Inactivation of highly transmissible livestock and avian viruses including influenza A and Newcastle disease virus for molecular diagnostics.

There is a critical need for an inactivation method that completely inactivates pathogens at the time of sample collection while maintaining the nucleic acid quality required for diagnostic PCR testing. This inactivation method is required to alleviate concerns about transmission potential, minimize shipping complications and cost, and enable testing in lower containment laboratories, thereby enhancing disease diagnostics through improved turn-around time. This study evaluated a panel of 10 surrogate viruses that represent highly pathogenic animal diseases. These results showed that a commercial PrimeStore® molecular transport media (PSMTM) completely inactivated all viruses tested by >99.99%, as determined by infectivity and serial passage assays. However, the detection of viral nucleic acid by qRT-PCR was comparable in PSMTM and control-treated conditions. These results were consistent when viruses were evaluated in the presence of biological material such as sera and cloacal swabs to mimic diagnostic sample conditions for non-avian and avian viruses, respectively. The results of this study may be utilized by diagnostic testing laboratories for highly pathogenic agents affecting animal and human populations. These results may be used to revise guidance for select agent diagnostic testing and the shipment of infectious substances.

Coxiella burnetii seroprevalence in domestic goat does in the United States: Prevalence, distribution, and associated risk factors.

Infection with the bacterium Coxiella burnetii can cause coxiellosis in animals and Q fever in humans. Coxiellosis a consistently underreported infectious disease. The infection can result in reproductive consequences for humans and animals. Ruminants are a reservoir for infection and humans are generally infected via aerosolized secretions, making it a public health concern. Studies of ruminant seroprevalence are generally limited in size and scope. This study determined seroprevalence in a large-scale U.S. population of female goats using serum samples from 7736 does from 24 states. This study identified C. burnetii seroprevalence in the United States domestic goat population. Overall, 14.5 % (SE = 2.3) of does were seropositive and 21.0 % (SE = 2.4) of operations had at least 1 seropositive doe. Further, operation demographics and herd management practices associated with seropositivity were as follows: the suspected or confirmed presence of caprine arthritis encephalitis (CAE), caseous lymphadenitis (CL), Johne's disease, or sore mouth in the herd in the previous 3 years, not cleaning or disinfecting the kidding areas or removing aborting does from other does, allowing visitors to access the kidding areas, and a lower percentage of adult goat inventory that were adult bucks or wethers. Furthermore, goat breed was associated with seropositivity. These data show C. burnetii seroprevalence in the United States and identify operation and animal characteristics and management practices associated with C. burnetii seropositivity. Together, this information can be used to help limit animal transmission, inform public health measures, and help educate and protect individuals working with goats.

Assessment of Quality of Life, Grief, and Psychosocial Need Among Bereaved Caregivers of Children with Cancer.

Cancer is the leading disease-related cause of death for children in the United States; however, limited data exists on caregivers' needs and evidence-based bereavement interventions are lacking. This is a cross-sectional study of primary caregivers of children who died from cancer. Participants completed five surveys assessing well-being and an optional semi-structured, in-depth qualitative interview. Caregiver's greatest unmet needs were finding meaning in the death, personal wellness, and social activities. Bereaved caregivers with greater unmet needs reported poorer quality of life in the energy/fatigue (p = .01), role limitations due to emotional problems (p = .01), pain (p = .01), and emotional well-being (p = .02) domains. Interview themes elicited include inadequate bereavement services, support for siblings, desired contact with the medical team, and connections to other bereaved caregivers. Findings support the need for intensive, evidence-based bereavement programs for families of children who died from cancer, to attempt to mitigate poor bereavement-related outcomes.

Impairment of health-related quality of life for children with acute lymphoblastic leukemia over the first year of therapy: A report from the DFCI ALL Consortium.

