Search

Alpha thalassemia major (ATM) is a hemoglobinopathy that usually results in perinatal demise if in utero transfusions (IUTs) are not performed. We established an international registry (NCT04872179) to evaluate the impact of IUTs on survival to discharge (primary outcome) as well as perinatal and neurodevelopmental secondary outcomes. Forty-nine patients were diagnosed prenatally, 11 were diagnosed postnatally, and all 11 spontaneous survivor genotypes had preserved embryonic zeta-globin levels. We compared 3 groups of patients; group 1, prenatally diagnosed and alive at hospital discharge (n = 14), group 2, prenatally diagnosed and deceased perinatally (n = 5), and group 3, postnatally diagnosed and alive at hospital discharge (n = 11). Group 1 had better outcomes than groups 2 and 3 in terms of the resolution of hydrops, delivery closer to term, shorter hospitalizations, and more frequent average or greater neurodevelopmental outcomes. Earlier IUT initiation was correlated with higher neurodevelopmental (Vineland-3) scores (r = −0.72, P = .02). Preterm delivery after IUT was seen in 3/16 (19%) patients who continued their pregnancy. When we combined our data with those from 2 published series, patients who received ≥2 IUTs had better outcomes than those with 0 to 1 IUT, including resolution of hydrops, delivery at ≥34 weeks gestation, and 5-minute appearance, pulse, grimace, activity, and respiration scores ≥7. Neurodevelopmental assessments were normal in 17/18 of the ≥2 IUT vs 5/13 of the 0 to 1 IUT group (OR 2.74; P = .01). Thus, fetal transfusions enable the survival of patients with ATM and normal neurodevelopment, even in those patients presenting with hydrops. Nondirective prenatal counseling for expectant parents should include the option of IUTs.

ObjectiveIn utero SMA treatment could improve survival and neurologic outcomes. We investigated the attitudes of patients and parents with SMA regarding prenatal diagnosis, fetal therapies, and clinical trials.MethodsA multidisciplinary team designed a questionnaire that Cure SMA electronically distributed to parents and patients (>18years old) affected by SMA. Multivariable ordinal logistic regression was used to analyze associations between respondent characteristics and attitudes.ResultsOf 114 respondents (60% of whom were patients), only 2 were prenatally diagnosed. However, 91% supported prenatal testing and 81% felt there had been a delay in their diagnosis. Overall, 55% would enroll in a phase I trial for fetal antisense oligonucleotide (ASO) while 79% would choose an established fetal ASO/small molecule therapy. Overall, 61% would enroll in fetal gene therapy trials and 87% would choose fetal gene therapies. Patients were less likely to enroll in a fetal gene therapy trial than parents enrolling a child (OR 0.31, p&nbsp

Background Perineal hernias can be secondarily acquired following abdominoperineal resection of the rectum. While transabdominal minimally invasive techniques have traditionally used laparoscopy, there are few studies published on the robotic platform, which has been gaining popularity for other types of hernia repairs. We review the existing literature, share a video vignette, and provide practical tips for surgeons interested in adopting this approach. Methods A literature search in Pubmed was performed to include all articles in English describing robotic repair of perineal hernias with identification of variables of interest related to repair. A case presentation with an accompanying video vignette and lessons learned from the experience are provided. Results Seven case reports (four containing video) published between 2019 and 2022 were included. Most articles (n = 5) utilized the Da Vinci Si or Xi, and most patients (n = 5) had undergone abdominoperineal resection with neoadjuvant chemotherapy to treat rectal cancer. Patients were positioned in Trendelenburg with rightward tilt (n = 2), modified lithotomy (n = 1), or a combination of the two (n = 1). All articles (n = 7) reported closing the defect and using mesh. Three articles describe placing five ports (one camera, three robotic, one assistant). There were no significant intraoperative or postoperative complications reported, and no recurrence noted at 3–27 months follow-up. Based on our experience, as shown in the video vignette, we recommend lithotomy positioning, using porous polypropylene mesh anchored to the periosteum of the sacrum and peritoneum overlying the bladder and side wall, and placing a drain above the mesh. Conclusions A robotic transabdominal approach to perineal hernia repair is a viable alternate to laparoscopy based on low complication rates and lack of recurrence. Prospective and longer duration data are needed to compare the techniques.

