bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of rheumatoid arthritis after regression of lymphoproliferative disorders in patients treated with methotrexate: a retrospective, multi-center descriptive study
Authors: Nakano Kazuhisa , Tanaka Yoshiya , Saito Kazuyoshi , Kaneko Yuko , Saito Shuntaro , Tanaka Masao , Saito Rintaro , Fujii Takao , Kuramoto Nobuo , Sugimoto Naoki , Takada Hideto , Harigai Masayoshi , Sasaki Sho , Suzuki Yasuo
Published: November 2020

Objectives

To identify the optimal treatment for rheumatoid arthritis (RA) after the regression of lymphoproliferative disorders (LPDs).

Methods

The subjects were 232 patients with RA who developed LPD between 2000 and 2017 at seven hospitals participating in the LPD-WG study. Kaplan-Meier and Cox proportional regression analyses were performed to determine the factors associated with the rate of LPD relapse and the retention of biological disease-modifying antirheumatic drugs (bDMARDs).

Results

Treatment for RA was resumed in 138 patients after spontaneous regression of LPD after the discontinuation of methotrexate and in 52 patients after chemotherapy for LPD (persistent-LPD). LPD relapses occurred in 23 patients. Not DMARDs use but Hodgkin’s lymphoma was identified as a risk factor for LPD relapse. In 88 RA patients treated with bDMARDs [tocilizumab, 39 patients; abatacept 20 patients; tumor necrosis factor inhibitor, 29 patients], the one-year retention rate was 67.8%. The risk factors for discontinuation of bDMARDs were persistent-LPD, non-diffuse large B-cell lymphomas (non-DLBCL), and a high clinical disease activity index (CDAI). Tocilizumab showed the highest retention rate among bDMARDs, particularly in DLBCL.

Conclusion

Although any bDMARD could be used in patients after LPD regression, effectiveness and risk for relapse should be carefully assessed for each LPD subtype.
Recent advances in 3D bioprinting of musculoskeletal tissues
Authors: Potyondy Tyler , Uquillas Jorge Alfredo , Tebon Peyton J , Byambaa Batzaya , Hasan Anwarul , Tavafoghi Maryam , Mary Heloise , Aninwene George E , Pountos Ippokratis , Khademhosseini Ali , Ashammakhi Nureddin
Published: November 2020

The musculoskeletal system is essential for maintaining posture, protecting organs, facilitating locomotion, and regulating various cellular and metabolic functions. Injury to this system due to trauma or wear is common, and severe damage may require surgery to restore function and prevent further harm. Autografts are the current gold standard for the replacement of lost or damaged tissues. However, these grafts are constrained by limited supply and donor site morbidity. Allografts, xenografts, and alloplastic materials represent viable alternatives, but each of these methods also has its own problems and limitations. Technological advances in three-dimensional (3D) printing and its biomedical adaptation, 3D bioprinting, have the potential to provide viable, autologous tissue-like constructs that can be used to repair musculoskeletal defects. Though bioprinting is currently unable to develop mature, implantable tissues, it can pattern cells in 3D constructs with features facilitating maturation and vascularization. Further advances in the field may enable the manufacture of constructs that can mimic native tissues in complexity, spatial heterogeneity, and ultimately, clinical utility. This review studies the use of 3D bioprinting for engineering bone, cartilage, muscle, tendon, ligament, and their interface tissues. Additionally, the current limitations and challenges in the field are discussed and the prospects for future progress are highlighted.
A novel antibody targeting TIM-3 resulting in receptor internalization for cancer immunotherapy
Authors: Kuang Zhihui , Li Li , Zhang Pan , Chen Bingliang , Wu Min , Ni Haiqing , Yi Shuai , Zou Jia , Liu Junjian
Published: November 2020

Background

Strategies to reinvigorate exhausted T cells have achieved great efficacy in certain subpopulations of tumor patients. Blocking the antibodies that target programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 induces durable responses in Hodgkin’s lymphoma, melanoma, renal and lung cancers. T cell immunoglobulin mucin-3 (TIM-3) is another well-defined inhibitory receptor that is expressed in terminally differentiated Th1/Tc1 cells, which produces interferon gamma and cytotoxic molecules. It is also significantly expressed on forkhead box P3+ regulatory T cells and innate immune cells such as dendritic cells and macrophages.

Methods

By immunizing BALB/c mice with recombinant TIM-3 and screening of 20 000 hybridoma clones, we selected a monoclonal TIM-3-blocking antibody (IBI104), which shows great efficacy in vitro and in vivo.

Results

IBI104 blocks phosphatidylserine interaction with TIM-3 but does not interfere with the interaction of TIM-3 with galectin-9 in ELISA assays. However, in vitro administration of IBI104 induces the potent internalization of TIM-3 in activated T cells to the extent that it will shut down the entire TIM-3 mediated signaling regardless of the ligands. IBI104 shows potent anti-tumor efficacy when combined with anti-PD1 in vivo.

Conclusions

Our results suggest that IBI104 is a promising blocking antibody for TIM-3-mediated suppressive signaling and can serve as effective cancer immunotherapy, especially in combination with anti-PD1.
Activation of the acute inflammatory phase response in idiopathic nephrotic syndrome: association with clinicopathological phenotypes and with response to corticosteroids
Authors: Roca Neus , Martinez Cristina , Jatem Elias , Madrid Alvaro , Lopez Mercedes , Segarra Alfons
Published: November 2020

Background

Data on the activation of the acute inflammatory response and its clinicopathological associations in idiopathic nephrotic syndrome (INS) are scarce and discordant.