BACKGROUND: Children treated for acute lymphoblastic leukemia (ALL) receive prolonged treatment, resulting in toxicities that affect health-related quality of life (HR-QoL). Longitudinal assessment of HR-QoL allows improved understanding of experiences with ALL. PROCEDURE: Parent-proxy and child self-report HR-QoL over the first year of chemotherapy were evaluated in the context of DFCI Protocol 05-001, a phase 3 therapeutic trial for childhood ALL. HR-QoL was assessed with the Pediatric Quality-of-Life inventory (PedsQL) domains for Pain and Hurt, Procedural Anxiety, Treatment Anxiety, Emotional Functioning, General Fatigue, and Sleep/Rest Fatigue. RESULTS: Total of 281 subjects participated, with 141 contributing at least one child report and 280 at least one parent report. Children with ALL experienced impairment in HR-QoL by both patient and parent report compared to the published PedsQL reference population at each time point on each subscale. Agreement between parent and child assessment of HR-QoL impairment was high, particularly among those for whom HR-QoL was not impaired. During the consolidation phase, which included intensive asparaginase administration, multivariable models demonstrated more impairment in Treatment Anxiety and Procedural Anxiety for children treated with intramuscular asparaginase than intravenous asparaginase, but randomized groups were otherwise similar in HR-QoL. Impairments in fatigue, both General and Sleep/Rest, were evident throughout and worse during intensive asparaginase therapy. CONCLUSIONS: This report examines HR-QoL for children with ALL during treatment longitudinally by parent and patient report across multiple domains. Children with ALL demonstrated substantial impairment in HR-QoL, particularly related to fatigue during intensive consolidation therapy including asparaginase.

Disparities in parental distress in a multicenter clinical trial for pediatric acute lymphoblastic leukemia.

BACKGROUND: Parent psychological distress during childhood cancer treatment has short- and long-term implications for parent, child, and family well-being. Identifying targetable predictors of parental distress is essential to inform interventions. We investigated the association between household material hardship (HMH), a modifiable poverty-exposure defined as housing, food, or utility insecurity, and severe psychological distress among parents of children aged 1-17 years with acute lymphoblastic leukemia (ALL) enrolled on the multicenter Dana-Farber ALL Consortium Trial 16-001. METHODS: This was a secondary analysis of parent-reported data. Parents completed an HMH survey within 32 days of clinical trial enrollment (T0) and again at 6 months into therapy (T1). The primary exposure was HMH at T0 and primary outcome was severe parental distress at T0 and T1, defined as a score greater than or equal to 13 on the Kessler-6 Psychological Distress Scale. Multivariable models were adjusted for ALL risk group and single parent status. RESULTS: Among 375 evaluable parents, one-third (32%; n = 120/375) reported HMH at T0. In multivariable analyses, T0 HMH was associated with over twice the odds of severe psychological distress at T0 and T1 HMH was associated with over 5 times the odds of severe distress at T1. CONCLUSIONS: Despite uniform clinical trial treatment of their children at well-resourced pediatric centers, HMH-exposed parents-compared with unexposed parents-experienced statistically significantly increased odds of severe psychological distress at the time of their child's leukemia diagnosis, which worsened 6 months into therapy. These data identify a high-risk parental population who may benefit from early psychosocial and HMH-targeted interventions to mitigate disparities in well-being.

A randomized controlled trial to examine the effect of the Pediatric Opioid Analgesia Self-Instruction System (PedOASIS) tool on pediatric hematology/oncology trainee education.

BACKGROUND: Many children with hematologic and oncologic diagnoses require opioids for management of pain, yet knowledge gaps persist among pediatric hematology/oncology (PHO) fellows. OBJECTIVE: Pediatric Opioid Analgesia Self-Instruction System (PedOASIS) is an interactive, case-based education tool designed for independent learning. The goal of this study was to evaluate its efficacy in increasing PHO fellows' knowledge and comfort with using opioids to manage pain. DESIGN/METHOD: PHO fellows were recruited from 74 American College of Graduate Medical Education-accredited US programs during the 2019-2020 academic year and randomized to receive access to PedOASIS (intervention) or usual PHO training (control). Surveys at baseline, immediately after accessing the tool, and 6 months later assessed knowledge and comfort related to prescribing opioids. RESULTS: A total of 64 PHO fellows completed the study, with 32 in the intervention group and 32 controls. At baseline, mean scores on the 10-question knowledge assessment were similar between groups (intervention: 5, control: 6; p = .8). Following intervention, mean score was significantly higher in the intervention group (9) versus controls (5; p < .0001). Six months later, scores in both groups decreased but remained significantly higher in the intervention group (7) compared to controls (5, p < .0001) and compared to baseline (p = .0002). Fellows in the intervention group reported significant increases in comfort dosing opioids after exposure to the tool (p = .02). CONCLUSION: PHO fellows exposed to the tool had improved scores on validated knowledge questions and greater comfort using opioids for pain management compared to controls. We therefore suggest that PedOASIS warrants further evaluation as a potential tool for PHO fellows.