Background To identify genes associated with congenital diaphragmatic hernia (CDH) to help understand the etiology and inform prognosis. Methods We performed exome sequencing on fetuses with CDH and their parents to identify rare genetic variants likely to mediate risk. We reviewed prenatal characteristics and neonatal outcomes. Results Data were generated for 22 parent-offspring trios. Six Likely Damaging (LD) variants were identified in five families (23 %). Three LD variants were in genes that contain variants in other CDH cohorts (NR2F2, PTPN11, WT1), while three were in genes that do not (CTR9, HDAC6, TP53). Integrating these data bolsters the evidence of association of NR2F2, PTPN11, and WT1 with CDH in humans. Of the five fetuses with a genetic diagnosis, one was terminated, two underwent perinatal demise, while two survived until repair. Conclusions Exome sequencing expands the diagnostic yield of genetic testing in CDH. Correlating CDH patients’ exomes with clinical outcomes may enable personalized counseling and therapies.

Patients with early-onset lysosomal storage diseases are ideal candidates for prenatal therapy because organ damage starts in utero. We report the safety and efficacy results of in utero enzyme-replacement therapy (ERT) in a fetus with CRIM (cross-reactive immunologic material)-negative infantile-onset Pompe's disease. The family history was positive for infantile-onset Pompe's disease with cardiomyopathy in two previously affected deceased siblings. After receiving in utero ERT and standard postnatal therapy, the current patient had normal cardiac and age-appropriate motor function postnatally, was meeting developmental milestones, had normal biomarker levels, and was feeding and growing well at 13 months of age.

Congenital diaphragmatic hernia is an anomaly that is often prenatally diagnosed and spans a wide spectrum of disease, with high morbidity and mortality associated with fetuses with severe defects. Congenital diaphragmatic hernia is thus an ideal target for fetal intervention. We review the literature on prenatal diagnosis, describe the history of fetal intervention for congenital diaphragmatic hernia, and discuss fetal endoscopic tracheal occlusion and the Tracheal Occlusion To Accelerate Lung growth trial results. Finally, we present preclinical studies for potential future directions.

A paucity of data exists about the current practice of fetal red blood cell (RBC) transfusion in the United States (US). This investigation describes intrauterine transfusion (IUT) RBC product selection and processing practices at different US institutions.A transfusion medicine and maternal-fetal medicine (MFM) team designed a survey to interrogate and characterize RBCs utilized for IUT. This survey was distributed to seventy US institutions with fetal treatment centers (October 2020-April 2021) identified through the NAFTNet (North American Fetal Therapy Network).Thirty-seven institutions responded (response rate 53%, 37/70), but five were excluded for not performing IUTs. Most (84%; 27/32) performed 1-24 IUTs annually; two performed50 IUTs/year. Group O, Rh(D) negative RBC units were always used by 66% (21/32), and 75% (24/32) provided hemoconcentrated RBCs by washing (17/24) or dry packing (6/24). Overall, 66% (21/32) targeted a hematocrit ≥75%. Fifty percent provided both leukocyte-reduced and CMV-negative RBC units. Irradiation of RBC units was performed within 6 h of issue at 63% (20/32) of sites. Most (81%, 26/32) used RBC units at7 days of age after collection, 56% (18/32) always provided washed RBC units, while 19% (6/32) issued washed RBC only if fresh units are unavailable. Implicated maternal RBC alloantibodies were matched for 78% (25/32) of the time. The transfused volume was universally determined by the MFMs.Heterogeneity and lack of standardization exist in RBC product selection and special processing steps for IUTs in the US. Hence, the establishment of a consensus to standardize IUT protocols is needed.