Objective

To analyse the associations between the activation of the inflammatory response, the clinicopathological characteristics of disease and the response to treatment with steroids in patients with INS.

Methods

A total of 101 patients with INS due to minimal change disease (MCD; n = 44), focal segmental glomerulosclerosis (FSGS; n = 33) and membranous nephropathy (MN; n = 24) and 50 healthy controls were included. At diagnosis, we measured the levels of haemopexin (Hx), haptoglobin (Hgl), interleukin-6 (IL-6), soluble urokinase-type plasminogen activator receptor (suPAR), tumour necrosis factor-α (TNF-α), soluble IL-1 receptor, interferon-γ and C-reactive protein. We analysed their clinicopathological associations. In MCD and FSGS patients, we determined the association between the levels of these variables and steroid resistance.

Results

The levels of Hx, Hgl, TNF-α, suPAR and IL-6 were higher in patients with INS than in healthy controls, and were not associated with proteinuria, estimated glomerular filtration rate or serum albumin. In MCD and FSGS patients, Hx, Hgl, IL-6 and TNF-α levels were similar and significantly higher than in MN patients. In patients with MCD and FSGS, multivariate analyses identified FSGS and the levels of Hx, Hgl or IL-6 as independent predictors of steroid resistance.

Conclusions

The activation of the inflammatory response in patients with INS is heterogeneous and more prevalent in MCD or FSGS patients than in those with MN. In MCD and FSGS, elevated levels of Hx, Hgl or IL-6 are independently associated with steroid resistance.
Identification of a TeO32− reductase/mycothione reductase fromRhodococcus erythropolisPR4
Authors: Butz Zachary J , Hendricks Alexander , Borgognoni Kanda , Ackerson Christopher J
Published: November 2020

A Rhodococcus erythropolis bacterium that tolerates normally lethal concentrations of Fe(II), Cu(II), AsO32−, SeO32−, TeO32−, Cd(II) and Zn(II) was identified from an environmental isolate. In characterizing the molecular basis for metal tolerance, a mycothione reductase (Mtr) with remarkable selectivity for TeO32− reduction over SeO32− was identified. In equimolar concentrations of TeO32− and SeO32−, the enzymatic product contains a 7-fold excess of Te. This selectivity is remarkable because the standard reduction potential of SeO32− is 0.20 V more favorable for reduction than TeO32. Selectivity of the enzyme for TeO32− decreases with increasing assay pH. Homology modeling of the enzyme identifies four aromatic residues near the active site, including two histidine residues, that are not present in a related SeO32− preferring reductase. On the basis of more favorable π-interactions for Te than for Se and the pH dependence of the selectivity, the Te-selectivity is attributed in part to these aromatic residues. The resulting Te0 enzymatic product resembles Te nanowires.
The Rise and Fall of Torah U’Madda*
Authors: Grossman Lawrence
Published: November 2020

Rabbi Norman Lamm, who assumed the presidency of Yeshiva University in 1976, sought to clarify the mission of the institution by using as its tagline the phrase Torah U'’Madda–denoting the dual aim of providing traditional Jewish study (Torah) along with a standard college curriculum (Madda, meaning knowledge). It would replace the word “Synthesis,” which generations of students, including Lamm himself, had found vague and confusing. Lamm launched what he called the Torah U'Madda Project, which ultimately included a campus lecture series, an annual journal, and a book entitled: Torah Umadda: The Encounter of Religious Learning and Worldly Knowledge in the Jewish Tradition. While denying any intention to construct a hard-and-fast institutional philosophy on how to integrate Orthodox Judaism and secular higher education, Lamm insisted that serious exposure to both Torah knowledge and the arts and sciences fulfilled the Torah's mandate to understand and appreciate all aspects of God's world. Lamm's initiative failed, however, because economic conditions induced many students to forsake the liberal arts for vocational and pre-professional courses, and the trend to the right in American Orthodoxy–expressed by rabbis at Yeshiva itself and abetted by the year or more spent at Israeli yeshivot before college–stressed single–minded concentration on Torah study and justified secular education only for the purpose of making a living.
Claims of Safety in Neurosurgical Literature: We Shouldn’t Call Something Safe Without Strong Justification
Authors: Khan Adam Alamgir , Haines Stephen John
Published: November 2020

BACKGROUND

Many articles published in the neurosurgical literature make claims of safety regarding interventions. The strength of evidence supporting these claims has not been systematically evaluated.

OBJECTIVE

To evaluate the quality of evidence supporting claims of safety in the neurosurgery literature.

METHODS

The 14 neurosurgical journals listed in the Web of Science database with the highest impact factors for 2018 were included in the study. The titles and abstracts of all the articles published in these journals in 2018 were searched for the word “safety” and reviewed by 2 independent observers to identify those making a claim of safety and assess their evidence.

RESULTS

The search identified 323 articles, representing 5% of the articles published in the 14 searched journals in 2018. Of these, 114 (1.8% of all articles and 35% of the identified articles) were judged to make a claim of safety of a neurosurgical intervention. A total of 98 (86%) of the 114 articles making a safety claim were retrospective cohort studies. Patient cohort sizes ranged from 1 to 1565 (median of 34), leading to wide variations in the CIs for estimated complication rates. No article made a statement of the assumptions underlying its claim of safety.

