bluuebunny/crossref_metadata_2025 huggingface dataset:
CRISPR/Cas9 mediated somatic gene therapy for insertional mutations: the vibrator mouse model
Authors: Fu Xin , Zhu Jie , Duan Yaou , Lu Paul , Zhang Kang
Published: August 2021

Somatic gene therapy remains technically challenging, especially in the central nervous system (CNS). Efficiency of gene delivery, efficacy in recipient cells, and proportion of cells required for overall benefit are the key points needed to be considered in any therapeutic approach. Recent efforts have demonstrated the efficacy of RNA-guided nucleases such as CRISPR/Cas9 in correcting point mutations or removing dominant mutations. Here we used viral delivered Cas9 plasmid and two guide RNAs to remove a recessive insertional mutation, vibrator (vb), in the mouse brain. The vb mice expressed ∼20% of normal levels of phosphatidylinositol transfer protein, α (PITPα) RNA and protein due to an endogenous retrovirus inserted in intron 4, resulting in early-onset tremor, degeneration of brainstem and spinal cord neurons, and juvenile death. The in situ CRISPR/Cas9 viral treatment effectively delayed neurodegeneration, attenuated tremor, and bypassed juvenile death. Our studies demonstrate the potential of CRISPR/Cas9-mediated gene therapy for insertional mutations in the postnatal brain.
Knock out of transcription factor WRKY53 thickens sclerenchyma cell walls, confers bacterial blight resistance
Authors: Xie Wenya , Ke Yinggen , Cao Jianbo , Wang Shiping , Yuan Meng
Published: August 2021

Plant cell walls are the first physical barrier against pathogen invasion, and plants thicken the cell wall to strengthen it and restrain pathogen infection. Bacterial blight is a devastating rice (Oryza sativa) disease caused by Xanthomonas oryzae pv. oryzae (Xoo), which typically enters the rice leaf through hydathodes and spreads throughout the plant via the xylem. Xoo interacts with cells surrounding the xylem vessel of a vascular bundle, but whether rice strengthens the sclerenchyma cell walls to stop pathogen proliferation is unclear. Here, we found that a WRKY protein, OsWRKY53, negatively confers resistance to Xoo by strengthening the sclerenchyma cell walls of the vascular bundle. OsMYB63 acts as a transcriptional activator and promotes the expression of three secondary cell wall-related cellulose synthase genes to boost cellulose accumulation, resulting in thickened sclerenchyma cell walls. Both OsWRKY53 and OsMYB63 are abundantly expressed in sclerenchyma cells of leaf vascular bundles. OsWRKY53 functions as a transcriptional repressor and acts genetically upstream of OsMYB63 to suppress its expression. The OsWRKY53-overexpressing and OsMYB63 knockout plants had thinner sclerenchyma cell walls, showing susceptibility to Xoo, while the OsWRKY53 knockout and OsMYB63-overexpressing plants had thicker sclerenchyma cell walls, exhibiting resistance to Xoo. These results suggest that modifying these candidate genes provides a strategy to improve rice resistance to bacterial pathogens.
The Impact of COVID-19 on Community-Based Exercise Classes for People With Parkinson Disease
Authors: Mañago Mark M , Swink Laura A , Hager Emily R , Gisbert Robyn , Earhart Gammon M , Christiansen Cory L , Schenkman Margaret
Published: August 2021

Objective

he purpose of the study was to determine the impact of novel coronavirus 2019 (COVID-19) restrictions on community-based exercise classes for people with Parkinson disease (PD) and their instructors.

Methods

Data were collected via custom-designed electronic surveys for people with PD and class instructors who reported attending or teaching PD-specific exercise class ≥1 time/week for ≥3 months prior to pandemic restrictions (March 2020). The PD group also completed the Godin Leisure-Time Questionnaire, Self-Efficacy for Exercise scale, Schwab-England scale, and Parkinson’s Disease Questionnaire 8.

Results

Eighty-seven people with PD (mean = 70 [7.3] years old) and 43 instructors (51 [12.1] years old) from the United States completed surveys (October 2020 to February 2021). Mean Schwab-England (84 [16]) and Parkinson’s Disease Questionnaire 8 (21 [15]) scores indicated low-to-moderate disability in the PD group. Ninety-five percent of the PD group had COVID-19 exposure concerns, and 54% reported leaving home ≤1 time/week. Although 77% of the PD group scored “active” on the Godin Leisure-Time Questionnaire, the mean Self-Efficacy for Exercise Scale score (55 [24]) indicated only moderate exercise self-efficacy, and >50% reported decreased exercise quantity/intensity compared with pre-COVID. There was decreased in-person and increased virtual class participation for both groups. The top in-person class barrier for the PD (63%) and instructor (51%) groups was fear of participant COVID-19 exposure. The top virtual class barriers were lack of socialization (20% of PD group) and technology problems (74% of instructor group).

