bluuebunny/crossref_metadata_2025 huggingface dataset:
The power of lipid registries for cardiovascular disease prevention
Authors: Nishikido Toshiyuki , Ray Kausik K.
Published: September 2021

Purpose of review

Lipid registry-based research is a valuable tool for assessing current lipid management in patients at risk of cardiovascular disease (CVD). Results of several registries are useful for improving clinical practice highlight gaps between guidelines and their implementation and potential impact on population health. We summarize recent clinical studies based on lipid registries.

Recent findings

Current guidelines for lipid management recommend high-intensity statins and concomitant therapies such as ezetimibe and proprotein convertase subtilisin-kexin type 9 inhibitors for high-risk patients. However, recent observational studies show that the majority of patients received inadequate lipid-lowering therapy (LLT), and the low-density lipoprotein-cholesterol (LDL-C) goal attainment rates are still unsatisfactory.

There is a clear gap between lipid guidelines and lipid management in clinical practice. Clinical studies based on registry databases represent real-world conditions, as opposed to clinical trials. Contemporary registry data reveal that only half of the patients received high-intensity statins, and less than half achieve the LDL-C <70 mg/dL in secondary prevention. In addition, the major reasons for insufficient therapy have been shown to be not only side effects of LLT, but poor adherence by patients to medication regimens and low use of combination therapies by physicians. The real-world evidence from lipid registries clarifies gaps, areas for focus for implementation, to improve CVD prevention.
Coronavirus disease 2019 in patients with inborn errors of immunity: lessons learned
Authors: Bucciol Giorgia , Tangye Stuart G. , Meyts Isabelle
Published: September 2021

Purpose of review

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused extreme concern for patients with inborn errors of immunity (IEIs). In the first 6  months of the pandemic, the case fatality rate among patients with IEIs resembled that of the general population (9%). This review aims at summarizing what we have learned about the course and outcome of coronavirus disease 2019 (COVID-19) in patients with different IEIs and what this can potentially teach us about the immune mechanisms that could confer protection or predisposition to severe disease.

Recent findings

A total of 649 patients with IEI and COVID-19 have been reported in the last year and a half, spanning all groups of the International Union of Immunological Societies classification of IEIs. For most patients, the underlying IEI does not represent an independent risk factor for severe COVID-19. In fact, some IEI may even be protective against the severe disease due to impaired inflammation resulting in less immune-mediated collateral tissue damage.

We review the characteristics of SARS-CoV-2 infection in a large number of patients with IEI. Overall, we found that combined immunodeficiencies, immune dysregulation disorders, and innate immune defects impairing type I interferon responses are associated with severe disease course.
The effect of coronavirus disease 2019 on newborns
Authors: Kyle Margaret H. , Dumitriu Dani
Published: September 2021

Purpose of review

To evaluate the available literature regarding effects of coronavirus disease 2019 (COVID-19) on newborns, ranging from effects related to in utero and perinatal exposure to maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, to pandemic-related stress and socioeconomic changes.

Recent findings

Several large studies and national registries have shown that the risk of vertical transmission from SARS-CoV-2-infected mothers to newborns is rare and does not appear to be related to postnatal care policies such as mother–newborn separation and breastfeeding. Newborns exposed to SARS-CoV-2 in utero are at higher risk for preterm delivery for reasons still under investigation. When newborns do acquire SARS-CoV-2 infection, their disease course is usually mild. Long-term follow-up data are lacking, but preliminary reports indicate that, similarly to prior natural disasters, being born during the pandemic may be associated with developmental risk.

Although risk of vertical or perinatal transmission is low across a range of postnatal care practices, early indicators suggest developmental risk to the generation born during the pandemic. Long-term follow-up data are critically needed to determine the developmental impact of in utero and early life exposure to SARS-CoV-2 and the COVID-19 pandemic.
Microbiota in heart and lung transplantation: implications for innate-adaptive immune interface
Authors: Bai Yun Zhu , Roberts Sophia H. , Kreisel Daniel , Nava Ruben G.
Published: September 2021

Purpose of review

Transplantation continues to be the only treatment option for end-stage organ failure when other interventions have failed. Although short-term outcomes have improved due to advances in perioperative care, long-term outcomes continue to be adversely affected by chronic rejection. Little is known about the role microbiota play in modulating alloimmune responses and potentially contributing to graft failure. Initial data have identified a correlation between specific changes of the recipient and/or donor microbiota and transplant outcomes. In this review, we will focus on recent findings concerning the complex interplay between microbiota and the innate immune system after heart and lung transplantation.

Recent findings

Gut microbiome derangements in heart failure promote an inflammatory state and have lasting effects on the innate immune system, with an observed association between increased levels of microbiota-dependent metabolites and acute rejection after cardiac transplantation. The lung allograft microbiome interacts with components of the innate immune system, such as toll-like receptor signalling pathways, NKG2C+ natural killer cells and the NLRP3 inflammasome, to alter posttransplant outcomes, which may result in the development of chronic rejection.