CONCLUSION

Almost no articles that make claims of safety for neurosurgical interventions explicitly state the (1) patient population, (2) comparison intervention, nor (3) specific outcomes. To assure that claims of safety are supported by high-quality evidence, authors should address these elements early and systematically when designing studies.
Transverse hilbert schemes, bi-hamiltonian systems and hyperkähler geometry
Authors: Bielawski Roger
Published: November 2020

We give a characterization of Atiyah’s and Hitchin’s transverse Hilbert schemes of points on a symplectic surface in terms of bi-Poisson structures. Furthermore, we describe the geometry of hyperkähler manifolds arising from the transverse Hilbert scheme construction, with particular attention paid to the monopole moduli spaces.
Spindles are highly heritable as identified by different spindle detectors
Authors: Goldschmied Jennifer R , Lacourse Karine , Maislin Greg , Delfrate Jacques , Gehrman Philip , Pack Frances M , Staley Bethany , Pack Allan I , Younes Magdy , Kuna Samuel T , Warby Simon C
Published: November 2020

Study Objectives

Sleep spindles, a defining feature of stage N2 sleep, are maximal at central electrodes and are found in the frequency range of the electroencephalogram (EEG) (sigma 11–16 Hz) that is known to be heritable. However, relatively little is known about the heritability of spindles. Two recent studies investigating the heritability of spindles reported moderate heritability, but with conflicting results depending on scalp location and spindle type. The present study aimed to definitively assess the heritability of sleep spindle characteristics.

Methods

We utilized the polysomnography data of 58 monozygotic and 40 dizygotic same-sex twin pairs to identify heritable characteristics of spindles at C3/C4 in stage N2 sleep including density, duration, peak-to-peak amplitude, and oscillation frequency. We implemented and tested a variety of spindle detection algorithms and used two complementary methods of estimating trait heritability.

Results

We found robust evidence to support strong heritability of spindles regardless of detector method (h2 > 0.8). However not all spindle characteristics were equally heritable, and each spindle detection method produced a different pattern of results.

Conclusions

The sleep spindle in stage N2 sleep is highly heritable, but the heritability differs for individual spindle characteristics and depends on the spindle detector used for analysis.
Exogenous dopamine and overexpression of the dopamine synthase gene MdTYDC alleviated apple replant disease
Authors: Gao Tengteng , Liu Yusong , Liu Xiaomin , Zhao Kai , Shan Lei , Wu Qian , Liu Yuan , Zhang Zhijun , Ma Fengwang , Li Chao
Published: November 2020

Apple replant disease (ARD) is a soil-borne disease that leads to economic losses due to reduced plant growth and diminished fruit yields. Dopamine is involved in interactions between plants and pathogens. However, it remains unclear whether dopamine can directly stimulate defense responses to ARD. In this study, an exogenous dopamine treatment and dopamine synthetase MdTYDC (tyrosine decarboxylase) transgenic plants were used to verify the role of dopamine in treating ARD. First, 2-year-old apple trees (Malus domestica cv. Fuji), grafted onto rootstock M26, were grown in replant soils. The addition of dopamine (100 μM) to the soil promoted seedling growth and changed the accumulation of mineral elements in plants in replant soils. Such supplementation improved the activity of invertase, urease, proteinase and phosphatase under replant conditions. Sequencing analysis of 16S rDNA and internal transcribed spacer (ITS) rDNA revealed that dopamine had a slight influence on bacterial diversity but had an obvious effect on the fungal diversity in replant soils. The application of dopamine to replant soil changed the composition of bacterial and fungal communities. Second, overexpression of MdTYDC in apple plants alleviated the effects of ARD. MdTYDC transgenic lines exhibited mitigated ARD through inhibited degradation of photosynthetic pigment, maintaining the stability of photosystems I and II and improving the antioxidant system. Furthermore, overexpression of MdTYDC improved arbuscular mycorrhizal fungi colonization by improving the accumulation of soluble sugars under replant conditions. Together, these results demonstrated that dopamine enhances the tolerance of apples to ARD.
Human actinomycetoma caused by Actinomadura mexicana in Sudan: the first report
Authors: Siddig Emmanuel Edwar , Nyuykonge Bertrand , Ahmed Mohammed Tayfour , Hassan Rowa , Saad Eiman Siddig Ahmed , Mhmoud Najwa Adam , Bakhiet Sahar Mubarak , van de Sande Wendy W J , Fahal Ahmed Hassan
Published: November 2020

Mycetoma is a localized, chronic, granulomatous disease that can be caused by fungi (eumycetoma) or bacteria (actinomycetoma). Of the 70 different causative agents implicated in mycetoma worldwide, Actinomadura madurae is the only one that causes multiple cases on all continents. Recently, new Actinomadura species were described as causative agents of human mycetoma. One of these new causative agents was Actinomadura mexicana, which was identified in Latin America. Here we demonstrate that this causative agent is not confined to Latin America and that it is also a causative agent of actinomycetoma in Sudan. The disease was managed by antibiotic treatment alone and resulted in complete cure after 6 months of treatment, which is quick when compared with actinomycetoma cases caused by other Actinomadura species.
Species limits, patterns of secondary contact and a new species in theTrogon rufuscomplex (Aves: Trogonidae)
Authors: Dickens Jeremy Kenneth , Bitton Pierre-Paul , Bravo Gustavo A , Silveira Luís Fábio
Published: November 2020

