Vesicoamniotic Shunting Improves Outcomes in a Subset of Prune Belly Syndrome Patients at a Single Tertiary Center

Objective: Review outcomes of Prune Belly Syndrome (PBS) with the hypothesis that contemporary management improves mortality.Methods: A retrospective chart review of inpatient and outpatient PBS patients referred between 2000 and 2018 was conducted to assess outcomes at our institution. Data collected included age at diagnosis, concomitant medical conditions, imaging, operative management, length of follow-up, and renal function.Results: Forty-five PBS patients presented during these 18 years. Prenatal diagnoses were made in 17 (39%); 65% of these patients underwent prenatal intervention. The remaining patients were diagnosed in the infant period (20, 44%) or after 1 year of age (8, 18%). Twelve patients died from cardiopulmonary complications in the neonatal period; the neonatal mortality rate was 27%. The mean follow-up among patients surviving the neonatal period was 84 months. Forty-two patients had at least one renal ultrasound (RUS); of the 30 patients with NICU RUSs, 26 (89%) had hydronephrosis and/or ureterectasis. Of the 39 patients who underwent voiding cystourethrogram (VCUG), 28 (62%) demonstrated VUR. Fifty-nine percent had respiratory distress. Nine patients (20%) were oxygen-dependent by completion of follow up. Thirty-eight patients (84%) had other congenital malformations including genitourinary (GU) 67%, gastrointestinal (GI) 52%, and cardiac 48%. Sixteen patients (36%) had chronic kidney disease (CKD) of at least stage 3; three patients (7%) had received renal transplants. Eighty-four percent of patients had at least one surgery (mean 3.4, range 0–6). The most common was orchiopexy (71%). The next most common surgeries were vesicostomy (39%), ureteral reimplants (32%), abdominoplasty (29%), nephrectomy (25%), and appendicovesicostomy (21%). After stratifying patients according to Woodard classification, a trend for 12% improvement in mortality after VAS was noted in the Woodard Classification 1 cohort.Conclusions: PBS patients frequently have multiple congenital anomalies. Pulmonary complications are prevalent in the neonate while CKD (36%) is prevalent during late childhood. The risk of CKD increased significantly with the presence of other congenital anomalies in our cohort. Mortality in childhood is most common in infancy and may be as low as 27%. Contemporary management of PBS, including prenatal interventions, reduced the neonatal mortality rate in a subset of our cohort

Evaluating Natural History and Follow Up Strategies for Non-obstructive Urolithiasis in Pediatric Population

Objective: While small non-obstructive stones in the adult population are usually observed with minimal follow-up, the same guidelines for management in the pediatric population have not been well-studied. We evaluate the clinical outcomes of small non-obstructing kidney stones in the pediatric population to better define the natural history of the disease.Methods: In this IRB-approved retrospective study, patients with a diagnosis of kidney stones from January 2011 to March 2017 were identified using ICD9 and ICD10 codes. Patients with ureteral stones, obstruction, or stones >5 mm in size were excluded. Patients with no follow-up after initial imaging were also excluded. Patients with a history of stones or prior stone interventions were included in our population. Frequency of follow-up ultrasounds while on observation were noted and any ER visits, stone passage episodes, infections, and surgical interventions were documented.Results: Over the 6-year study period, 106 patients with non-obstructing kidney stones were identified. The average age at diagnosis was 12.5 years and the average stone size was 3.6 mm. Average follow-up was 17 months. About half of the patients had spontaneous passage of stones (54/106) at an average time of 13 months after diagnosis. Stone location did not correlate with spontaneous passage rates. Only 6/106 (5.7%) patients required stone surgery with ureteroscopy and/or PCNL at an average time of 12 months after initial diagnosis. The indication for surgery in all 6 cases was pain. 17/106 (16%) patients developed febrile UTIs and a total of 43 ER visits for stone-related issues were noted, but no patients required urgent intervention for an infected obstructing stone. Median interval for follow-up was every 6 months with renal ultrasounds, which then was prolonged to annual follow up in most cases.Conclusions: The observation of pediatric patients with small non-obstructing stones is safe with no episodes of acute obstructive pyelonephritis occurring in these patients. The sole indication for intervention in our patient population was pain, which suggests that routine follow-up ultrasounds may not be necessary for the follow-up of pediatric non-obstructive renal stones ≤5 mm in size

