bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of ordered-subset expectation maximization and filtered back projection reconstruction based on quantitative outcome from dynamic [18F]NaF PET images
Authors: Wong James M. , Puri Tanuj , Siddique Muhammad Musib , Frost Michelle L. , Moore Amelia E. B. , Blake Glen M. , Fogelman Ignac
Published: February 2021

[18F]NaF PET imaging is a useful tool for measuring regional bone metabolism. However, due to tracer in urine, [18F]NaF PET images of the hip reconstructed using filtered back projection (FBP) frequently show streaking artifacts in slices through the bladder leading to noisy time-activity curves unsuitable for quantification. This study compares differences between quantitative outcomes at the hip derived from images reconstructed using the FBP and ordered-subset expectation maximization (OSEM) methods. Dynamic [18F]NaF PET data at the hip for four postmenopausal women were reconstructed using FBP and nine variations of the OSEM algorithm (all combinations of 1, 5, 15 iterations and 10, 15, 21 subsets). Seven volumes of interest were placed in the hip. Bone metabolism was measured using standardized uptake values, Patlak analysis (Ki-PAT) and Hawkins model Ki-4k. Percentage differences between the standardized uptake values and Ki values from FBP and OSEM images were assessed. OSEM images appeared visually smoother and without the streaking artifacts seen with FBP. However, due to loss of counts, they failed to recover the quantitative values in VOIs close to the bladder, including the femoral head and femoral neck. This was consistent for all quantification methods. Volumes of interest farther from the bladder or larger and receiving greater counts showed good convergence with 5 iterations and 21 subsets. For VOIs close to the bladder, including the femoral neck and femoral head, 15 iterations and 10, 15 or 21 subsets were not enough to obtain OSEM images suitable for measuring bone metabolism and showed no improvement compared to FBP.
Erythroid cells and malaria parasites: it's a match!
Authors: Neveu Gaëlle , Lavazec Catherine
Published: February 2021

Purpose of review

The current review outlines recent discoveries on the infection of erythroid cells by Plasmodium parasites, focusing on the molecular interactions governing the tropism of parasites for their host cell and the implications of this tropism for parasite biology and erythroid cell maturation.

Recent findings

Although most studies about the interactions of Plasmodium parasites and their host cell focused on the deadliest human malaria parasite, Plasmodium falciparum, and the erythrocyte, there is increasing evidence that several Plasmodium species, including P. falciparum, also develop within erythroid precursors. These interactions likely modify the remodeling of the host cell by the parasite and affect the maturation of erythroblast and reticulocytes.

A better understanding of the remodeling of immature erythroid cells by Plasmodium parasites will have important implications for the development of antimalarial drugs or vaccines. In addition, deciphering how Plasmodium parasites interfere with erythropoiesis will provide new insights on how these parasites contribute to anemia in malaria patients.
Immunotherapy for head and neck cancer: from recurrent/metastatic disease to (neo)adjuvant treatment in surgically resectable tumors
Authors: Specenier Pol
Published: February 2021

Purpose of review

We aim to summarize the current evidence on the role of immune checkpoint inhibitors in the (neo)adjuvant treatment of squamous cell carcinoma of the head and neck (HNSCC), with a particular focus on surgically treated patients.

Recent findings

Pembrolizumab +/– chemotherapy improves the outcome in patients with previously untreated recurrent/metastatic HNSCC. Nivolumab is superior to chemotherapy after platinum failure. The addition of avelumab to chemoradiation failed to improve the outcome in patients with locally advanced HNSCC. Neoadjuvant presurgical programmed cell death 1 receptor (PD-1) blockade is safe and associated with encouraging overall response rate. KEYNOTE-689 randomizes patients with resectable stage III/IVA HNSCC to surgery and adjuvant standard of care +/– neoadjuvant and adjuvant pembrolizumab. ADHERE assigns surgically treated HNSCC at high risk of recurrence to chemoradiotherapy (CRT) and either durvalumab or placebo. MK-3475–689 evaluates the role of pembrolizumab in patients with resectable HNSCC. NIVOPOSTOP evaluates the addition of nivolumab to CRT in patients with surgically treated pStage III/IV HNSCC or pT3N1/pT4N1 oropharyngeal cancer with at least 20 packs/year at high risk of relapse.

Multiple trials are currently evaluating the role of immunotherapy in HNSCC amenable to surgery. Neoadjuvant presurgical PD-1 blockade is feasible and safe and is associated with an encouraging overall response rate.
Alternative diets among adolescents: facts or fads?
Authors: Athanasian Christian E. , Lazarevic Bojan , Kriegel Elana R. , Milanaik Ruth L.
Published: February 2021

Purpose of review

With rising rates of chronic noninfectious diseases across the United States thought to be associated with the average American diet, many have adopted alternative diets. Most of these diets promise weight reduction via adherence to strict dietary guidelines, often removing certain types of food. With access to a plethora of information online, it is easy for adolescents to become confused when making dietary decisions. Although these diets promise benefits, it is important to understand common shortcomings and how to overcome them for safe implementation among adolescents.

Recent findings

This review discusses the theory, implementation, and risks associated with intermittent fasting as well as vegetarian, vegan, ketogenic, Atkins, Paleolithic, and Mediterranean diets. These considerations are further modified for pediatric populations with a focus on the social influences on dieting.