The black-throated trogon, Trogon rufus, is a widespread, polytypic species-complex with a convoluted taxonomic history. Here, we integrated morphological, vocal and genetic datasets, including spectral data and digital quantification of barred plumage, to assess and redefine its species limits according to the foremost species concepts. We suggest the recognition of four named and one new species. Trogon tenellus and T. cupreicauda are divergent across Central and South America without geographic overlap or intermediates. Trogon chrysochloros in the Atlantic Forests of Brazil is phenotypically, genetically and ecologically distinct. In Amazonia, Trogon rufus consists of three phenotypically distinct subspecies intergrading with each other in a ring-like formation around central Amazonian rivers. Trogon rufus rufus in the Guiana Shield, Trogon rufus amazonicus in south-eastern Amazonia and Trogon rufus sulphureus in western Amazonia, with contact across the Lower Amazon and Madeira rivers, likely due to secondary contact between incompletely diverged lineages. The unique combination of song, morphology and mtDNA features of an unnamed, isolated population in the Atlantic Forest of north-eastern Brazil resulted in its description as a new species, known only from the type locality and considered here as Critically Endangered, requiring urgent conservation actions.
Executive Functioning in Youth With and Without Chronic Pain
Authors: Turner Kailyn M. , Wilcox Gabrielle , Nordstokke David W. , Dick Bruce , Schroeder Meadow , Noel Melanie
Published: November 2020

Objectives:

Preliminary research in youth with chronic pain suggests differences in attention and working memory, which has been similarly demonstrated in adults with chronic pain. There has been little research on other aspects of executive functioning (EF) in this population despite its critical role in problem solving, school functioning, and coping. This study aimed to examine differences in several aspects of EF between youth with chronic pain and a nonchronic pain comparison group using performance-based neuropsychological tests and a behavior rating scale.

Materials and Methods:

Participants completed ratings of pain; physical, emotional, social, and school functioning; sleep quality; medication; and a general intelligence screener. Standardized neuropsychological tests were used to examine EF with a focus on working memory, divided and alternating attention, inhibition, flexibility, incidental memory, and planning. A parent-report and self-report behavior rating of EF was also administered.

Results:

Recruitment from 2 tertiary-care pain clinics resulted in a sample of 26 youth with chronic pain (80.8% girls) and their parents. A comparison group of 30 youth without chronic pain and their parents were recruited from the community. Participants with chronic pain had significantly lower scores on several performance-based tests of working memory/divided attention, inhibition, and flexibility/alternating attention than the comparison group. Statistically significant group differences were also found on behavior ratings of emotion control, shifting, task initiation and completion, working memory, planning and organization, overall emotion and cognitive regulation as well as global EF. Covariate analysis was conducted in all analyses where there were significant group differences and several observed group differences remained.

Discussion:

This study is one of few multidimensional examinations of EF in youth with chronic pain, using a comprehensive neuropsychological test battery combined with behavior ratings. Our findings suggest EF differences in youth with chronic pain, across a variety of domains and may suggest risk for specific cognitive processing weaknesses in this population. Medical and educational teams should work toward identification, treatment, and compensatory support for EF within individualized pain management for youth.
Complications and 30-Day Mortality Rate After Hip Fracture Surgery in Superobese Patients
Authors: Chaudhry Yash P. , Rao Sandesh S. , Puvanesarajah Varun , Amin Raj M. , Khanuja Harpal S. , Oni Julius K. , Hasenboehler Erik A. , Sterling Robert S.
Published: November 2020

Objective:

Paradoxically, overweight and obesity are associated with lower odds of complications and death after hip fracture surgery. Our objective was to determine whether this “obesity paradox” extends to patients with “superobesity.” In this study, we compared rates of complications and death among superobese patients with those of patients in other body mass index (BMI) categories.

Methods:

Using the National Surgical Quality Improvement Program database, we identified >100,000 hip fracture surgeries performed from 2012 to 2018. Patients were categorized as underweight (BMI <18.5), normal weight (BMI 18.5–24.9), overweight (BMI 25–29.9), obese (BMI 30–39.9), morbidly obese (BMI 40–49.9), or superobese (BMI ≥50). We analyzed patient characteristics, surgical characteristics, and 30-day outcomes. Using multivariate regression with normal-weight patients as the referent, we determined odds of major complications, minor complications, and death within 30 days by BMI category.

Results:

Of 440 superobese patients, 20% had major complications, 33% had minor complications, and 5.2% died within 30 days after surgery. When comparing patients in other BMI categories with normal-weight patients, superobese patients had the highest odds of major complications [odds ratio (OR): 1.6, 95% confidence interval (CI), 1.2–2.0] but did not have significantly different odds of death (OR: 0.91, 95% CI, 0.59–1.4) or minor complications (OR: 1.2, 95% CI, 0.94–1.4).

Conclusion:

Superobese patients had significantly higher odds of major complications within 30 days after hip fracture surgery compared with all other patients. This “obesity paradox” did not apply to superobese patients.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a Complete Description of Levels of Evidence.
Is Timing to Surgery an Independent Risk Factor for Complications Following Operative Treatment of Periprosthetic Lower Extremity Fractures?
Authors: Copp Jonathan , Sivasundaram Lakshmanan , Abola Matthew V. , Schell Adam , Trivedi Nikunj N. , Ochenjele George
Published: November 2020

Objective:

To identify whether timing to surgery was related to major 30-day morbidity and mortality rates in periprosthetic hip and knee fractures [OTA/AO 3 (IV.3, V.3), OTA/AO 4 (V4)].

