bluuebunny/crossref_metadata_2025 huggingface dataset:
Ineffective erythropoiesis in sickle cell disease: new insights and future implications
Authors: El Nemer Wassim , Godard Auria , El Hoss Sara
Published: February 2021

Purpose of review

Sickle cell disease (SCD) is a hemolytic anemia caused by a point mutation in the β globin gene leading to the expression of an abnormal hemoglobin (HbS) that polymerizes under hypoxic conditions driving red cell sickling. Circulating red cells have been extensively characterized in SCD, as their destruction and removal from peripheral blood are the major contributors to anemia. However, few reports showed cellular abnormalities during erythropoiesis in SCD, suggesting that anemia could also be influenced by defects of central origin.

Recent findings

El Hoss et al. demonstrated ineffective erythropoiesis (IE) in SCD and deciphered the molecular mechanism underlying cell death during the hemoglobin synthesis phase of terminal differentiation. They showed that HbS polymerization induces apoptosis of differentiating erythroblasts and that fetal hemoglobin rescues these cells through its antipolymerization function.

IE is the major cause of anemia in β-thalassemia patients, and it is generally surmised that it contributes little to anemia of SCD. Recent reports demonstrate the occurrence of IE in SCD patients and show important alterations in the hematopoietic and erythroid niches, both in SCD patients and in the humanized Townes SCD mouse model. This implies that therapeutic strategies initially designed to improve red cell survival in the circulation of SCD patients would also positively impact erythropoiesis and bone marrow cellularity.
Evaluation and fetal intervention in severe fetal hydronephrosis
Authors: Safdar Adnan , Singh Kristianna , Sun Raphael C. , Nassr Ahmed A.
Published: February 2021

Purpose of review

Fetal hydronephrosis secondary to congenital anomalies of the kidney and urinary tract (CAKUT) can adversely affect neonates in the postnatal period with long-term consequences. A prenatal diagnosis of CAKUT can have an early fetal intervention to minimize these consequences. This review aims to provide an overview of the possible fetal intervention with severe hydronephrosis.

Recent findings

Clinical course and outcomes of CAKUT are predicted based on biochemical markers and radiological findings. In spite of advancements and accurately diagnosing the severity of hydronephrosis, there are many controversies surround on selection of cases with antenatal hydronephrosis (ANH) that will benefit from fetal intervention. Despite better diagnosis and techniques fetal intervention is limited to mainly lower urinary tract obstruction patients to improve amniotic fluid volume and assist in lung development.

ANH can potentially detect the severity of congenital renal anomalies but unable to recognize a specific disease. A multidisciplinary approach is required to diagnose and properly stage cases of severe CAKUT and potential surgical intervention can be considered.
Consequences of the SARS-CoV-2 pandemic in the perinatal period
Authors: Hudak Mark L.
Published: February 2021

Purpose of review

To provide an update on the consequences of severe acute respiratory syndrome (SARS)-CoV-2 infection on the health and perinatal outcomes of pregnant women and their infants.

Recent findings

The severity of SARS-CoV-2 infection is greater in pregnant compared to nonpregnant women as measured by rates of admission to intensive care units, mechanical ventilation, mortality, and morbidities including myocardial infarction, venous thromboembolic and other thrombotic events, preeclampsia, preterm labor, and preterm birth. The risk of transmission from mother-to-infant is relatively low (1.5–5%) as quantitated by neonatal SARS-CoV-2 testing. Infants appear to be at higher risk of testing positive for SARS-CoV-2 if the mother has tested positive within 1 week of delivery or is herself symptomatic at the time of maternity admission. The rate of positivity is not higher in infants who room in with the mother compared to infants who are initially separated and cared for in a SARS-CoV-2-free environment. Infants who test positive in the hospital have no or mild signs of disease, most of which may be attributable to prematurity, and rarely require readmission for clinical signs consistent with COVID-19.

Pregnant women should take precautions to avoid infection with SARS-CoV-2. Infants born to mothers who test positive for SARS-CoV-2 can receive normal neonatal care in-hospital with their mothers if mother and staff adhere to recommended infection control practices.
Role of the purinergic signaling network in lung ischemia-reperfusion injury
Authors: Haywood Nathan , Ta Huy Q. , Rotar Evan , Daneva Zdravka , Sonkusare Swapnil K. , Laubach Victor E.
Published: February 2021

Purpose of review

Primary graft dysfunction (PGD) is the leading cause of early mortality following lung transplantation and is typically caused by lung ischemia-reperfusion injury (IRI). Current management of PGD is largely supportive and there are no approved therapies to prevent lung IRI after transplantation. The purinergic signaling network plays an important role in this sterile inflammatory process, and pharmacologic manipulation of said network is a promising therapeutic strategy. This review will summarize recent findings in this area.

Recent findings

In the past 18 months, our understanding of lung IRI has improved, and it is becoming clear that the purinergic signaling network plays a vital role. Recent works have identified critical components of the purinergic signaling network (Pannexin-1 channels, ectonucleotidases, purinergic P1 and P2 receptors) involved in inflammation in a number of pathologic states including lung IRI. In addition, a functionally-related calcium channel, the transient receptor potential vanilloid type 4 (TRPV4) channel, has recently been linked to purinergic signaling and has also been shown to mediate lung IRI.