Although these diets may be promising, successful adherence to them requires addressing possible shortcomings associated with a certain diet. Pediatricians should be aware of how these dietary strategies may be properly implemented in order to prevent any harm to the patient. Empowering the patient and their families through informational resources is recommended. Pediatricians should also discuss motivations underlying their patient's dietary changes in order to determine whether these motivations are healthy.
Editorial: COVID-19 immunology and organ transplantation
Authors: Bery Amit I. , Kulkarni Hrishikesh S. , Kreisel Daniel
Published: February 2021

Purpose of review

The aim of this study was to provide a critical appraisal of the literature on the effects of the COVID-19 pandemic on organ transplantation, with a specific focus on lung transplantation given the predominant pulmonary involvement of the virus.

Recent findings

There was a significant decrease in lung transplant volumes during the first wave of the COVID-19 pandemic due to a combination of reduced availability of donors and an imbalance between waitlist additions and inactivations. SARS-CoV-2 infection was subsequently associated with an exuberant immune response that can lead to the development of postinfectious fibrotic lung disease. Few lung transplants have been performed in previously infected recipients and long-term outcomes remain unknown. Although the lung transplant volume rebounded during the second wave, it is unclear what the long-term effects of healthcare resource limitation and public health measures will have on transplant volumes in the future. Outcomes after SARS-CoV-2 infection in previous lung transplant recipients appear to be worse than the general public, and, although an immunosuppressed state likely contributes to these outcomes, whether immunosuppression should be altered in those exposed to or infected with SARS-CoV-2 remains unanswered in the absence of unequivocal data.

The COVID-19 pandemic has presented a number of challenges for lung transplant programs across the globe. Multiple research questions remain to be answered in order to optimally manage lung transplant recipients in the context of this pandemic.
Oncologic indications of liver transplantation and deceased donor liver allocation in the United States
Authors: Kubal Chandrashekhar , Mihaylov Plamen , Holden John
Published: February 2021

Purpose of review

Liver transplantation is a standard therapy for certain liver cancers. The majority of liver transplantation in the United States is through deceased donor liver transplantation (DDLT). A significant disparity between the demand of livers and patients awaiting liver transplantation still remains, relying on United Network for Organ Sharing (UNOS) to make policies to determine priority amongst recipients, including for patients with liver cancer. We review the scope of liver transplantation in patients with liver cancer with a focus on hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and unresectable colorectal liver metastases (CRLM) with respect to current liver allocation policy.

Recent findings

Recently, liver allocation changed in the United States. Under the current allocation policy, select patients with HCC and hilar CCA (hCCA) receive priority with an exception score of median MELD score at transplant (MMAT)-3. There is scope for other liver cancers, such as iCCA and CRLM to be considered, as reasonable outcomes have been achieved in these patients outside of the United States through DDLT and living donor liver transplantation (LDLT).

With the growing experience of liver transplantation for nonconventional oncologic indications, the current policy for prioritization of liver cancer within deceased donor liver allocation may need to be re-evaluated.
Severe Acute Respiratory Syndrome Coronavirus‐2 Infection in Children With Liver Transplant and Native Liver Disease
Authors: Kehar Mohit , Ebel Noelle H. , Ng Vicky L. , Baquero Jairo Eduardo Rivera , Leung Daniel H. , Slowik Voytek , Ovchinsky Nadia , Shah Amit A. , Arnon Ronen , Miloh Tamir , Gupta Nitika , Mohammad Saeed , Kogan‐Liberman Debora , Squires James E. , Sanchez Maria Camila , Hildreth Amber , Book Linda , Chu Christopher , Alrabadi Leina , Azzam Ruba , Chepuri Bhavika , Elisofon Scott , Falik Rachel , Gallagher Lisa , Kader Howard , Mogul Douglas , Mujawar Quais , Namjoshi Shweta S. , Valentino Pamela L. , Vitola Bernadette , Waheed Nadia , Zheng Ming‐Hua , Lobritto Steven , Martinez Mercedes
Published: February 2021

Objective:

Increased mortality risk because of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV2) infection in adults with native liver disease (LD) and liver transplant (LT) is associated with advanced age and comorbid conditions. We aim to report outcomes for children with LD and LT enrolled in the NASPGHAN/SPLIT SARS‐CoV2 registry.

Methods:

In this multicenter observational cohort study, we collected data from 91 patients <21 years (LD 44, LT 47) with laboratory‐confirmed SARS‐CoV2 infection between April 21 and September 17, 2020.

Results:

Patients with LD were more likely to require admission (70% vs 43% LT, P = 0.007) and pediatric intensive care unit (PICU) management (32% vs 4% LT, P = 0.001). Seven LD patients required mechanical ventilation (MV) and 2 patients died; no patients in the LT cohort died or required MV. Four LD patients presented in pediatric acute liver failure (PALF), 2 with concurrent multisystem inflammatory syndrome in children (MIS‐C); all recovered without LT. Two LD patients had MIS‐C alone and 1 patient died. Bivariable logistic‐regression analysis found that patients with nonalcoholic fatty LD (NAFLD) (odds ratio [OR] 5.6, P = 0.02) and LD (OR 6.1, P = 0.01, vs LT) had higher odds of severe disease (PICU, vasopressor support, MV, renal replacement therapy or death).

