bluuebunny/crossref_metadata_2025 huggingface dataset:
ENHANCE: Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Adjunctive Pimavanserin for Schizophrenia in Patients With an Inadequate Response to Antipsychotic Treatment
Authors: Bugarski-Kirola Dragana , Bitter Istvan , Liu I-Yuan , Abbs Brandon , Stankovic Srdjan
Published: January 2022

Inadequate response to antipsychotic treatment is common in patients with schizophrenia. This study evaluated pimavanserin, a 5-HT2A receptor inverse agonist/antagonist, as adjunctive treatment in patients with inadequate response. This was a 6-week, randomized, double-blind, placebo-controlled, study conducted in North America and Europe. Adult outpatients with schizophrenia and inadequate response to current antipsychotic were enrolled. Inclusion criteria included Positive and Negative Syndrome Scale (PANSS) total score ≥65 and ≤110 and retrospective antipsychotic treatment stability of 8 weeks. Pimavanserin 20 mg/day or placebo added to ongoing antipsychotic was tested in a flexible-dose paradigm with dose adjustments allowed during the first 3 weeks. The primary efficacy endpoint, PANSS total score change from baseline to week 6, was not met, although improvement was greater with pimavanserin than placebo (LS mean difference: –2.1, [95% CI: –4.5, 0.4]; P = .094). As a hierarchical testing procedure was used, additional efficacy analyses were exploratory. Clear separation from placebo was observed with pimavanserin at week 6 for the PANSS Negative Symptoms subscale (LS mean difference: –0.7, [95% CI: –1.5, 0.0]) and Marder Negative Symptom Factor score (–0.9, [–1.7, –0.1]). Analysis of European sites (81.5% of patients) revealed a difference for pimavanserin versus placebo on PANSS total score (LS mean difference: –3.1, [95% CI: –5.8, –0.4]) and Clinical Global Impressions–Severity score (–0.2, [–0.4, –0.0]). Treatment-emergent adverse events occurred in 39.9% with pimavanserin and 36.4% with placebo. Although statistical significance for the primary endpoint was not met, a trend toward improvement in negative symptoms was observed with pimavanserin, warranting further study.
Homogenous Japan? An Empirical Examination on Public Perceptions of Citizenship
Authors: Woo Yujin
Published: January 2022

Does the Japanese public consider shared ancestry the most essential condition for inclusion of an individual as a member of their country’s citizenry? This paper empirically assesses how the public in the ethnic nation views citizenship acquisition criteria. The originally conducted survey based on a conjoint format in Japan (2015) displays interesting results. Overall, Japanese people most heavily rely on the nationalities of parents in judging who qualifies as ‘Japanese’, confirming the contentions of previous works that highlight Japanese people’s belief in a mono-ethnic Japan. More detailed statistical analyses further reveal that Japanese people consider ethnic heritage through the father as the most essential criterion while the mother’s nationality and country of upbringing are also relevant. These results seem to reflect Japan’s long-lasting beliefs in cultural homogeneity as well as patriarchal values, which are reinforced by a patrilineal tradition of citizenship. This research advances the discussion on how to classify citizenship features by disaggregating ethnic lineage into paternal and maternal lines. Furthermore, it suggests a reevaluation of Japan’s institutional and social attachment to patrilineal ethnic heritage in order to ease multiple layers of discrimination posed against (particularly female) migrants and to realize a sound multiethnic society.
Novel Mesenchymal Stem Cell Spheroids with Enhanced Stem Cell Characteristics and Bone Regeneration Ability
Authors: Ohori-Morita Yumi , Niibe Kunimichi , Limraksasin Phoonsuk , Nattasit Praphawi , Miao Xinchao , Yamada Masahiro , Mabuchi Yo , Matsuzaki Yumi , Egusa Hiroshi
Published: January 2022

Mesenchymal stem cells (MSCs) exhibit self-renewal, multi-lineage differentiation potential and immunomodulatory properties, and are promising candidates for cellular therapy of various tissues. Despite the effective function of MSCs, the gradual loss of stem cell characteristics that occurs with repeated passages may significantly limit their therapeutic potential. A novel 3D shaking method was previously established to generate MSC spheroids in growth medium (GM-spheroids) and successfully maintain the multipotency of expanded MSCs, yet the expression of MSC-related genes was still low. In this study, we used a neurosphere culture technique to optimize the shaking culture method using human bone marrow-derived MSCs (BM-MSCs). MSC spheroids generated in neurosphere medium (NM-spheroids) maintained high expression of MSC-related genes during 3 weeks of prolonged shaking culture. Moreover, NM-spheroids generated from expanded MSCs showed high viability, upregulation of MSC-related and immune-related genes, and recovery of differentiation potential in vitro. Expanded adherent MSCs, GM-spheroids, and NM-spheroids were transplanted into a rat femur bone defect model to investigate their therapeutic potential in bone repair. Adherent MSCs and GM-spheroids showed delayed bone healing. In contrast, NM-spheroids showed high transplantation efficiency and enhanced bone regeneration. These data suggest that NM-spheroids generated using modified neurosphere culture conditions under continuous shaking recovered their stem cell characteristics in vitro and enhanced bone regeneration in vivo. Therefore, NM-spheroids should have great clinical potential for bone and tissue regenerative therapies as a stem cell-based biomaterial therapy.
The Crosstalk Between Adipose-Derived Stem or Stromal Cells (ASC) and Cancer Cells and ASC-Mediated Effects on Cancer Formation and Progression—ASCs: Safety Hazard or Harmless Source of Tropism?
Authors: Guillaume Vincent G J , Ruhl Tim , Boos Anja M , Beier Justus P
Published: January 2022