Agents targeting components of the purinergic signaling network are promising potential therapeutics to limit inflammation associated with lung IRI and thus decrease the risk of developing PGD.
Intestinal transplantation
Authors: Garcia Jennifer , Selvaggi Gennaro , Tekin Akin , Vianna Rodrigo
Published: February 2021

Purpose of review

Intestinal transplantation has evolved to be a viable treatment option for patients with intestinal failure. This review shows the most current tendencies and practices of intestinal transplant centers and an overall comparison to intestinal rehabilitation.

Recent findings

This review outlines that timing for referral and advances in preoperative and postoperative care of intestinal and multivisceral transplant candidates are crucial to achieve results comparable to intestinal rehabilitation.

Current practices have shown that intestinal transplantation continues to improve overall results and could be considered in patients with permanent home parenteral nutrition. Timing for referral and preoperative and postoperative management are crucial to optimize long-term results.
Current status: meeting the regulatory goals of your liver transplant program
Authors: Batra Ramesh K. , Mulligan David C.
Published: February 2021

Purpose of review

The regulatory framework set by the Organ Procurement and Transplantation Network (OPTN) and Center for Medicare and Medicaid Services (CMS) for practice of liver transplantation in US is periodically updated and risk adjusted. Therefore, it is prudent for transplant centers to know the rules of engagement as it pertains to their practice.

Recent findings

OPTN besides providing the regulatory oversight for safe and continued practice of transplant centers, provides necessary tools like: advanced statistical models and technological platforms to aid, and guide transplant centers including the necessary safeguards for high-quality transplant care.

CMS regulations although had different thresholds to flag underperformance, often covered common grounds similar to the OPTN, therefore considered duplicative and unnecessary. But with much deliberation and consideration CMS undertook a major overhaul to the final rule for re-approval applications, a giant leap in the positive direction for transplant innovation and growth.

The duplicative regulatory framework of OPTN and CMS has although achieved the goal of improving 1-year patient outcomes, it has proven costly in terms of slowing innovation, increasing organ discard and stunting growth of transplant volume. But the new updates in effect and also in the pipeline are a long-awaited opportunity for waiting transplant patients.
Nutritional Management of the Critically Ill Neonate
Authors: Moltu Sissel Jennifer , Bronsky Jiri , Embleton Nicholas , Gerasimidis Konstantinos , Indrio Flavia , Köglmeier Jutta , de Koning Barbara , Lapillonne Alexandre , Norsa Lorenzo , Verduci Elvira , Domellöf Magnus ,   ESPGHAN Committee on Nutrition
Published: February 2021

Objectives:

The nutritional management of critically ill term neonates and preterm infants varies widely, and controversies exist in regard to when to initiate nutrition, mode of feeding, energy requirements, and composition of enteral and parenteral feeds. Recommendations for nutritional support in critical illness are needed.

Methods:

The ESPGHAN Committee on Nutrition (ESPGHAN‐CoN) conducted a systematic literature search on nutritional support in critically ill neonates, including studies on basic metabolism. The Medline database and the Cochrane Library were used in the search for relevant publications. The quality of evidence was reviewed and discussed before voting on recommendations, and a consensus of 90% or more was required for the final approval. Important research gaps were also identified.

Results:

This position paper provides clinical recommendations on nutritional support during different phases of critical illness in preterm and term neonates based on available literature and expert opinion.

Conclusion:

Basic research along with adequately powered trials are urgently needed to resolve key uncertainties on metabolism and nutrient requirements in this heterogeneous patient population.
Clinical Characterization of Pediatric Gastroparesis Using a Four‐hour Gastric Emptying Scintigraphy Standard
Authors: Wolfson Sharon , Wilhelm Zoe , Opekun Antone R. , Orth Robert , Shulman Robert J. , Chumpitazi Bruno P.
Published: February 2021

Objectives:

Four‐hour gastric emptying scintigraphy (GES) is the recommended method to identify both adult and childhood gastroparesis (GP). Previous pediatric studies have, however, not used this standard. We sought to determine the characteristics and outcomes of children versus adolescents with GP using the 4‐hour GES evaluation.

Methods:

We performed a retrospective chart review of pediatric patients diagnosed with GP by 4‐hour GES (>10% retention at 4 hours). Demographics, body mass index, GP‐related symptoms, comorbidities, etiologies, therapies (eg, medications), healthcare utilization, and response to therapy were captured systematically. Symptoms were compared from the initial versus last gastroenterology visit. Outcomes were categorized as no improvement; improvement (resolution of at least 1 symptom while remaining on therapy); and complete resolution of symptoms.

Results:

A total of 239 subjects (12.1 ± 4.1 years [mean ± standard deviation], 70% girls) were included. The identified characteristics of childhood GP were broad with idiopathic GP being the most common etiology. Outcomes over a median of 22 months (25%–75%: 9.0–45.5 months) were 34.8% no improvement, 34.8% some improvement, and 30.3% with complete symptom resolution. Compared to younger children, adolescents had a higher female predominance (P < 0.01) and were more likely to have nausea (P = 0.006). Girls were more likely to have abdominal pain (P = 0.001), nausea (P = 0.03), and a documented diagnosis of dysautonomia (P = 0.03). Boys were more likely to have regurgitation (P = 0.006), gastroesophageal reflux disease (P = 0.02), and rumination (P = 0.02).