OBJECTIVES A third of infants with congenital diaphragmatic hernia (CDH) require a gastrostomy tube (GT) for nutritional support. We compared CDH infants who are GT-dependent to those able to meet their nutritional needs orally, to identify factors associated with requiring a GT and evaluate their long-term growth. METHODS Patients with CDH repaired at a single institution between 2012 and 2020 were included. Charts were retrospectively reviewed for demographic, surgical, and post-operative details. Mann-Whitney test and Fischer exact test were performed to compare GT-dependent neonates (n = 38, experimental) with orally fed neonates (n = 63, control). Significance was set at

INTRODUCTION: The incidence of fetal gallstones is estimated at 0.45% and its clinical relevance after birth remains unknown. This study aimed to describe the natural history of fetal gallstones and their clinical sequelae after birth. METHODS: We queried a database of fetuses referred for second and third trimester sonograms performed for high-risk pregnancies, and identified cases with fetal gallstones (1996–2019). Demographics, prenatal/postnatal imaging findings, and clinical sequelae were collected. A literature review was performed according to PRISMA guidelines. RESULTS: We screened approximately 200,000 obstetric sonograms; 34 fetuses were found to have cholelithiasis. The median gestational age at the time of US was 35 weeks (range 22 – 38). Fifty-six percent were female and 11.8% were twin pregnancies with one affected fetus. Median maternal age was 28 years (range 17–42). Eight fetuses underwent postnatal imaging and 4 had persistent cholelithiasis. There was one case of in utero demise. Two patients had structural anomalies (renal and cardiac) by US. A subset of 17 patients was followed long-term (range 3–20 years), and none developed clinical sequelae from cholelithiasis. DISCUSSION/CONCLUSIONS: No child developed postnatal clinical sequelae related to cholelithiasis identified in utero. Fetal cholelithiasis can be managed expectantly without follow-up imaging in asymptomatic patients.

IntroductionOutpatient opioid prescribing is associated with opioid misuse in young adults, but the longitudinal association between general healthcare exposure and opioid misuse has not been explored. The objective of this study is to examine the association between healthcare exposure in young adulthood and future opioid misuse.MethodsData were drawn from the National Longitudinal Study of Adolescent to Adult Health (2001-2018) and analyzed in 2021. Healthcare exposure (i.e., inpatient hospitalization and visits to the clinic, emergency department, mental-health facility, or dentist) between individuals aged 18 and 26 years was the primary independent variable; only patients who did not report opioid misuse at baseline were included. Opioid misuse was defined as using prescription painkillers without a doctor's permission and was measured 17 years after exposure. Multivariable logistic regression was used to examine any associations with opioid misuse (ages 33-43 years).ResultsA total of 8,225 young adults with a mean baseline age of 21.8 (SE=0.12) years met inclusion criteria. Approximately 13.7% reported new opioid misuse at follow-up. Those reporting opioid misuse at follow-up were more likely to be White, lack a college education, or report depression. Those exposed to inpatient hospitalization, emergency departments, or mental-health facilities had an increased risk of future opioid misuse.ConclusionsIn young adults reporting no opioid misuse at baseline, healthcare exposure was associated with an increased risk of opioid misuse later in adulthood in this large, national cohort. Physicians encounter this at-risk population daily, reinforcing the importance of responsible prescribing practices and the need for targeted screening, patient education, and intervention efforts in the healthcare setting.