Conclusions:

Although not directly comparable, LT recipients had lower odds of severe SARS‐CoV2 infection (vs LD), despite immunosuppression burden. NAFLD patients reported to the registry had higher odds of severe SARS‐CoV2 disease. Future controlled studies are needed to evaluate effective treatments and further stratify LD and LT patients with SARS‐CoV2 infection.
Reliable Detection of Intrapulmonary Shunts Using Contrast‐Enhanced Echocardiography in Children With Portal Hypertension or Portosystemic Shunt
Authors: Rock Nathalie M. , Beghetti Maurice , Tissot Cécile , Willi Jean‐Pierre , Bouhabib Maya , McLin Valérie A. , Maggio Albane B.R.
Published: February 2021

Objectives:

The aim of this study was to analyze if contrast‐enhanced echocardiography (CEE) is as reliable as lung perfusion scintigraphy (LPS) to detect intrapulmonary shunting (IPS) in children with portal hypertension (PHTN) or congenital/surgical portosystemic shunts (PSS) and to define the number of cardiac cycles required to exclude intrapulmonary shunting.

Methods:

Inclusion criteria for this cross‐sectional study were: (1) presence of PHTN or PSS diagnosed on abdominal ultrasound, (2) technically valid saline contrast echocardiography, (3) lung perfusion scintigraphy within 6 months of CEE. The number of cardiac cycles between right atrial opacification and the arrival of contrast in the left atrium were counted. We analyzed our CEE data at three and five cardiac cycles and compared them with LPS results.

Results:

The study population was composed of 78 children (38 girls, 49%) ages 2.1–18.8 years (mean 9.8). Sixty‐nine patients had PHTN (88%), and nine had a PSS (11%). Eleven subjects (14%) presented evidence of IPS on LPS. Peripheral oxygen saturation was lower in the subjects with IPS detected on LPS (95.3 ± 1.7% vs 99.0 ± 1.4%; P < 0.01). Comparison of LPS with CEE before three and five cardiac cycles showed that CEE is highly specific (95.7%) as early as three cardiac cycles with markedly better sensitivity (72.7%) when using five cardiac cycles. Furthermore, a negative study using five cardiac cycles ruled out IPS with a 95% negative predictive value. The cardiac cycle at which the bubbles appeared in the left atrium was inversely correlated to the shunt index measured using LPS (r = −0.563; P = 0.001).

Conclusion:

CEE is sufficient for the screening of IPS in children with PHTN or congenital/surgical PSS, obviating the need for LPS.
Seroprevalence of Hepatitis C in Children Without Identifiable Risk‐Factors
Authors: Melikoki Vasiliki , Kourlaba Georgia , Kanavaki Ino , Fessatou Smaragdi , Papaevangelou Vassiliki
Published: February 2021

Objectives:

Hepatitis C virus (HCV) remains a major public health burden for >30 years since its discovery. It is estimated that >80 million people have been already infected. Direct‐acting antiviral (DAA) treatment is now approved for young children over the age of 3 years. Treating children before the development of high‐risk behaviors is optimal. Thus, assessing the current epidemiology of HCV in children becomes important and may promote awareness.

Methods:

Articles describing the prevalence of hepatitis C in children, were systematically reviewed. To assess HCV infection prevalence in the general population, studies discussing high‐risk groups alone were excluded.

Results:

Data from 58 studies were analyzed. National data was scarce. An overall prevalence of HCV in children of 0.87% was found, ranging from 0.34% in Europe to 3.02% in Africa. Prevalence of viremic infection is important and data synthesis from available data indicated that HCV viremia was detected in 56.8% of children. The prevalence of HCV according to sex was described in 25 studies but no difference between sexes was detected. HCV prevalence was significantly higher in children older than 10 years (0.97%) when compared to those ages under 10 years old (0.75%, P < 0.001).

Conclusions:

Considering probable underdiagnosis of HCV infection in children, this information reveals that prevalence is substantial. One may argue that future strategies aiming towards HCV elimination, may need to include antiviral treatment of pre‐adolescent children as well.
Validity and Responsiveness of the Patient‐reported Outcomes Measurement Information System in Children With Ulcerative Colitis
Authors: Brenner Erica J. , Long Millie D. , Mann Courtney M. , Lin Li , Chen Wenli , Reyes Camila , Bahnson Kirsten M. , Reeve Bryce B. , Kappelman Michael D.
Published: February 2021

Objectives:

Patient‐reported outcome measures allow children to directly report on their health and well‐being. We assessed the construct validity and responsiveness of the Patient‐Reported Outcomes Measurement Information System (PROMIS) Pediatric measures in children and adolescents with ulcerative colitis (UC).

Methods:

Through the Inflammatory Bowel Disease Partners Kids & Teens’ Internet‐based cohort, children with UC reported symptoms related to disease activity (Pediatric Ulcerative Colitis Activity Index), IMPACT‐III health‐related quality of life measure, and 5 PROMIS Pediatric measures (anxiety, depressive symptoms, pain interference, fatigue, and peer relationships). We included participants aged 9 to 17 years and conducted cross‐sectional and longitudinal, mixed‐linear regression analyses to examine the extent to which PROMIS Pediatric scores are associated with and respond to changes in Pediatric Ulcerative Colitis Activity Index and IMPACT‐III.

Results:

We evaluated 91 participants with UC (mean age 13 years, 57% girls). Better PROMIS Pediatric scores were associated with lower disease activity, in both cross‐sectional and longitudinal analyses. For a change from moderate/severe to remission, observed effect estimates were −5.1 points for anxiety, −5.0 for depressive symptoms, −14.7 for pain interference, −13.7 for fatigue, and 5.3 for peer relationships (P < 0.05 for all domains). Better PROMIS Pediatric scores were associated with improved IMPACT‐III scores (P values <0.01), and changes in scores were moderately correlated with changes in IMPACT‐III over time (adjusted P values <0.01).