Conclusions:

Using the 4‐hour GES standard, childhood GP has broad clinical characteristics and outcomes. There are several significant age‐ and sex‐based differences in childhood GP.
Clinical and Esophagogastroduodenoscopy Findings in Pediatric Patients With Severe Obesity Evaluated Before Bariatric Surgery
Authors: Sivan Rachel Frenklak , Bar Lev Michal Rozenfeld , Silbermintz Ari , Mozer‐Glassberg Yael , Seguier‐Lipzyc Emmanuelle , Shalitin Shlomit , Stafler Patrick , Tiroler Simona , Shamir Raanan , Waisbourd‐Zinman Orith
Published: February 2021

Objectives:

Severe obesity in the pediatric population has lifelong consequences. Bariatric surgery has been suggested for selected adolescents with severe obesity after careful evaluation. The indications for preoperative esophagogastroduodenoscopy (EGD) in this age group are not clear, despite its established usefulness in adults. We aimed to assess the usefulness of EGD before bariatric surgery in pediatric patients with severe obesity and metabolic comorbidities.

Methods:

We conducted a retrospective chart review in a single tertiary pediatric medical center of adolescents treated during 2011 to 2018. Data collected from electronic medical records included patient demographics, endoscopic findings, and laboratory parameters.

Results:

A total of 80 patients (40 boys) underwent evaluation. Macroscopic abnormalities were detected in 54% of the endoscopies, including gastritis, esophagitis, and duodenitis in 46%, 16%, and 13%, respectively. Forty‐nine percentage of the biopsies showed histological abnormalities; in 35 (44%) patients, Helicobacter pylori was detected. Thirty‐three patients (41%) received medical treatment and 2 (2.5%) required a second EGD. Metabolic comorbidities included hypertriglyceridemia (38% of the patients), low high‐density lipoprotein (23%), and prediabetic (16%) or diabetic levels of HbA1C (4%). Fifty‐five percentage of the cohort had elevated alanine aminotransferase (ALT), suggestive of nonalcoholic fatty liver disease (NAFLD).

Conclusions:

Endoscopies performed before bariatric surgeries suggest a higher prevalence of clinically significant findings, many of which required treatment. These findings support incorporating an EGD into the preoperative evaluation of this patient population.
Comparison of Total Body Irradiation–based Versus Chemotherapy-based Conditionings for Early Complications of Allogeneic Hematopoietic Stem Cell Transplantation in Children With ALL
Authors: Yalcin Koray , Pehlivan Berrin , Celen Suna , Bas Elif Gulsah , Kabakci Canan , Pashayev Dayanat , Daloglu Hayriye , Zhumatayev Suleyman , Uygun Vedat , Karasu Gulsun Tezcan , Hazar Volkan , Yesilipek Akif
Published: February 2021

Background:

Total body irradiation (TBI) is the cornerstone of conditioning regimens in pediatric hematopoietic stem cell transplantation for acute lymphoblastic leukemia. As the late effects and survival comparison between TBI and chemotherapy were well analyzed before, in this study, we aim to focus on the first 100 days and early complications of transplantation.

Methods:

This retrospective study involves 72 pediatric patients (0 to 18 y) underwent first hematopoietic stem cell transplantation for acute lymphoblastic leukemia between October 2015 and May 2019. Patients are divided into 2 groups regarding conditioning regimens. Conditionings includes either TBI 1200 cGy/6 fractions/3 days and etoposide phosphate or busulfan, fludarabine, and thiotepa. Busulfan was administered IV and according to body weight.

Results:

The incidences of acute graft versus host disease grade 2 to 4, veno-occlusive disease, capillary leakage syndrome, thrombotic microangiopathy, blood stream infection, hemorrhagic cystitis and posterior reversible encephalopathy syndrome before day 100 were similar for both conditioning regimens; however, patients received TBI-based conditioning had significantly longer neutrophil engraftment time (17.5 vs. 13 d, P=0.001) and tended to have more engraftment syndrome (ES) (45.5% for TBI vs. 24.0% for chemotherapy, P=0.069). Multivariate analysis showed that TBI-based conditioning was associated with a longer neutrophil engraftment time (hazard ratio [HR]=1.20, P=0.006), more cytomegalovirus (CMV) reactivation (HR=3.65, P=0.038) and more ES (HR=3.18, P=0.078).

Conclusions:

Our findings support chemotherapy-based regimens with early neutrophil engraftment, less ES and CMV reactivation compared with TBI. Although there is no impact on survival rates, increased incidence of ES and CMV reactivation should be considered in TBI-based regimens.
Assessing Safe Discharge Criteria for Pediatric Oncology Patients Admitted for Febrile Neutropenia
Authors: Huschart Emily , Ducore Jonathan , Chung Jong
Published: February 2021

Recent studies suggest outpatient therapy, oral antibiotics, or earlier discharge could be appropriate in some pediatric patients admitted with febrile neutropenia; supporting data are lacking. Retrospective chart review of patients admitted from September 2005 through October 2016 identified 131 “early discharge” febrile neutropenia admissions with discharge absolute neutrophil count (ANC) <500/µl and negative cultures. All were afebrile and discharged without outpatient antibiotics. Eleven of 131 patients (8%) were readmitted. Two patients called back for late positive cultures. Nine were readmitted with febrile neutropenia; 2 had positive cultures on readmission. All 4 patients with positive cultures were safely treated with appropriate antibiotics. The remaining 7 patients had uneventful readmissions. Average ANC (SD) at discharge was lower for patients readmitted versus those not readmitted (69 [70] vs. 196 [145], P≤0.001), as was absolute phagocyte count (APC) at discharge (97 [82] vs. 453 [431], P≤0.001). APC on admission was not significantly lower for those readmitted (165 [254] vs. 321 [388], P=0.09). Few patients required readmission; those with bacterial infections were easily identified and appropriately treated. Higher ANC or APC criteria for discharge would increase length of hospital stay without decreasing morbidity. A subset of patients admitted with febrile neutropenia can be safely discharged before count recovery without oral antibiotics.
Association of Multiple Gene Polymorphisms Including Homozygous NUDT15 R139C With Thiopurine Intolerance During the Treatment of Acute Lymphoblastic Leukemia
Authors: Kudo Ko , Sato Tomohiko , Takahashi Yuka , Yuzawa Kentaro , Kobayashi Akie , Kamio Takuya , Sasaki Shinya , Shimada Jun , Otani Katsuki , Tusjimoto Shinichi , Kato Motohiro , Toki Tsutomu , Terui Kiminori , Ito Etsuro
Published: February 2021