Adipose-derived stem or stromal cells (ASCs) possess promising potential in the fields of tissue engineering and regenerative medicine due to their secretory activity, their multilineage differentiation potential, their easy harvest, and their rich yield compared to other stem cell sources. After the first identification of ASCs in humans in 2001, the knowledge of their cell biology and cell characteristics have advanced, and respective therapeutic options were determined. Nowadays, ASC-based therapies are on the verge of translation into clinical practice. However, conflicting evidence emerged in recent years about the safety profile of ASC applications as they may induce tumor progression and invasion. Numerous in-vitro and in-vivo studies demonstrate a potential pro-oncogenic effect of ASCs on various cancer entities. This raises questions about the safety profile of ASCs and their broad handling and administration. However, these findings spark controversy as in clinical studies ASC application did not elevate tumor incidence rates, and other experimental studies reported an inhibitory effect of ASCs on different cancer cell types. This comprehensive review aims at providing up-to-date information about ASCs and cancer cell interactions, and their potential carcinogenesis and tumor tropism. The extracellular signaling activity of ASCs, the interaction of ASCs with the tumor microenvironment, and 3 major organ systems (the breast, the skin, and genitourinary system) will be presented with regard to cancer formation and progression.
Surgical Management of Delayed Brachial Plexopathy After Clavicle Nonunion
Authors: McGillivray Meghan K. , Doherty Christopher , Bristol Sean G. , Lawlor David Kirk , Baxter Keith A. , Lefaivre Kelly A.
Published: January 2022

Brachial plexopathy after conservative therapy or surgical treatment of clavicular fractures is an uncommon, yet serious complication that is associated with compression of the brachial plexus or the subclavian artery and vein because they traverse through the thoracic outlet. Surgical decompression of the brachial plexus is the recommended treatment if this condition is to occur. Although there are multiple reports of these cases in the literature, at present, there are no clear guidelines for their management. We are highlighting an institutional management algorithm, illustrated by a small retrospective case series, that uses a multidisciplinary approach in an effort to minimize complications associated with the management of clavicle nonunion.
Use of Extracorporeal Membrane Oxygenation in Acutely Poisoned Pediatric Patients in United States: A Retrospective Analysis of the Extracorporeal Life Support Registry From 2003 to 2019
Authors: Di Nardo Matteo , Alunni Fegatelli Danilo , Marano Marco , Danoff Jacob , Kim Hong K.
Published: January 2022

OBJECTIVES:

To describe the use of extracorporeal membrane oxygenation (ECMO) in the management of pediatric poisoning in the United States and to identify predictors of mortality.

DESIGN:

Retrospective cohort study.

SETTING:

Data reported to the Extracorporeal Life Support Organization by 76 U.S. ECMO centers from 2003 to 2019.

PATIENTS:

Pediatric patients (0–18 yr) receiving ECMO for poisoning.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

During our study period, 86 cases of acute poisoning were identified and included in the analysis. The median age was 12.0 year and 52.9% were female. The most commonly reported substance exposures were hydrocarbon (n = 17; 19.8%), followed by chemical asphyxiants (n = 14; 16.3%), neuroactive agents (n = 14; 16.3%), opioid/analgesics (n = 13; 15.1%), and cardiovascular agents (n = 12; 14.0%). Single substance exposures were reported in 83.7% of the cases. The intention of the exposure was unknown in 65.1%, self-harm in 20.9% and 10.5% was unintentional exposure. Fifty-six patients (65.1%) survived. Venoarterial ECMO was used more frequently than venovenous ECMO, and its use increased significantly during the study period (p < 0.01). A bimodal distribution of ECMO support was observed among two age groups: less than or equal to 3 years (n = 34) and 13–17 years (n = 41). Hemodynamic and metabolic parameters improved for all patients with ECMO. Persistent systolic hypotension, acidemia/metabolic acidosis, and elevated Pao
2) after 24 hours of ECMO support were associated with mortality. Time from PICU admission to ECMO cannulation was not significantly different between survivors (24.0 hr; interquartile range [IQR], 11.0–58.0 hr) and nonsurvivors (30.5 hr; IQR, 10.0–60.2 hr; p = 0.58). ECMO duration and PICU length of stay were significantly longer in survivors than in nonsurvivors (139.5 vs 70.5 hr; p = 0.007 and 25.0 vs 4.0 d; p = 0.002, respectively).