The innate immune system is influenced by alterations in the microbiome before and after heart and lung transplantation, thereby offering potential therapeutic targets for prolonging allograft survival.
Diagnosis and Management of Oral Extraintestinal Manifestations of Pediatric Inflammatory Bowel Disease
Authors: Shazib Muhammad Ali , Byrd Kevin M. , Gulati Ajay S.
Published: September 2021

Inflammatory bowel diseases (IBD) represent a group of chronic inflammatory disorders of the gastrointestinal tract that lead to impaired quality of life and substantial health care costs. Up to 50% of pediatric IBD cases present with manifestations in the oral cavity. These may develop in nearly every oral tissue, including the soft tissues, tongue, lips, teeth, and lymph nodes. The goal of this review is to offer a systematic approach to diagnose and manage commonly encountered oral manifestations of pediatric IBD. This knowledge is critical for enhancing the comprehensive care and quality of life of children with these debilitating diseases.
The Initial Timing and Burden of Viral Gastrointestinal Infections in Australian Infants
Authors: Mihala Gabor , Grimwood Keith , Lambert Stephen Bernard , Ware Robert Stuart
Published: September 2021

The timing and nature of initial infections by potentially vaccine‐preventable gastrointestinal viruses (group‐F adenoviruses, classic human astrovirus, norovirus I/II, and sapovirus I/II/IV/V) was investigated in a community‐based birth cohort. Weekly stool samples were collected from 158 children aged <2 years in an Australian subtropical city. Median age at initial infection was lowest for norovirus II (13.8 months) followed by sapovirus (14.3 months) and classic human astrovirus (17.6 months), and was >24 months for the remaining viruses. Norovirus II and sapovirus were most often associated with acute gastroenteritis symptoms (57% and 44%, respectively). Overall, healthcare was sought for 45% of symptomatic initial infections, which varied between 17% for norovirus I to 55% for norovirus II. Age at initial infection was lower when participants were exposed to other children. Norovirus II and sapovirus were the most important pathogens in this cohort, providing further evidence for them being priority targets for vaccine development.
An Immersive Virtual Reality Curriculum for Pediatric Hematology Clinicians on Shared Decision-making for Hydroxyurea in Sickle Cell Anemia
Authors: Real Francis J. , Hood Anna M. , Davis David , Cruse Bradley , Klein Melissa , Johnson Yolanda , McTate Emily , Brinkman William B. , Hackworth Rogelle , Hackworth Kenyon , Quinn Charles T. , Crosby Lori E.
Published: September 2021

Although hydroxyurea (HU) is an effective treatment for sickle cell anemia, uptake remains low. Shared decision-making (SDM) is a recommended strategy for HU initiation to elicit family preferences; however, clinicians lack SDM training. We implemented an immersive virtual reality (VR) curriculum at 8 pediatric institutions to train clinicians on SDM that included counseling virtual patients. Clinicians’ self-reported confidence significantly improved following the VR simulations on all communication skills assessed, including asking open-ended questions, eliciting specific concerns, and confirming understanding (Ps≤0.01 for all). VR may be an effective method for educating clinicians to engage in SDM for HU.
Can Machine Learning Models Predict Asparaginase-associated Pancreatitis in Childhood Acute Lymphoblastic Leukemia
Authors: Nielsen Rikke L. , Wolthers Benjamin O. , Helenius Marianne , Albertsen Birgitte K. , Clemmensen Line , Nielsen Kasper , Kanerva Jukka , Niinimäki Riitta , Frandsen Thomas L. , Attarbaschi Andishe , Barzilai Shlomit , Colombini Antonella , Escherich Gabriele , Aytan-Aktug Derya , Liu Hsi-Che , Möricke Anja , Samarasinghe Sujith , van der Sluis Inge M. , Stanulla Martin , Tulstrup Morten , Yadav Rachita , Zapotocka Ester , Schmiegelow Kjeld , Gupta Ramneek
Published: September 2021

Asparaginase-associated pancreatitis (AAP) frequently affects children treated for acute lymphoblastic leukemia (ALL) causing severe acute and persisting complications. Known risk factors such as asparaginase dosing, older age and single nucleotide polymorphisms (SNPs) have insufficient odds ratios to allow personalized asparaginase therapy. In this study, we explored machine learning strategies for prediction of individual AAP risk. We integrated information on age, sex, and SNPs based on Illumina Omni2.5exome-8 arrays of patients with childhood ALL (N=1564, 244 with AAP 1.0 to 17.9 yo) from 10 international ALL consortia into machine learning models including regression, random forest, AdaBoost and artificial neural networks. A model with only age and sex had area under the receiver operating characteristic curve (ROC-AUC) of 0.62. Inclusion of 6 pancreatitis candidate gene SNPs or 4 validated pancreatitis SNPs boosted ROC-AUC somewhat (0.67) while 30 SNPs, identified through our AAP genome-wide association study cohort, boosted performance (0.80). Most predictive features included rs10273639 (PRSS1-PRSS2), rs10436957 (CTRC), rs13228878 (PRSS1/PRSS2), rs1505495 (GALNTL6), rs4655107 (EPHB2) and age (1 to 7 y). Second AAP following asparaginase re-exposure was predicted with ROC-AUC: 0.65. The machine learning models assist individual-level risk assessment of AAP for future prevention trials, and may legitimize asparaginase re-exposure when AAP risk is predicted to be low.
Is Low-level Laser Therapy a Candidate to Be a Good Alternative in the Treatment of Mucositis in Childhood Leukemia?
Authors: Karaman Kamuran , Sarica Ayca , Tunc Serap Keskin , Karaman Serap
Published: September 2021

Background and Aim:

Oral mucositis (OM) is a common side effect of systemic chemotherapy (CT) in cancer patients. The aim was to evaluate the effect of low-level laser therapy (LLLT) for the treatment of CT-induced OM children.

