Recent Advances in the Genetic Pathogenesis, Diagnosis, and Management of Esophageal Atresia and Tracheoesophageal Fistula: A Review.

Infants born with esophageal atresia and tracheoesophageal fistula, a complex congenital malformation occurring in 1/2500-4000 live births, may suffer threats to their cardiac, respiratory, and digestive health in addition to anomalies that may exist in the genitourinary and musculoskeletal systems. Optimal care for these patients throughout their lives is best achieved through a coordinated, multidisciplinary approach that our health care system is not always well-equipped to provide. This review, though not exhaustive, highlights the components of care that pertain to initial surgical reconstruction and subsequent diagnosis and management of the complications that are most frequently encountered. Authors from among the many specialties involved in the care of these patients summarize the current best practice with attention to the most recent advances. Assessment and improvement of quality of life and transition to adult specialists as children grow to adulthood is also reviewed.

Cost of pediatric laryngotracheal reconstruction: Differences between single-versus double-stage procedures.

OBJECTIVE: Examine differences in cost between single stage (ss) versus double stage (ds) laryngotracheal reconstruction (LTR) for pediatric subglottic stenosis. STUDY DESIGN: Retrospective chart review of children who underwent ssLTR or dsLTR from 2014 to 2018 at a single institution. METHODS: Costs related to LTR and post-operative care up to one year after tracheostomy decannulation were extrapolated from charges billed to the patient. Charges were obtained from the hospital finance department and the local medical supplies company. Patient demographics including baseline severity of subglottic stenosis and co-morbidities were noted. Variables assessed include duration of hospital admission, number of ancillary procedures, duration of sedation wean, cost of tracheostomy maintenance, and time to tracheostomy decannulation. RESULTS: Fifteen children underwent LTR for subglottic stenosis. D Ten patients underwent ssLTR, while five underwent dsLTR. Grade 3 subglottic stenosis was more prevalent in patients who underwent dsLTR (100%) than ssLTR (50%). The average per-patient hospital charges for ssLTR was $314,383 versus $183,638 for dsLTR. When estimated mean cost of tracheostomy supplies and nursing care until tracheostomy decannulation was included, the mean total charges associated with dsLTR patients was $269,456. Average hospital stay after initial surgery was 22 days for ssLTR versus 6 days for dsLTR. Average time to tracheostomy decannulation for dsLTR was 297 days. Average number of ancillary procedures needed was 3 versus 8 for ssLTR versus dsLTR. CONCLUSION: For pediatric patients with subglottic stenosis, dsLTR may have a lower cost than ssLTR. Although ssLTR has the benefit of immediate decannulation, it is associated with higher patient charges, as well as longer initial hospitalization and sedation. For both patient groups, fees associated with nursing care comprised the majority of charges. Recognizing the factors that contribute to cost differences between ssLTR and dsLTR may be useful when performing cost-benefit analyses and assessing value in health care delivery.

Cost-effectiveness Analysis of Subcutaneous Infliximab for Inflammatory Bowel Diseases in Sequential Biologic Treatment.

BACKGROUND: Inflammatory bowel disease (IBD) guidelines recommend tumor necrosis factor-α inhibitors (TNFis) for patients who have not responded to conventional therapy, and vedolizumab in case of inadequate response to conventional therapy and/or TNFis. Recent studies have shown that vedolizumab may also be effective in the earlier treatment lines. Therefore, we conducted cost-effectiveness analyses to determine the optimal treatment sequence in patients with IBD. METHODS: A Markov model with a 10-year time horizon compared the cost-effectiveness of different biologic treatment sequences in patients with moderate to severe ulcerative colitis (UC) and Crohn's disease (CD) from the UK and French perspectives. Subcutaneous formulations of infliximab, vedolizumab, and adalimumab were evaluated. Comparative effectiveness was based on a network meta-analysis of clinical trials and real-world evidence. Costs included pharmacotherapy, surgery, adverse events, and disease management. RESULTS: The results indicated that treatment sequences starting with infliximab were less costly and more effective than those starting with vedolizumab for patients with UC in the United Kingdom and France, and patients with just CD in France. For patients with CD in the United Kingdom, treatment sequences starting with infliximab resulted in better health outcomes with incremental cost-effectiveness ratios (ICERs) near the threshold. CONCLUSIONS: Based on the ICERs, treatment sequences starting with infliximab are the dominant option for patients with UC in the United Kingdom, and patients with UC and CD in France. In UK patients with CD, ICERs were near the assumed "willingness to pay" threshold. These results reinforce the UK's National Institute for Health and Care Excellence recommendations for using infliximab prior to using vedolizumab in biologics-naïve patients.