Feasibility of serial neurocognitive assessment using Cogstate during and after therapy for childhood leukemia.

PURPOSE: Neurocognitive impairment is frequently observed among survivors of childhood acute lymphoblastic leukemia (ALL) within the domains of attention, working memory, processing speed, executive functioning, and learning and memory. However, few studies have characterized the trajectory of treatment-induced changes in neurocognitive function beginning in the first months of treatment, to test whether early changes predict impairment among survivors. If correct, we hypothesize that those children who are most susceptible to early impairment would be ideal subjects for clinical trials testing interventions designed to protect against treatment-related neurocognitive decline. METHODS: In this pilot study, we prospectively assessed neurocognitive functioning (attention, working memory, executive function, visual learning, and processing speed), using the Cogstate computerized battery at six time points during the 2 years of chemotherapy treatment and 1-year post-treatment (Dana-Farber Cancer Institute ALL Consortium protocol 11-001; NCT01574274). RESULTS: Forty-three patients with ALL consented to serial neurocognitive testing. Of the 31 participants who remained on study through the final time point, 1 year after completion of chemotherapy, 28 (90%) completed at least five of six planned Cogstate testing time points. Performance and completion checks indicated a high tolerability (≥ 88%) for all subtests. One year after completion of treatment, 10 of 29 patients (34%) exhibited neurocognitive function more than 2 standard deviations below age-matched norms on one or more Cogstate subtests. CONCLUSIONS: Serial collection of neurocognitive data (within a month of diagnosis with ALL, during therapy, and 1-year post-treatment) is feasible and can be informative for evaluating treatment-related neurocognitive impairment.

Perioperative opioid dispensing and persistent use after benign hysterectomy: a systematic review and meta-analysis.

OBJECTIVE: This meta-analysis was conducted to (1) assess the quantity and dose of perioperatively dispensed opioids for benign hysterectomy by procedure route and (2) identify the predictors of persistent opioid use after the procedure. DATA SOURCES: PubMed, Web of Science, and Embase were systematically searched from study inception to 25 March 2022. STUDY ELIGIBILITY CRITERIA: Studies reporting data on opioid dispensing among patients undergoing benign hysterectomy were considered eligible. The primary outcome was the dosage of opioids dispensed perioperatively (from 30 preoperative days to 21 postoperative days). The secondary outcome was the predictors of persistent opioid use after benign hysterectomy (from 3 months to 3 years postoperatively). Total opioid dispensing was measured in morphine milligram equivalents units. METHODS: The random-effects model was used to pool the mean differences or odds ratios and the corresponding 95% confidence intervals. RESULTS: A total of 8 studies presenting data on 377,569 women undergoing benign hysterectomy were included. Of these women, 83% (95% confidence interval, 81-84) were dispensed opioids during the perioperative period. The average amount of perioperatively dispensed opioids was 143.5 morphine milligram equivalents (95% confidence interval, 40-247). Women undergoing vaginal hysterectomy were dispensed a significantly lower amount of opioids than those undergoing laparoscopic or abdominal hysterectomies. The overall rate of persistent opioid use after benign hysterectomy was 5% (95% confidence interval, 2-8). Younger patient age (odds ratio, 1.38; 95% confidence interval, 1.17-1.63), smoking history (odds ratio, 1.87; 95% confidence interval, 1.67-2.10), alcohol use (odds ratio, 3.16; 95% confidence interval, 2.34-4.27), back pain (odds ratio, 1.50; 95% confidence interval, 1.10-2.05), and fibromyalgia (odds ratio, 1.60; 95% confidence interval, 1.39-1.83) were significantly associated with a higher risk of persistent opioid use after benign hysterectomy. However, there was no significant effect of hysterectomy route and operative complexity on persistent opioid use postoperatively. CONCLUSION: Perioperative opioid dispensing was significantly dependent on the route of hysterectomy, with the lowest dispensed morphine milligram equivalents of opioids for vaginal hysterectomy and the highest for abdominal hysterectomy. Nevertheless, hysterectomy route did not significantly predict persistent opioid use postoperatively, whereas younger age, smoking, alcohol use, back pain, and fibromyalgia were significantly associated with persistent opioid use.