Design:

Retrospective database review.

Setting:

Hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database.

Patients:

Patients in the NSQIP database with periprosthetic hip or knee fractures between 2007 and 2015.

Intervention:

Surgical management of periprosthetic hip and knee fractures including revision or open reduction internal fixation.

Main Outcome Measurements:

Major 30-day morbidity and mortality after operative treatment of periprosthetic hip or knee fractures.

Results:

A total of 1265 patients, mean age 72, including 883 periprosthetic hip and 382 periprosthetic fractures about the knee were reviewed. Delay in surgery greater than 72 hours is a risk factor for increased 30-day morbidity in periprosthetic hip and knee fractures [relative risk = 2.90 (95% confidence interval: 1.74–4.71); P-value ≤ 0.001] and risk factor for increased 30-day mortality [relative risk = 8.98 (95% confidence interval: 2.14–37.74); P-value = 0.003].

Conclusions:

Using NSQIP database to analyze periprosthetic hip and knee fractures, delay to surgery is an independent risk factor for increased 30-day major morbidity and mortality when controlling for patient functional status and comorbidities. Although patient optimization and surgical planning are paramount, minimizing extended delays to surgery is a potentially modifiable risk factor in the geriatric periprosthetic lower extremity fracture patient.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Long non-coding RNAs during normal erythropoiesis
Authors: Xu Changlu , Shi Lihong
Published: November 2020

The transcription of essentially the entire eukaryotic genome produces a huge amount of non-coding RNAs. Among them, long non-coding RNAs (lncRNAs) consist of a significant portion that widely exists across mammal genome, generating from high-throughput transcriptomic studies in the last decade. Although the functions of most lncRNAs remain to be further investigated, many of them have already been shown to play critical roles during normal development and disease conditions. Increasing evidence indicates that lncRNAs involve in versatile biological processes during erythroid proliferation and differentiation, including erythroid cell survival, heme metabolism, globin switching and regulation, erythroid enucleation, etc, via cis- or trans-mediated molecular mechanisms. In this review, we focus on recent advances regarding the functions and mechanisms of lncRNAs in normal erythropoiesis.
HOXC4 up-regulates NF-κB signaling and promotes the cell proliferation to drive development of human hematopoiesis, especially CD43+ cells
Authors: Zeng Jiahui , Sun Wencui , Chang Jing , Yi Danying , Zhu Lijiao , Zhang Yonggang , Pan Xu , Zhou Ya , Lai Mowen , Bian Guohui , Zhou Qiongxiu , Liu Jiaxin , Chen Bo , Ma Feng
Published: November 2020

The hematopoietic function of HOXC4 has not been extensively investigated. Our research indicated that induction of HOXC4 in co-culture system from D10 significantly promoted productions of most hematopoietic progenitor cells. CD34−CD43+ cells could be clearly classified into CD34−CD43low and CD34−CD43high sub-populations at D14. The former cells had greater myelogenic potential, and their production was not significantly influenced by induction of HOXC4. By contrast, the latter cells had greater potential to differentiate into megakaryocytes and erythroid cells, and thus had properties of erythroid–megakaryocyte common progenitors, which abundance was increased by ∼2-fold when HOXC4 was induced from D10. For CD34−CD43low, CD34+CD43+, and CD34−CD43high sub-populations, CD43 level served as a natural index for the tendency to undergo hematopoiesis. Induction of HOXC4 from D10 caused more CD43+ cells sustain in S-phase with up-regulation of NF-κB signaling, which could be counteracted by inhibition of NF-κB signaling. These observations suggested that promotion of hematopoiesis by HOXC4 is closely related to NF-κB signaling and a change in cell-cycle status, which containing potential of clinical applications.
Anti-programmed cell death-1 therapy in octogenarian and nonagenarian advanced/metastatic melanoma patients
Authors: Cybulska-Stopa Bożena , Ziętek Marcin , Kamińska-Winciorek Grażyna , Czarnecka Anna M. , Piejko Karolina , Galus Łukasz , Ziółkowska Barbara , Kieszko Stanisław , Kempa-Kamińska Natasza , Calik Jacek , Zemełka Tomasz , Kubiatowski Tomasz , Suwiński Rafał , Mackiewicz Jacek , Rutkowski Piotr
Published: November 2020