CONCLUSIONS:

ECMO may improve the hemodynamic and metabolic status of poisoned pediatric patients. Persistent hypotension, acidemia/acidosis, and elevated Pao
2 after 24 hours of ECMO were associated with mortality.
Baby Wet Wipes: An Unusual Culprit of Lymphomatoid Contact Dermatitis Mimicking Mycosis Fungoides
Authors: Coleman Emily , Bhawan Jag
Published: January 2022

Lymphomatoid contact dermatitis (LCD) is a rare, benign pseudolymphoma with clinicopathologic features of both allergic contact dermatitis and cutaneous T-cell lymphoma (CTCL). In this article, we report a fascinating case of LCD secondary to chronic baby wet wipe use with clinical features of allergic contact dermatitis and histopathologic changes of mycosis fungoides, a subtype of CTCL. We argue that LCD should be added to the list of mimickers of mycosis fungoides, a subtype of CTCL.
The Effects of Peripheral Inflammation on the Brain—A Neuroimaging Perspective
Authors: Millett Caitlin E. , Burdick Katherine E. , Kubicki Marek R.
Published: January 2022

In the field of neuropsychiatry, neuroinflammation is one of the prevailing hypotheses to explain the pathophysiology of mood and psychotic disorders. Neuroinflammation encompasses an ill-defined set of pathophysiological processes in the central nervous system that cause neuronal or glial atrophy or death and disruptions in neurotransmitter signaling, resulting in cognitive and behavioral changes. Positron emission tomography for the brain-based translocator protein has been shown to be a useful tool to measure glial activation in neuropsychiatric disorders. Recent neuroimaging studies also indicate a potential disruption in the choroid plexus and blood-brain barrier, which modulate the transfer of ions, molecules, toxins, and cells from the periphery into the brain. Simultaneously, peripheral inflammatory markers have consistently been shown to be altered in mood and psychotic disorders. The crosstalk (i.e., the communication between peripheral and central inflammatory pathways) is not well understood in these disorders, however, and neuroimaging studies hold promise to shed light on this complex process. In the current Perspectives article, we discuss the neuroimaging insights into neuroimmune crosstalk offered in selected works. Overall, evidence exists for peripheral immune cell infiltration into the central nervous system in some patients, but the reason for this is unknown. Future neuroimaging studies should aim to extend our knowledge of this system and the role it likely plays in symptom onset and recurrence.
Does discectomy improve low back pain as well as radiating pain in patients with lumbar herniated intervertebral disc (HIVD)?
Authors: Ko Sangbong , Kwon Jaebum
Published: January 2022

Most postoperative patients with herniated lumbar disc complained of lower leg radiating pain (LRP), referred buttock pain (RBP), and low back pain (LBP). When discectomy is performed, improvement in LRP is observed due to spinal nerve irritation. However, long-term LBP due to degenerative changes in the disc may occur postoperatively. In addition, limited research has been reported on the short-term (within 1 year) improvement in LBP after discectomy. This study aimed to evaluate the effectiveness of discectomy in reducing LBP within 1 year postoperatively.

Among the 183 patients who underwent discectomy performed by a single surgeon from January 2010 to December 2016, 106 who met the inclusion and exclusion criteria were enrolled. In the 106 patients who underwent lumbar discectomy, 3 types of spine-related pain were pre-operatively assessed and 3, 6, and 12 months postoperatively. Functional outcomes were evaluated, and quality of life was assessed 12 months postoperatively by using the Short-Form 36 questionnaire, which was subdivided into mental and physical components.

LBP showed both statistical and clinical improvement within the first 3 months postoperatively, but the improvement was not observed until 12 months postoperatively. RBP and LRP showed both statistical and clinical improvement within the first 3 months and further consistently showed statistical improvement. LBP improved clinically only until 3 months postoperatively regardless of the type of herniation.

LBP showed improvement within the first 3 months postoperatively and plateaued afterward, and RBP and radiculopathy showed consistent improvement until 12 months postoperatively. This may explain why patients from 12-month follow-up showed improvement in RBP and radiculopathy but not LBP.
Analysis of the active components and mechanism of Shufeng Jiedu capsule against COVID-19 based on network pharmacology and molecular docking
Authors: Simayi Jimilihan , Nuermaimaiti Maimaitiming , Wumaier Ainiwaer , Khan Nawaz , Yusufu Maierdan , Nuer Muhadaisi , Maihemuti Nulibiya , Bayinsang  , Adurusul Kaysar , Zhou Wenting
Published: January 2022

This study investigates the active components and mechanism of Shufeng Jiedu Capsules (SFJDC) against novel coronavirus through network pharmacology and molecular docking.

The TCMSP, TCMID, and BATMAN-TCM databases were used to retrieve the components of SFJDC. The active components were screened by ADME (absorption, distribution, metabolism, and excretion) parameters, and identified by Pubchem, Chemical Book, and ChemDraw softwares. The molecular docking ligands were constructed. SARS Coronavirus-2 Major Protease (SARS-CoV-2-Mpro) and angiotension converting enzyme 2 (ACE2) were used as molecular docking receptors. AutoDock software was used for molecular docking. Cytoscape 3.7.1 software was used to generate an herbs-active components-targets network. Gene Ontology gene function and Kyoto Encyclopedia of Genes and Genomes signal pathway analysis were performed by DAVID data.

A total of 1244 components were identified from SFJDC, and 210 active components were obtained. Among them, 97 active components were used as docking ligands to dock with SARS-CoV-2-Mpro and ACE2. There were 48 components with good binding activity to SARS-CoV-2-Mpro. Ten active components (including 7-Acetoxy-2-methylisoflavone, Kaempferol, Quercetin, Baicalein, Glabrene, Glucobrassicin, Isoglycyrol, Wogonin, Petunidin, and Luteolin) combined with SARS-CoV-2-Mpro and ACE2 simultaneously. Among them, Kaempferol, Wogonin, and Baicalein showed higher binding activity. The herbs-active components-targets network contained 7 herbs, 10 active components, and 225 targets. The 225 target targets were involved in 653 biological processes of Gene Ontology analysis and 130 signal pathways (false discovery rate ≤ 0.01) of Kyoto Encyclopedia of Genes and Genomes analysis.