Patients and Methods:

The study was carried out in 40 pediatric patients 3 to 18 years of age, who were hospitalized for the diagnosis of leukemia and underwent CT between June 1, 2019, and December 31, 2019. They were randomly divided into 2 groups with 20 cases in each group. The LLLT group was treated with GaAlAs diode laser (l): 830 nm (infrared), power: 150 mW, dose: 4.5 J/cm2 and the control group underwent bicarbonate treatment. Patients received intervention for 3 days. The grade of OM was clinically assessed by the World Health Organization (WHO) Common Toxicity Criteria Scale. Visual Analog Scale was used on the same days with OM grade to evaluate the pain status.

Results:

While there was no significant difference between the groups in terms of OM grade at the beginning of the treatment and on the first, second, fourth, and 11th days of the treatment, the average OM grade of the LLLT group was found to be statistically significantly lower on the third, fifth, sixth, and seventh days of the treatment. The Visual Analog Scale score of the LLLT group was statistically significantly lower compared with the control group at all examinations starting from the first day of treatment (P<0.05).

Conclusion:

In the treatment of oral OM that occurs in children after CT, both standard care and LLLT treatment improve the grade and pain of OM.
Transition Preparation and Satisfaction of Care Among Adolescents and Young Adults With Sickle Cell Disease at the Ghana Institute of Clinical Genetics
Authors: Kwarteng-Siaw Miriam , Benneh-Akwasi Kuma Amma , Green Nancy S.
Published: September 2021

Expanding services in Ghana for people with sickle cell disease is expected to increase childhood survival and need for transition to adult care. Little is known about patient transition experiences in sub-Saharan Africa. We sought to understand those experiences of adolescents and young adults at an adult sickle cell clinic in Accra, Ghana. Individuals 13 to 22 years of age receiving sickle cell care at the Ghana Institute of Clinical Genetics were interviewed to recall their advance preparation and early experiences in adult sickle cell clinic. Mean age of the 100 participants interviewed was 17.9±2.9 years, 65% female. Most had hemoglobin SS (77%) or hemoglobin SC (20%). Twenty-nine participants recalled pretransition preparation; 93% of them (27) had received care at Korle Bu Pediatric Sickle Cell Clinic. Among the remaining 71 who did not recall advance preparation, 54% (34) had received pediatric care at that clinic (P<0.001). More in the group recalling preparation had positive feelings about needing to transition care compared with those not recollecting preparation (55% vs. 32%, P=0.04). Our results suggest that pretransition preparation may ease the peritransition experience. Conduct and evaluation of a program for transitioning into adult sickle cell care in Ghana may facilitate the transfer process.
Rate of Rise of Platelet Count After IVIG for Pediatric Immune Thrombocytopenia
Authors: Mikhail Daniella , Zhu Junjia , Pradhan Sandeep , Freiberg Andrew S.
Published: September 2021

Immune thrombocytopenia (ITP) is an autoimmune disease causing platelet destruction, and is a common cause of symptomatic thrombocytopenia in children. Intravenous immune globulin (IVIG) is a treatment for ITP that increases the platelet counts of most patients within 24 to 48 hours. This study aimed to calculate the rate of rise in pediatric ITP after a dose of IVIG and to analyze if patient characteristics affected the rate. For 116 children treated for ITP with IVIG at Hershey Medical Center, the rate of rise of the platelet count for all patients was calculated. The rate of rise ranged from −0.1 to +4.2 K/µL/hour (average 1.3, median 1.2). 78% of patients had a rate of rise of over 0.5 K/µL/hour. There was a statistically significant correlation between the rate rise of the platelet count and the initial platelet count (P=0.0197), but rate was not affected by age or sex. This study was able to demonstrate that IVIG is effective in most patients and that demographic features do not affect the rate of rise. By providing a nomogram showing when to expect a meaningful rise in the platelet count after IVIG, we give guidance for timing of the postinfusion platelet count to avoid administering a second dose. Future studies are needed to test this nomogram prospectively.
Transition for Adolescents and Young Adults With Sickle Cell Disease in a US Midwest Urban Center: A Multilevel Perspective on Barriers, Facilitators, and Future Directions
Authors: Calhoun Cecelia , Luo Lingzi , Baumann Ana A. , Bauer Anna , Shen Evelyn , McKay Virginia , Hooley Cole , James Aimee , King Allison A.
Published: September 2021

Background:

Sickle cell disease (SCD), an inherited red blood cell disorder, primarily affects African Americans in the United States. Adolescents and young adults with SCD (AYA-SCD) are at risk of high morbidity and mortality when transitioning from pediatric to adult care. The goal of this qualitative study was to understand factors associated with optimal implementation of the AYA-SCD transition.

Methods:

Participants were recruited from a large hospital system and the community. Interview guides included topics on access to primary and specialized care, beliefs and practices related to pain control, transition from pediatric to adult care, and patient experiences in the emergency department. Data were coded and analyzed using an inductive thematic coding approach in combination with a deductive coding approach using domains from the Consolidated Framework for Implementation Research (CFIR).

Results:

Fifty-nine participants, including 21 AYA-SCD from both the pediatric and adult clinics, 17 caregivers, 9 pediatric SCD providers, 6 adult SCD providers, and 6 emergency department providers, completed 11 focus groups and 5 semistructured interviews. Results identified multiple factors within the domains of CFIR including the outer setting, inner setting, individual characteristics, and intervention characteristics. Results were incorporated into a transition framework to inform local practice improvement.