A Markov model compared the cost-effectiveness of biologic treatment sequences in patients with moderate to severe inflammatory bowel diseases from a European perspective. The results indicated that treatment sequences starting with infliximab are the dominant option than those starting with vedolizumab.

Budget impact analysis of the subcutaneous infliximab (CT-P13 SC) for treating inflammatory bowel disease in the Big-5 European (E5) countries.

BACKGROUND: In 2020, the European Medicines Agency approved infliximab subcutaneous (SC) for the treatment of inflammatory bowel disease. This new mode of infliximab administration will reduce outpatient visits and costs of intravenous (IV) administration. This article describes a budget impact analysis of introducing infliximab SC to the Big-5 European (E5) market (Germany, France, Italy, Spain and UK) for 5 years, from the healthcare payer's perspective. METHODS: A prevalence-based budget impact model was developed to examine the financial impact of infliximab SC. "World with" versus "world without" infliximab SC scenarios were compared, including the potential administration costs of IV administration. RESULTS: Introducing infliximab SC in patients with Crohn's disease (CD) for 5 years resulted in cost savings of €42.0 million in the UK, €59.4 million in Germany, and €46.4 million in France and Italy, but increased budget expenditure in Spain by €3.8 million. For ulcerative colitis (UC), cost savings of €42.7 million in the UK, €44.9 million in Germany, €44.3 million in France, and €53.0 million in Italy occurred, but with no savings in Spain for 5 years. Cost-savings per patient was calculated by diving the net budget saving by number of treatment eligible patients. Maximum and minimum saving per patient per year ranged between €38.25 and €575.74 in CD, both from Germany, and €105.06 (France) and €647.25 (Germany) in UC. CONCLUSION: Healthcare payers in the UK, Germany, France, and Italy, but not in Spain, will make budget savings by using infliximab SC for the treatment of inflammatory bowel disease.

Comparative efficacy and safety of infliximab and vedolizumab therapy in patients with inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND AND AIMS: There are limited comparative data for infliximab and vedolizumab in inflammatory bowel disease patients. METHODS: We conducted a systematic review and meta-analysis to compare the efficacy and safety of infliximab and vedolizumab in adult patients with moderate-to-severe Crohn's disease or ulcerative colitis. RESULTS: We identified six eligible Crohn's disease and seven eligible ulcerative colitis trials that randomised over 1900 participants per disease cohort to infliximab or vedolizumab. In the Crohn's disease and ulcerative colitis cohorts, infliximab yielded better efficacy than vedolizumab for all analysed outcomes (CDAI-70, CDAI-100 responses, and clinical remission for Crohn's disease and clinical response and clinical remission for ulcerative colitis) during the induction phase, with non-overlapping 95% confidence intervals. In the maintenance phase, similar proportions of infliximab- or vedolizumab-treated patients achieved clinical response, clinical remission, or mucosal healing in both Crohn's disease and ulcerative colitis. For the safety outcomes, rates of adverse events, serious adverse events, and discontinuations due to adverse events were similar in infliximab- and vedolizumab-treated patients in both diseases. The infection rate was higher in infliximab for Crohn's disease and higher in vedolizumab when treating patients with ulcerative colitis. There was no difference between the treatments in the proportions of patients who reported serious infections in both indications. CONCLUSIONS: Indirect comparison of infliximab and vedolizumab trials in adult patients with moderate-to severe Crohn's disease or ulcerative colitis demonstrated that infliximab has better efficacy in the induction phase and comparable efficacy during the maintenance phase and overall safety profile compared to vedolizumab.

Budget Impact Analysis of the Introduction of Subcutaneous Infliximab (CT-P13 SC) for the Treatment of Rheumatoid Arthritis in the United Kingdom.