Immunotherapy with anti-programmed cell death-1 (PD-1) agents is an effective treatment for metastatic melanoma. Octogenarians and nonagenarians represent a significant cohort of melanoma patients. This multicenter retrospective analysis enrolled 499 patients treated with nivolumab or pembrolizumab. Seventy-three patients were aged 80–100, 218 patients were aged 65–79, and 208 patients were <65 years old. Baseline parameters were comparable. The median overall survival (OS) was 14.7, 18.7, 25.9, and the median progression-free survival (PFS) was 8.7, 7.7, and 6.2 months in the age groups of 80–100, 65–79, and <65 years, respectively. The median melanoma-specific survival (MSS) was 22.5, 27.8, and 31.6 months in the age groups of 80–100, 65–79, and <65 years, respectively. There was no statistically significant difference in OS (P = 0.2897), PFS (P = 0.7155), and MSS (P = 0.9235) between the group of 80–100 years old vs. 65–79 and vs. <65 years old patients. Overall response rate and disease control rate was similar in all groups (P = 0.06974 and P = 0.89435, respectively). Overall, the immune-related adverse event (irAE) rate was comparable in the three age groups (41, 34, and 37.5% in the groups of patients aged 80–100, 65–79, and <65 years, respectively). Also, the rates of G3 and G4 irAEs were comparable (4, 6, and 7% in the groups of patients, respectively). The efficacy and toxicity of anti-PD-1 therapy in octogenarians and nonagenarians with metastatic melanoma are similar as in patients aged <65 years and 65–79 years. The patients’ age should not be considered as an exclusion criterion for anti-PD-1 treatment.
Mother-Adolescent Discrepancies in Ratings of Adolescents' Adjustment: Associations with Maternal Mental Health and Family Factors
Authors: Rana Marya , Delker Erin , East Patricia , Blanco Estela , Burrows Raquel , Lozoff Betsy , Gahagan Sheila
Published: November 2020

Objective:

Many children and adolescents are assessed for potential psychological and behavioral problems through the parent-completed Child Behavior Checklist (CBCL) and Youth Self-Report (YSR) questionnaires. However, because these assessments are based on individual reports, they are subject to disagreement. This study considered multiple family factors and aspects of mothers' mental health in discrepancies between mothers' and youths' ratings on the CBCL and YSR.

Method:

This study involved 926 mothers and their adolescent children (48.7% female children, mean age = 14.4 years) who completed the CBCL and YSR questionnaires, respectively.

Results:

Mothers who experienced more severe mental health problems reported more internalizing symptoms of their adolescent relative to the adolescent's ratings.

Conclusion:

Findings indicate that mothers' poor mental health is related to their reports of more frequent psychological problems in their adolescents. To verify the accuracy of maternal reports, additional raters and additional methods, such as behavioral observation and clinical interview, would be helpful.
Angiotensin-Converting Enzyme Inhibitor–based Versus Angiotensin Receptor Blocker–based Optimal Medical Therapy After Percutaneous Coronary Intervention: A Nationwide Cohort Study
Authors: Park Sangwoo , Kim Yong-Giun , Ann Soe Hee , Park Hyun Woo , Suh Jon , Roh Jae-Hyung , Cho Young-Rak , Han Seungbong , Park Gyung-Min
Published: November 2020

Optimal medical therapy (OMT) plays a crucial role in the secondary prevention of established coronary artery disease. The renin–angiotensin system (RAS) is an important target of OMT. However, there is limited evidence on whether there is any difference in the combined effect of OMT according to the classes of RAS blockade [angiotensin-converting enzyme inhibitor (ACEI) vs. angiotensin receptor blocker (ARB)]. Based on the nationwide National Health Insurance database in South Korea, 39,096 patients who received OMT after percutaneous coronary intervention between July 2013 and June 2017 were enrolled. Patients were stratified into either acute myocardial infarction (AMI) or angina cohort and analyzed according to the class of RAS blockade included in OMT at discharge (ACEI vs. ARB). The primary end point was all-cause mortality. The study population had a median follow-up of 2.3 years (interquartile range, 1.3–3.3 years). In the propensity score-matched AMI cohort (8219 pairs), the risk for all-cause mortality was significantly lower in patients with ACEI-based OMT than in those with ARB-based OMT (hazard ratio 0.83 of ACEI, 95% confidence interval 0.73–0.94, P = 0.003). However, in the propensity score-matched angina cohort (6693 pairs), the mortality risk was comparable, regardless of the class of RAS blockade (hazard ratio 1.13, 95 confidence interval 0.99–1.29, P = 0.08). In conclusion, in this nationwide cohort study involving patients receiving OMT after percutaneous coronary intervention, ACEI-based OMT was associated with a significantly lower risk of all-cause mortality in patients with AMI in comparison with ARB, but not in those with angina.
Necrotizing Enterocolitis-like Pneumatosis Intestinalis in an Infant With COVID-19
Authors: Mehl Steven C. , Whitlock Richard S. , Marcano Daniela C. , Rialon Kristy L. , Arrington Amy S. , Naik-Mathuria Bindi
Published: November 2020

We report an infant with COVID-19 who presented with bloody stools, lethargy and imaging findings significant for pneumatosis intestinalis. The infant was treated with conservative therapy, including resuscitation, bowel rest and intravenous antibiotics, successfully avoiding surgical intervention.
Training Physician Assistants to Use Medical Interpreters Effectively
Authors: Gillette Chris , Blalock Jamie , Hildebrandt Carol , Peacock Brian , Crandall Sonia
Published: November 2020

Purpose

To examine the internal consistency of a validated instrument for physician assistant (PA) communication skills with interpreters and evaluate a training activity focused on effectively working with interpreters during a standardized patient assessment.

Methods

Six cohorts of PA students completed training on how to communicate with patients who required an interpreter. Students then completed an assessment with a limited English-proficient patient and interpreter. Student competency was assessed using a previously validated measure. Data were analyzed using a multivariable Poisson regression model.

Results

There were usable data on 439 PA students. The median number of areas that students performed/partially performed was 10 out of 12 (inter-quartile range: 3). The Poisson regression model revealed significant differences between cohorts. Areas for further training include using Teach-Back (n = 203) and thanking the interpreter (n = 170).