Although thiopurine is a crucial drug for treating acute lymphoblastic leukemia, individual variations in intolerance are observed due to gene polymorphisms. A 3-year-old boy with B-cell precursor acute lymphoblastic leukemia who was administered thiopurine developed mucositis, sepsis, and hemophagocytic lymphohistiocytosis due to prolonged hematologic toxicity, chronic disseminated candidiasis, and infective endocarditis that triggered multiple brain infarctions. The patient was found to harbor 3 gene polymorphisms associated with thiopurine intolerance including homozygous NUDT15 R139C, heterozygous ITPA C94A, and homozygous MTHFR C677T and heterozygous RFC1 G80A. Thus, the combined effect of intolerance via multiple gene polymorphisms should be considered in case of unexpected adverse reactions.
Cognitive Functioning and Educational Support Plans in Youth With Sickle Cell Disease
Authors: Connolly Megan E. , Bills Sarah E. , Hardy Steven J.
Published: February 2021

Children with sickle cell disease (SCD) face academic challenges because of direct and indirect disease-related events. This study examined the proportion of youth with SCD with educational plans and whether cognitive functioning is associated with educational support. Ninety-one youth (7 to 16 y) with SCD completed the WISC-V; caregivers reported educational support (504 Plan/Individualized Education Program) and completed the Behavior Rating Inventory of Executive Function. χ2 square and t test analyses explored whether overall intelligence (full-scale intelligence quotient [FSIQ]), relative weaknesses in processing speed and working memory (> 1SD below FSIQ), and parent-reported executive functioning were associated with educational plans. Participants with a FSIQ<90 were more likely to have support (74%) compared with youth with a FSIQ≥90 (47%; P=0.012). Those with FSIQ≥90 and FSIQ=80 to 89 were less likely to have support (47%, 58%, respectively) compared with those with FSIQ≤79 (89%; P=0.004). Relative weaknesses in processing speed were associated with educational support (83% vs. 52%, P=0.018) as well as behavioral aspects of executive functioning (Ps<0.05). Despite universal eligibility for a 504 Plan, 42% of youth with SCD in our sample did not have educational support. Significant deficits in intellectual functioning, processing speed, and parent-observed executive functioning are associated with having a plan, but children with subtle deficits seem less likely to be identified for educational support.
Clinicopathologic Features of Childhood Rhabdomyosarcoma and Treatment Outcomes in Ibadan, Nigeria: A 10-year Review
Authors: Brown Biobele J. , Ogun Gabriel O. , Akinmoladun Victor I. , Ogundoyin Olakayode O. , Abdus-Salam Abbas , Olulana Dare I. , Lawal Taiwo A.
Published: February 2021

The objectives of this study were to describe the clinicopathologic features and treatment outcomes of childhood rhabdomyosarcoma in a resource-constrained setting. All cases of childhood rhabdomyosarcoma seen over a 10-year period (July 2006 to June 2016) at the University College Hospital, Ibadan, Nigeria were reviewed. Data were extracted from the database of the pediatric Hematology/Oncology Unit of the hospital and analyzed. Ethical approval was obtained from the Institutional Ethics Committee. Fifty children were seen comprising 30 men and 20 women with bimodal ages of 4 and 5 years. Median duration of illness was 16 weeks and the most common primary tumor site was the head-and-neck region in 27 (54%) of cases. The histologic subtypes were embryonal in 30 (60%), alveolar in 9 (18%), and not specified in 11 (22%). The Intergroup Rhabdomyosarcoma Study group TNM Pretreatment stages were stage I in 15 (30%), stage III in 17 (34%), and stage IV in 18 (36%). Treatment included chemotherapy, surgery, and radiotherapy and abandoned in 20 (40%) cases. Median survival was 45 weeks (95% confidence interval: 16.4-73.6) and 5 (10%) patients were alive and disease free, 4 years or more after diagnosis. Outcome of childhood rhabdomyosarcoma is poor and early diagnosis and improved access to treatment are recommended.
Examining the Effect of Travel Distance to Pediatric Cancer Centers and Rurality on Survival and Treatment Experiences: A Systematic Review
Authors: Tarnasky Aaron M. , Olivere Lindsey A. , Ledbetter Leila , Tracy Elisabeth T.
Published: February 2021