Conclusion:

Our study highlights the importance of multilevel barriers and facilitators for AYA-SCD transition from pediatric to adult care. Future studies could use implementation science frameworks to understand local context and identify strategies and intervention characteristics to improve transition programming. These efforts will ultimately reduce health disparities and ensure health equity.
Acute Left Ventricular Dysfunction Following Gemtuzumab Ozogamicin in Two Pediatric AML Patients
Authors: McNerney Kevin O. , Oranges Katelyn , Seif Alix E. , Oshrine Benjamin , Ky Bonnie , Lin Kimberly Y. , Getz Kelly D. , Aplenc Richard
Published: September 2021

Gemtuzumab ozogamicin (GO) is an anti-CD33 antibody-tumor antibiotic conjugate with proven efficacy in pediatric and adult patients with CD33+ acute myeloid leukemia. Adverse effects commonly associated with GO include hyperbilirubinemia, elevated transaminases, and sinusoidal obstruction syndrome. Cardiotoxicity has not been a commonly described adverse event. We describe 2 pediatric patients with relapsed/refractory acute myeloid leukemia who received fractionated GO monotherapy and subsequently developed severe acute left ventricular dysfunction. Both patients achieved remission, recovered cardiac function with medical therapy, and tolerated subsequent stem cell transplantation.
Is There An Association Between Vitamin B12 Level and Vitamin D Status in Children?
Authors: Karabayir Nalan , Teber Burcu G. , Dursun Hatice K. , Pehlivan Lale S.
Published: September 2021

Vitamin B12 (vit B12) or cobalamin is a water-soluble vitamin that acts as a coenzyme and is effective in the formation of a healthy nervous system and erythrocytes. In its deficiency, except fatigue and weakness, may cause serious signs and symptoms such as macrocytic anemia, cognitive-developmental delay, irreversible neurological damage. In this study, hemoglobin, leukocyte, thrombocyte, iron, iron-binding, ferritin, and vit B12 levels were evaluated retrospectively during the routine controls of 689 children 5 to 18 years old without any complaints. In addition, the relationship between serum 25-Hydroxyvitamin D (vit D) levels and vit B12 levels, which were evaluated in 487 of the cases, was investigated. Vit B12 deficiency was diagnosed in a total of 160 (23.2%) cases, 99 (24.4%) girls and 61 (21.4%) boys. Vit B12 level was significantly lower in children over 12 years old. Vitamin D deficiency was found to be 49.3% in 487 cases and was significantly higher in the group under 12 years and girls. The frequency of anemia was 7.2% in this group. There was a significant relationship between vit D deficiency and vit B12 deficiency. In conclusion, vit B12 deficiency is common in school-age children, especially in the adolescent age group. It should be known that vit D deficiency may also be present in vit B12 deficiency cases. More comprehensive studies are needed to reveal the relationship between B12 and vit D deficiency.
A Novel NUP98/RARG Gene Fusion in Pediatric Acute Myeloid Leukemia Resembling Acute Promyelocytic Leukemia
Authors: Zhang Jingying , Shen Heping , Song Hua , Shen Diying , Liao Chan , Fang Meixin , Wang Yan , Tang Yongmin , Zhu Honghu
Published: September 2021

Here, we introduced the first case of acute myeloid leukemia (AML) with RARG-NUP98 in a pediatric patient. The young male presented with structural and functional abnormalities similar to hypergranular acute promyelocytic leukemia, but was resistant to all transretinoic acids and arsenic trioxide. Till date, only 12 adult AML cases involving RARG rearrangement have been reported. At present, there is no standardized or optimal treatment option for this AML subtype. Disease management may typically require a joint treatment strategy involving chemotherapy, immunotherapy, and support therapy. In this study, we report the clinical manifestations and experimental results of a 10-year-old male and review other cases of RARG gene rearrangement reported in the literature.
Capillaritis as a Skin Manifestation of Hepatosplenic Gamma-Delta T-Cell Lymphoma
Authors: Jakharia-Shah Nihull , Ho Bernard , Lolatgis Helena , Alarcon Lida , Abdul-Wahab Alya
Published: September 2021

We present the case of a 10-year-old boy who was admitted with 3 months of episodic febrile neutropenia and a new petechial rash. Routine bloods identified neutropenia, thrombocytopenia, and a raised alanine aminotransferase. The dermatology team was consulted in light of the symmetrical petechial eruption of the upper torso. A punch biopsy of the lesion was consistent with early capillaritis. The results showed superficial dermal red blood cell extravasation with mild perivascular lymphohistiocytic inflammatory infiltrate. There was no evidence of an atypical lymphoid infiltrate in the skin biopsy. An initial bone marrow aspirate showed an abnormal mature T-cell population consisting of CD4 and CD8 T cells with gamma-delta positivity. Karyotyping was also done, which demonstrated isochromosome 7q. These findings were consistent with a diagnosis of hepatosplenic T-cell lymphoma (HSTL). The patient underwent fourth-line chemotherapy due to refractory relapsing disease but sadly passed away within 12 months of diagnosis. HSTL is a rare and aggressive subset of peripheral T-cell lymphoma. Prognosis is poor with a median survival of <1 year from diagnosis. However, reports suggest improved outcomes if intensive, early, high-dose chemotherapy is used alongside hematopoietic stem cell transplantation. Therefore, there is an impetus to attain early diagnosis for aggressive early treatment and improved patient outcomes. Capillaritis, presenting as asymptomatic nonpalpable purpura, can be a rare presenting feature of HSTL. Dermatologists could play a pivotal role in the early recognition of this rare but aggressive hematological malignancy and promote prompt treatment resulting in better patient outcomes.
Breakthrough Trichosporon asahii in a Patient With New Diagnosis B-ALL on Echinocandin Prophylaxis: A Case Report
Authors: Mahoney David , Aftandilian Catherine
Published: September 2021