Oral Mercaptopurine Adherence in Pediatric Acute Lymphoblastic Leukemia: A Survey Study From the Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia Consortium.

Background: Oral chemotherapy nonadherence is a challenge in clinical oncology. During therapy for acute lymphoblastic leukemia (ALL), poor adherence to 6-mercaptopurine (6MP) increases relapse risk. Clinically significant nonadherence is reported in 30% of children treated for ALL on Children's Oncology Group (COG) trials. Whether nonadherence rates vary across regimens with different treatment schedules and modes of administration is unknown. Methods: We conducted an exploratory, cross-sectional survey study on parents of children (1-18 years) receiving continuation therapy on, or as per Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocol 11-001. Treatment required weekly visits to the clinic and 14 days of oral 6MP every 3 weeks. Survey assessed self-reported sociodemographics, medication-taking, chemotherapy comprehension, and 6MP adherence; adherence survey items were developed from published surveys. Patients were grouped as nonadherent if they endorsed missing one 6MP dose during the last cycle, or more than one dose during prior cycles, for nonmedical reasons. Results: Sixty-two families completed the surveys, all of whom had evaluable adherence data. In total, 25% of patients met the study definition of nonadherence. Twenty-three percent reported that it was "not easy" to follow administration guidelines around the dairy intake and 57% requested more teaching and educational resources. Conclusion: Self-reported nonadherence to oral 6MP in the DFCI ALL Consortium is high, with rates similar to those observed in the COG. This suggests that the additional contact during weekly infusions on the DFCI is insufficient to address barriers affecting oral chemotherapy adherence.

Health-related Internet Use by Caregivers of Children and Adolescents With Cancer.

Caregivers of children with cancer have needs for information and social support related to their child's diagnosis. The internet serves as a resource to help meet these needs. There is growing interest in health-related internet use (HRIU) by caregivers of pediatric patients as the internet rapidly evolves. This survey study describes patterns of internet use by caregivers of children with cancer and examines associations between socioeconomic status and internet use. 114 caregivers participated between 2014 and 2016. The majority (82%) reported frequent general internet use, but fewer (25-54%) reported frequent HRIU. Very few respondents (4%) reported difficulty accessing the internet; those reporting difficulty were more likely to report lower income, public/no insurance, and lower educational attainment. There were no consistent associations between socioeconomic status variables and frequency of HRIU. Less than half (43%) of caregivers reported that their internet use raised questions that they discussed or planned to discuss with the child's nurse or doctor, and only 4% reported having changed medical decisions based on information found on the internet. We conclude that caregivers of children with cancer engage in HRIU, and this is an area for improvement in oncology anticipatory guidance and family-centered care.

Feasibility of oncology clinical trial-embedded evaluation of social determinants of health.

Social determinants of health (SDoH) are associated with stark disparities in cancer outcomes, but systematic SDoH data collection is virtually absent from oncology clinical trials. Trial-based SDoH data are essential to ensure representation of marginalized populations, contextualize outcome disparities, and identify health-equity intervention opportunities. We report the feasibility of a pediatric oncology multicenter therapeutic trial-embedded SDoH investigation. Among 448 trial participants, 392 (87.5%) opted-in to the embedded SDoH study; 375 (95.7%) completed baseline surveys, with high longitudinal response rates (88.9-93.1%) over 24 months. Trial-embedded SDoH data collection is feasible and acceptable and must be consistently included within future oncology trials.

Management of childhood cancer survivors at risk for thyroid function abnormalities: A Delphi study.