BACKGROUND: CT-P13 subcutaneous (SC)-the first and only SC version of infliximab-is approved by the European Medicines Agency for the treatment of rheumatoid arthritis (RA). This new mode of infliximab administration will allow patients to self-inject at home, significantly reducing the number of outpatient visits and costs of intravenous (IV) administration. This paper describes the economic impact of introducing CT-P13 SC to the market from the UK societal perspective. OBJECTIVE: The budget impact analysis was conducted to assess the financial impact of the adoption of CT-P13 SC over a 5-year period. METHODS: A prevalence-based budget impact model was developed incorporating epidemiological data, administration cost data, and market share data. The analysis compared a "world with" CT-P13 SC scenario to a "world without" CT-P13 SC. A sensitivity analysis included dose escalation up to 4.1 mg/kg to reflect the real-world care delivery setting. RESULTS: Compared to the "world without" scenario, the introduction of CT-P13 SC resulted in cost savings of £69.3 million in the UK over a 5-year period. In the scenario analysis, the saving increased to £173.5 million over 5 years. CONCLUSION: Use of CT-P13 SC may lead to substantial cost savings for the UK society.

A Qualitative Study of the Barriers and Benefits to Resident Education in Ambulatory Surgical Centers.

OBJECTIVE: As Ambulatory Surgical Centers (ASCs) become more common in academic medical centers, large hospital systems must determine how to shift resident education from inpatient to outpatient surgical centers. This study aims to define stakeholders' views regarding the integration of surgical residents into ASCs. DESIGN: Long-form interviews lasting 30 to 60 minutes were conducted. Interviews were hand-transcribed and analyzed by qualitative analysis to determine benefits of learning in ASCs for residents, challenges that arise from integrating residents, and recommendations to improve resident incorporation. SETTING: Interviews were conducted using a video conferencing platform. PARTICIPANTS: Residency program directors, attending surgeons, graduate medical learners, and a nursing manager were interviewed. Twenty-one total interviews were conducted, representing ten different departments. RESULTS: Stakeholders agreed that residents benefit from being placed in ASCs because the fast, surgical pace allows the residents to engage in more cases. However, different stakeholders highlighted different challenges, all centered around the notion of inter-stakeholder conflict due to conflicting priorities among residents, attending physicians, and administration. Likewise, recommendations differed by stakeholder group-faculty members sought more defined learning objectives and enhanced communication, whereas residents desired that ambulatory surgical time be more structured. CONCLUSIONS: Despite the pressures of rapid case turnover, stakeholders agreed that there are many benefits to resident education in ASCs. Findings related to challenges and recommendations support the need to strengthen communication between stakeholder groups and better plan for resident integration into ASCs.

Delayed Rise of Oral Fluid Antibodies, Elevated BMI, and Absence of Early Fever Correlate With Longer Time to SARS-CoV-2 RNA Clearance in a Longitudinally Sampled Cohort of COVID-19 Outpatients.

BACKGROUND: Sustained molecular detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in the upper respiratory tract (URT) in mild to moderate coronavirus disease 2019 (COVID-19) is common. We sought to identify host and immune determinants of prolonged SARS-CoV-2 RNA detection. METHODS: Ninety-five symptomatic outpatients self-collected midturbinate nasal, oropharyngeal (OP), and gingival crevicular fluid (oral fluid) samples at home and in a research clinic a median of 6 times over 1-3 months. Samples were tested for viral RNA, virus culture, and SARS-CoV-2 and other human coronavirus antibodies, and associations were estimated using Cox proportional hazards models. RESULTS: Viral RNA clearance, as measured by SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR), in 507 URT samples occurred a median (interquartile range) 33.5 (17-63.5) days post-symptom onset. Sixteen nasal-OP samples collected 2-11 days post-symptom onset were virus culture positive out of 183 RT-PCR-positive samples tested. All participants but 1 with positive virus culture were negative for concomitant oral fluid anti-SARS-CoV-2 antibodies. The mean time to first antibody detection in oral fluid was 8-13 days post-symptom onset. A longer time to first detection of oral fluid anti-SARS-CoV-2 S antibodies (adjusted hazard ratio [aHR], 0.96; 95% CI, 0.92-0.99; P = .020) and body mass index (BMI) ≥25 kg/m2 (aHR, 0.37; 95% CI, 0.18-0.78; P = .009) were independently associated with a longer time to SARS-CoV-2 viral RNA clearance. Fever as 1 of first 3 COVID-19 symptoms correlated with shorter time to viral RNA clearance (aHR, 2.06; 95% CI, 1.02-4.18; P = .044). CONCLUSIONS: We demonstrate that delayed rise of oral fluid SARS-CoV-2-specific antibodies, elevated BMI, and absence of early fever are independently associated with delayed URT viral RNA clearance.