Conclusion

During COVID-19, there has been less in-person and more virtual exercise class participation in people with PD and decreased exercise quantity and intensity. Virtual classes may not fully meet the needs of people with PD, and primary barriers include technology and lack of socialization.

Impact

As COVID-19 restrictions wane, it is imperative to help people with PD increase exercise and activity. The barriers, needs, and facilitators identified in this study might help inform approaches to increase participation in exercise and activity for people with PD.

Lay Summary

During COVID-19, there has been less in-person and more virtual exercise class participation in people with PD and a decrease in exercise quantity and intensity. If you have PD, virtual classes might not fully meet your needs. Primary barriers may include technology problems and lack of social interaction.
Ultrasound assessment of hands and feet for synovitis at time of first clinical visit markedly reduces time to diagnosis in routine care
Authors: Ammitzbøll-Danielsen Mads , Fana Viktoria , Døhn Uffe Møller , Møller Torsten , Ng Sin Ngai , Secher Anne Emilie , Lykkegaard Jens Jørgen , Terslev Lene
Published: August 2021

Objectives

The role of musculoskeletal US (MSUS) in routine care for diagnosing arthritis is not fully elucidated, but US is more sensitive than clinical joint examination for detecting synovitis. Therefore, the use of US may facilitate diagnosis of arthritis. The aim of the study was to assess whether MSUS examination of hands and feet in relation to the first clinical visit had an impact on the time to reach a final diagnosis and the number of clinical follow-up visits needed after first consultation.

Methods

Two cohorts referred to the outpatient arthritis clinic with suspected arthritis were compared with each other, (i) MSUS (October 2017 to June 2018) of hands and feet performed prior to the first clinical visit and (ii) MSUS (November 2016 to June 2017) was performed ad hoc, for the following aspects: time to clinical diagnosis, number of clinical visits needed, and number of US examinations.

Results

In total, 163 and 109 patients were included in the MSUS and comparative cohorts, respectively. Adding MSUS to the first clinical visit reduced the time to diagnosis from mean 31 (32.2) days to 12 (17.3) days (P < 0.01). The number of clinical visits needed was reduced from mean 2.8 (1.1) to 2.1 (1.3) (P < 0.01), corresponding to a reduction of 114 visits in the MSUS cohort. A final diagnosis with inflammatory arthritis was found in 76 (47%) of patients in the MSUS cohort vs 29 (27%) in the comparative cohort (P < 0.01).

Conclusion

In patients referred for suspected arthritis, routine MSUS in relation to the first clinical visit significantly reduces time to diagnosis and number of clinical visits needed to reach a final diagnosis.
RADON INFILTRATION BUILDING ENVELOPE TEST SYSTEM: EVALUATION OF BARRIER MATERIALS
Authors: Gaskin Janet , Li Yunyi Ethan , Ganapathy Gnanamurugan , Nong Gang , Whyte Jeffrey , Zhou Liang Grace
Published: August 2021

The performance of radon barrier materials currently available for housing foundations was evaluated using a unique radon infiltration building envelope test system that was designed to test radon prevention and mitigation systems using real world construction techniques. The reduction in radon concentration measured across the air barrier in the foundations has been used to evaluate five representative barrier materials installed in the radon infiltration building envelope test facility. The reduction in radon concentration in the mock house varied from 68% for 6 mil polyethylene to 98% for the spray polyurethane foam. The five representative barrier materials were selected after determining the radon diffusion coefficient and the corresponding radon resistance from samples of 14 barrier materials in a radon diffusion testing chamber. The Canadian experience evaluating whether radon barrier materials would satisfy building code requirements was described.
Site specificity of blastocyst hatching significantly influences pregnancy outcomes in mice
Authors: An Liyou , Liu Yanhong , Li Mingyang , Liu Zhihui , Wang Zhisong , Dai Yujian , Presicce Giorgio Antonio , Du Fuliang
Published: August 2021