BACKGROUND: Thyroid function abnormalities can occur after treatment for childhood cancer. Evidence for the management of thyroid dysfunction among asymptomatic childhood cancer survivors (CCS) is lacking. We used a Delphi consensus methodology to expand guidelines for screening asymptomatic CCS at risk for thyroid dysfunction and explore recommendations for the clinical management of abnormal results. PROCEDURE: A Delphi panel of 40 expert physicians representing oncology, endocrinology, and primary care participated in three rounds of anonymous, iterative questionnaires formatted as clinical scenarios. Consensus is defined as ≥ 90% of panelists agree with recommendation and disagreement as < 70% agree. RESULTS: Panelists reached consensus that CCS treated with radiation including neck, total body, whole brain, brain including the hypothalamic-pituitary axis (HPA), and therapeutic meta-iodobenzylguanidine (MIBG) should have annual, lifelong screening using serum thyroid-stimulating hormone (TSH) and free T4 starting within one year off-treatment (98%). Panelists disagreed on continuing to screen CCS for thyroid dysfunction after immunotherapy associated with acute thyroid injury (31%-50%). There was also disagreement on indications for brain (17%-43%) or thyroid (50%-65%) imaging, laboratory tests to assess the HPA (29%-75%), and TSH threshold to initiate treatment of subclinical hypothyroidism. Lack of evidence was the most frequent rationale panelists offered for not recommending additional testing or medications. Panelists' recommendations did not vary by geography, specialty, or survivorship clinical experience. CONCLUSIONS: Consensus was reached on most recommendations for screening and management of cancer treatment-related thyroid dysfunction. Screening after completion of thyroid-toxic immunotherapy, indications for imaging, and treatment of subclinical hypothyroidism are areas of disagreement for further investigation.

Predictors of thrombosis in children receiving therapy for acute lymphoblastic leukemia: Results from Dana-Farber Cancer Institute ALL Consortium trial 05-001.

BACKGROUND/OBJECTIVES: Although thromboembolism (TE) is a serious complication in patients with acute lymphoblastic leukemia (ALL), thromboprophylaxis is not commonly used due to the inherent bleeding risk in this population. Identifying prothrombotic risk factors will help target thromboprophylaxis to those at highest thrombotic risk. We aimed to define predictors and the impact of TE on ALL outcome in children (1-18 years) treated on the Dana-Farber Cancer Institute ALL 05-001 trial. METHODS: Clinical and laboratory data including TE events were prospectively collected. PCR-based allelic discrimination assay identified single-nucleotide polymorphisms (SNP) for prothrombin G20210A (rs1799963) and Factor V G1691A (rs6025). Univariate and multivariable competing risk regression models evaluated the effect of diagnostic clinical (age, sex, body mass index, ALL-immunophenotype, risk group) and laboratory variables (presenting leukocyte count, blood group, SNPs) on the cumulative incidence of TE. Cox regression modeling explored the impact of TE on survival. RESULTS: Of 794 patients [median age 4.97 (range, 1.04-17.96) years; males 441], 100 developed TE; 25-month cumulative incidence 13.0% (95% CI, 10.7%-15.5%). Univariate analyses identified older age (≥10 years), presenting leucocyte count, T-ALL, high-risk ALL, and non-O blood group as risk factors. Age and non-O blood group were independent predictors of TE on multivariable regression; the blood group impact being most evident in patients 1-5 years of age (P = 0.011). TE did not impact survival. Induction TE was independently associated with induction failure (OR 6.45; 95% CI, 1.64-25.47; P = 0.008). CONCLUSION: We recommend further evaluation of these risk factors and consideration of thromboprophylaxis for patients ≥10 years (especially those ≥15 years) when receiving asparaginase.

Direct CNS administration of rituximab and epratuzumab in a pediatric patient with relapsed refractory CNS B-cell acute lymphoblastic leukemia.

Relapsed central nervous system (CNS) leukemia presents a therapeutic challenge to pediatric oncologists. Systemic monoclonal antibody therapy has shown recent promise in patients with relapsed acute lymphoblastic leukemia, however its effect on CNS disease in this population is not well established. We describe a case of multiply relapsed and refractory CNS leukemia in an adolescent patient who responded to the intra-CNS delivery of rituximab (anti-CD20) and epratuzumab (anti-CD22) therapy, demonstrating the practical use and potential efficacy of a novel route of monoclonal antibody administration in difficult-to-treat CNS leukemia.