The active components of SFJDC (such as Kaempferol, Wogonin, and Baicalein) may combine with ACE2 and act on multiple signaling pathways and targets to exert therapeutic effect on novel coronavirus.
Effects of MBSR therapy on negative emotions, fatigue, and sleep quality in “post-ICU patients”
Authors: Chen Yu , Wang Renying , Yu Jie , Zhu Liping , Lu Yiming , Deng Xueqin
Published: January 2022

Background:

Survivors of intensive care unit (ICU) transfer to the common ward are often accompanied by psychological distress, negative emotions, fatigue, and sleep disturbances that affect recovery. Mindfulness-based stress reduction (MBSR) has achieved reliable results in improving physical and mental health. However, no clinical study has been conducted to evaluate the effects of MBSR on negative emotions, fatigue and sleep quality of patients who survived ICU and were transferred to general wards.

Methods:

This is a prospective randomized controlled trial (RCT) examining the effects of MBSR on negative emotions, fatigue, and sleep quality in inpatients transferred from ICU to general ward. Participants were randomly divided into the treatment group and the control group in a ratio of 1:1. On the basis of the same nursing plan and health education, the treatment group received MBSR therapy, while the control group received no other interventions, and all the patients were followed up for 3 months after 2 weeks of continuous treatment. The indicators included negative mood indicators [Self-rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS)], fatigue index [Fatigue Severity Scale (FSS) and Brief Fatigue Inventory (BFI)], and sleep quality index [Pittsburgh Sleep Quality Index (PSQI)]. Finally, SPSS 20.0 software was used for statistical analysis of the data.

Discussion:

This study will evaluate the effects of MBSR on negative emotions, fatigue, and sleep quality in hospitalized patients transferred from ICU to general ward. The results of this study will provide a reference for MBSR to improve psychological distress in ICU survivors transferred to general ward.

Trial registration:

This study protocol was registered in the Open Science Framework (OSF) (registration number: DOI 10.17605/OSF.IO/PD7SU).
Effect of mindfulness-based stress reduction on stigma, coping styles, and quality of life in patients with permanent colorectal cancer stoma
Authors: Li Jing , Yuan En , Zhu Dan , Chen Mei , Luo QingHua
Published: January 2022

Background

: Colorectal cancer patients with permanent colostomy may suffer stigma, negative coping style, and low quality of life at varying degrees, which may be improved by the mindfulness-based stress reduction (MBSR). In recent years, MBSR has been used in the comprehensive treatment of colorectal cancer with permanent colostomy, hoping to bring a positive outcome. However, the practical application effect of MBSR has not been elucidated so far. Therefore, this study conducted a meta-analysis to evaluate the effects of MBSR on stigma, coping style, and quality of life in colorectal cancer patients with permanent colostomy, providing reliable evidence for clinical application.

Methods

: Randomized controlled trials (RCTs) reporting MBSR on stigma, coping style, and quality of life in patients with permanent stoma of colorectal cancer published before December 2021 will be searched in online databases such as the PubMed, Web of Science, The Cochrane Library, Embase, China National Knowledge Infrastructure, Wanfang Database, China Biomedical Literature Database, and Chinese Scientific Journal Database. The quality of the literature will be evaluated using the risk of bias assessment tool in Revman 5.4. Meta-analysis will be performed using Revman 5.4 software.

Results

: The Social Impact Scale (SIS), Simplified Coping Style Questionnaire (SCSQ), and quality of life scale will be used to evaluate the effects of MBSR on stigma, coping style, and quality of life in colorectal cancer patients with permanent colostomy.

Conclusion

: This study will provide a reliable evidence-based basis for MBSR to reduce stigma, improve coping style, and improve quality of life for colorectal cancer patients with permanent colostomy.

OSF REGISTRATION NUMBER:

DOI 10.17605/OSF.IO/CD4PV.
Case series: 3D printed orthopedic brace combined with traditional manipulative physiotherapy to treat new-onset scoliosis in adults
Authors: Jin Hui , Zhang Ziyu , Gao Yao , He Huan , Feng Shibin , Xu Rui , Li Qiang , Zuo Hao
Published: January 2022

Introduction

New-onset scoliosis in adults is different from that in congenital and idiopathic scoliosis. We applied personalized custom 3D printed orthopedic braces combined with traditional manipulative physiotherapy to treat adult patients with new-onset scoliosis and observed the effectiveness of the treatment.

Patient concerns

Nine patients aged 20–52 years presented with unequal height of hips and asymmetrical waist. One shoulder was obviously protruding or enlarged compared to the other; when lying on the bed, the legs were not equal in length, and when bending down, the back was not equal on the left and right.

Diagnosis

New-onset scoliosis.

Interventions

Application of individual customized 3D printing brace combined with traditional treatment. Evaluation of clinical efficacy after treatment, including functional exercise test (FMS) before and after treatment, ability of daily living (ADL), visual analog pain score (VAS), and scoliosis angle (Cobb angle).

Outcomes

The total effective treatment rate was 100.00% (9/9). The VAS score, Cobb angle of the spine, FMS test, and ADL test were significantly improved compared with those before treatment.