Blastocysts hatch from the zona pellucida (ZP) to enable implantation into the uterine endometrial epithelium, but little is known regarding the effect of hatching sites on pregnancy outcomes. Murine hatching embryos were categorized into five groups based on initial trophectoderm projection (TEP)/ZP position corresponding to the inner cell mass center. In blastocysts (3.5 dpc) post‐12 hours in vitro culture, TEP rates of A‐site (44.4%) and B‐site (38.6%) embryos were higher than those of C‐site (12.5%) and D‐site (3.1%) embryos, while the O‐site (1.4%) was the lowest (P < .05). Post‐ET A‐site (55.6%) and B‐site (65.6%) birth rates were higher than those of C‐site embryos (21.3%) and controls (P < .05). Furthermore, live birth rate of B‐site embryos remained higher than C‐site embryos (68.8% vs 31.3%; P < .05) when both were transferred into the same recipients. Different TEP site blastocysts exhibited different implantation competences: the implantation rate of C‐site embryos was lower than that of both A‐ and B‐site groups (67.7% vs 84.3% and 83.2%, respectively; P < .05) at 2 days post‐ET. C‐site embryos also had a distinctly higher ratio of developmental defects (47.5%) than A‐ and B‐site embryos (22.5% and 14.6%, respectively), with implantation failure mainly associated with poor birth rate, a finding corroborated by differential gene expression analysis such as LIF, LIFR, and S100a9. Surprisingly, acidified Tyrode's solution (AAH)‐treated B‐site blastocysts had a significantly increased birth rate (77.1%) than C‐site (55.3%) and controls (43.4%). Site specificity and differential gene expression during embryo hatching can be applied in ART screening. More importantly, assisted hatching by AAH is effective and feasible for improving pregnancy and term development, particularly at the B‐site, for humans and in animal husbandry.
Understanding “Kyphosis” and “Lordosis” for Sagittal Balancing in Two Common Standing Postures
Authors: Hey Hwee Weng Dennis , Lin Shuxun , Tay Hui Wen , Tay Yuan Jie , Liu Gabriel Ka-Po , Wong Hee-Kit
Published: August 2021

Study Design.

Cross-sectional radiographic comparison study.

Objective.

The aim of this study was to understand whole-body balancing in directed and natural standing postures, through comparison of kypholordotic ratios on whole-body radiographs of young, healthy subjects.

Summary of Background Data.

Recent studies highlighted the importance of understanding whole-body balancing, proposing the use of the more physiological natural standing posture, together with the conventional directed standing posture, for imaging.

Methods.

Sixty healthy, 21-year-old subjects (36 males, 24 females) were recruited. EOS whole-body radiographs of subjects in directed and natural standing postures were obtained. Radiographic parameters compared include C2-sagittal vertical axis (C2-SVA), C7-SVA, C2-7-SVA, global cervical angles (C0-T1 and C2-C7), regional cervical angles (C0-C2, C2-C4, C4-C7), T1-slope, global thoracic angles (T1-T12 and T1-inflection vertebra [Inf]), thoracolumbar angle (T11-L2), global lumbar angles (T12-S1 and Inf-S1), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), spinocoxa angle (SCA), and femoral alignment angle (FAA). Kypholordotic ratios of T1-12/T12-S1, T1-Inf/Inf-S1, Tl-Inf/SCA, and (T1-Inf + FAA)/(T1-slope + SCA) were calculated and compared.

Results.

Compared to directed standing, natural standing has greater C2-SVA and C7-SVA, more lordotic global and regional cervical angles (except C0-2 angle), higher T1-slope, larger T1- T12 and T1-Inf kyphotic angles, smaller T12-S1 and Inf-S1 lordotic angles, larger PT, more lordotic SCA, and smaller SS and FAA angles. T1-12/T12-S1 and T1-Inf/Inf-S1 ratios in natural standing, and (Tl-Inf + FAA)/(T1-slope + SCA) ratio in both postures approximate 1. There were significant differences between postures for Tl-l2/Tl2-Sl, Tl-Inf/Inf-Sl and Tl-Inf/SCA ratios.

Conclusion.

Whole-body balancing requires understanding of the balance between kyphosis and lordosis, which varies with the posture of patients. Analysis of kypholordotic ratios obtained in this study allude to the importance of performing whole-body imaging in the directed standing posture, and whole-spine or whole-body imaging in the natural standing posture, so as to fully understand spinal and whole body balancing for spinal realignment surgeries.

Level of Evidence: Level 3
Growing Racial Disparities in the Utilization of Adult Spinal Deformity Surgery
Authors: Wang Kevin Y. , Puvanesarajah Varun , Xu Amy , Zhang Bo , Raad Micheal , Hassanzadeh Hamid , Kebaish Khaled M.
Published: August 2021

Study Design.

Retrospective.

Objective.