Accessing pediatric cancer treatment remains problematic for rural families or those living at increased distances from specialized centers. Rural adult cancer patients or those living far removed from treatment may present with later stage disease, receive different treatments than their closer counterparts, and experience worsened survival. While the financial and psychosocial strain of increased travel is well documented, effects of travel distance on similar outcomes for pediatric cancer patients remain ill-defined. We conducted a systematic review to synthesize literature examining the effect of travel distance and/or rurality (as a proxy for distance) on pediatric cancer treatment experiences and survival outcomes. Included studies examined travel distance to specialized centers or rural status for patients above 21 years of age. Studies were excluded if they focused on financial or quality of life outcomes. We analyzed 24 studies covering myriad malignancies and outcomes, including location of care, clinical trial participation, and likelihood of receiving specialized treatments such as stem cell transplants or proton beam therapy. Most were retrospective, and 9 were conducted outside the United States. While some studies suggest rural patients may experience worsened survival and those traveling furthest may experience shorter hospitalization times/rates, the available evidence does not uniformly assert negative effects of increased distance.
Transcranial Doppler Screening in a Current Cohort of Children With Sickle Cell Anemia: Results From the DISPLACE Study
Authors: Kanter Julie , Phillips Shannon , Schlenz Alyssa M. , Mueller Martina , Dooley Mary , Sirline Logan , Nickel Robert , Brown Robert Clark , Hilliard Lee , Melvin Cathy L. , Adams Robert J.
Published: February 2021

Stroke prevention guidelines for sickle cell anemia (SCA) recommend transcranial Doppler (TCD) screening to identify children at stroke risk; however, TCD screening implementation remains poor. This report describes results from Part 1 of the 28-site DISPLACE (Dissemination and Implementation of Stroke Prevention Looking at the Care Environment) study, a baseline assessment of TCD implementation rates. This report describes TCD implementation by consortium site characteristics; characteristics of TCDs completed; and TCD results based on age. The cohort included 5247 children with SCA, of whom 5116 were eligible for TCD implementation assessment for at least 1 study year. The majority of children were African American or Black, non-Hispanic and received Medicaid. Mean age at first recorded TCD was 5.9 and 10.5 years at study end. Observed TCD screening rates were unsatisfactory across geographic regions (mean 49.9%; range: 30.9% to 74.7%) independent of size, institution type, or previous stroke prevention trial participation. The abnormal TCD rate was 2.9%, with a median age of 6.3 years for first abnormal TCD result. Findings highlight real-world TCD screening practices and results from the largest SCA cohort to date. Data informed the part 3 implementation study for improving stroke screening and findings may inform clinical practice improvements.
Use of rFVIIa in Preventing Recurrent Intra-articular Hemorrhages in a 15-Year-Old Patient With Glanzmann Thrombasthenia
Authors: Laguna Pawel
Published: February 2021

Glanzmann thrombasthenia is a rare congenital thrombocytopathy. The first-line treatment in severe life-threatening bleeding is a transfusion of platelet concentrate or recombinant factor VIIa in the case of platelet transfusion refractoriness. We present the case of a 16-year-old boy with Glanzmann thrombasthenia who was admitted to hospital with severe bleeding into the quadriceps femoris muscle. At the age of 15 years, he was hospitalized again because of chronic bleeding into the right ankle joint, resulting in joint destruction. Here we give a scheme of management and treatment of this patient. Hemostatic therapy followed by radiosynovectomy of the right ankle joint and introduction of secondary preventive treatment with recombinant factor VIIa proved to be efficacious and safe.
The Role of Granulocyte Transfusions in Optimizing Candidacy for Chimeric Antigen Receptor T-cell Therapy in Patients With Treatment-refractory Infections
Authors: Tambaro Francesco P. , Ragoonanan Dristhi , Tewari Priti , Petropoulos Demetrios , Aung Fleur M. , Mahadeo Kris M. , Khazal Sajad
Published: February 2021

While advancements in cellular therapy have improved outcomes for patients with refractory leukemia, severe infections may hinder access. Granulocyte transfusions, in combination with anti-microbial therapy, may be a safe option to facilitate candidacy for chimeric antigen receptor T-cell therapy in patients with leukemia and prolonged immune-compromised status.
A Novel Germline TP53 Mutation in a Patient With Li-Fraumeni Syndrome: Resolving a Variant of Uncertain Significance
Authors: Douglass David P. , Stine Kimo C. , Farrar Jason E.
Published: February 2021

Increasing availability of genomic testing poses new challenges to clinicians, particularly where variant interpretation from commercial sources may be equivocal. The authors report a patient with recurrent rhabdomyosarcoma and subsequent bilateral breast cancer who was found to harbor a previously undescribed germline TP53 sequence alteration annotated by the commercial laboratory as a variant of uncertain significance. By investigating publicly available databases of aggregated normal germline and malignant somatic genomic sequences, the authors conclude that this missense variant, c.476C>T (p.A159V), is a novel, pathogenic Li-Fraumeni syndrome mutation and demonstrate the utility of these resources in clinical pediatric hematology and oncology practice.
Challenges in the Management of Childhood Intracranial Germ Cell Tumors in Middle-Income Countries: A 20-Year Retrospective Review From a Single Tertiary Center in Malaysia
Authors: Rajagopal Revathi , Leong Sheng Hoay , Jawin Vida , Foo Jen Chun , Ahmad Bahuri Nor Faizal , Mun Kein Seong , Azman Raja Rizal , Loh Jasmin , Yap Tsiao Yi , Ariffin Hany , Moreira Daniel C. , Gottardo Nicholas G. , Bouffet Eric , Ganesan Dharmendra
Published: February 2021

Background:

A higher incidence of pediatric intracranial germ cell tumors (iGCTs) in Asian countries compared with Western countries has been reported. In Malaysia, the literature regarding pediatric iGCTs have been nonexistent. The aim of this study was to review the management, survival, and long-term outcomes of pediatric iGCTs at a single tertiary center in Malaysia.