Conclusions:

This study provides evidence for the construct validity and longitudinal responsiveness of the PROMIS Pediatric measures in pediatric patients with UC, thus supporting their use in clinical research and patient care.
Clinical Predictors of Morbidity and Mortality in Hospitalized Pediatric Patients With Ascites
Authors: Ingviya Thammasin , Wasuwanich Paul , Scheimann Ann O. , Felix Grace , Laengvejkal Pavis , Vasilescu Alexandra , Imteyaz Hejab , Seaberg Eric C. , Karnsakul Wikrom
Published: February 2021

Objectives:

Ascites is a pathologic buildup of fluid in the peritoneal cavity. Knowledge is lacking in clinical outcome in pediatric patients with ascites. We aim to identify and assess clinical variables, associated with morbidity and mortality in pediatric patients who are hospitalized with ascites.

Methods:

A retrospective cohort study was performed on patients ages 0 to 21 hospitalized at Johns Hopkins Hospital between 1983 and 2010 with an ICD‐9 discharge diagnosis of ascites (789.5, 789.51, 789.59). A total of 518 pediatric patients were studied, all with a diagnosis of ascites during hospitalization. Study outcomes included hospital length of stay (LOS) as a proxy for morbidity and death at hospital discharge for mortality. Variables analyzed included demographic data, ascites etiology and grade, comorbidities, and laboratory markers. Variables were analyzed by log‐linear regression and competing risk model.

Results:

Among the 3 age groups (0–5, 6–12, and 13–21), the 0 to 5 age group experienced significantly increased LOS (P < 0.001) and mortality (P = 0.027). Ascites etiology of veno‐occlusive disease (VOD) and the presence of hydrothorax or thrombocytopenia was also significantly associated with increased LOS. Ascites with the etiology of congestive hepatopathy and the presence of grade 3 ascites, hepatic encephalopathy, hepatorenal syndrome, hydrothorax, hyponatremia, and thrombocytopenia were associated with increased mortality. Additionally, black pediatric patients have an increased risk of mortality (P = 0.027). Other factors including sex, leukopenia, portal vein thrombosis, and splenomegaly were not associated with LOS or mortality.

Conclusions:

Morbidity and mortality in pediatric patients hospitalized with ascites are associated with specific demographic and clinical factors. Further studies are required to apply this knowledge to predict the clinical outcomes.
Safety of High‐Volume Plasmapheresis in Children With Acute Liver Failure
Authors: Jørgensen Marianne Hørby , Rasmussen Allan , Christensen Vibeke Brix , Jensen Anne‐mette Bæk , Fonsmark Lise , Andreassen Bente Utoft , Damholt Mette Brimnes , Larsen Fin Stolze
Published: February 2021

Objectives:

Paediatric acute liver failure (P‐ALF) is a rare condition and is associated with a high mortality rate. Management of P‐ALF aims to stabilise vital organ functions and to remove circulating toxins and provide vital plasma factors that are lacking. High‐volume plasmapheresis (HVP) removes protein‐bound substances and improves survival in adult ALF. It is unknown if this effect can be extrapolated to P‐ALF. The aim of this study is to report the safety and feasibility of HVP in P‐ALF.

Methods:

Children with P‐ALF were offered HVP if bilirubin was higher than 200 μmol/L or if the aetiology was toxic hepatitis. HVP was performed with fresh frozen plasma corresponding to 10% of the body weight on a minimum of 3 consecutive days. Diagnostics, biochemical and clinical data during HVP as well as outcome data after 3 months were collected from 2012 to 2019 and retrospectively analysed.

Results:

Sixteen children were treated by HVP and completed at least one series of three treatment sessions with HVP. The only complication seen was an increase in pH > 7.55 in three children within the first 12 hours and was corrected with hydrochloric acid. No bleeding or septic episodes were noted during HVP. Eight children survived without liver transplantation, two survived after successful grafting and a total of six children died. The liver injury unit score between survivors with their own liver and the rest, the two groups was significantly different (P = 0.005).

Conclusion:

HVP with fresh frozen plasma is feasible and well tolerated in children with P‐ALF. No serious adverse events and no procedure‐related mortality were observed.
Successful High-dose Chemotherapy in Combination With Autologous Peripheral Blood Stem Cell Transplantation in an Anuric Child With Neuroblastoma
Authors: Inoguchi Tomohiro , Hamada Riku , Kubota Wataru , Terano Chikako , Harada Ryoko , Honda Masataka , Yamaoka Shoko , Yokokawa Yuichi , Yuza Yuki , Hataya Hiroshi
Published: February 2021

No reports describe high-dose chemotherapy (HDCT) with autologous peripheral blood stem cell transplantation (auto-PBSCT) in pediatric patients with neuroblastoma and end-stage renal disease. Here, we report the case of a patient with high-risk neuroblastoma who developed anuria during treatment. HDCT with auto-PBSCT under hemodialysis, with strict attention to the ultrafiltration volume and dose modification of alkylating agents, was performed. Although the first auto-PBSCT led to engraftment failure, the second auto-PBSCT resulted in successful myeloid engraftment 8 months after anuria. This case demonstrated that HDCT with auto-PBSCT can be safely performed in children with renal failure under hemodialysis.
High Rates of Central Venous Line Replacement or Revision in Children With Cancer at US Children’s Hospitals
Authors: Buonpane Christie L. , Lautz Timothy B. , Langer Monica
Published: February 2021

Background:

Most children with cancer utilize a central venous line (CVL) for treatment. Complications often necessitate early replacement, revision, or addition (RRA), but the rate of these procedures is not known. This study sought to determine rates of RRA in pediatric oncology patients, and associated risk factors.