COVID-19 and its effect on Instagram adoption by #OBGYN residency programs.

OBJECTIVES: Instagram (IG) is becoming one of the larger resource tools within medicine. Since the onset of the COVID-19 pandemic, it is becoming important for programs to improve virtual presence and outreach. We evaluated the adoption of IG by OB/GYN residency programs in the United States and aimed to see if highly ranked programs had higher utilization rates. METHODS: IG presence and engagement metrics were extracted for all ACGME accredited OB/GYN programs. Doximity residency navigator tool was used to obtain nationwide program rankings, and statistical analysis was performed to prove any significant correlation. Mann-Whitney U test, Cochran-Armitage test and Analysis of variance were used for analysis. IRB exemption was obtained. RESULTS: Seventy percent of programs (202/287) have IG presence, with the majority creating presence after the COVID pandemic began (115/202; 57%). Seventy-two percent (83/115) of these programs created their IG account once virtual interviews were announced. The top 25% of programs, as ranked on Doximity, have a higher number of posts, followers and likes when compared to the rest of the programs. CONCLUSIONS: The COVID-19 pandemic has led to increased adoption of IG by residency programs. Highly ranked and reputed programs have higher rates of activity, popularity, and engagement on IG.

Development and Validation of Pediatric Opioid Analgesia Self-Instruction System (PedOASIS): An Opioid Knowledge Tool for Pediatric Clinicians.

BACKGROUND: Acute pain is common in children and young adults with cancer and sickle cell disease. Current training curricula fail to adequately impart skills for pain management. We sought to develop and validate an education and assessment tool to address the safe effective use of opioids for pain management by pediatrics trainees. METHODS: The first version of the tool contained 10 case-based, multiple-choice questions. It was pilot tested within a medium-sized pediatric residency program using preintervention and postintervention surveys to assess residents' knowledge and comfort related to prescribing opioids. Content validation was performed through an expert panel of physicians. Internal reliability was tested by administering the tool to learners and practitioners with varying levels of training. RESULTS: Comfort with choosing and converting between opioids increased significantly in pilot testing (P=0.005). Mean objective knowledge scores increased from 51% to 85.9% (P<0.001). The revised tool showed internal reliability within each group (Cronbach alpha 0.71 to 0.78) and significant differences in mean scores between groups (F ratio=9.45, P=0.0002). CONCLUSIONS: This tool demonstrates validity and internal reliability. Its use was associated with short-term educational gains and it garnered overall favorable feedback from users. Further testing is needed to assess the duration of these gains.

Robotic Transvaginal Natural Orifice Transluminal Endoscopic Surgery for Resection of Parametrial and Bowel Deeply Infiltrated Endometriosis.

STUDY OBJECTIVE: To demonstrate stepwise techniques for the successful utilization of the Robotic-assisted transvaginal Natural Orifice Transluminal Endoscopy Surgery (NOTES) technique for safely surgically managing deeply infiltrated endometriosis (DIE). DESIGN: Stepwise demonstration with narrated video footage. SETTING: An academic tertiary care hospital. INTERVENTIONS: A 38-year-old woman-G3P3, who had 1 normal spontaneous vaginal delivery and 1 cesarean delivery for twin pregnancy-with worsening chronic pelvic pain. History of laparoscopic ablation of endometriosis 10 years ago. Magnetic resonance imaging demonstrated adenomyosis, deeply infiltrated endometriosis, and intrapelvic adhesions. Robotic transvaginal NOTES hysterectomy has been demonstrated to be feasible and safe in the surgical management of benign gynecology disease compared with traditional NOTES hysterectomy; however, it can be technically challenging to perform, particularly in managing of additional deep infiltrated endometriosis removal surgery after hysterectomy. The researchers demonstrated that robotic vaginal NOTES surgeries are feasible in complex benign gynecologic procedures such as endometriosis and sacrocolpopexy [1-3]. The robotic wristed instruments with 3D visualization, resulting in delicate tissue dissection and easier suturing and knot tying, are beneficial to surgeons for overcoming the cumbersome surgical techniques in transvaginal NOTES complete endometriosis removal [4,5]. Integration of robotic transvaginal single site surgery and resection of DIE is a novel alternative minimally invasive route that is more cosmetic and less painful. The procedure was successfully performed in approximately 200 minutes, with unevenly postoperative recovery. The patient was discharged home the same day. Her pain level was 7 out of 10 in the first week, 5 out of 10 in the second week, and 2 out of 10 in the third week. Pathology confirmed uterine adenomyosis, endometriosis in the right ureteral, right uterine artery pedicle, and rectum with muscular propria involvement. CONCLUSION: Robotic transvaginal NOTES for deeply invasive endometriosis is challenging but feasible in patients with parametrial and rectal involvement. The advantages of articulating instrumentation and 3D visualization are especially pivotal in complex transvaginal NOTES surgery.

