONS: In this post-hoc analysis of the phase 3 AMPOWER study, the PRO results demonstrate a high level of sexual satisfaction with VPM. STRENGTHS AND LIMITATIONS: The primary strength of this analysis was the large study size of 1,330 women. Limitations included the non-randomized study design, the post-hoc nature of the analysis, and the fact that sexual satisfaction was an exploratory endpoint. CONCLUSION: As a non-hormonal, woman-controlled, on-demand, lubricating contraceptive gel, VPM offers women a unique set of benefits with positive impacts on their sexual health. Thomas MA, Morlock R, Dart C, Howard B. Sexual Satisfaction Results With the Vaginal pH Modulator From the Phase 3 AMPOWER Study. J Sex Med 2022;19:975-982.

E4orf1 Suppresses E1B-Deleted Adenovirus Vaccine-Induced Immune Responses.

As demonstrated by the recent COVID pandemic, vaccines can reduce the burden arising from infectious agents. Adenoviruses (Ads) with deletion of the early region 1B55K (ΔE1B Ad) are currently being explored for use in vaccine delivery. ΔE1B Ads are different from Ads with deletions in early region 1 and early region 3 (ΔE1/E3) used in most Ad vaccine vectors in that they contain the Ad early region 1A (E1A), and therefore the ability to replicate. Common to almost all Ads that are being explored for clinical use is the Ad early region 4 (E4). Among the E4 genes is open reading frame 1 (E4orf1), which mediates signals through the PI3-kinase/Akt pathway that is known to modulate immune responses. This suggests that E4orf1 might also modulate immune responses, although it has remained unexplored in ΔE1B Ad. Here, we show that cells infected with an E1B55K and E4orf1-deleted (ΔE41) Ad exhibited reduced levels of phosphorylated Akt (Ser473 and Thr308)) and expressed different intrinsic innate immune cytokines from those induced in cells infected with an E4orf1-containing, ΔE1B parental Ad that exhibited elevated levels of phosphorylated Akt. Rhesus macaques immunized with a ΔE41 Ad that expressed rhFLSC (HIV-1BaL gp120 linked to rhesus CD4 D1 and D2), exhibited higher levels of rhFLSC-specific interferon γ-producing memory T-cells, higher titers of rhFLSC-specific IgG1 binding antibody in serum, and antibodies able to mediate antibody-dependent cellular cytotoxicity (ADCC) with greater killing capacity than the ΔE1B Ad. Therefore, E4orf1, perhaps by acting through the PI3-kinase/Akt pathway, limits intrinsic innate and system-wide adaptive immune responses that are important for improved ΔE1B Ad-based vaccines.

Disruption of NBS1/MRN Complex Formation by E4orf3 Supports NF-κB That Licenses E1B55K-Deleted Adenovirus-Infected Cells to Accumulate DNA>4n.

Cells increase their DNA content greater than the G2/M (DNA > 4n) phases along the path to cancer. The signals that support this increase in DNA content remain poorly understood. Cells infected with adenovirus (Ad) similarly develop DNA > 4n and share a need to bypass the DNA damage response (DDR) signals that trigger cell cycle arrest, and/or cell death. Ads with deletion in early region 1B55K (ΔE1B Ad) are oncolytic agents that are currently being explored for use in vaccine delivery. Interestingly, they promote higher levels of DNA > 4n than Ads that contain E1B55K. Existing in these and almost all Ads that are being explored for clinical use, is early region 4 (E4). The Ad E4 open reading frame 3 (E4orf3) is a viral oncogene that interferes with the ability of cells to respond to DNA damage by disrupting MRN complex formation. Our study reveals that E4orf3 is required for the enhanced fraction of ΔE1B Ad-infected cells with DNA > 4n. For that reason, we explored signaling events mediated by E4orf3. We found that in ΔE1B Ad-infected cells, E4orf3, as reported by others, isolates NBS1 in nuclear dots and tracks. This allows for elevated levels of phosphorylated ATM that is linked to transcriptionally active NF-κB. Pharmacological inhibition of NF-κB reduced the fraction of ΔE1B Ad-infected cells with DNA > 4n while pharmacological inhibition of ATM reduced the levels of nuclear NF-κB and the fraction of ΔE1B Ad-infected cells with DNA > 4n and increased the fraction of dead or dying cells with fragmented DNA. This ability of E4orf3 to disrupt MRN complex formation that allows cells to bypass the cell cycle, evade death, and accumulate DNA > 4n, may be linked to its oncogenic potential. IMPORTANCE Genome instability, a hallmark of cancer, exists as part of a cycle that leads to DNA damage and DNA > 4n that further enhances genome instability. Ad E4orf3 is a viral oncogene. Here, we describe E4orf3 mediated signaling events that support DNA > 4n in ΔE1B Ad-infected cells. These signaling events may be linked to the oncogenic potential of E4orf3 and may provide a basis for how some cells survive with DNA > 4n.