Conclusions

Although the PA students performed well, there is considerable room for improvement in certain communication techniques.
The Arthroscopic Bankart Repair: State of the Art in 2020: Decision-making and Operative Technique
Authors: Gowd Anirudh K. , Waterman Brian R.
Published: November 2020

Traumatic anterior shoulder instability is prevalent among young athletes, and recurrent dislocations can result in compromised upper extremity function, increasing glenohumeral bone loss, and ultimately, posttraumatic arthritis. Although management algorithms have evolved in response to contemporary data and technical innovation, the arthroscopic Bankart repair continues to be a mainstay for the primary surgical management of first-time or recurrent anterior shoulder instability with marginal attritional glenoid bone loss (ie, <10% to 15%) and/or “on track” Hill-Sachs defects. The advantages of arthroscopic stabilization include its minimally invasive technique, high cost effectiveness, and relatively low recurrence rates and propensity for perioperative complications. The current article reviews contemporary indications/contraindications, management of the first-time dislocator, critical glenoid bone loss, surgical technique, and reported clinical outcomes of the arthroscopic Bankart repair.
Can Dizziness Handicap Inventory and Activities-Specific Balance Confidence Scores Assess Vestibular Loss After Vestibular Schwannoma Excision?
Authors: Erbele Isaac D. , MacDowell Sara G. , Arriaga Moisés A.
Published: November 2020

Objective:

Evaluate and compare the Dizziness Handicap Inventory with Activities-specific Balance Confidence scores shortly after vestibular schwannoma excision.

Study Design:

Retrospective database review.

Setting:

Tertiary care center.

Patients:

Adults undergoing vestibular schwannoma excision between January 2015 and December 2019.

Intervention:

Diagnostic, therapeutic, and rehabilitative.

Main Outcome Measures:

Postoperative change in Dizziness Handicap Inventory scores and Activities-specific Balance Confidence scores 2 to 3 weeks after surgical intervention in relation to preoperative vestibular testing.

Results:

A total of 49 patients met inclusion criteria. The average change in the Dizziness Handicap Inventory was 6 (p = 0.07, 95% CI 0–13). This was weakly correlated to preoperative caloric testing values (r = −0.31, p = 0.03), but not cervical vestibular evoked myogenic potentials (cVEMP) values (r = −0.17, p = 0.23). The average change in Activities-specific Balance Confidence was −10% (p = 0.007, 95% CI −3 to −17%). This change was moderately correlated with preoperative caloric values (r = 0.42, p = 0.006), but it was not correlated with cVEMP (r = 0.07, p = 0.66).

Conclusions:

In vestibular schwannoma patients, factors other than preoperative vestibular function likely affect postoperative Dizziness Handicap Inventory and Activities-specific Balance Confidence scores. The change in Activities-specific Balance Confidence was slightly more consistent with expected physiological vestibular loss, and it represents another tool in a multidisciplinary vestibular evaluation of the postoperative patient.
Diffuse Intracerebral Hemorrhage in an Infant With a Novel Homozygous Variant Leading to Severe Protein C Deficiency
Authors: Martin Georgina , Thomas Mary Ann , Wei Xing-Chang , Le Doan
Published: November 2020

Protein C is a circulating anticoagulant that inhibits factor Va and VIIIa and promotes fibrinolysis. Compound heterozygous or homozygous variants in the Protein C gene (PROC) lead to severe deficiency of protein C and affected neonates typically present shortly after birth with purpura fulminans. We describe an infant who suffered a diffuse intracranial hemorrhage as a neonate and presented with purpura fulminans as an older infant which led to investigations that were consistent with severe protein C deficiency. We demonstrate subacute findings on neuroimaging and suggest this condition should be considered with neonatal presentations of bilateral intraparenchymal hemorrhage.
Impact of ABO Blood Group on the Development of Venous Thromboembolism in Children With Cancer: A Systematic Review and Meta-Analysis
Authors: Lam Shin Cheung Jeffrey , Lam Shin Cheung Victor , Athale Uma
Published: November 2020

Background:

Few studies have evaluated the impact of ABO blood group on the risk of venous thromboembolism (VTE) in pediatric populations. We performed a systematic review to determine whether children (0 to 18 y old) with non-O blood group have an increased risk of developing VTE compared with those with O blood group.

Methods:

We searched Ovid Medline, Embase, PubMed, Cochrane, Web of Science, and CINAHL online databases from inception to December 2018 to find studies involving blood grouping and VTE. Data was collected regarding patients’ underlying diseases, sex, age, ABO blood group, and VTE frequency. A meta-analysis using the random effect model was performed, and heterogeneity was assessed with the I
2 value.

Results:

Among 1280 unique articles identified, 7 studies (3 conference abstracts, 4 peer-reviewed journal articles) involving 609 VTE cases were included in the systematic review. Six studies were eligible for a meta-analysis; all involved patients with cancer. Blood group O was protective against VTE (odds ratio, 0.56; 95% confidence interval, 0.43-0.79). Findings were similar across sensitivity analyses.