Materials and Methods:

Data queried from the Pediatric Health Information System including patients ≤18 years old with malignancy and CVL placement. Analysis included: first CVL placement of the calendar year and subsequent procedures for 6 months thereafter.

Results:

A total of 6553 children met inclusion criteria (55.9% male, median age 6 years, interquartile range: 2 to 12). RRA within 6 months was required in 25.6% of patients, with 1.7% requiring 5 or more lines. Patients with Central Line-Associated Bloodstream Infection (CLABSI) were 2.78 times more likely to require RRA within 6 months of initial CVL placement, but accounted for only 16% of RRA patients. Factors associated with RRA were age below 1 year, CLABSI, hematologic malignancy, malnutrition, clotting disorder, deep vessel thromboembolism, and obesity. Patients with implantable ports as initial CVL (42%) were less likely to need RRA.

Conclusion:

Twenty-five percent require at least 1 RRA within 6 months, with associated morbidity and costs. Though strongly associated, most revisions were not related to CLABSI episodes.
A Case of Ewing Sarcoma of the Bladder Presenting in Early Infancy
Authors: Howe Adam S. , Pearce Jennifer , Lian Fei , Ribbons Lisa , Chumbalkar Vaibhav , Nazeer Tipu , Kogan Barry A.
Published: February 2021

A 6-week-old female presented with gross hematuria and was diagnosed with Ewing sarcoma of the bladder through ultrasound and cystoscopic biopsies, along with a negative metastatic workup. She was treated with transurethral resection, chemotherapy consisting of with vincristine, cycolphosphamide, doxorubicin, ifosfamide and etoposide, and partial cystectomy. After completing chemotherapy, the patient has been doing well with no evidence of disease. There have been 14 other cases, 4 pediatric, of Ewing sarcoma of the bladder reported. To our knowledge, our case is the youngest patient reported with this disease.
Pediatric Malignant Peritoneal Mesothelioma With Meningeal Metastasis
Authors: Aldrian Denise , Neu Nikolaus , Oberhuber Georg , Kropshofer Gabriele , Müller Thomas , Vogel Georg-Friedrich
Published: February 2021

Malignant peritoneal mesothelioma (MPM) is an extremely rare entity with a poor prognosis. We report on a 16-year-old boy with ascites and abdominal distension. A computed tomography scan showed peritoneal thickening and a mass adjacent to the transverse colon. Neither repeated cytologic testing of ascitic fluid, nor peritoneal tissue biopsy detected malignant cells. After the patient became progressively comatose, a magnetic resonance imaging scan of the brain showed leptomeningeal enhancement. An autopsy showed MPM infiltrating the pleura and the meninges. This is the first report on meningeal metastasis of MPM in a pediatric patient illustrating the enigmatic behavior of the tumor and highlighting the diagnostic pitfalls.
Underlying CTLA4 Deficiency in a Patient With Juvenile Idiopathic Arthritis and Autoimmune Lymphoproliferative Syndrome Features Successfully Treated With Abatacept—A Case Report
Authors: Mazzoni Marta , Dell’Orso Gianluca , Grossi Alice , Ceccherini Isabella , Viola Stefania , Terranova Paola , Micalizzi Concetta , Guardo Daniela , Massaccesi Erika , Palmisani Elena , Calvillo Michaela , Fioredda Francesca , Malattia Clara , Dufour Carlo , Ravelli Angelo , Miano Maurizio
Published: February 2021

Background:

Functional variants of the cytotoxic T-lymphocyte antigen-4 (CTLA4) could contribute to the pathogenesis of disorders characterized by abnormal T-cell responses.

Case Presentation:

We report a case of a 13-year-old girl who first presented with polyarticular juvenile idiopathic arthritis poorly responsive to treatment. During the following years the patient developed cytopenias, chronic lymphoproliferation, high values of T-cell receptor αβ+ CD4- CD8- double-negative T cells and defective Fas-mediated T cells apoptosis. Autoimmune lymphoproliferative syndrome was diagnosed and therapy with mycophenolate mofetil was started, with good hematological control. Due to the persistence of active polyarthritis, mycophenolate mofetil was replaced with sirolimus. In the following months the patient developed hypogammaglobulinemia and started having severe diarrhea. Histologically, duodenitis and chronic gastritis were present. Using the next generation sequencing-based gene panel screening, a CTLA4 mutation was detected (p.Cys58Serfs*13). At the age of 21 the patient developed acute autoimmune hemolytic anemia; steroid treatment in combination with abatacept were started with clinical remission of all symptoms, even arthritis.