Making an African American REI physician: a story of mentorship.

Few African American men graduating from medical school find a home as a provider in obstetrics and gynecology. This is a story of mentorship at every level of the medical pipeline and should serve as a primer on how to help future leaders from diverse backgrounds.

Relationship of parity and prior cesarean delivery to levonorgestrel 52 mg intrauterine system expulsion over 6 years.

OBJECTIVE: Assess the relationship between parity and prior route of delivery to levonorgestrel 52 mg intrauterine system (IUS) expulsion during the first 72 months of use. STUDY DESIGN: We evaluated women enrolled in the ACCESS IUS multicenter, Phase 3, open-label clinical trial of the Liletta levonorgestrel 52 mg IUS. Investigators evaluated IUS presence at 3 and 6 months after placement and then every 6 months and during unscheduled visits. We included women with successful placement and at least one follow-up assessment. We evaluated expulsion rates based on obstetric history; for prior delivery method subanalyses, we excluded 12 participants with missing delivery data. We determined predictors of expulsion using multivariable regression analyses. RESULTS: Of 1714 women with IUS placement, 1710 had at least one follow-up assessment. The total population included 986 (57.7%) nulliparous women. Sixty-five (3.8%) women experienced expulsion within 72 months, 50 (76.9%) within the first 12 months. Expulsion rates among nulliparous women (22/986 [2.2%]) or parous women with any pregnancy ending with a Cesarean delivery (6/195 [3.1%]) differed from parous women who only experienced vaginal deliveries (37/517 [7.2%]) (p < 0.001). In multivariable regression, obesity (adjusted odds ratio [aOR] 2.2, 95% confidence interval [CI] 1.3-3.7), parity (aOR 2.2, 95% CI 1.2-4.1), and non-white race (aOR 1.8, 95% CI 1.1-3.2) predicted expulsion. Among parous women, obesity (aOR 2.2, 95% CI 1.2-4.2) increased the odds and having ever had a cesarean delivery (aOR 0.4, 95% CI 0.1-0.9) decreased the odds of expulsion. CONCLUSION: IUS expulsion occurs in less than 4% of users over the first 6 years of use and occurs mostly during the first year. Expulsion is more likely among obese and parous women. IMPLICATIONS: Levonorgestrel 52 mg intrauterine system expulsion occured more commonly in parous than nulliparous women; the increase in parous women is primarily in women who had vaginal deliveries only. The association between obesity, delivery route, and IUS expulsion needs further elucidation.

The immunological impact of adenovirus early genes on vaccine-induced responses in mice and nonhuman primates.

Adenovirus (Ad) is being explored for use in the prevention and treatment of a variety of infectious diseases and cancers. Ad with a deletion in early region 3 (ΔE3) provokes a stronger immune response than Ad with deletions in early regions 1 and E3 (ΔE1/ΔE3). The ΔE1/ΔE3 Ads are more popular because they can carry a larger transgene and because of the deleted E1 (E1A and E1B), are perceived safer for clinical use. Ad with a deletion in E1B55K (ΔE1B55K) has been in phase III clinical trials for use in cancer therapy in the US and has been approved for use in head and neck tumor therapy in China, demonstrating that Ad containing E1A are safe for clinical use. We have shown previously that ΔE1B55K Ad, even while promoting lower levels of an inserted transgene, promoted similar levels of transgene-specific immune responses as a ΔE3 Ad. Products of the Ad early region 4 (E4) limit the ability of cells to mount an innate immune response. Using this knowledge, we deleted the Ad E4 open reading frames 1-4 (E4orf1-4) from the ΔE1B55K Ad. Here, we show that innate cytokine network genes are elevated in the ΔE4 Ad-infected cells beyond that of ΔE3 Ad-infected cells. Further, in immunized mice the IgG2a subclass was favored as was the IgG1 subclass in immunized nonhuman primates. Thus, Ad E4 impacts immune responses in cells, in immunized mice, and immunized nonhuman primates. These Ad may offer advantages that are beneficial for clinical use.Importance: Adenovirus (Ad) is being explored for use in the prevention and treatment of a variety of infectious diseases and cancers. Here we provide evidence in cells, mice, and nonhuman primates supporting the notion that Ad early gene-products limit specific immune responses. Ad constructed with deletions in early genes and expressing HIV envelope protein was shown to induce greater HIV-specific cellular immune responses and higher titer antibodies compared to the parental Ad with the early genes. In addition to eliciting enhanced immunity, the deleted Ad possesses more space for insertion of additional or larger transgenes needed for targeting other infectious agents or cancers.