Invasive fungal disease is a difficult to diagnose complication of therapy in patients with hematologic malignancy. Antifungal prophylaxis is recommended in high-risk populations, but its use in other populations is less clear. This brief report describes a patient with Trisomy 21 on caspofungin prophylaxis who died of disseminated Trichosporon asahii during induction therapy for new diagnosis low-risk B-cell acute lymphoblastic leukemia, accompanied by a review of similar cases in the literature. Her case highlights the utility of relatively novel diagnostic modalities and reinforces the need for caution in placing patients on antifungal prophylaxis.
STEPS to Enhance Physical Activity After Hematopoietic Cell Transplantation for Multiple Myeloma
Authors: Hacker Eileen Danaher , Richards Rae Lee , Abu Zaid Mohammad , Chung Shu-Yu , Perkins Susan , Farag Sherif Shafik
Published: September 2021

Background

Finding effective ways to increase physical activity immediately following high-dose chemotherapy and autologous hematopoietic cell transplantation (HCT) for treatment of multiple myeloma (MM) is challenging.

Objective

This pilot randomized clinical trial tested the acceptability, feasibility, and preliminary effects of a free-living physical activity intervention (STEPS) compared with usual care (UC) on physical activity, fatigue, muscle strength, functional ability, sleep, and quality of life following treatment for MM with HCT.

Methods

Using a 2-group pretest/posttest design (N = 32), this study compared the 6-week STEPS intervention to UC. Data were collected using self-report questionnaires, functional performance tests, and wrist actigraphy before HCT and 7 weeks following hospital discharge.

Results

The STEPS group achieved their physical activity goals on 53% of intervention days. The STEPS group experienced greater appetite loss, more diarrhea, and slept more than UC regardless of time point. Both groups reported improvements in mental fatigue, emotional functioning, pain, sleep disturbance, anger, anxiety, and depression but climbed stairs slower and had weaker hand grips after intervention. Both groups subjectively reported fewer sleep disturbances but objectively experienced more wakefulness after sleep onset and an increased number of awakenings postintervention.

Conclusions

The STEPS intervention is acceptable and feasible for people with MM treated with HCT. Both groups reported some improved symptoms but experienced some declines in physical performance postintervention.

Implications for Practice

Nurses strive to optimize health and promote well-being. Helping people increase their physical activity after treatment for MM with HCT may improve symptoms, but additional studies are needed.
Anal Human Papillomavirus Prevalence Among Vaccinated and Unvaccinated Gay, Bisexual, and Other Men Who Have Sex With Men in Canada
Authors: Chambers Catharine , Deeks Shelley L. , Sutradhar Rinku , Cox Joseph , de Pokomandy Alexandra , Grennan Troy , Hart Trevor A. , Lambert Gilles , Moore David M. , Coutlée François , Burchell Ann N. ,   the Engage-HPV Study Team
Published: September 2021

Background

Starting in 2015, human papillomavirus (HPV) vaccine has been publicly funded for gay, bisexual, and other men who have sex with men (GBM) 26 years or younger in Canada.

Methods

Self-identified GBM who reported having sex with another man within the past 6 months were enrolled using respondent-driven sampling (RDS) between February 2017 and August 2019 in Montreal, Toronto, and Vancouver, Canada. Men aged 16 to 30 years self-collected anal specimens for HPV-DNA testing. Prevalence was estimated using RDS-II weights. We compared the prevalence of quadrivalent (HPV-6/11/16/18) and 9-valent (HPV-6/11/16/18/31/33/45/52/58) vaccine types between GBM who self-reported HPV vaccination (≥1 dose) and those reporting no vaccination using a modified Poisson regression for binary outcomes.

Results

Among 645 GBM who provided a valid anal specimen (median age, 26 years; 5.9% HIV positive), 40.3% reported receiving ≥1 dose of HPV vaccine, of whom 61.8% received 3 doses. One-quarter were infected with ≥1 quadrivalent type (crude, 25.7%; RDS weighted, 24.4%). After adjustment for potential confounders, vaccinated GBM had a 27% lower anal prevalence of quadrivalent types compared with unvaccinated GBM (adjusted prevalence ratio [aPR], 0.73; 95% confidence interval [CI], 0.54–1.00). Lower prevalence ratios were found among vaccinated participants who were vaccinated >2 years before enrollment (aPR, 0.47; 95% CI, 0.25–0.86) or received their first vaccine dose at age ≤23 years (aPR, 0.64; 95% CI, 0.42–0.99). Point estimates were similar for ≥2 or 3 doses and 9-valent types.

Conclusions

Human papillomavirus vaccination was associated with a lower anal prevalence of vaccine-preventable HPV types among young, sexually active GBM. Findings will help inform shared decision making around HPV vaccination for GBM and their healthcare providers.
Identification of United States Counties at Elevated Risk for Congenital Syphilis Using Predictive Modeling and a Risk Scoring System, 2018
Authors: Cuffe Kendra M. , Torrone Elizabeth A. , Hong Jaeyoung , Leichliter Jami S. , Gift Thomas L. , Thorpe Phoebe G. , Bernstein Kyle T.
Published: September 2021

Background

The persistence of congenital syphilis (CS) remains an important concern in the United States. We use the 2018 data to refine a previous predictive model that identifies US counties at elevated risk for CS in 2018.