Conclusions:

This systematic review has documented that O blood group is protective against new-onset VTE in children with cancer. Larger studies across different ethnic backgrounds and disease categories are needed to confirm these findings.
Narrative Review of Clinical Practice Guidelines for Rehabilitation of People With Spinal Cord Injury
Authors: Gerber Lynn H. , Deshpande Rati , Prabhakar Shruthi , Cai Cindy , Garfinkel Steven , Morse Leslie , Harrington Amanda L.
Published: November 2020

Clinical practice guidelines provide reliable, vetted, and critical information to bring research to practice. Some medical specialties (e.g., physical medicine and rehabilitation) provide multidomain treatment for various conditions. This presents challenges because physical medicine and rehabilitation is a small specialty, a diverse patient base in terms sociodemographics and diagnosis, treatments are difficult to standardize, and rehabilitation research is underfunded. We wished to identify quality and applicability of clinical practice guidelines and searched “Spinal Cord Injury AND Clinical Practice Guidelines AND Rehabilitation” and vetting process.

Three hundred fifty-nine articles were identified of which 58 met all criteria for full-text review of which 13 were included in the final selection. Additional publications were accessed from a nondatabase search. Five articles addressed postacute care, community treatment. Nine articles had no recorded vetting process but addressed rehabilitation as an outcome and were included separately. Many of the clinical practice guidelines were developed without evidence from randomized controlled trials, one had input from stakeholders, and some are out of date and do not address important aspects of changes in demographics of the affected population and the use of newer technologies such as sensors and robotics and devices. Identification of these gaps may help stimulate treatment that is clinically relevant, accessible, and current.
Psychotherapy in the Post-COVID-19 Era
Authors: PLAKUN ERIC M.
Published: November 2020

This column anticipates challenges likely to be faced by psychotherapists and their patients after the coronavirus disease 2019 (COVID-19) pandemic subsides. It looks beyond the current impact of loneliness, isolation, thwarted belongingness, and loss toward the longer term impact of moral injury and blocked opportunities for mourning.
Promoting Medication Adherence Among Psychiatric Patients With a History of Nonadherence: A Clinical Practice Improvement Program
Authors: XIA XIANGBING SHEPHERD , POREMSKI DANIEL , UBANA REGINA L. , RAVICHANDRAN NIGILA
Published: November 2020

Background:

People with serious mental illness may require long-term psychotropic medications. However, nonadherence is prevalent after discharge, often leading to re-admission. Several strategies exist to reduce nonadherence. The current project uses clinical practice improvement methodologies to test and adjust strategies to improve medication adherence at the Institute of Mental Health in Singapore.

Methods:

Two focus groups (one of which involved nonadherent individuals and the other adherent individuals) were conducted to explore the root cause of our service users’ nonadherence. On the basis of the causes identified, the team developed and implemented a person-centered medication adherence counseling intervention, incorporating motivational interviewing and psychoeducation. Data from all service users (n=156) who were nonadherent to psychotropic medications upon admission to our men’s ward between October 2017 and December 2018 were examined, with 63 of the men serving as the baseline sample and 93 receiving the adherence intervention. The team also reduced medication frequency and actively explored patients’ willingness to switch to long-acting injectable antipsychotics. A validated visual analogue self-reporting scale was used to measure adherence at screening and 30 days after discharge. Interrupted time series analysis was used to assess the effects.

Results:

After an intervention involving 3 specific strategies that addressed the concerns identified during the focus groups, the percentage of people who adhered to their treatment regimen 30 days after discharge increased by 33% (95% confidence interval: 15%-51%, P=0.001). Our balance measure (a secondary outcome that may be negatively or positively affected by efforts to influence the primary outcome), which was the percentage of people readmitted within 30 days of their discharge, showed a significant improvement (ie, a decrease in percentage readmitted).

Conclusions:

Quality improvement methodologies can be used to solve common problems with context-specific solutions. The implementation of person-centered medication adherence counseling led by an advanced practice nurse in concert with optimization of medication regimens appears to be a promising strategy for improving adherence in nonadherent patients admitted to the psychiatric ward.
Cognitive Remediation for Outpatients With Recurrent Mood Disorders: A Feasibility Study
Authors: DOUGLAS KATIE M. , JORDAN JENNIFER , INDER MAREE L. , CROWE MARIE T. , MULDER ROGER , LACEY CAMERON , BEAGLEHOLE BEN , BOWIE CHRISTOPHER R. , PORTER RICHARD J.
Published: November 2020

Current first-line treatments for mood disorders often improve mood symptoms but do little to reduce cognitive and functional impairment. This 10-week, uncontrolled, feasibility study evaluated a cognitive remediation (CR) intervention for individuals with recurrent mood disorders. Adults with recurrent major depressive disorder or bipolar disorder, who had recently been treated and discharged from specialized mental health services, were eligible for inclusion. Twenty patients completed the CR intervention, which involved weekly individual sessions with a therapist, as well as the practice of computerized CR exercises between sessions. The study assessed the acceptability of the assessment and treatment as well as outcomes in terms of mood symptoms, general functioning, and cognitive functioning. Patients reported that they were generally satisfied with the CR intervention and were close to reaching the recommended amount of practice between therapist-led sessions. The retention rate from baseline to posttreatment was 87%. When within-group effects were examined, large effect sizes over time (>0.9) were seen for 2 cognitive variables that measured executive function: Category Switching–Total Words and Total Switching Score. Findings from the current feasibility study will inform the development of a large randomized controlled trial of an adapted version of the CR intervention for mood disorders assessed in this preliminary study, with the goal of translating the intervention into clinical practice.