Patients and Methods:

We retrospectively reviewed data from patients below 18 years of age with iGCTs treated at the University Malaya Medical Center (UMMC) from 1998 to 2017.

Results:

Thirty-four patients were identified, with a median follow-up of 3.54 years. Sixteen (47%) patients had pure germinoma tumors (PGs), and the remaining patients had nongerminomatous germ cell tumors (NGGCTs). The median age was 12 years, with a male:female ratio of 4.7:1. Abnormal vision, headache with vomiting, and diabetes insipidus were the commonest presenting symptoms. Twenty-eight patients received initial surgical interventions, 24 were treated with chemotherapy, and 28 received radiotherapy. Eight patients experienced relapses. The 5- and 10-year event-free survival rates were similar at 61.1%±12.6% and 42.9%±12.1% for PG and NGGCT, respectively. The 5- and 10-year overall survival rates were the same at 75.5%±10.8% and 53.3%±12.3% for PG and NGGCT, respectively. Four patients died of treatment-related toxicity. Most of the survivors experienced good quality of life with satisfactory neurologic status.

Conclusions:

The survival rate of childhood iGCTs in UMMC was inferior to that reported in developed countries. Late diagnosis, poor adherence to treatment, and treatment-related complications were the contributing factors. Although these results highlight a single institution experience, they most likely reflect similar treatment patterns, outcomes, and challenges in other centers in Malaysia.
The Status of Pediatric Patients With Hematologic Malignancy During COVID-19 Pandemic in Wuhan City, China
Authors: Wang Zhujun , Shen Yaqing , Jin Runming , Yu Hui , Zhou Fen , Xu Jiawei , Qiu Yining , Wang Lin , Wu Xiaoyan
Published: February 2021

Data regarding the epidemiologic characteristics and clinical features of pediatric hematologic patients are limited in this corona virus disease 2019 (COVID-19) crisis. We investigated the status of 113 pediatric hematologic patients in Wuhan union hospital during the COVID-19 pandemic from January 23 to March 10, 2020. All the patients had routine blood and biochemical examination, as well as chest computed tomography scans, and the nucleic acid, immunoglobulin G-immunoglobulin M combined antibodies tests for SARS-CoV-2. After admission, all patients were single-room isolated for 5 to 7 days. The results showed that only 1 (0.88%) child with leukemia was confirmed to have SARS-CoV-2 infection and 15 (13.2%) children were considered as suspected cases. Comparing to the nonsuspected patients, the suspected cases had lower white blood cell count, hemoglobin level, neutrophil count, serum calcium ion level and serum albumin concentration, as well as higher levels of C-reactive protein. All the suspected cases were ruled out of SARS-CoV-2 infection by twice negative tests for the virus. Therefore, the incidence of SARS-CoV-2 infection in hematologic malignancy children was low during the COVID-19 pandemic in China. COVID-19 got early detected and the virus spread out in the ward was effectively blocked by increasing test frequency and using single-room isolation for 5 to 7 days after admission.
Comfort Needs of Cancer Family Caregivers in Outpatient Palliative Care
Authors: Washington Karla T. , Benson Jacquelyn J. , Chakurian Daphne E. , Popejoy Lori L. , Demiris George , Rolbiecki Abigail J. , Oliver Debra Parker
Published: February 2021

Rapid expansion of outpatient palliative care has been fueled by the growing number of people living with cancer and other chronic illnesses whose symptoms are largely managed in the community rather than inpatient settings. Nurses and other palliative care professionals support seriously ill patients and their families, yet little research has specifically examined the needs of cancer family caregivers receiving services from outpatient palliative care teams. To address this gap in the knowledge base, researchers conducted a reflective thematic analysis of qualitative interviews conducted with 39 family caregivers, using Comfort Theory as a theoretical guide. Seven themes describing caregivers' comfort needs were identified, including the need to understand, need for self-efficacy, need to derive meaning, need for informal support, need for formal support, need for resources, and need for self-care. Findings have clear implications for palliative nursing, as they directly address cancer family caregivers' needs in 5 of the 8 domains of care delineated by the National Consensus Project for Quality Palliative Care's Clinical Practice Guidelines. Comprehensive, holistic nursing assessment is suggested to identify family caregivers' needs and plan for delivery of evidence-based interventions shown to decrease burden and improve quality of life.
Music Therapy and Nursing Cotreatment in Integrative Hospice and Palliative Care
Authors: Potvin Noah , Hicks Molly , Kronk Rebecca
Published: February 2021

Integrative hospice and palliative care is a philosophy of treatment framing patients as whole persons composed of interrelated systems. The interdisciplinary treatment team is subsequently challenged to consider ethical and effective provision of holistic services that concomitantly address these systems at the end of life through cotreatment. Nurses and music therapists, as direct care professionals with consistent face-to-face contact with patients and caregivers, are well positioned to collaborate in providing holistic care. This article introduces processes of referral, assessment, and treatment that nurses and music therapists may engage in to address family support, spirituality, bereavement, and telehealth. Clinical vignettes are provided to illustrate how cotreatment may evolve and its potential benefits given diverse circumstances. As part of this framing, music therapy is positioned as a core—rather than alternative or complementary—service in hospice that satisfies the required counseling services detailed in Medicare's Conditions of Participation for hospice providers. The systematic and intentional partnering of nurses and music therapists can provide patients and caregivers access to quality comprehensive care that can cultivate healthy transitions through the dying process.
Creating a Model for Mindfulness in Nursing Professional Development Using Concept Analysis
Authors: McNulty Denise Stage
Published: February 2021