Background Robotic transanal minimally invasive surgery (R-TAMIS) is an appealing alternative to transanal minimally invasive surgery (TAMIS) and transanal endoscopic microsurgery (TEM) for benign and early malignant rectal lesions that are not amenable to traditional open transanal excision. However, no studies to our knowledge have directly compared the three techniques. This study sought to compare peri-operative and pathologic outcomes of the three approaches. Methods The records of 29 consecutive patients who underwent TEM, TAMIS, or R-TAMIS at a single academic center between 2016 and 2020 were reviewed. Intra-operative details, pathological diagnosis and margins, and post-operative outcomes were recorded. The three groups were compared using chi-square and Kruskal–Wallis tests. Results Overall, 16/29 patients were women and the median age was 57 (interquartile range (IQR): 28–81). Thirteen patients underwent TEM, six had TAMIS, and 10 had R-TAMIS. BMI was lower in the R-TAMIS patients (24.7; IQR 23.8–28.7), than in TEM (29.3; IQR 19.9–30.2), and TAMIS (30.4; IQR 26.6–32.9) patients. High grade dysplasia and/or invasive cancer was more common in TAMIS (80%) and R-TAMIS (66.7%) patients than in TEM patients (41.7%). The three groups did not differ significantly in tumor type or distance from the anal verge. No R-TAMIS patients had a positive surgical margin compared to 23.1% in the TEM group and 16.7% in the TAMIS group. Length of stay (median 1 day for TEM and R-TAMIS patients, 0 days for TAMIS patients) and 30-day readmission rates (7.7% of TEM, 0% of TAMIS, 10% of R-TAMIS patients) also did not differ among the groups. Median operative time was 110 min for TEM, 105 min for TAMIS, and 76 min for R-TAMIS patients. Conclusions R-TAMIS may have several advantages over other advanced techniques for transanal excisions. R-TAMIS tended to be faster and to more often result in negative surgical margins compared to the two other techniques.

Prenatal gene therapy could provide a cure for many monogenic diseases. Prenatal gene therapy has multiple potential advantages over postnatal therapy, including treating before the onset of disease, the ability to induce tolerance and cross the blood-brain barrier. In this chapter, we will describe in utero gene therapy and its rationale, clinical trials of postnatal gene therapy, preclinical studies of in utero gene therapy, and potential risks to the mother and fetus.

A third of infants with congenital diaphragmatic hernia (CDH) require a gastrostomy tube (GT) for nutritional support. We compared CDH infants who are GT-dependent to those able to meet their nutritional needs orally, to identify factors associated with requiring a GT and evaluate their long-term growth.Patients with CDH repaired at a single institution between 2012 and 2020 were included. Charts were retrospectively reviewed for demographic, surgical, and post-operative details. Mann-Whitney test and Fischer exact test were performed to compare GT-dependent neonates (n = 38, experimental) with orally fed neonates (n = 63, control). Significance was set at0.05.Thirty-eight percent received a GT (median 67 days, interquartile range [IQR] 50-88). GT-dependent neonates were significantly more likely to have a lower lung-to-head ratio (median 1.2, IQR 0.9-1.4, vs 1.6, IQR 1.3-2.0, IQR P 0.0001), undergone patch or flap repair (79% vs 33%, P 0.0001), and been hospitalized longer (median 47, IQR 24-75 vs 28 days, P 0.0001). Fourteen of 38 had their GT removed (median 26 months, IQR 14-36). GT-dependent neonates initiated oral feeds (calculated as time since extubation) later (median 21, IQR 8-26, vs 8 days, IQR 4-13, P = 0.006). Height-for-age z scores remained stable after GT removal, while weight-for-age z scores dropped initially and began improving a year later.The need for a gastrostomy for nutritional support is associated with more severe CDH. Over a third of patients no longer needed a GT at a median of 26 months. Linear growth generally remains stable after removal. These results may help counsel parents regarding nutritional expectations.