Maternal Pregnancy Intention and Developmental Outcomes in Brazilian Preschool-Aged Children.

OBJECTIVE: This study aims to characterize the association between maternal pregnancy intention and socioemotional developmental outcomes in a Brazilian sample of preschool-aged children. METHODS: Data from children aged 4 to 5 years and their primary caregivers in Embu das Artes, a Brazilian municipality in the state of São Paulo, were collected in 2016. Maternal pregnancy intention was defined as intended or unintended, which was then further stratified as mistimed or unwanted. Outcomes included socioemotional developmental delay, internalizing and externalizing behaviors, and school readiness. We estimated risk ratios (RRs) for unadjusted and inverse-probability-weighted regression adjustment (IPWRA) analyses using 2-level (intended vs unintended) and 3-level (intended vs mistimed vs unwanted) exposure definitions. RESULTS: Of 1,034 total mothers, 40.7% reported their pregnancy as intended, 46.0% as mistimed, and 13.4% as unwanted. In both unadjusted and IPWRA analyses comparing intended and unintended pregnancies, all associations failed to reach statistical significance. In the IPWRA analysis using the 3-level exposure definition, unwanted pregnancies were associated with higher risk of socioemotional developmental delay (RR = 1.14; 95% confidence interval [CI], 1.01-1.28) and co-occurring internalizing and externalizing behaviors (RR = 1.11, 95% CI, 1.00-1.22), compared with intended pregnancies. CONCLUSION: There was higher risk of poor child outcomes among unwanted compared with intended pregnancies, whereas mistimed pregnancies were not associated with poor outcomes. Further research using standardized definitions of pregnancy intention along with targeted interventions that increase access to family planning services and counseling for parents of children born after unintended pregnancies is needed.

Pregnancy alters interleukin-1 beta expression and antiviral antibody responses during severe acute respiratory syndrome coronavirus 2 infection.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2, the disease-causing pathogen of the coronavirus disease 2019 pandemic, has resulted in morbidity and mortality worldwide. Pregnant women are more susceptible to severe coronavirus disease 2019 and are at higher risk of preterm birth than uninfected pregnant women. Despite this evidence, the immunologic effects of severe acute respiratory syndrome coronavirus 2 infection during pregnancy remain understudied. OBJECTIVE: This study aimed to assess the impact of severe acute respiratory syndrome coronavirus 2 infection during pregnancy on inflammatory and humoral responses in maternal and fetal samples and compare antibody responses to severe acute respiratory syndrome coronavirus 2 among pregnant and nonpregnant women. STUDY DESIGN: Immune responses to severe acute respiratory syndrome coronavirus 2 were analyzed using samples from pregnant (n=33) and nonpregnant (n=17) women who tested either positive (pregnant, 22; nonpregnant, 17) or negative for severe acute respiratory syndrome coronavirus 2 (pregnant, 11) at Johns Hopkins Hospital. We measured proinflammatory and placental cytokine messenger RNAs, neonatal Fc receptor expression, and tetanus antibody transfer in maternal and cord blood samples. In addition, we evaluated antispike immunoglobulin G, antispike receptor-binding domain immunoglobulin G, and neutralizing antibody responses to severe acute respiratory syndrome coronavirus 2 in serum or plasma collected from nonpregnant women, pregnant women, and cord blood. RESULTS: Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection expressed more interleukin-1 beta, but not interleukin 6, in blood samples collected within 14 days vs >14 days after performing severe acute respiratory syndrome coronavirus 2 test. Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection also had reduced antispike receptor-binding domain immunoglobulin G titers and were less likely to have detectable neutralizing antibody than nonpregnant women. Although severe acute respiratory syndrome coronavirus 2 infection did not disrupt neonatal Fc receptor expression in the placenta, maternal transfer of severe acute respiratory syndrome coronavirus 2 neutralizing antibody was inhibited by infection during pregnancy. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of coronavirus disease 2019 treatment in pregnancy. In addition, the long-term implications of placental inflammation for neonatal health require greater consideration.

Delayed rise of oral fluid antibodies, elevated BMI, and absence of early fever correlate with longer time to SARS-CoV-2 RNA clearance in an longitudinally sampled cohort of COVID-19 outpatients.