The purpose of this study was to assess trends in utilization rates of adult spinal deformity (ASD) surgery, as well as perioperative surgical metrics between Black and White patients undergoing operative treatment for ASD in the United States.

Summary of Background Data.

Racial disparities in access to care, complications, and surgical selection have been shown to exist in the field of spine surgery. However, there is a paucity of data concerning racial disparities in the management of ASD patients.

Methods.

Adult patients undergoing ASD surgery from 2004 to 2014 were identified in the nationwide inpatient sample (NIS). Utilization rates, major complications rates, and length of stay (LOS) for Black patients and White patients were trended over time. Utilization rates were reported per 1,000,000 people and determined using annual census data among subpopulations stratified by race. All reported complication rates and prolonged hospital stay rates are adjusted for Elixhauser Comorbidity Index, income quartile by zip code, and insurance payer status.

Results.

From 2004 to 2014, ASD utilization for Black patients increased from 24.0 to 50.9 per 1,000,000 people, whereas ASD utilization for White patients increased from 29.9 to 73.1 per 1,000,000 people, indicating a significant increase in racial disparities in ASD utilization (P-trend < 0.001). There were no significant differences in complication rates or rates of prolonged hospital stay between Black and White patients across the time period studied (P > 0.05 for both).

Conclusion.

Although Black and White patients undergoing ASD surgery do not differ significantly in terms of postoperative complications and length of hospital stay, there is a growing disparity in utilization of ASD surgery between White and Black patients from 2004 to 2014 in the United States. There is need for continued focus on identifying ways to reduce racial disparities in surgical selection and perioperative management in spine deformity surgery.

Level of Evidence: 3
Effect of statins use on risk and prognosis of breast cancer: a meta-analysis
Authors: Zhao Guodong , Ji Yanjun , Ye Qing , Ye Xin , Wo Guanqun , Chen Xi , Shao Xinyi , Tang Jinhai
Published: August 2021

The findings regarding the association between statins use and breast cancer are inconsistent. Given the widely and long-term use of statins as first choice drug for dyslipidemia, we conducted this meta-analysis for better understanding the associations between statins use and the risk and prognosis of breast cancer. Articles regarding effect of statins use on risk, prognosis of breast cancer and published before January 2021 were searched in the following databases: Web of Science, PubMed, EMBASE, Medline and Google Scholar. Odds ratios (ORs)/relative risks (RRs) or hazard ratios (HRs) and their 95% confidence intervals (CIs) were computed to generate a pooled effect size and 95% CI. The meta-analysis showed no significant association between statins use and risk of breast cancer (OR/RR = 1.02; 95% CI, 0.97–1.08; I
2 = 76.1%; P < 0.001). The meta-analysis showed that statins use was associated with lower breast cancer recurrence, all-cause mortality and disease-specific mortality (breast cancer recurrence: HR = 0.75; 95% CI, 0.67–0.84; I
2 = 31.7%; P = 0.154; all-cause mortality: HR = 0.82; 95% CI, 0.77–0.89; I
2 = 67.5%; P < 0.001; and disease-specific mortality: HR = 0.82; 95% CI, 0.72–0.93; I
2 = 83.6%; P < 0.001). Overall, in this report we demonstrated that the use of statins can improve the prognosis of breast cancer patients including lower risks of breast cancer recurrence, all-cause and cancer-specific mortality, though statins therapy may not have an impact on reducing the risk of breast cancer.
The prognostic values of prognostic nutritional index in extensive-stage small-cell lung cancer
Authors: Bahçeci Aykut , Kötek Sedef Ayşe , Işik Deniz
Published: August 2021

We aimed to assess the prognostic and predictive significance of pretreatment Prognostic Nutritional Index (PNI) in extensive-stage small-cell lung cancer (ES-SCLC) patients treated with first-line chemotherapy. We designed this study to evaluate the prognostic role of PNI in 147 ES-SCLC patients treated with platinum-based combination regimen between 2011 and 2018. Kaplan–Meier survival analyses and Cox proportional hazard models were used to examine the effects of basal PNI on overall survival (OS). The median age of the patients was 61 (range 38–81). The cutoff value for PNI was determined for whole group and patients were dichotomized into high (≥49.17) and low (<49.17). Seventy-eight (53.1%) patients had low PNI score and 69 (46.9%) patients had high PNI score. Patients with the high PNI score had better OS than those with low PNI (13 versus 12 months, respectively, and P = 0.03). The relationship between PNI score and OS was more prominent in patients over 65 years of age (13 versus 10 months, respectively, and P = 0.03). Progression-free survival of patients with complete response to first-line treatment was statistically significantly better than the other patients (8 versus 7 months, respectively, and P = 0.02). Similarly, OS was statistically significantly better than the other patients (15 versus 8 months, respectively, and P = 0.001). The results of our study show that PNI score is useful in evaluating the OS of patients with ES-SCLC. PNI is a cost-effective prognostic marker and should therefore be included in routine clinical practice.
Long noncoding RNA ALOX12-AS1 inhibits cervical cancer cells proliferation via targeting miR-3171
Authors: Yang Weiwei , Wang Xiaoyan , Song Shujie , Chu Yongli , Sun Dengjun , Yu Xiang , Zou Yanfen
Published: August 2021