Conclusions:

Targeted immunologic screening and appropriate genetic tests could help in the diagnosis of a specific genetically mediated immune dysregulation syndrome, allowing to select those patients who can take advantage of target therapy, as in the case of abatacept in CTLA4 deficiency.
A Review of Web-Based COVID-19 Resources for Palliative Care Clinicians, Patients, and Their Caregivers
Authors: Tark Aluem , Kamalumpundi Vijayvardhan , Song Jiyoun , Chae Sena , Stone Patricia W. , Gilbertson-White Stephanie , Buck Harleah
Published: February 2021

Palliative and end-of-life care has been pushed to the forefront of medical care during the pandemic caused by the coronavirus-2019 (COVID-19). Palliative care organizations have responded to the growing demand for the rapid dissemination of research, clinical guidance, and instructions for care to clinicians, patients with COVID-19, and their caregivers by creating COVID-19 resource Web pages. Here, end users can access resources that can be updated in real time. These Web pages, however, can be variable in what resources they offer and for whom they are designed for (clinicians, patients, caregivers). Therefore, this project was conducted to consolidate these resources via summary tables of specific contents available through each Web page grouped by palliative care domains (eg, care discussion and planning, communication, symptom management, care access) and to identify the target audience. This environmental scan was conducted by compiling a comprehensive list of COVID-19 resource Web pages of palliative care organizations generated by reviewing previously published research studies and consulting with palliative care research experts. Snowballing techniques were used to identify resource Web pages not captured in the initial scan. Two reviewers independently evaluated eligible Web pages for content via a form developed for the study, and Cohen κ statistic was calculated to ensure interrater reliability. The final κ statistic was 0.76. Of the 24 websites screened, 15 websites met our eligibility criteria. Among the eligible resource Web pages, most (n = 12, 80%) had specific target audiences and care settings, whereas the rest presented information targeted to all audiences. Although 11 Web pages offered resources that addressed all 4 domains, only 1 Web page conveyed all 12 subdomains. We recommend the use of this guide to all frontline clinicians who require guidance in clinically managing patients with COVID-19 receiving palliative care and/or end-of-life care.
Expectations of Motherhood and Quality of Life
Authors: Adams Mary K. , Byrn Mary , Penckofer Sue , Bryant Fred , Almonte Angelica
Published: February 2021

Purpose:

The purpose of this study was to examine 1) discrepancies between expectations of motherhood and the experience of motherhood in the first 6 to 12 weeks postpartum, 2) relationships between maternal quality of life, mood, parental attitudes, and expectations, and 3) predictors of quality of life.

Study Design and Methods:

We used a descriptive, correlational design. The sample consisted of first-time mothers who were at or beyond 34 weeks pregnant with no reported history of anxiety or depression. The following questionnaires were administered during pregnancy and 6 to 12 weeks postpartum: Parenting Expectations Measure, General Anxiety Disorder 7, Edinburgh Postnatal Depression Screen, Intensive Parenting Attitudes Questionnaire, and Ferrans and Powers Quality of Life Index.

Results:

Sixty-one mothers participated. Based on scores from the Parenting Expectations Measure, 44% of participants had expectations of motherhood that were not met. Expectations were a significant predictor of quality of life during pregnancy and postpartum.

Clinical Implications:

Unmet expectations are important to understand when identifying modifiable risk factors of postpartum anxiety and depression in women without other risk factors. A discussion of expectations during antepartum care may minimize poor quality of life which is associated with anxiety and depression in women without anxiety and depressive symptoms.
Prevention of Pruritis following Spinal Morphine for Scheduled Cesarean Birth
Authors: Payne Christopher , Curtis Brian , Dan Devon , Dunston Shaun , Moore Chad , Hefley Justin
Published: February 2021

Background:

Intrathecal morphine provides effective analgesia after cesarean birth, yet up to 90% of women who receive it experience excessive itching, an undesirable dose-dependent effect. Pruritis may increase nursing workload, delay breastfeeding, and decrease patient satisfaction. When 0.1 mg spinal morphine is given, pruritis is markedly reduced while analgesia is preserved.

Purpose:

The purpose of this project was to determine possible causes and solutions for pruritus after cesarean birth.

Methods:

Anesthesia providers were educated and encouraged to limit spinal morphine to 0.1 mg as a strategy to prevent pruritus. In a repeated measures design, the rate of treatment-required pruritus and opioid consumption were measured 24 hours after surgery. The project included an evaluation of 30 medical records before and 30 medical records after the project intervention.

Results:

Preintervention rate of treatment-required pruritis was 37%, all received spinal morphine ≥ 1.5 mg. Postintervention rate of treatment-required pruritis was 13% and 57% after spinal morphine 0.1 mg and 0.2 mg, respectively. Opioid consumption was similar between groups.

Clinical Implications:

Mother–baby nurses can have an impact on the practice of anesthesia providers by advocating for evidence-based dosing of intrathecal morphine to reduce the incidence of pruritis while maintaining effective analgesia for women after cesarean birth.
Metacognition Mediates the Relationship Between Maladaptive Personality Traits and Levels of Personality Functioning
Authors: Pedone Roberto , Barbarulo Anna Maria , Colle Livia , Semerari Antonio , Grimaldi Pietro
Published: February 2021

The impaired ability to reflect on one's own state of mind and that of others (called metacognition or mentalization) is a central feature of personality disorders (PDs). Metacognition involves different specific abilities, which can be selectively impaired with different PDs and personality maladaptive traits. Moreover, research in the field of PDs has indicated that personality features and metacognitive abilities are associated with the severity of personality pathologies. In this study, we tested a mediation model of the interactions between these variables on predicting levels of personality functioning in a sample of adults taken from the general population (N = 775). Results showed that the relationship between personality traits and personality functioning is partially mediated by metacognitive abilities. These findings support the hypothesis that metacognition plays a significant role in predicting the levels of impairment in personality functioning. These findings have several clinical implications.
Job Satisfaction and Retention of an Advanced Practice Registered Nurse Fellowship Program
Authors: Cartwright Cathy C.
Published: February 2021