Methods

Using county-level socioeconomic and health-related data from various sources, we developed a logistic regression predictive model to identify county-level factors associated with a county having had 1 or more CS case reported to the National Notifiable Diseases Surveillance System in 2018. We developed a risk scoring algorithm, identified the optimal risk score cutpoint to identify counties at elevated risk, and calculated the live birth to CS case ratio for counties by predicted risk level to compare counties at elevated risk with counties not at elevated risk.

Results

We identified several county-level factors associated with a county having 1 or more CS case in 2018 (area under the curve, 88.6%; Bayesian information criterion, 1551.1). Using a risk score cutoff of 8 or higher (sensitivity, 83.2%; specificity, 79.4%), this model captured 94.7% (n = 1,253) of CS cases born in 2018 and identified 850 (27%) counties as being at elevated risk for CS. The live birth to CS case ratio was lower in counties identified as at elevated risk (2,482) compared with counties categorized as not at elevated risk (10,621).

Conclusions

Identifying which counties are at highest risk for CS can help target prevention efforts and interventions. The relatively low live birth to CS case ratio in elevated risk counties suggests that implementing routine 28-week screening among pregnant women in these counties may be an efficient way to target CS prevention efforts.
Association of Bacterial Vaginosis With Higher Vaginal Indole Levels
Authors: Sharma Jyoti , Gupta Kanupriya , Schwebke Jane R. , Geisler William M. , Muzny Christina A.
Published: September 2021

We adapted a simple hydroxylamine-based indole assay to detect indole from stored vaginal swab specimens from women with and without bacterial vaginosis (BV). Women with BV had significantly higher vaginal indole levels compared with women without BV (6451.5 vs 5632.4 μM; P = 0.01), suggesting that indole-producing bacteria are a component of BV.
Sampling and Reporting of Inflammatory Bowel Disease
Authors: Brown Ian S. , Liu Cheng , Miller Gregory C.
Published: September 2021

Pathologists have an important and expanding role in the diagnosis and management of inflammatory bowel disease. This role includes the initial diagnosis of the disease, assessment of the response to treatment and the identification of short-term complications such as cytomegalovirus infection and long-term complications such as dysplasia. Furthermore, the assessment of resection specimens for complication of disease is important to determining the risk of subsequent disease or inflammation within an ileal pouch. Adequate sampling of the disease at endoscopy and from the surgical resection specimen is vital to determining the ultimate information that can be provided by the pathologist. This sampling is determined by the clinical scenario. Similarly, a standardized approach to reporting and synthesizing the histologic findings will improve patient management. This is best exemplified by the increasing interest in histologic activity indices, such as the Nancy index in ulcerative colitis, and in the standardized reporting for inflammatory bowel disease dysplasia recommended by the SCENIC international consensus.
Low-grade Oncocytic Fumarate Hydratase-deficient Renal Cell Carcinoma: An Update on Biologic Potential, Morphologic Spectrum, and Differential Diagnosis With Other Low-grade Oncocytic Tumors
Authors: Hamza Ameer , Sirohi Deepika , Smith Steven C. , Amin Mahul B.
Published: September 2021

Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is typically considered a high-grade, aggressive subtype of RCC that frequently arises in the setting of hereditary leiomyomatosis-renal cell carcinoma (HLRCC) syndrome. Increasing experience with HLRCC-associated RCC and FH-deficient RCC has resulted in recognition of tumors with lower grade morphologic features, overlapping with those of succinate dehydrogenase–deficient RCC and other low-grade oncocytic tumors. In this review article, we report a previously unpublished case that was recently encountered in our practice and review cases in the current literature with an aim of getting a better understanding of these oncocytic tumors and their morphologic spectrum. The 13 cases reviewed were approximately equally distributed across males and females, occurred at a younger age, and were more frequently seen in the right kidney, with both unifocal and multifocal presentations. While most presented an exclusive, low-grade oncocytic morphology, in 4 cases they were associated with either separate high-grade tumors, or as a secondary pattern in an otherwise conventional high-grade FH-deficient RCC. Loss of FH and 2 succinyl cysteine (2SC) positivity by immunohistochemistry supported their diagnosis, and are recommended to be performed alongside CD117, CK7, and CK20 in to aid classification in challenging oncocytic tumors. When occurring in isolation, these tumors are distinctive from their high-grade counterparts, with no reported adverse outcomes in cases reported thus far. As such, accurate diagnosis of this low-grade pattern among FH-deficient RCCs is worthwhile not only due to its association with HLRCC and need of genetic counseling and surveillance, but also due to more favorable prognosis. Finally, increasing experience with the low-grade end of the morphologic spectrum of FH deficient RCC reiterates that not all tumors of this subtype of RCC have a uniformly aggressive outcome.
A Review of Artificial Intelligence in Precise Assessment of Programmed Cell Death-ligand 1 and Tumor-infiltrating Lymphocytes in Non−Small Cell Lung Cancer
Authors: Wu Jianghua , Lin Dongmei
Published: September 2021