Infants with congenital diaphragmatic hernia (CDH) who require non-invasive positive pressure ventilation or high flow nasal cannula are at risk for aspiration and delayed initiation of oral feeding. We developed a dysphagia provider-led protocol that involved early consultation with an occupational therapist or speech/language pathologist and modified barium swallow study (MBSS) to assess for readiness for oral feeding initiation/advancement on non-invasive positive pressure ventilation. The objective of this study was to retrospectively compare this intervention cohort to a historical control cohort to evaluate the protocol's impact on the time to initiate oral feeding. We describe the development and implementation of the protocol, the MBSS findings of the intervention cohort, and compared the control (n = 64) and intervention (n = 37) cohorts using Fischer's exact test and Mann-Whitney test. We found that both cohorts had similar prenatal and neonatal characteristics including age at extubation. Significantly more infants in the intervention cohort were on non-invasive positive pressure ventilation or high flow nasal cannula at the time of oral feeding initiation (84% vs. 28%, p 0.0001). None of the control cohort infants underwent MBSS while on respiratory support. Of the intervention cohort, 15 infants underwent a MBSS while on non-invasive positive pressure ventilation; 6 had no evidence of laryngeal penetration and/or aspiration during swallowing. Infants in the control cohort initiated oral feeds significantly sooner after extubation (6 versus 11 days, p = 0.001) and attained full oral feeds earlier (20 days versus 28 days, p = 0.02) than the intervention group. There was no difference in the rate of gastrostomy tube placement (38%). Appropriate monitoring by a dysphagia provider and evaluation with clinical and radiological means are crucial to determine the safety of initiating oral feeding in term infants with CDH. Continued surveillance is needed to determine the long-term impact on oral feeding progression in this population.

Disparities are prevalent in numerous areas of healthcare. We sought to investigate whether there were racial/ethnic disparities among pregnant women with the most severe form of alloimmunization who require intrauterine transfusions (IUT). We reviewed patients who underwent IUT for alloimmunization at a single fetal treatment center between 2015 and 2020. This "IUT cohort" was compared to an "Alloimmunization cohort": patients seen at our institution with a diagnosis of alloimmunization during pregnancy, who did not receive IUT. We collected maternal demographics including self-identified race/ethnicity and primary language, transfusion, and antibody characteristics. The cohorts were compared using unpaired t-tests, Mann-Whitney tests, and Fischer's exact tests, as appropriate. The IUT cohort included 43 patients and the alloimmunization cohort included 1049 patients. Compared to the alloimmunization cohort, there were significantly more patients of Latina descent in the IUT cohort (23.3% vs. 3.4%, p

OBJECTIVE: To examine potential disparities in patient access to elective procedures during the recovery phase of the COVID-19 pandemic. SUMMARY BACKGROUND DATA: Elective surgeries during the pandemic was limited acutely. Access to surgical care was restored in a recovery phase but backlogs and societal shifts are hypothesized to impact surgical access. METHODS: Adults with electronic health record orders for procedures ("procedure requests"), from March 16 to August 25, 2019 and March 16 to August 25, 2020, were included. Logistic regression was performed for requested procedures that were not scheduled. Linear regression was performed for wait time from request to scheduled or completed procedure. RESULTS: The number of patients with procedure requests decreased 20.8%, from 26,789 in 2019 to 21,162 in 2020. Patients aged 36-50 and >65 years, those speaking non-English languages, those with Medicare or no insurance, and those living > 100 miles away had disproportionately larger decreases. Requested procedures had significantly increased adjusted odds ratios (aORs) of not being scheduled for patients with primary languages other than English, Spanish, or Cantonese (aOR 1.60, 95% confidence interval [CI] 1.12-2.28); unpartnered marital status (aOR 1.21, 95% CI 1.07-1.37); uninsured or self-pay (aOR 2.03, 95% CI 1.53-2.70). Significantly longer wait times were seen for patients aged 36-65 years; with Medi-Cal insurance; from ZIP codes with lower incomes; and from ZIP codes > 100 miles away. CONCLUSIONS: Patient access to elective surgeries decreased during the pandemic recovery phase with disparities based on patient age, language, marital status, insurance, socioeconomic status, and distance from care. Steps to address modifiable disparities have been taken.