BACKGROUND: Sustained molecular detection of SARS-CoV-2 RNA in the upper respiratory tract (URT) in mild to moderate COVID-19 is common. We sought to identify host and immune determinants of prolonged SARS-CoV-2 RNA detection. METHODS: Ninety-five outpatients self-collected mid-turbinate nasal, oropharyngeal (OP), and gingival crevicular fluid (oral fluid) samples at home and in a research clinic a median of 6 times over 1-3 months. Samples were tested for viral RNA, virus culture, and SARS-CoV-2 and other human coronavirus antibodies, and associations were estimated using Cox proportional hazards models. RESULTS: Viral RNA clearance, as measured by SARS-CoV-2 RT-PCR, in 507 URT samples occurred a median (IQR) 33.5 (17-63.5) days post-symptom onset. Sixteen nasal-OP samples collected 2-11 days post-symptom onset were virus culture positive out of 183 RT-PCR positive samples tested. All participants but one with positive virus culture were negative for concomitant oral fluid anti-SARS-CoV-2 antibodies. The mean time to first antibody detection in oral fluid was 8-13 days post-symptom onset. A longer time to first detection of oral fluid anti-SARS-CoV-2 S antibodies (aHR 0.96, 95% CI 0.92-0.99, p=0.020) and BMI ≥ 25kg/m 2 (aHR 0.37, 95% CI 0.18-0.78, p=0.009) were independently associated with a longer time to SARS-CoV-2 viral RNA clearance. Fever as one of first three COVID-19 symptoms correlated with shorter time to viral RNA clearance (aHR 2.06, 95% CI 1.02-4.18, p=0.044). CONCLUSIONS: We demonstrate that delayed rise of oral fluid SARS-CoV-2-specific antibodies, elevated BMI, and absence of early fever are independently associated with delayed URT viral RNA clearance.

Endoscopic Posterior Cricoid Split and Rib Graft Without Tracheostomy: Case and Literature Review.

Endoscopic posterior cricoid split and rib grafting (EPCS/RG) for the treatment of posterior laryngeal stenosis has some advantages over traditional open approaches, including improved surgical visualization and decreased morbidity. Many pediatric patients who undergo EPCS/RG have indwelling tracheostomy, which may be utilized to help manage the airway perioperatively. The role for de novo tracheostomy placement at the time of EPCS/RG is less clear. We present three cases from a tertiary children's hospital in which EPCS/RG was safely performed without tracheostomy. For patients with posterior laryngeal stenosis but without tracheostomy, EPCS/RG with endotracheal tube stenting might be a safe option. Laryngoscope, 131:E2599-E2602, 2021.

The Clinical Course of COVID-19 in the Outpatient Setting: A Prospective Cohort Study.

BACKGROUND: Outpatient coronavirus disease 2019 (COVID-19) has been insufficiently characterized. To determine the progression of disease and determinants of hospitalization, we conducted a prospective cohort study. METHODS: Outpatient adults with positive reverse transcription polymerase chain reaction results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were recruited by phone between April 21 and July 23, 2020, after receiving outpatient or emergency department testing within a large health network in Maryland, United States. Symptoms were collected by participants on days 0, 3, 7, 14, 21, and 28, and portable pulse oximeter oxygen saturation (SaO2), heart rate, and temperature were collected for 15 consecutive days. Baseline demographics, comorbid conditions, and vital signs were evaluated for risk of subsequent hospitalization using negative binomial and logistic regression. RESULTS: Among 118 SARS-CoV-2-infected outpatients, the median age (interquartile range [IQR]) was 56.0 (50.0-63.0) years, and 50 (42.4%) were male. Among individuals in the first week of illness (n = 61), the most common symptoms included weakness/fatigue (65.7%), cough (58.8%), headache (45.6%), chills (38.2%), and anosmia (27.9%). Participants returned to their usual health a median (IQR) of 20 (13-38) days from symptom onset, and 66.0% of respondents were at their usual health during the fourth week of illness. Over 28 days, 10.9% presented to the emergency department and 7.6% required hospitalization. The area under the receiver operating characteristics curve for the initial home SaO2 for predicting subsequent hospitalization was 0.86 (95% CI, 0.73-0.99). CONCLUSIONS: Symptoms often persisted but uncommonly progressed to hospitalization among outpatients with COVID-19. Home SaO2 may be a helpful tool to stratify risk of hospitalization.