Urban Particulate Matter Impairment of Airway Surface Liquid-Mediated Coronavirus Inactivation.

Air pollution particulate matter (PM) is associated with SARS-CoV-2 infection and severity, although mechanistic studies are lacking. We tested whether airway surface liquid (ASL) from primary human airway epithelial cells is antiviral against SARS-CoV-2 and human alphacoronavirus 229E (CoV-229E) (responsible for common colds), and whether PM (urban, indoor air pollution [IAP], volcanic ash) affected ASL antiviral activity. ASL inactivated SARS-CoV-2 and CoV-229E. Independently, urban PM also decreased SARS-CoV-2 and CoV-229E infection, and IAP PM decreased CoV-229E infection. However, in combination, urban PM impaired ASL's antiviral activity against both viruses, and the same effect occurred for IAP PM and ash against SARS-CoV-2, suggesting that PM may enhance SARS-CoV-2 infection.

Whole-transcriptome analysis in acute lymphoblastic leukemia: a report from the DFCI ALL Consortium Protocol 16-001.

The molecular hallmark of childhood acute lymphoblastic leukemia (ALL) is characterized by recurrent, prognostic genetic alterations, many of which are cryptic by conventional cytogenetics. RNA sequencing (RNA-seq) is a powerful next-generation sequencing technology that can simultaneously identify cryptic gene rearrangements, sequence mutations and gene expression profiles in a single assay. We examined the feasibility and utility of incorporating RNA-seq into a prospective multicenter phase 3 clinical trial for children with newly diagnosed ALL. The Dana-Farber Cancer Institute ALL Consortium Protocol 16-001 enrolled 173 patients with ALL who consented to optional studies and had samples available for RNA-seq. RNA-seq identified at least 1 alteration in 157 patients (91%). Fusion detection was 100% concordant with results obtained from conventional cytogenetic analyses. An additional 56 gene fusions were identified by RNA-seq, many of which confer prognostic or therapeutic significance. Gene expression profiling enabled further molecular classification into the following B-cell ALL (B-ALL) subgroups: high hyperdiploid (n = 36), ETV6-RUNX1/-like (n = 31), TCF3-PBX1 (n = 7), KMT2A-rearranged (KMT2A-R; n = 5), intrachromosomal amplification of chromosome 21 (iAMP21) (n = 1), hypodiploid (n = 1), Philadelphia chromosome (Ph)-positive/Ph-like (n = 16), DUX4-R (n = 11), PAX5 alterations (PAX5 alt; n = 11), PAX5 P80R (n = 1), ZNF384-R (n = 4), NUTM1-R (n = 1), MEF2D-R (n = 1), and others (n = 10). RNA-seq identified 141 nonsynonymous mutations in 93 patients (54%); the most frequent were RAS-MAPK pathway mutations. Among 79 patients with both low-density array and RNA-seq data for the Philadelphia chromosome-like gene signature prediction, results were concordant in 74 patients (94%). In conclusion, RNA-seq identified several clinically relevant genetic alterations not detected by conventional methods, which supports the integration of this technology into front-line pediatric ALL trials. This trial was registered at www.clinicaltrials.gov as #NCT03020030.