Mindfulness has many benefits, but its mechanisms of action are not universally understood. This analysis explores mindfulness and informs a model for its practical applications in health care and professional development. A mindful nursing professional development practitioner can use metacognitive thought processes to enhance interpersonal connections and create better learning environments to facilitate practice change. The literature supports the testing of this model in nursing professional development.
Outside the Box
Authors: Rogers Amber , Burke Cindy
Published: February 2021

Nurse educators play an important role in implementing changes within hospital orientation, supporting a learner-focused orientation. Utilizing different learning styles and delivery methods, an orientation can promote an environment where registered nurses are active participants and guide the learning. This article discusses the process of incorporating multiple learning styles and modalities into an experienced registered nurse orientation program, creating a learner-centered environment promoting engagement, increased satisfaction, and retention of experienced staff.
HIV Prevention and Treatment Cascades Among Female Sex Workers in Benin, West Africa
Authors: Morin Laurianne , Béhanzin Luc , Guédou Fernand A. , Kêkê René Kpèmahouton , Bushman Lane , Anderson Peter L. , Gangbo Flore , Diabaté Souleymane , Nagot Nicolas , Alary Michel
Published: February 2021

Background

Benin has a long-standing history of HIV prevention programs aimed at female sex workers (FSWs). We used data from a national survey among FSWs (2017) to assess the prevention and care cascades in this population.

Methods

Female sex workers were recruited through cluster sampling of sex work sites. A questionnaire was administered, and HIV tested. HIV-positive participants were asked to provide dried blood spots and were tested for antiretroviral and viral load. We assessed 2 prevention cascades (HIV testing and safer sex) and the treatment cascade, using a combination of self-reported and biological variables.

Results

Mean age of the 1086 FSWs was 30 years. Half of them were Beninese, and two-thirds had a primary school education level or less. Almost all FSWs had ever heard of HIV/AIDS. More than half (79.1%) had ever been tested, and 84.1% of the latter had been tested in the last year. In the previous 6 months, 90.1% were exposed to prevention messages. Women exposed to any HIV prevention message reported a higher level of consistent condom use in the last month (69.0%) than those who were not (48.5%, P < 0.0001). HIV prevalence was 7.7%. Among HIV-positive women, 60.6% knew their status; among those, 90.5% were on antiretroviral and 81.8% of them had a suppressed viral load.

Conclusions

Despite long-standing HIV prevention programs for FSWs, the prevention indicators were often low. Linkage to care was good, viral suppression was suboptimal, but knowledge of HIV-positive status was low. Exposing women to prevention messages is necessary, as to increase HIV testing.
Evaluation of Polymerase Chain Reaction over Routine Microbial Diagnosis for the Diagnosis of Fungal Keratitis
Authors: Behera Himanshu Sekhara , Srigyan Deepankar
Published: February 2021

SIGNIFICANCE

The significance of the study is that, although conventional culture remains the criterion standard for identifying the causative fungal pathogens, polymerase chain reaction (PCR) may serve as a powerful and high-throughput tool for the early and definitive diagnosis of high-risk patients with mycotic keratitis owing to high sensitivity and specificity.

PURPOSE

This study was focused on comparing the results of PCR with traditional microbial studies for the detection and identification of fungal pathogens in patients with clinically suspected fungal keratitis.

METHODS

Corneal scrapings were collected from 59 patients with clinically suspected fungal keratitis for routine culture, staining, and seminested PCR assay for fungal pathogen identification. The results of PCR were compared with a conventional microbial workup (smear and culture). The samples that were unidentified by culture but were amplified by PCR were further identified by nucleotide sequencing.

RESULTS

Of the 59 patients with suspected fungal keratitis, 38 (64.40%) were found to be positive by PCR assay, 24 (40.67%) by culture, 18 (20.3%) by potassium hydroxide wet mount, and 8 (13.5%) by Gram stains for fungal pathogens. All the 24 isolates found positive with culture were also positive with PCR, so they had not been sequenced for molecular identification. The remaining 14 isolates that were positive with PCR but negative with culture were further identified as Cladosporium cladosporioides, Simplicillium species, Fusarium solani, Alternaria tenuissima, Chaetomium globosum, Penicillium citrinum, and Rhizopus microsporus by sequencing up to the species level.

CONCLUSIONS

The PCR was able to detect the presence of fungal pathogens in a high proportion of culture-negative cases. This study suggests that PCR may serve as a rapid, important complement to traditional culture with high-throughput means of fungal pathogen identification in patients with clinically suspected fungal keratitis.
Case Report: Crying Blood
Authors: Idowu Oluwatobi O. , Kaidonis Georgia , Husain Sameera , Winn Bryan J.
Published: February 2021

SIGNIFICANCE

Hemolacria (bloody tears) is a rare clinical presentation with varied underlying etiologies. Thorough clinical evaluation is essential to diagnosis and management.

PURPOSE

This study aimed to report unilateral hemolacria in a known contact lens wearer with an occult, palpebral, conjunctival pyogenic granuloma and review the literature.