Conclusion

The customized 3D printed orthopedic brace combined with traditional techniques to treat scoliosis and innovatively combined human bionic technology with traditional medicine to achieve the continuity and precise correction of scoliosis treatment is a clinically effective technique.
Fetal intracranial hemorrhage and maternal vitamin K deficiency induced by total parenteral nutrition
Authors: Lee Subeen , Kim Hyun Mi , Kang Juyeon , Seong Won Joon , Kim Mi Ju
Published: January 2022

Rationale:

Fetal brain hemorrhage is rare. It is caused mainly by maternal trauma or fetal coagulation disorder, but in some cases, vitamin K deficiency may be the cause.

Patient concerns:

We describe the case of a pregnant woman with bowel obstruction who was susceptible to vitamin K deficiency due to oral diet restriction, decreased intestinal absorption, and limited intravenous vitamin K supplementation.

Diagnosis:

After 18 days of intermittent total parenteral nutrition, acute onset of severe fetal brain hemorrhage developed.

Interventions:

After acute onset of fetal brain hemorrhage, the patient underwent an emergency cesarean section at 25 + 3 weeks of gestation due to fetal non-reassuring fetal monitoring.

Outcomes:

The Apgar score at birth was 0/0, and despite cardiopulmonary resuscitation, neonatal death was confirmed. After the baby was delivered, we checked the maternal upper abdominal cavity and found a massive adhesion in the small bowel to the abdominal wall near the liver and stomach with an adhesion band. The adhesion band, presumably a complication of previous hepatobiliary surgery, appeared to have caused small bowel obstruction. Adhesiolysis between the small bowel and abdominal wall was performed.

Lessons:

This case demonstrates that even relatively short-term total parenteral nutrition can cause severe fetal brain hemorrhage. Vitamin K supplementation is required for mothers who are expected to be vitamin K deficient, especially if they are on total parenteral nutrition for more than 3 weeks.
Association of the VEGFR2 single nucleotide polymorphism rs2305948 with glioma risk
Authors: Sun Shushu , Li Xiaotian , Qu Bingkun , Xie Kunming , Li Jinlei , Miao Junjie
Published: January 2022

Background:

Many studies have reported a relationship between the vascular endothelial growth factor receptor 2 single nucleotide polymorphism (SNP) rs2305948 and glioma, but their conclusions have been controversial. A meta-analysis was performed to assess the association between rs2305948 and glioma susceptibility.

Methods:

Inclusion criteria and a strategy for screening of original literature were created. Eligible articles on the correlation between the SNP rs2305948 and glioma were identified in the PubMed, Embase, Web of Science, Cochrane Library, CNKI and Wanfang databases. After extracting the data, Stata 12. 0 software was used to perform statistical analysis under 5 genetic models and to calculate the combined odds ratio (OR) value and its 95% confidence interval (CI).

Results:

Four case-control studies including 1595 cases and 1657 controls were entered into the study. The overall analysis showed that no obvious association existed between rs2305948 and glioma risk (allele: OR = 1.20, 95% CI = 0.93–1.54, P = .162; dominant: OR = 1.17, 95% CI = 0.93–1.46, P = .174; recessive: OR = 1.72, 95% CI = 0.94–3.15, P = .076; heterozygous: OR = 1.11, 95% CI = 0.94–1.30, P = .226; homozygous: OR = 1.74, 95% CI = 0.92–3.29, P = .088). The subgroup analysis suggested that the SNP rs2305948 was related to glioma susceptibility under allele, dominant, recessive and homozygote models in the Asian population (allele: OR = 1.34, 95% CI = 1.16–1.55, P < .001; recessive: OR = 2.24, 95% CI = 1.49–3.36, P < .001; homozygous: OR = 2.32, 95% CI = 1.54–3.50, P < .001).

Conclusion:

The vascular endothelial growth factor receptor 2 rs2305948 gene polymorphism may be related to glioma susceptibility in the Asian population. However, the association is not clear in non-Asian populations, for which there has been less research.
Biphasic synovial sarcoma with a striking morphological divergence from the main mass to lymph node metastasis
Authors: Woo Ha Young
Published: January 2022

Rationale:

Synovial sarcoma accounts for 5% to 10% of all soft tissue sarcomas and involves almost any anatomic site, particularly the deep soft tissue of the extremities of young adults. The incidence rate of lymph node metastases in synovial sarcoma is 3% to 7%, but the detailed morphological features of the metastatic tumors in the lymph node have not been documented.

Patient concerns:

A 64-year-old Korean man presented with a huge mass in the left lower thorax and multiple hypermetabolic lymph nodes along the mediastinal, supraclavicular, internal mammary, and retrocrural regions.

Diagnoses:

The patient was diagnosed with primary pleuropulmonary biphasic synovial sarcoma with lymph node metastases, where the main mass mostly comprised spindle cells (>95%) and the metastatic lymph nodes comprised only epithelial cells.

Interventions:

Left lower lobe lobectomy with the resection of the chest wall (including left ribs 8-10) and diaphragm and mediastinal lymph node dissection were performed.

Outcomes:

In the 2-month follow-up period, there have been no complications so far, and the attending physician is currently planning for the adjuvant chemotherapy.