The purpose of this study was to determine how an advanced practice registered nurse (APRN) fellowship program affects job satisfaction and retention after the first year of practice. The Misener Nurse Practitioner Job Satisfaction Scale was administered to nine novice APRNs at a large Midwestern children’s hospital after program completion. Job satisfaction scores and retention rates were measured. Results indicate that transition-to-practice programs are helpful in bridging the gap between graduation and professional practice as an APRN.
Preparing Mentors
Authors: Council Kristen D. , Bowers Cynthia J.
Published: February 2021

The purpose of this literature review is to evaluate the preparation provided to nurse mentors. The nine studies reviewed revealed four themes related to preparation of nurse mentors. Nursing professional development practitioners should use current literature to develop nurse mentor preparation tools to improve the outcomes of the nursing mentor–mentee relationship and impact patient care.
COVID-19 as a disruptor: innovation and value in a national virtual fracture conference
Authors: Stein Matthew K. , Webb Matthew Loren , DeAngelis Ryan D. , Kerbel Yehuda E. , Mehta Samir , Donegan Derek J.
Published: February 2021

Objectives:

The aim of this study was to determine the educational value of a national virtual fracture conference implemented during the COVID-19 disruption of resident education.

Design:

Survey study.

Setting:

National virtual conference administered by the Orthopaedic Trauma Association.

Participants:

Attendees of virtual fracture conference.

Intervention:

Participation at a national virtual fracture conference.

Main outcome measure:

Surveys of perception of quality and value of virtual conferences relative to in-person conferences.

Results:

Ninety-six percent of participants rated the virtual fracture conference as similar or improved educational quality relative to conventional in-person fracture conference. Participants also felt they learned as much (35%) or more (57%) at each virtual fracture conference compared to the amount learned in-person. The quality of interpersonal interactions at both the resident–faculty level and faculty–faculty level was also perceived to be overall superior to those at participants’ own institutions. Learners felt they were more likely to engage the primary literature as well. Overall, 100% of participants were likely to recommend virtual conference to their colleagues and 100% recommended continuing this conference even after COVID-19 issues resolve.

Conclusions:

We found that learners find significant educational value in a national virtual fracture conference compared to in-person fracture conferences at their own institution. COVID-19 has proven to be a disruptor not only in health care but in medical education as well, accelerating our adoption of innovative and novel resident didactics.

Level of Evidence:

Therapeutic Level III.
Inadequate Engagement in HIV Care Among People With HIV Newly Diagnosed With a Sexually Transmitted Disease: A Multijurisdictional Analysis
Authors: Norkin Sarah K. , Benson Samantha , Civitarese Anna M. , Reich Amanda , Chomsky Albright Madison , Convery Christine , Kasarskis Irina M. , Cassidy-Stewart Hope , Howe Katharine , Wang Xueyan , Golden Matthew R. , Khosropour Christine M. , Glick Sara N. , Kerani Roxanne P.
Published: February 2021

Background

A key challenge of HIV surveillance–based HIV care reengagement is locating people living with HIV (PLWH) who seem to be out of care to reengage them in care. Providing reengagement services to PLWH diagnosed with a sexually transmitted disease (STD)—individuals who are in jurisdiction and connected to the health care system—could be an efficient means of promoting HIV treatment and reducing HIV transmission.

Methods

Early and late syphilis (ES/LS) and gonorrhea (GC) cases diagnosed in 2016 and 2017 in Louisiana, Michigan, Mississippi, Oregon, Rhode Island, and Texas were matched to each state's HIV surveillance data to determine the proportion of PLWH with these infections who (1) did not have evidence of a CD4 count or viral load in the prior ≥13 months (out of care) or (2) had a viral load ≥1500 copies/mL on their most recent HIV RNA test before STD diagnosis (viremic).

Results

Previously diagnosed HIV infection was common among persons diagnosed with ES (n = 6942; 39%), LS (n = 4329; 27%), and GC (n = 9509; 6%). Among these ES, LS, and GC cases, 26% (n = 1543), 33% (n = 1113), and 29% (n = 2391) were out of HIV medical care or viremic at the time of STD diagnosis.

Conclusions

A large proportion of STD cases with prior HIV diagnosis are out of care or viremic. Integrating relinkage to care activities into STD partner services and/or the use of matching STD and HIV data systems to prioritize data to care activities could be an efficient means for relinking patients to care and promoting viral suppression.
Structural and Environmental Influences Increase the Risk of Sexually Transmitted Infection in a Sample of Female Sex Workers
Authors: Sherman Susan G. , Tomko Catherine , White Rebecca Hamilton , Nestadt Danielle Friedman , Silberzahn Bradley E. , Clouse Emily , Haney Katherine , Galai Noya
Published: February 2021

Background

Female sex workers (FSWs) have elevated rates of sexually transmitted infections (STIs) including HIV, yet few studies in the United States have characterized the STI burden in this population.

Methods

Data were derived from the EMERALD study, a structural community-based intervention with FSWs in Baltimore, MD. Participants (n = 385) were recruited through targeted sampling on a mobile van. Prevalent positive chlamydia or gonorrhea infections were determined by biological samples. Multivariable logistic regressions modeled correlates of confirmed positive STI (gonorrhea or chlamydia).