Background Intimate partner violence (IPV) commonly affects surgical patients, particularly trauma patients. However, baseline knowledge of IPV is poor among surgeons and screening is variable. We designed a project to educate surgical residents on IPV and standardize screening in all trauma patients. Materials and Methods Quality improvement frameworks and the Modified Provider Survey were used to examine residents’ attitudes and behaviors regarding IPV at a level one trauma center. An educational curriculum was designed with a trainee-led, multidisciplinary team to address knowledge gaps, barriers, and relevant reporting laws, and provide framing language that normalized screening. Results Fifty-seven surgical residents (64% response rate) spanning post-graduate years 1-7 completed surveys. All respondents believed IPV was relevant to their patients, yet only 4% correctly identified the prevalence of IPV. Only 15% felt comfortable screening for IPV and 75% felt they had received inadequate training. The most common barriers to screening were insufficient knowledge of community resources and what to do if patients screened positive. Most residents grossly underestimated the incidence of IPV and 19% believe healthcare providers have a limited role in being able to help IPV victims. There were no significant differences in responses between male and female residents or among residents from different postgraduate levels. Conclusions Surgical residents believe IPV is relevant, but few feel they have adequate training. Residents vastly underestimated the societal prevalence of IPV and the majority never screened patients for IPV. A residency-wide curriculum can address common misperceptions and perceived barriers.

Background/purposeCholedochal cysts are congenital dilations of the bile ducts, and are associated with an increased risk of malignant transformation. The purpose of this study is to report the outcomes of a large series of patients with choledochal cysts and to highlight our analysis of one patient who developed malignancy after cyst resection.MethodsWe conducted a retrospective review of patients

Kidney transplant recipients are frequently prescribed excess opioids at discharge relative to their inpatient requirements. Recipients who fill prescriptions after transplant have an increased risk of death and graft loss. This study examined the impact of standardized prescriptions on discharge amount and number of outpatient refills.A historical cohort (Group 1) was compared to a cohort without patient-controlled analgesia (Group 2) and a cohort in which providers prescribed no opioids to patients who required none on the day prior to discharge, and 10 pills to those who required opioids on the day prior (Group 3). Demographics, oral morphine equivalents (OMEs) prescribed on the day prior to and at discharge, and outpatient refills were collected.270 recipients were included. There was a nonsignificant trend towards lower OMEs on the day prior to discharge in Groups 2 and 3. Nonopioid adjunct use increased (P0.001). Discharge OMEs significantly decreased (mean 87.2 in Group 1, 62.8 in Group 2, 26.6 in Group 3, P0.001). The number of patients discharged without opioids increased (23.8% of Group 1, 37.5% of Group 2, 60.6% of Group 3, P0.001). Group 3, Asian descent, and lower OMEs on the day prior were factors significantly associated with decreased discharge OMEs on multivariable linear regression. Twelve percent of Group 2 and 2% of Group 3 patients received an outpatient refill (P = 0.02).A protocol targeting discharge opioids significantly reduced the amount of opioids prescribed in kidney transplant recipients; most patients subsequently received no opioids at discharge.

BACKGROUND Share 35 was a policy implemented in 2013 to increase regional sharing of deceased donor livers to patients with model for end-stage liver disease ≥ 35 to decrease waitlist mortality for the sickest patients awaiting liver transplantation (LT). The purpose of this study was to determine whether live donor liver transplantation (LDLT) volume was impacted by the shift in allocation of deceased donor livers to patients with higher model for end-stage liver disease scores. METHODS Using Network for Organ Sharing/Organ Procurement and Transplantation Network Standard Transplant Analysis and Research files, we identified all adults who received a primary LT between October 1, 2008, and March 31, 2018. LT from October 1, 2008, through June 30, 2013, was designated as the pre-Share 35 era and July 1, 2013, through March 31, 2018, as the post-Share 35 era. Primary outcomes included transplant volumes, graft survival, and patient survival in both eras. RESULTS In total, 48 779 primary adult single-organ LT occurred during the study period (22 255 pre-Share 35, 26 524 post). LDLT increased significantly (6.8% post versus 5.7% pre, P