Budget Impact Analysis of the Introduction of Rituximab and Trastuzumab Intravenous Biosimilars to EU-5 Markets.

BACKGROUND: Biologic treatments impose a large financial burden on healthcare payers. Subcutaneous formulations of trastuzumab and rituximab offer administration cost savings relative to the intravenous products through reduced preparation and infusion times. However, intravenous biosimilars have the potential to offset administration costs through lower drug costs. OBJECTIVE: The objective was to develop a budget impact model (BIM) from a payer's perspective for the EU-5 countries (UK, France, Germany, Spain, Italy) to demonstrate the economic impact of using intravenous trastuzumab and rituximab biosimilars. METHODS: An incidence-based BIM was developed to estimate the net budget impact utilising epidemiology data from the literature, market research data on the use of relevant treatments in all approved indications, and corresponding costs. The budget impact was estimated for 5 years following introduction of the biosimilars. RESULTS: Analysis using the base-case results indicated that adoption of the biosimilars trastuzumab and rituximab would result in net cost savings. At year 5, the net budget saving ranged from €4.05 million to 303.86 million for rituximab and from €19 million to 172 million for trastuzumab. The cost saving could potentially extend treatment to 291-15,671 more patients with rituximab and 622-3688 more patients with trastuzumab. CONCLUSION: This budget impact analysis emphasised that increased use of intravenous rituximab and trastuzumab biosimilars may result in cost savings from the payer's perspective across the EU-5 countries.

Dysregulated immunity in SARS-CoV-2 infected pregnant women.

IMPORTANCE: The effects of SARS-CoV-2 infection on immune responses during pregnancy have not been systematically evaluated. OBJECTIVE: To assess the impact of SARS-CoV-2 infection during pregnancy on inflammatory and humoral responses in maternal and fetal samples and compare antibody responses to SARS-CoV-2 among pregnant and non-pregnant women. DESIGN: Immune responses to SARS-CoV-2 were analyzed using samples from pregnant and non-pregnant women who had either tested positive or negative for SARS-CoV-2. We measured, proinflammatory and placental cytokine mRNAs, neonatal Fc receptor (FcRn) receptor expression, and tetanus antibody transfer in maternal and cord blood samples. Additionally, we measured anti-spike (S) IgG, anti-S-receptor binding domain (RBD) IgG, and neutralizing antibody (nAb) responses to SARS-CoV-2 in serum or plasma collected from non-pregnant women, pregnant women, and cord blood. SETTING: Johns Hopkins Hospital (JHH). PARTICIPANTS: Pregnant women were recruited through JHH outpatient obstetric clinics and the JHH Labor & Delivery unit. Non-pregnant women were recruited after receiving outpatient SARS-CoV-2 testing within Johns Hopkins Health System, USA. Adult non-pregnant women with positive RT-PCR results for SARS-CoV-2, within the age range of 18-48 years, were included in the study. EXPOSURES: SARS-CoV-2. MAIN OUTCOMES AND MEASURES: Participant demographic characteristics, antibody titers, cytokine mRNA expression, and FcRn receptor expression. RESULTS: SARS-COV-2 positive pregnant women expressed more IL1ß , but not IL6 , in blood samples collected within 14 days versus > 14 days after a confirmed SARS-CoV-2 test, with similar patterns observed in the fetal side of placentas, particularly among asymptomatic pregnant women. Pregnant women with confirmed SARS-CoV-2 infection also had reduced anti-S-RBD IgG titers and were less likely to have detectable nAb as compared with non-pregnant women. Although SARS-CoV-2 infection did not disrupt FcRn expression in the placenta, maternal transfer of nAb was inhibited by SARS-CoV-2 infection during pregnancy. CONCLUSIONS AND RELEVANCE: SARS-CoV-2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of COVID-19 therapeutics in pregnancy. The long-term implications of placental inflammation for neonatal health also requires greater consideration.

COVID-19 in pregnancy: Placental and neonatal involvement.

Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over 12 million infections and more than 550 000 deaths.1 Morbidity and mortality appear partly due to host inflammatory response.2 Despite rapid, global research, the effect of SARS-CoV-2 on the developing fetus remains unclear. Case reports indicate that vertical transmission is uncommon; however, there is evidence that placental and fetal infection can occur.3-7 Placentas from infected patients show inflammatory, thrombotic, and vascular changes that have been found in other inflammatory conditions.8,9 This suggests that the inflammatory nature of SARS-CoV-2 infection during pregnancy could cause adverse obstetric and neonatal events. Exposure to intrauterine inflammation and placental changes could also potentially result in long-term, multisystemic defects in exposed infants. This review will summarize the known literature on the placenta in SARS-CoV-2 infection, evidence of vertical transmission, and possible outcomes of prenatal exposure to the virus.

COVID-19 and the US response: accelerating health inequities.

Health inequities have long defined health and the healthcare system in the USA. The clinical and research capacity across the USA is unparalleled, yet compared to other high and even some middle-income countries, the average health indicators of the population remain suboptimal in 2020, a finding at least in part explained by inequity in healthcare access. In this context, COVID-19 has rapidly emerged as a major threat to the public's health. While it was initially thought that severe acute respiratory syndrome coronavirus 2 would be the great equaliser as it would not discriminate, it is clear that COVID-19 incidence and mortality have rapidly reinforced health disparities drawn by historical and contemporary inequities. Here, we synthesise the data highlighting specific risks among particular marginalised and under-resourced communities including those in jails, prisons and detention centers, immigrants and the undocumented, people with disabilities and people experiencing homelessness across the USA. The drivers of these disparities are pervasive structural risks including limited access to preventive services, inability to comply with physical distancing recommendations, underlying health disparities and intersecting stigmas particularly affecting racial and ethnic minorities across the country, including African Americans, Latinx Americans and Native Americans. Advancing the COVID-19 response, saving lives and restarting the economy necessitate rapidly addressing these inequities rather than ignoring and even reinforcing them.

Cancer in Syrian refugees in Jordan and Lebanon between 2015 and 2017.

Protracted conflicts in the Middle East have led to successive waves of refugees crossing borders. Chronic, non-communicable diseases are now recognised as diseases that need to be addressed in such crises. Cancer, in particular, with its costly, multidisciplinary care, poses considerable financial and ethical challenges for policy makers. In 2014 and with funding from the United Nations High Commissioner for Refugees, we reported on cancer cases among Iraqi refugees in Jordan (2010-12) and Syria (2009-11). In this Policy Review, we provide data on 733 refugees referred to the United Nations High Commissioner for Refugees in Lebanon (2015-17) and Jordan (2016-17), analysed by cancer type, demographic risk factors, treatment coverage status, and cost. Results show the need for increased funding and evidence-based standard operating procedures across countries to ensure that patients have equitable access to care. We recommend a holistic response to humanitarian crises that includes education, screening, treatment, and palliative care for refugees and nationals and prioritises breast cancer and childhood cancers.

Injection laryngoplasty in infants with unilateral vocal cord paralysis: A survey of ASPO members.

INTRODUCTION: Unilateral vocal cord paralysis (UVCP) in infants may be managed medically or surgically, with the latter including injection laryngoplasty (IL). However, there is limited information regarding injection laryngoplasty in infants. We therefore proposed a survey of American Society of Pediatric Otolaryngology (ASPO) members to elucidate current practices, outcomes, and complications. METHODS: An online survey was distributed to all 548 ASPO members via email. The survey was closed for data analysis 2 months after initial distribution. Statistical analysis was deferred due to the primarily descriptive nature of the data and lack of comparative studies. RESULTS: We received 113 responses for a response rate of 20.6%. Only 31% of the respondents (n = 36) reported performing IL in infants 12 months old or younger. The most commonly cited reasons for not injecting in this age group were preference for non-surgical management and concern for increased risk of airway obstruction. IL was most commonly performed to treat persistent aspiration despite attempts at medical management. The majority (66%) reported no complications, while the remainder noted stridor requiring intensive care unit observation. Re-intubation due to airway obstruction occurred in 6% (n = 2 of 33). Carboxymethylcellulose gel (Prolaryn Gel) was the most commonly used injectable material, but a variety of other materials were used as well. Two respondents noted they perform reinnervation procedures in children, but not in infants, as they require at least a 12 month period of observation for possible spontaneous recovery before considering the option. DISCUSSION: There is limited data regarding management of UVCP in infants with IL, and considerable variation among those who do perform the procedure. While adverse events are rare, multi-institutional studies should be considered to help determine best practices.