Advances in immunotherapy have increased the need for stratified predictive biomarkers in patients with non−small cell lung cancer. However, precise evaluation of tumor tissue-based immune biomarkers, such as programmed cell death-ligand 1 (PD-L1) and the characteristics of tumor infiltrating lymphocytes (TILs), is a challenge in clinical practice. In recent years, the digitization of whole-slide images of tissue has accelerated the implementation of artificial intelligence (AI) approaches in tumor pathology and provided an opportunity to use AI tools to improve the interpretation of immune biomarkers. This review describes the current challenges in the assessment of PD-L1 scoring and TILs and demonstrates the role of AI in helping pathologists integrate PD-L1 and biomarkers of the tumor immune microenvironment. Computer-aided PD-L1 scoring is highly consistent with pathologists and reduces the variation among interobservers, providing a promising diagnostic tool in pathology clinics. In addition, applications of image analysis algorithms, in combination with multiplex staining, enable in-depth quantitative and spatial analysis of the broader tumor microenvironment. Upon combining digital pathology and AI, an automatic analysis system of PD-L1 and TILs, which was established using a set of digital staining images and deep learning algorithms, might be an effective way to overcome the challenges in the precise assessment of immune biomarkers.
Utility of D2-40, Cytokeratin 5/6, and High–Molecular-weight Cytokeratin (Clone 34βE12) in Distinguishing Intraductal Spread of Urothelial Carcinoma From Prostatic Stromal Invasion
Authors: Iakymenko Oleksii A. , Briski Laurence M. , Delma Katiana S. , Jorda Merce , Kryvenko Oleksandr N.
Published: September 2021

Intraductal spread of urothelial carcinoma (UC) is not an uncommon finding in bladder cancer that requires appropriate clinical management. The presence of prostatic stromal invasion in non–muscle-invasive bladder cancer upstages the disease, necessitating cisplatin-based neoadjuvant chemotherapy and subsequent cystroprostatectomy. However, the identification of prostatic stromal invasion can be challenging, especially in biopsy and transurethral resection specimens. We assess the utility of D2-40, CK5/6, and high–molecular-weight cytokeratin (HMWCK) immunohistochemistry as an ancillary tool to differentiate prostatic stromal invasion from intraductal UC spread. We reviewed 13 cystoprostatectomies performed for UC with prostatic involvement. The presence of stromal invasion was histologically determined by the presence of circumferential retraction artifact, paradoxical differentiation, complex architecture, and desmoplastic reaction. The areas of interest were subsequently stained with D2-40, CK5/6, and HMWCK (clone 34βE12). Four bladder biopsies were used as a control to assess labeling in the benign urothelium. Nine cases had histologic evidence of prostatic stromal invasion (4 transmurally through bladder wall). D2-40 highlighted basal cells in all benign prostatic ducts and was consistently negative in UC, benign urothelium, prostatic adenocarcinoma, and benign luminal prostatic epithelium. D2-40 and CK5/6 performed similarly for intraductal UC, labeling only the basal cell layer with the exception of 1 case with squamous differentiation where CK5/6 exhibited full thickness staining. HMWCK diffusely stained 9 of 10 intraductal UCs without squamous differentiation and 1 intraductal UC with squamous differentiation. All 8 cases of invasive UC without squamous differentiation were negative for D2-40. Seven of these cases had focal CK5/6 and diffuse HMWCK staining. In 1 case of invasive UC with squamous differentiation, all stains were positive. D2-40 is expressed in prostatic basal cells, but it is not expressed in the benign or neoplastic urothelium. D2-40 and CK5/6 effectively highlight the intraductal spread of UC. While invasive UC is negative for D2-40, CK5/6 is usually patchy and localized to the periphery of the tumor nests. HMWCK often demonstrates diffuse staining in both scenarios. However, these stains do not perform well in cases of UC with squamous differentiation. Thus, D2-40 can be used as an ancillary tool to rule out prostatic stromal invasion.
Association Between Anticholinergic Drug Burden and Adequacy of Enteral Nutrition in Critically Ill, Mechanically Ventilated Pediatric Patients
Authors: Martinez Enid E. , Dang Hongxing , Franks Jennifer , Callif Charles G. , Tasker Robert C. , Madden Kate , Mehta Nilesh M.
Published: September 2021

OBJECTIVES:

Enteral nutrition delivery is limited by intolerance and interruptions in critically ill children. Anticholinergic properties of frequently administered medications may contribute to altered gastric motility and enteral nutrition intolerance in this population. We examined the association between the anticholinergic burden of administered medications using the Anticholinergic Drug Scale and adequacy of enteral nutrition delivery.

DESIGN:

Secondary analysis of data from a previously characterized PICU cohort.

SETTING:

Multidisciplinary PICU in a quaternary academic medical center.

PATIENTS:

Younger than or equal to 18 years, on mechanical ventilation and received enteral nutrition within the first 3 days of PICU admission.

MEASUREMENTS AND MAIN RESULTS:

Daily Anticholinergic Drug Scale score, demographic data, and clinical data were obtained from the primary study. Percent enteral energy adequacy ([kcal delivered ÷ kcal prescribed] × 100) during the first 3 days of PICU admission was calculated. Forty-two patients received enteral nutrition, with median age (interquartile range) 5 years (1.09–12.54 yr), and 62% were male. Median Anticholinergic Drug Scale score was inversely correlated with energy adequacy, with a median 9% decline in energy adequacy per 1-point increase in Anticholinergic Drug Scale score (coefficient, –9.3; 95% CI, –13.43 to –5.27; R
2 = 0.35; p < 0.0001). Median hours of enteral nutrition interruptions directly correlated with Anticholinergic Drug Scale score (coefficient, 1.5; 95% CI, 0.531–2.54; R
2 = 0.19; p = 0.004). Severity score was greater in patients with less than or equal to 25% enteral energy adequacy and directly correlated with median Anticholinergic Drug Scale score.