BackgroundSix percent of opioid-naïve patients develop opioid dependence post-operatively. We implemented a protocol in our renal transplant recipients that eliminated opioid patient-controlled analgesia (PCA) and included a multi-modal non-opioid regimen. The purpose of this study was to examine the impact of PCA elimination on opioid requirements at discharge in renal transplant recipients.MethodsWe reviewed adult renal transplant recipients for the three months prior to, and following, the protocol's implementation. Patients with an intra-abdominal transplant, pancreas-renal transplant, or chronic pain were excluded. The number of opioid pills prescribed on the day prior to discharge were categorized as A) 0, B) 1-3, and C) ≥4. Discharge opioid prescriptions were then evaluated based on a recent recommendation that group A receive 0 pills, group B 15 pills, and group C 30 pills, to satisfy the outpatient pain needs of 85% of patients. Pre- and post-intervention metrics were compared using independent t-tests and Chi squared tests.Results150 recipients were included (79 pre-intervention, 71 post; 51% male). PCA use decreased significantly (81% vs. 4.2%, p&nbsp

Background: Prune belly syndrome (PBS) and congenital pouch colon (CPC) are rare congenital syndromes with a low incidence in the United States (U.S.) with most CPC cases being from India. In this case report, we describe, to the best of our knowledge, the first PBS variant and CPC patient in the U.S. Case Presentation: A 30-year-old G2P0010 woman was referred to a tertiary center after an 18-week ultrasound showed a fetal abdominal mass. A prenatal MRI showed a dilated loop of bowel containing a mixture of urine and meconium, oligohydramnios, and a protuberant abdominal wall. Born at 37 weeks, the child’s physical exam was notable for a distended abdomen with thin abdominal musculature, non-palpable bilateral testes, no anal opening, and flat buttocks. Intra-operatively, a dilated cecum/ascending colon was noted with an abrupt change in caliber at the transverse colon, bilateral enlarged ureters, a left testis at the internal ring and no visualized right testis. A colostomy and mucous fistula were created 5 cm from the sigmoid pouch. Conclusion: While most reported cases of CPC undergo single stage repair (one operation) at 1 day of life, our patient underwent the first procedure of a staged repair at 16 hours of life given his clinical instability at the time as well as his unknown urological anatomy in the setting of urinary obstruction. This case demonstrates the importance of fetal imaging, multidisciplinary approach at a tertiary care center, and reinforces a staged repair when necessary.