Amplified centrosomes and mitotic index display poor concordance between patient tumors and cultured cancer cells

Centrosome aberrations (CA) and abnormal mitoses are considered beacons of malignancy. Cancer cell doubling times in patient tumors are longer than in cultures, but differences in CA between tumors and cultured cells are uncharacterized. We compare mitoses and CA in patient tumors, xenografts, and tumor cell lines. We find that mitoses are rare in patient tumors compared with xenografts and cell lines. Contrastingly, CA is more extensive in patient tumors and xenografts (~35–50% cells) than cell lines (~5–15%), although CA declines in patient-derived tumor cells over time. Intratumoral hypoxia may explain elevated CA in vivo because exposure of cultured cells to hypoxia or mimicking hypoxia pharmacologically or genetically increases CA, and HIF-1α and hypoxic gene signature expression correlate with CA and centrosomal gene signature expression in breast tumors. These results highlight the importance of utilizing low-passage-number patient-derived cell lines in studying CA to more faithfully recapitulate in vivo cellular phenotypes

Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer

Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors1,2, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Probing effective field theory operators in the associated production of top quarks with a Z boson in multilepton final states at root s=13 TeV

Peer reviewe

Search for long-lived particles decaying to jets with displaced vertices in proton-proton collisions at root s=13 Te V

A search is presented for long-lived particles produced in pairs in proton-proton collisions at the LHC operating at a center-of-mass energy of 13 TeV. The data were collected with the CMS detector during the period from 2015 through 2018, and correspond to a total integrated luminosity of 140 fb(-1). This search targets pairs of long-lived particles with mean proper decay lengths between 0.1 and 100 mm, each of which decays into at least two quarks that hadronize to jets, resulting in a final state with two displaced vertices. No significant excess of events with two displaced vertices is observed. In the context of R-parity violating supersymmetry models, the pair production of long-lived neutralinos, gluinos, and top squarks is excluded at 95% confidence level for cross sections larger than 0.08 fb, masses between 800 and 3000 GeV, and mean proper decay lengths between 1 and 25 mm.Peer reviewe

Search for top squark production in fully hadronic final states in proton-proton collisions at root s=13 TeV

A search for production of the supersymmetric partners of the top quark, top squarks, is presented. The search is based on proton-proton collision events containing multiple jets, no leptons, and large transverse momentum imbalance. The data were collected with the CMS detector at the CERN LHC at a center-of-mass energy of 13 TeV, and correspond to an integrated luminosity of 137 fb(-1). The targeted signal production scenarios are direct and gluino-mediated top squark production, including scenarios in which the top squark and neutralino masses are nearly degenerate. The search utilizes novel algorithms based on deep neural networks that identify hadronically decaying top quarks and W bosons, which are expected in many of the targeted signal models. No statistically significant excess of events is observed relative to the expectation from the standard model, and limits on the top squark production cross section are obtained in the context of simplified supersymmetric models for various production and decay modes. Exclusion limits as high as 1310 GeVare established at the 95% confidence level on the mass of the top squark for direct top squark production models, and as high as 2260 GeV on the mass of the gluino for gluino-mediated top squark production models. These results represent a significant improvement over the results of previous searches for supersymmetry by CMS in the same final state.Peer reviewe

Measurement of the W gamma Production Cross Section in Proton-Proton Collisions at root s=13 TeV and Constraints on Effective Field Theory Coefficients

A fiducial cross section for W gamma production in proton-proton collisions is measured at a center-of-mass energy of 13 TeV in 137 fb(-1) of data collected using the CMS detector at the LHC. The W -> e nu and mu nu decay modes are used in a maximum-likelihood fit to the lepton-photon invariant mass distribution to extract the combined cross section. The measured cross section is compared with theoretical expectations at next-to-leading order in quantum chromodynamics. In addition, 95% confidence level intervals are reported for anomalous triple-gauge couplings within the framework of effective field theory.Peer reviewe