Lessons:

The main mass and the metastatic lesion can be clearly different morphologically. In tumors with biphasic differentiation, such as synovial sarcoma, cells that constitute only a small fraction of the main mass may appear as the dominant cells in metastatic lesions.
Bibliometric analysis of toll-like receptor agonists associated with cancer therapy
Authors: Li Wei , Wan Li , Duan Shaojun , Xu Jingjing
Published: January 2022

Background:

Toll-like receptors (TLRs), a family of innate pattern-recognition receptors, have been exploited as a target for antitumor strategy. An increasing number of TLR agonists, serving as immunotherapeutics or vaccine adjuvants, were developed. This study aimed at exploring the status and trend of current researches on TLR agonists through bibliometric analysis.

Methods:

Original publications on TLR agonists were collected from the Web of Science Core Collection. Data were analyzed in terms of publication outputs, journals, countries, institutions, authors, co-authorship, co-citation, research hotspots, and evolution trends through VOSviewer and CiteSpace.

Results:

A total of 1914 TLR agonists-related articles, published in 612 academic journals between 2000 and 2019, were enrolled in the study. The Journal of Immunology published the most publications, followed by PLoS One and Blood. The USA that is in possession of the largest number of articles and the most extensive cooperators was the most leading country in this field. University of Minnesota ranked the first in terms of paper totality, but its average citations ranking was lower than University of Pennsylvania. Gudkov AV was the most productive author, whose team reported a TLR5 agonist that had radioprotective activity in mouse and primate models in 2008. The paper of Akira Shizuo, professor of Osaka University, was widely cited by international peers. The research trend of TLR agonists has undergone 3 periods: mechanisms of TLR signalings in immunotherapy (2000–2010), discovery of TLR agonists (2011–2014), application, therapeutic evaluation, and drug design of TLR agonists (2015–2019).

Conclusion:

This study provides investigators a landscape of TLR agonists research from the perspective of bibliometrics.
A novel frameshift c.22_25dupGCAT mutation of the NDP gene in a Chinese infant with Norrie disease
Authors: Wang He , Liu Zeyuan , Zhou Yuantao , Ma Yuanyuan , Tao Dan
Published: January 2022

Rationale:

Norrie disease (ND) is a rare X-linked recessive disease characterized by bilateral congenital blindness and auditory impairments. According to the previous studies, Norrin cystine knot growth factor (NDP) gene have been found to be responsible for ND. Herein, we report a case of ND with a novel mutation in NDP and elucidate the clinical and molecular characteristics of this patient.

Patient concerns:

A 2-month-old Chinese male infant presented with gray-white opacification in the bilateral cornea. Vitreous opacity and retinal detachment were observed on ocular ultrasound. Furthermore, a novel de novo hemizygous mutation (c.22_25dupGCAT, p.S9Cfs∗18) in exon 2 of the NDP gene was identified by next-generation sequencing. SWISS-MODEL predicted that the c.22_25dupGCAT mutation truncated the NDP protein.

Diagnosis:

Based on the above clinical and genetic evidence, this patient was eventually diagnosed with ND.

Interventions:

Currently, no clinical therapy is available for ND.

Outcomes:

In addition to the typical ocular symptoms, no other abnormalities were observed. The patient's vital signs remained stable and normal.

Lesson:

A novel causative mutation of NDP was identified using next-generation sequencing. Our report expands the pathogenic mutation spectrum of NDP and facilitates genetic counseling and prenatal diagnosis. Additionally, we emphasize the importance of molecular genetic testing in the diagnosis of ND.
Research progress of diagnosing methodology for lumbar segmental instability
Authors: Wang Yingfeng , Huang Kai
Published: January 2022

Objective:

Lumbar segmental instability (LSI) is due to a pathologic movement of the vertebral body on the vertebra below and often causes clinical symptoms. The study was to achieve the research progress of diagnosing methodology for lumbar segmental instability and help clinicians make treatment choices.

Methods:

The data for this study were collected from the MEDLINE, Springer, Web of Science, PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, Evidence Based Medicine Reviews, VIP, and CNKI. The search terms were integrated as follows: “(∗lumbar instability∗ OR ∗lumbar spondylolisthesis∗) and (∗image∗ or ∗diagnosis∗)”. Studies without clear radiographic instable criteria, case reports, letter, and basic research were excluded.

Result:

In total, 39 articles published met our inclusion criteria. The various modalities were used to diagnosis LSI in these studies included radiographs, facet joint degeneration and physical examination tests.

Conclusion:

Overall, there have been a variety of researches to develop the diagnosing methodology for LSI, and many have been successful, although no consensus has been reached yet. However, it is believed that the diagnosis of LSI will become easier and more accurate in the near future.
Antineutrophil cytoplasmic antibody-associated vasculitis with alveolar hemorrhage and ruptured renal aneurysm
Authors: Tong Jin , Zhou Zhi-Yu , Liu Xi , Wang Dao-Xin , Deng Wang
Published: January 2022

Rationale:

Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is characterized by necrotizing damage to small-vessel vasculitis and mainly occurs in the kidney or lung. We report a rare case of AAV manifesting as alveolar hemorrhage and a renal aneurysm.

Patient concerns:

A 50-year-old Chinese man presented with repeated coughing, expectoration, fever, hypoxemia, and respiratory failure. The patient suffered from rupture of the renal aneurysm during immunosuppressive therapy.