CASE REPORT

A 21-year-old female contact lens wearer presented to the clinic after three episodes of sudden painless bloody tears from the right eye. She was referred to the oculoplastic clinic for evaluation. On everting her right upper lid, a fleshy, nontender, ovoid, pedunculated mass was found attached to the palpebral conjunctiva of the right, nasal, upper tarsus. Surgical excision was performed in the office, and pathological examination of the lesion was consistent with pyogenic granuloma.

CONCLUSIONS

Unilateral hemolacria should raise clinical suspicion for a hidden conjunctival lesion such as pyogenic granuloma, although other more sinister causes of hemolacria must also be considered. Thorough evaluation including eyelid eversion is critical in identifying and managing occult conjunctival lesions.
Optimization of Mouse-on-Mouse Immunohistochemistry by Utilizing Fluorescent-dye Conjugated Secondary Anti-Mouse Antibody
Authors: Moein Shiva , Adibi Rezvan , Amouheidari Alireza , Gheisari Yousof
Published: February 2021

The application of mouse monoclonal antibody for immunostaining the mouse tissues results in a high rate of background noise because of the interaction of the secondary antibody with endogenous immunoglobulins and other immune components. The most advised blocking strategy for the mouse-on-mouse immunostaining is the use of anti-mouse Fab fragments. Nevertheless, the commercial kits containing Fab fragment are costly and unavailable in many research laboratories. In this study, we provide evidence showing the potential of the fluorescent-dye conjugated secondary anti-mouse antibody for reducing the background noise in the mouse-on-mouse immunohistochemistry. Furthermore, our findings demonstrate the inadequacy of goat serum/protein-blocking solution alone as an immunohistochemistry blocking system for reducing the background noise.
The Role of CK7, S100A1, and CD82 (KAI1) Expression in the Differential Diagnosis of Chromophobe Renal Cell Carcinoma and Renal Oncocytoma
Authors: Sari Zeliha B. , Açikalin Mustafa F. , Arik Deniz , Özen Ata , Can Cavit , Çolak Ertuğrul
Published: February 2021

Renal oncocytoma is a benign renal tumor originated from intercalated cells of collecting ducts like chromophobe renal cell carcinoma (RCC). The differential diagnosis of these 2 tumors is important because while they are histologically and cytologically similar, they show different biological behavior. For the differential diagnosis, several immunohistochemical markers have been investigated. But, differential diagnostic challenges remain and the identification of additional markers is needed. Cytokeratin 7 (CK7) is one of ductal-type keratins, which is expressed in tumors of breast, pancreas, lung, thyroid, ovary, endometrium, urinary bladder, and the kidney. S100A1 is the first defined member of the calcium-binding S100 protein family and it organizes several cellular functions including cell cycle progression and cell differentiation.CD82 is a tetraspanin membrane protein, which functions as a metastasis supressor. In this study, we immunohistochemically investigated the expressions of CK7, S100A1, and CD82 in 30 chromophobe RCC (23 classic and 7 eosinophilic variant) and 19 oncocytomas. When these markers were evaluated separately and together, their expressions in chromophobe RCC and renal oncocytoma show statistically significant difference (P<0.001). Similar statistically significant results were also seen between eosinophilic chromophobe RCC and oncocytoma (P<0.001). For both classic and eosinophilic-variant chromophobe RCCs, CK7+/S100A1−/CD82+ profile being the most common. In oncocytomas, the most frequently observed profile was CK7−/S100A1+/CD82−. Our results showed that the application of a panel consisting of CK7, S100A1, and CD82 may provide accurate categorization of the tumors in difficult cases.
GPBAR1 Promotes Proliferation of Serous Ovarian Cancer by Inducing Smad4 Ubiquitination
Authors: Li Haixia , Zhao Juanhong , Shi Xiaoyan
Published: February 2021

Background:

Ovarian cancer (OC) is the most lethal malignancy of all female cancers and lacks an effective prognostic biomarker. Serous ovarian cancer (SOC) is the most common OC histologic type. The expression and function of bile acid receptor, G-protein-coupled bile acid receptor-1 (GPBAR1), in tumor progression remains controversial, and its clinical significance in SOC is unclear.

Materials and Methods:

In our study, we detected the expression of GPBAR1 in SOCs and normal ovarian tissues with quantitative real-time polymerase chain reaction and immunohistochemistry to detect its expression pattern. Moreover, the prognostic significance of GPBAR1 was investigated with univariate and multivariate analyses. The function of GPBAR1 in regulating SOC proliferation was studied and the underlying mechanism was investigated with experiments in vitro.

Results:

GPBAR1 was overexpressed in SOCs compared with the normal ovarian tissues. In the 166 SOCs, subsets with low and high GPBAR1 accounted for 57.23% and 42.77%, respectively. Moreover, our results suggested that GPBAR1 expression was significantly associated with poor prognosis and can be considered as an independent prognostic biomarker. With experiments in vitro, we suggested that GPBAR1 promoted SOC proliferation by increasing Smad4 ubiquitination, which required the involvement of GPBAR1-induced ERK phosphorylation.

Conclusions:

GPBAR1 was overexpressed in SOC and predicted the poor prognosis of SOC. We showed that GPBAR1 promoted SOC proliferation by activating ERK and ubiquitining Smad4. Our results suggested that GPBAR1 was a supplement to better classify SOC on the basis of the molecular profile and that GPBAR1 may be a potential drug target of SOC.