Results

Confirmed STI positive prevalence was 28%, 15% chlamydia and 18% gonorrhea. Approximately two-thirds of the sample (64%) was younger than 40 years, one-third (36%) were Black, and 10% entered sex work in the past year. The sample was characterized by high levels of structural vulnerabilities (e.g., housing instability and food insecurity) and illicit substance use. Female sex workers were more likely to have a positive STI if they had financial dependent(s) (P = 0.04), experienced food insecurity at least weekly (P = 0.01), entered sex work in the past year (P = 0.002), and had 6 or more clients in the past week (P = 0.01). Female sex workers were less likely to have a positive STI test result if they were 40 years or older compared with FSW 18 to 29 years old (P = 0.02), and marginally (P = 0.08) less likely with high (vs. low) social cohesion.

Conclusions

More than a quarter of FSWs had confirmed chlamydia or gonorrhea. In addition to STI risks at the individual level, STIs are driven by structural vulnerabilities. Results point to a number of salient factors to be targeted in STI prevention among FSWs.
Oropharyngeal Squamous Cell Carcinoma With Discordant p16 and HPV mRNA Results
Authors: Shinn Justin R. , Davis Seth J. , Lang-Kuhs Krystle A. , Rohde Sarah , Wang Xiaowei , Liu Ping , Dupont William D. , Plummer Dale , Thorstad Wade L. , Chernock Rebecca D. , Mehrad Mitra , Lewis James S.
Published: February 2021

Early studies estimate that 5% to 10% of oropharyngeal squamous cell carcinomas overexpress p16 but are unassociated with transcriptionally-active high-risk human papillomavirus (HPV). Patients with discordant HPV testing may experience clinical outcomes that differ from traditional expectations. To document the rate of p16 and HPV mRNA positivity, characterize patients with discordant testing, and identify features that may warrant selective use of HPV-specific testing after p16 IHC, a multi-institutional, retrospective review of oropharyngeal squamous cell carcinoma patients with p16 IHC and HPV mRNA testing by reverse transcriptase polymerase chain reaction was performed. Of the 467 patients, most had T1 or T2 tumors (71%), 82% were p16 positive, and 84% were HPV mRNA positive. Overall, most tumors were nonkeratinizing (378, 81%), which was strongly associated with p16 and HPV positivity (93% and 95%, respectively). Overall, 81% of patients were double positive, 14% double negative, and 4.9% discordant (3.4% p16 negative/HPV mRNA positive and 1.5% p16 positive/HPV mRNA negative). The survival rates of these discordant patient groups fell squarely between the 2 concordant groups, although in multivariate analysis for both disease-free survival and overall survival, discordant patients were not found to have statistically significantly different outcomes. Reclassifying patients by applying HPV mRNA testing when p16 results and morphology do not match, or when p16 results are equivocal, improved prognostication slightly over p16 or HPV mRNA testing alone. Patients with discordant testing demonstrate a borderline significant trend toward survival differences from those with concordant tests. When evaluated independently, patients who were p16 negative but HPV mRNA positive had a prognosis somewhat closer to double-positive patients, while those who were p16 positive, but HPV mRNA negative had a prognosis closer to that of double-negative patients. We suggest an algorithm whereby confirmatory HPV mRNA testing is performed in patients where p16 status is not consistent with tumor morphology. This captures a majority of discordant patients and improves, albeit modestly, the prognostication.
Salivary Mucinous Adenocarcinoma Is a Histologically Diverse Single Entity With Recurrent AKT1 E17K Mutations
Authors: Rooper Lisa M. , Argyris Prokopios P. , Thompson Lester D.R. , Gagan Jeffrey , Westra William H. , Jordan Richard C. , Koutlas Ioannis G. , Bishop Justin A.
Published: February 2021

Mucin-producing salivary adenocarcinomas were historically divided into separate colloid carcinoma, papillary cystadenocarcinoma, and signet ring cell carcinoma diagnoses based on histologic pattern, but have recently been grouped together in the adenocarcinoma not otherwise specified category. It is currently unclear if these tumors represent 1 or more distinct entities and how they are related to well-circumscribed papillary mucinous lesions with recurrent AKT1 E17K mutations that were recently described as salivary intraductal papillary mucinous neoplasm. Here, we sought to evaluate the clinicopathologic and molecular features of salivary mucinous adenocarcinomas to clarify their classification. We identified 17 invasive mucin-producing salivary adenocarcinomas, 10 with a single histologic pattern, and 7 with mixed patterns. While most tumors demonstrated papillary growth (n=15), it was frequently intermixed with colloid (n=6) and signet ring (n=3) architecture with obvious transitions between patterns. All were cytokeratin 7 positive (100%) and cytokeratin 20 negative (0%). Next-generation sequencing performed on a subset demonstrated recurrent AKT1 E17K mutations in 8 cases (100%) and TP53 alterations in 7 cases (88%). Of 12 cases with clinical follow-up (median: 17 mo), 4 developed cervical lymph node metastases, all of which had colloid or signet ring components. Overall, overlapping histologic and immunohistochemical features coupled with recurrent AKT1 E17K mutations across patterns suggests that mucin-producing salivary adenocarcinomas represent a histologically diverse single entity that is closely related to tumors described as salivary intraductal papillary mucinous neoplasm. We propose a unified mucinous adenocarcinoma category subdivided into papillary, colloid, signet ring, and mixed subtypes to facilitate better recognition and classification of these tumors.