Estimation of fractional myocardial blood volume and water exchange using ferumoxytol-enhanced magnetic resonance imaging.

Fractional myocardial blood volume (fMBV) estimated using ferumoxytol-enhanced magnetic resonance imaging (MRI) (FE-MRI) has the potential to capture a hemodynamic response to myocardial hypoperfusion during contrast steady state without reliance on gadolinium chelates. Ferumoxytol has a long intravascular half-life and its use for steady-state MRI is off-label. The aim of this prospective study was to optimize and evaluate a two-compartment model for estimation of fMBV based on FE-MRI. Nine healthy swine and one swine with artificially induced single-vessel coronary stenosis underwent MRI on a 3.0 T clinical magnet. Myocardial longitudinal spin-lattice relaxation rate (R1) was measured using the 5(3)3(3)3 modified Look-Locker inversion recovery (MOLLI) sequence before and at contrast steady state following seven ferumoxytol infusions (0.125-4.0 mg/kg). fMBV and water exchange were estimated using a two-compartment model. Model-fitted fMBV was compared to simple fast-exchange fMBV approximation and percent change in pre- and postferumoxytol R1. Dose undersampling schemes were investigated to reduce acquisition duration. Variation in fMBV was assessed using one-way analysis of variance. Fast-exchange fMBV and ferumoxytol dose undersampling were evaluated using Bland-Altman analysis. Healthy normal swine showed a mean mid-ventricular fMBV of 7.2 ± 1.4% and water exchange rate of 11.3 ± 5.1 s-1 . There was intersubject variation in fMBV (p < 0.05) without segmental variation (p = 0.387). fMBV derived from eight-dose and four-dose sampling schemes had no significant bias (mean difference = 0.07, p = 0.541, limits of agreement -1.04% [-1.45, -0.62%] to 1.18% [0.77, 1.59%]). Pixel-wise fMBV in one swine model with coronary artery stenosis showed elevated fMBV in ischemic segments (apical anterior: 11.90 ± 4.00%, apical septum: 16.10 ± 5.71%) relative to remote segments (apical inferior: 9.59 ± 3.35%, apical lateral: 9.38 ± 2.35%). A two-compartment model based on FE-MRI using the MOLLI sequence may enable estimation of fMBV in studies of ischemic heart disease. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 2.

Conception rates in women desiring pregnancy after levonorgestrel 52 mg intrauterine system (Liletta®) discontinuation.

OBJECTIVE: Evaluate reproductive function in nulligravid and gravid women after levonorgestrel 52 mg intrauterine system (IUS) discontinuation based on time to pregnancy. STUDY DESIGN: We evaluated women participating in the ACCESS IUS multicenter, Phase 3, open-label clinical trial of the Liletta(®) levonorgestrel 52 mg IUS who discontinued the IUS within 60 months of use and desired pregnancy. Study staff contacted participants every three months after IUS discontinuation for up to 12 months to determine whether pregnancy occurred. We excluded women who opted to stop attempting to conceive before 12 months. We evaluated 12-month conception rates in participants 16-35 years at IUS placement, comparing dichotomous outcomes using Fisher's exact test. We performed a multivariable analysis to assess the association of baseline characteristics, age at discontinuation, duration of IUS use, and positive sexually transmitted infection testing during IUS use with conception. RESULTS: Among 165 women who attempted to conceive, 142 (86.1%) did so within 12 months with a median time to conception of 92 days. The 12-month conception rates did not differ between nulligravid (66/76 [86.8%]) and gravid (76/89 [85.4%]) women (p = 0.83) and nulliparous (78/90 [86.7%]) and parous (64/75 [85.3%]) women (p = 0.83). In multivariable analysis, only obesity (aOR 0.3 [95% CI 0.1-0.8]) was associated with ability to conceive. CONCLUSIONS: After levonorgestrel 52 mg IUS discontinuation, women have rapid return of fertility in the year post-removal. Fertility rates after IUS removal do not vary based on gravidity, parity, age at discontinuation, or duration of IUS use. IMPLICATIONS: This contemporary IUS study included a large population of nulligravid and nulliparous women. IUS use over many years does not effect spontaneous fertility after IUS discontinuation, regardless of gravidity or parity. Providers and patients should have no concern about the impact of IUS use on future fertility.