CONCLUSIONS:

Anticholinergic burden from medications administered in the PICU is a potentially modifiable factor for suboptimal enteral nutrition delivery.
Relationship of Recovery of Contralesional Ankle Weakness With the Corticospinal and Corticoreticular Tracts in Stroke Patients
Authors: Jang Sung Ho , Cho Min Kyeong
Published: September 2021

Objective

We investigated the relationship between contralesional ankle weakness recovery and the corticospinal tract and corticoreticular tract in stroke patients with complete injuries of the ipsilesional corticospinal tract and corticoreticular tract.

Design

Thirty-six patients with complete injuries of the ipsilesional corticospinal tract and corticoreticular tract were recruited. Medical Research Council and the Functional Ambulation Category were used to determine motor function of ankle dorsiflexor and gait function. Patients were assigned into two groups: group A (poor recovery) and group B (good recovery). Fractional anisotropy, apparent diffusion coefficient, and tract volume were obtained for diffusion tensor imaging parameter.

Results

A total of 58.3% of patients showed good recovery of contralesional ankle dorsiflexor weakness, with remainder having poor recovery. Tract volume of the contralesional corticoreticular tract in group B was higher than that in group A (P < 0.05); no other diffusion tensor imaging parameters were significantly different between two groups. Tract volume of the contralesional corticoreticular tract and corticospinal tract showed strong (r = 0.521) and moderate (r = 0.399) positive correlations with Medical Research Council score of contralesional ankle dorsiflexor, respectively (P < 0.05).

Conclusions

We found that the number of fibers of the contralesional corticospinal tract and corticoreticular tract was closely related to the recovery of contralesional ankle dorsiflexor weakness in stroke patients with complete injuries of the ipsilesional corticospinal tract and corticoreticular tract. Moreover, the contralesional corticoreticular tract had a closer relationship to recovery than the contralesional corticoreticular tract.
Challenges and Lessons Learned for Acute Inpatient Rehabilitation of Persons With COVID-19
Authors: Maltser Susan , Trovato Erika , Fusco Heidi N. , Sison Cristina P. , Ambrose Anne Felicia , Herrera Joseph , Murphy Sean , Kirshblum Steven , Bartels Matthew N. , Bagay Leslie , Oh-Park Mooyeon , Stein Adam B. , Cuccurullo Sara , Nori Phalgun , Donovan Jayne , Dams-O’Connor Kristen , Amorapanth Prin , Barbuto Scott A. , Bloom Ona , Escalon Miguel X.
Published: September 2021

Objective

The aim of the study was to present: (1) physiatric care delivery amid the SARS-CoV-2 pandemic, (2) challenges, (3) data from the first cohort of post–COVID-19 inpatient rehabilitation facility patients, and (4) lessons learned by a research consortium of New York and New Jersey rehabilitation institutions.

Design

For this clinical descriptive retrospective study, data were extracted from post–COVID-19 patient records treated at a research consortium of New York and New Jersey rehabilitation inpatient rehabilitation facilities (May 1–June 30, 2020) to characterize admission criteria, physical space, precautions, bed numbers, staffing, employee wellness, leadership, and family communication. For comparison, data from the Uniform Data System and eRehabData databases were analyzed. The research consortium of New York and New Jersey rehabilitation members discussed experiences and lessons learned.

Results

The COVID-19 patients (N = 320) were treated during the study period. Most patients were male, average age of 61.9 yrs, and 40.9% were White. The average acute care length of stay before inpatient rehabilitation facility admission was 24.5 days; mean length of stay at inpatient rehabilitation facilities was 15.2 days. The rehabilitation research consortium of New York and New Jersey rehabilitation institutions reported a greater proportion of COVID-19 patients discharged to home compared with prepandemic data. Some institutions reported higher changes in functional scores during rehabilitation admission, compared with prepandemic data.

Conclusions

The COVID-19 pandemic acutely affected patient care and overall institutional operations. The research consortium of New York and New Jersey rehabilitation institutions responded dynamically to bed expansions/contractions, staff deployment, and innovations that facilitated safe and effective patient care.
Effects of custom-made insoles on foot pressure redistribution, gait parameters, and pain in calcaneal apophysitis—a pretest and posttest study
Authors: Feyzioğlu Özlem , Öztürk Özgül , Muğrabi Selim
Published: September 2021

Background:

Calcaneal apophysitis is a self-limiting disorder that often affects adolescents with a high level of activity and leads to increased pain severity, impairments in gait parameters, and poor health-related quality of life.

Objective:

To investigate the combination of custom-made insoles and exercise on foot pressure distribution, spatial–temporal gait parameters, and pain intensity in patients with calcaneal apophysitis.

Study design:

A one-group pretest–posttest design.

Methods:

Forty patients, aged between 8 and 15 years, diagnosed with calcaneal apophysitis, were included in this study. Patients were asked to use the custom-made insoles and to perform a home exercise program for 3 days a week. The duration of treatment was 4 weeks. The pain severity was evaluated with the Visual Analog Scale. The spatial–temporal gait parameters and foot pressure distribution were assessed with the Zebris FDM-THM-S treadmill system before and after the treatment.

Results:

At posttreatment assessment, there were significant changes in step length, stance phase percentage, swing phase percentage, and gait speed (P < 0.05), except step width and cadence (P > 0.05). Moreover, significant differences were found in forefoot, midfoot, and rearfoot pressure distribution (P < 0.05). There was also a significant decrease in pain intensity during activity compared to the pretreatment (P < 0.05).

Conclusion:

Our study results suggest that the combination of the custom-made insoles and exercise program created improvements in spatial–temporal gait parameters and foot pressure distribution by reducing the pain severity.