Introduction: Alpha globin mutations are very common worldwide, and the severity of resulting anemia depends on the number and type of mutated alleles. While the 4 gene mutation (alpha thalassemia major, ATM) was previously deemed fatal except in rare cases, emerging evidence indicates that survival to birth and good postnatal outcomes are possible with in utero transfusions. We hypothesized that the embryonic zeta globin gene, which is expressed early in gestation prior to alpha globin, may compensate for the lack of alpha globin and that induction of zeta globin after it has naturally been silenced may become a new therapy for patients with ATM. Methods: We evaluated mutations in the UCSF international registry of patients with ATM to understand factors related to patient survival with and without in utero transfusions. We then engineered Human Umbilical Cord Derived Erythroid Progenitor Cells (HUDEP-2 cells) carrying the common SEA alpha globin deletion, in which zeta globin expression is preserved (H-SEA), as well as those on which the zeta globin genes were deleted (HBZ-/-) using CRISPR-Cas9. We evaluated the expression of alpha and zeta globins using qPCR, Western blot, and flow cytometry. We generated lentiviral vectors expressing zeta globin under the control of beta-globin promoters to examine changes in both zeta and alpha globin in a dynamic way. Results: None of the registry patients who survived to birth spontaneously (n=11) had a mutation that involves a concomitant deletion in zeta globin (such as the -FIL, -THAI, or -MEDII mutation), while alpha globin mutations extending into the zeta globin gene were found in 14 of 37 (38%) patients who were diagnosed prenatally, suggesting that the presence of zeta globin may play a role in the ability to survive to birth without fetal therapy. Interestingly, we found that H-SEA clones express higher levels of zeta globin than WT cells, as illustrated by quantitative real-time PCR (Fig 1A), Western blot (Fig 1B) and flow cytometry (Fig 1C). These cells also developed beta globin dimers due to excess unpaired beta-globin chains, as demonstrated by Western blotting with and without reducing agents, indicating that they are an appropriate cell model for ATM. We next generated HUDEP-2 clones lacking zeta globin (HBZ KO) and transduced these clones with lentiviral vectors expressing high levels of zeta globin (lenti-zeta) (Fig 1D). Western blotting revealed that increasing the levels of zeta globin in these cells resulted in decreased expression of alpha globin, suggesting reciprocal control between these genes (Fig 1E). Most importantly, we saw a reduction in toxic beta-globin dimers in H-SEA cells expressing high levels of zeta-globin after transduction with lenti-zeta, suggesting that zeta globin could functionally replace the missing alpha-globin (Fig 1 F,G). To understand transcriptomic differences in H-SEA cells that may result in increased zeta globin expression, we performed bulk RNA sequencing of wild type and H-SEA clones. We confirmed that zeta expression is significantly upregulated in H-SEA compared to wild type (log2 fold change of 4.25, p=2.24E-38). Pathway analysis of differentially expressed genes is ongoing. Conclusions: Our international patient registry suggests that expression of zeta globin may play a role in the spontaneous survival to birth in a subset of patients. Zeta globin expression is increased in the setting of H-SEA cells in vitro, and restoration of zeta expression by lentivirus results in a reduction of toxic beta globin dimers in these ATM cells. Furthermore, expressing zeta globin at high levels in H-WT cells decreased alpha globin expression, suggesting a reciprocal regulation of these two genes. This concept is similar to the relationship between fetal gamma and adult beta globins which has been exploited for therapeutic editing approaches in patients with beta-thalassemia. At this point, the natural repressor of zeta globin is not yet known, but our data suggests that a strategy of upregulating zeta globin could potentially be developed to mimic the ongoing trials of using the BCL11A repressor to induce gamma globin in patients with beta thalassemia and sickle cell disease. Disclosures Wienert: Integral Medicines: Current Employment. Kohn:Allogene Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Orchard Therapeutics: Consultancy, Patents & Royalties, Research Funding. MacKenzie:Acrigen: Membership on an entity's Board of Directors or advisory committees; Ultragenyx: Research Funding.

BACKGROUND/PURPOSE: The differential diagnosis for prenatal suprarenal masses (SRM) is broad and includes neuroblastoma, adrenal hemorrhage and subdiaphragmatic extralobar pulmonary sequestration (SEPS). We sought to elucidate the appropriate postnatal management for fetuses found to have a SRM. METHODS: We conducted a retrospective review of patients prenatally diagnosed with SRM at our institution between 1998 and 2018. Prenatal characteristics, imaging, and neonatal outcomes were collected. We also performed a PubMed literature search and pooled analysis of all patients with a prenatally diagnosed SRM previously described in the literature. RESULTS: The literature review yielded 32 studies, of which 19 were single case reports. In our case series, twelve patients were included. Seven patients were delivered vaginally, one was terminated. Postnatal diagnoses included: SEPS (n=5), adrenal hemorrhage (n=3), polycystic kidney (n=2), splenic cyst (n=1), and unknown for one patient. All but two of the final diagnoses had been on the initial diagnostic differential. With the exception of the terminated fetus, all remain alive today. On pooled analysis, patients who underwent operative management were diagnosed later 32 weeks versus 24 weeks) and had a significant predominance of left-sided lesions (59.5% vs. 39.2%). The published literature demonstrates a trend towards observation versus resection over the past 30 years. CONCLUSIONS: Patients prenatally diagnosed with a SRM have an excellent prognosis. Our series demonstrates a high incidence of SEPS, which were all resected, and adrenal hemorrhage, which were observed with repeat imaging. These patients can be followed with serial postnatal ultrasounds to determine the diagnosis prior to deciding the appropriate treatment.