Diagnosis:

Considering the clinical picture (fever, progressive hypoxemia, renal insufficiency, hemorrhagic bronchoalveolar lavage fluid, and left retroperitoneal hematoma) along with cANCA-PR3 positivity, and lung biopsy findings, the patient was finally diagnosed with granulomatosis with polyangiitis complicated by alveolar hemorrhage and renal aneurysm.

Interventions:

The patient was initially treated with immunosuppressive therapy combined with plasma exchange and subsequently with renal arterial embolization due to rupture of the renal aneurysm.

Outcomes:

The general condition and inflammatory reaction improved with immunosuppressive therapy combined with plasma exchange. Unfortunately, the patient did not respond to treatment and eventually died of respiratory failure and acute kidney injury after the rupture of the renal aneurysm.

Lessons:

We encountered unprecedented difficulties and challenges with renal aneurysm rupture. The possibility of aneurysmal rupture should be carefully considered and frequently checked for immunosuppressive therapy for AAV.
Above and Beyond the Call of Duty
Authors: McMillan Libba Reed , Elliott Brenda , Chargualaf Katie A.
Published: January 2022

Approximately 4.7 million Veterans live in rural areas and face challenges receiving support and care for complex service-connected healthcare needs. The purpose of this qualitative descriptive study was to explore nurses' experiences caring for Veterans in rural home care/hospice settings. Semistructured interviews (N = 14) were conducted between August 2020 and March 2021. Content and thematic analysis resulted in three central themes: Mission readiness: Ensuring safe home environments, Partnering with Veterans: Knowing when to lead and when to follow, and It's my duty: Caring with purpose and honor. Study findings highlight the need for cultural competence in both rural and Veteran cultures. Implications for practice reinforce currently emerging national priorities, including personal safety considerations and need for further professional development associated with screening for firearms and gun safety. Other implications for home care/hospice agencies, as well as nursing education, are discussed.
Caring for Aging Skin
Authors: Kirkland-Kyhn Holly , Zaratkiewicz Sunniva , Teleten Oleg , Young Heather M.
Published: January 2022

This article is part of a series, Supporting Family Caregivers: No Longer Home Alone, published in collaboration with the AARP Public Policy Institute. Results of focus groups, conducted as part of the AARP Public Policy Institute's No Longer Home Alone video project, supported evidence that family caregivers aren't given the information they need to manage the complex care regimens of family members. This series of articles and accompanying videos aims to help nurses provide caregivers with the tools they need to manage their family member's health care at home.

The articles in this new installment of the series provide simple and useful instructions that nurses should reinforce with family caregivers who perform wound care tasks. Each article also includes an informational tear sheet—Information for Family Caregivers—that contains links to instructional videos. To use this series, nurses should read the article first, so they understand how best to help family caregivers, and then encourage caregivers to watch the videos and ask questions. For additional information, see Resources for Nurses.
Teaching Wound Care to Family Caregivers
Authors: Kirkland-Kyhn Holly , Generao Stephanie Anne , Teleten Oleg , Young Heather M.
Published: January 2022

This article is part of a series, Supporting Family Caregivers: No Longer Home Alone, published in collaboration with the AARP Public Policy Institute. Results of focus groups, conducted as part of the AARP Public Policy Institute's No Longer Home Alone video project, supported evidence that family caregivers aren't given the information they need to manage the complex care regimens of family members. This series of articles and accompanying videos aims to help nurses provide caregivers with the tools they need to manage their family member's health care at home.

The articles in this new installment of the series provide simple and useful instructions that nurses should reinforce with family caregivers who perform wound care tasks. Each article also includes an informational tear sheet—Information for Family Caregivers—that contains links to instructional videos. To use this series, nurses should read the article first, so they understand how best to help family caregivers, and then encourage caregivers to watch the videos and ask questions. For additional information, see Resources for Nurses.
Thyroid Disease in Pregnancy: A Descriptive Review of Guidelines
Authors: Tsakiridis Ioannis , Giouleka Sonia , Kourtis Anargyros , Mamopoulos Apostolos , Athanasiadis Apostolos , Dagklis Themistoklis
Published: January 2022

Importance

Thyroid disorders represent one of the most frequent complications of pregnancy associated with adverse obstetric, fetal, and neonatal outcomes, especially in case of delayed diagnosis and suboptimal management.

Objective

The aim of this study was to review and compare the recommendations of the most recently published guidelines on the diagnosis and management of these common conditions.

Evidence Acquisition

A descriptive review of guidelines from the Endocrine Society, the European Thyroid Association, the Royal Australian and New Zealand College of Obstetricians and Gynecologists, the American Thyroid Association, and the American College of Obstetricians and Gynecologists on thyroid disease in pregnancy was carried out.

Results

There is an overall consensus regarding the diagnosis of overt and subclinical hypothyroidism and hyperthyroidism in pregnancy using the pregnancy-specific reference ranges and the definition of postpartum thyroiditis. The reviewed guidelines unanimously discourage universal screening for thyroid function abnormalities before and during pregnancy and support targeted screening of high-risk patients by measuring serum thyroid-stimulating hormone levels. Moreover, they all highlight the need of treating overt hypothyroidism and hyperthyroidism, not only during pregnancy, but also before conception, suggesting similar management policies and treatment targets. There is also agreement regarding the management of gestational transient hyperthyroidism with hyperemesis gravidarum, suspected fetal thyrotoxicosis, postpartum thyroiditis, and thyroid malignancy. Scanning or treating with radioactive iodine is contraindicated during pregnancy and breastfeeding. On the other hand, there is controversy on the management of subclinical thyroid disease, thyroid function surveillance protocols, and iodine nutrition recommendations. Of note, the American College of Obstetricians and Gynecologists makes some specific recommendations on the treatment of thyroid storm and thyrotoxic heart failure in pregnant women, whereas the American Thyroid Association makes a special reference to the management of women with thyroid cancer.

Conclusions

As the disorders of the thyroid gland affect a significant proportion of pregnant women, it is of paramount importance to develop uniform international evidence-based protocols for their accurate diagnosis and optimal management, in order to safely guide clinical practice and eventually improve perinatal outcomes.

Target Audience

Obstetricians and gynecologists, family physicians

Learning Objectives

After participating in this activity, the physician should be better able to define and diagnose overt and subclinical hypothyroidism and hyperthyroidism in pregnant women; explain the recommended antenatal and postnatal management for hypothyroidism; and describe the treatment plan for hyperthyroidism in each trimester of pregnancy.
Sialocele of Submandibular Gland, an Unreported Complication of Bilateral Sagittal Split Osteotomy
Authors: Dediol Emil , Harmicar David , Borumandi Farzad
Published: January 2022

Bilateral sagittal split osteotomy is a routine procedure with predictable and well-known complications. The authors report a thitherto unreported complication of bilateral sagittal split osteotomy presenting as a postoperative sialocele of submandibular salivary gland tissue in the floor of the mouth. The sialocele was probably caused by overinstrumentation and injury to sublingual salivary tissues or Wharton's duct during bicortical drilling or screw fixation. This iatrogenic sialocele was managed conservatively with multiple aspiration and compression dressings. Although rare and unreported so far this complication may be included in the preoperative consent process.
A Preliminary Management Algorithm for Velopharyngeal Insufficiency in Cleft-Orthognathic Patients
Authors: Sasson Daniel C. , Reategui Alvaro , Phillips Sarah , Smetona John T. , Lopez Joseph , Parsaei Yassmin , Steinbacher Derek M.
Published: January 2022

Purpose:

Patients born with a cleft palate often suffer from velopharyngeal insufficiency (VPI) due to the soft palate musculature's abnormal structure. Surgical correction of the palate at a young age can hinder maxillary growth, requiring surgical correction of the maxillomandibular discrepancy at skeletal maturity. Orthognathic surgery can then cause or further exacerbate VPi in these patients. The purpose of this paper is to assess cleft-orthog-nathic patients under the lens of persistent or newly-developed VPi, to understand outcomes and generate a targeted management algorithm.

Methods:

A retrospective study was performed inspecting cleft-orthognathic patients presenting to a single surgeon. Patients with sufficient follow-up were placed into predefined algorithmic cohorts by their VPi development pattern in relation to orthognathic surgery. They were further stratified into groups by level of adherence to our algorithm to evaluate VPi outcomes. Demographic factors, risk factors, and outcomes were compared between groups via Welch t test and Fisher exact test.

Results:

Fifty-one patients were examined, including 16 with VPI. Velopharyngeal insufficiency fully resolved amongst all algorithmically adherent patients and remained in nonadherent patients (P < 0.001).

Conclusions:

Our targeted algorithm may improve symptoms and the management of VPI in cleft-orthognathic patients. Multi-centered studies with larger sample sizes and prospective studies are encouraged to validate our proposed treatment algorithm further.
Dexamethasone Induces Apoptosis of Embryonic Palatal Mesenchymal Cells Through the GATA-6/Bone Morphogenetic Protein-2/p38 MAPK Pathway
Authors: Lan Shijie , Yang Xiaoguang , Li Tian , Yang Tianye , Rong Li
Published: January 2022

Exposure to dexamethasone (DEX) causes cleft palate at high rates. Our previous studies proved that GATA binding protein 6 (GATA-6)/bone morphogenetic protein-2 (BMP-2) mediated apoptosis is related to DEX-induced cleft palate, but the specific mechanism is still unclear. The goal of this research was to understand the mechanism of apoptosis in cleft palate formation induced by DEX. Palatal mesenchymal cells from mouse embryos on embryonic day 13 were isolated as the experimental group, GATA-6 was silenced by GATA-6 small interfering Ribonucleic Acid (RNA). Cell Counting Kit-8, flow cytometry and Western Blot were applied to detect cell proliferation ability, cell cycle, the proportion of apoptotic cells, and the expression of apoptosis- related proteins of GATA-6 knockdown palatal mesenchymal cells. Further proteins on the BMP-2/Mitogen-activated protein kinase (MAPK) pathways were detected using Western Blot. T results showed that knockdown of GATA-6 by siRNA significantly decreased cell proliferation and increased the expression of apoptosis-related proteins. Bone morphogenetic protein-2/P38 mitogen Activated protein kinase (P38 MARK) pathway proteins decreased significantly among the GATA-6 knockdown group, DEX-cleft palate group and control +DEX groups. The results indicated that the GATA-6/BMP-2/P38 MAPK athway was involved in the apoptosis caused by GATA-6 silencing, which may be the possible mechanism of DEX inducing cleft palate.