Cervical cancer is a common female malignancy worldwide, and the molecular mechanism of cervical tumorigenesis remains poorly understood. A large piece of evidence have demonstrated the important roles of long noncoding RNAs (lncRNAs) in tumorigenesis, cancer progression and drug resistance. In this study, we comprehensively analyzed the lncRNAs expression pattern in cervical cancer using RNA sequencing and microarray data from the cancer genome atlas, gene expression omnibus and Genotype Tissue Expression. Moreover, we assessed the correlation between lncRNA expression levels and cervical cancer patient’s survival. We uncovered hundreds of lncRNAs that are upregulated or downregulated in cervical cancer tissues. Among these aberrantly lncRNAs, some are significantly associated with cervical patients’ poorer prognosis, such as ALOX12-AS1 and LINC00173. ALOX12-AS1 expression is downregulated in cervical cancer, and over-expression of ALOX12-AS1 could inhibit cervical cancer cells proliferation in vitro. Further, mechanistically investigation revealed that ALOX12-AS1 could interact with AGO2 and sponge miR-3171, thereby antagonizing its’ repression of tumor suppressor phosphatase and tensin homolog expression in cervical cancer cell. Taken together, this study provides lncRNA candidates in cervical cancer and highlights the critical role of ALOX12-AS1 in cervical cancer.
Cost-effectiveness analysis of a lung cancer screening programme in Spain
Authors: Gómez-Carballo Natalia , Fernández-Soberón Silvia , Rejas-Gutiérrez Javier
Published: August 2021

Objective

To evaluate the cost-effectiveness of the implementation of national lung cancer (LC) screening programme (SP) in a high-risk population from the perspective of the Spanish National Health System (NHS).

Methods

A cost-effectiveness analysis for a LC SP was carried out on a lifetime horizon. A Markov model was designed that assumed two scenarios, one with the implementation of the SP and another one without it. Effectiveness and cost of LC management, diagnosis and screening were included in the different health states. Deterministic and probabilistic sensitivity analyses were conducted to evaluate its robustness. A discount rate was set at 3% both for effectiveness and cost.

Results

In the base-case, an increase of 4.80 quality-adjusted life years (QALY) per patient was obtained, resulting in an incremental cost-effectiveness ratio of €2345/QALY. Probabilistic sensitivity analysis showed the national LC SP to be cost-effective in 80% of cases (probability=0.8) for a willingness-to-pay threshold equivalent to the gross domestic product per capita in Spain, which was set at €25 854/QALY in 2018 based on the per capita income of Spain. The sensitivity analysis indicates that the obtained results are robust in terms of changes in the presentation rates and costs, and the cost-effectiveness thresholds.

Conclusions

This analysis suggests that the implementation of a LC SP in the high-risk Spanish population would be a cost-effective strategy for the Spanish NHS.
Is the use of augmented reality-assisted surgery beneficial in urological education? A systematic review
Authors: Alrishan Alzouebi Ibraheem , Saad Sanad , Farmer Tom , Green Sophie
Published: August 2021

Background:

Google Glass is an optical head-mounted display that has been used in multiple medical and surgical settings to enhance delivery of education and training. This systematic review focuses solely on the use of this technology in urology operating theaters for the purpose of surgical education.

Materials and methods:

A systematic search strategy was employed using EMBASE (1996–2019), Medline (1946–2019) and PubMed. Search terms included optical head-mounted displays, Google Glass and urological surgical training. Use of this technology in a nonurological setting, nonteaching sessions, case reports, reviews, editorials, abstracts, and articles not in English were rejected. Three studies were identified following the exclusion criteria.

Results:

All 3 studies received positive feedback from trainees regarding this technology in relation to enhanced surgical education. In addition, in all studies the trainees felt the technology had a place for educational training in the future. All studies described disadvantages to the technology as well including battery life, comfort, and cost.

Conclusions:

Studies describe a big potential for Google Glass and similar head-mounted devices for the role of surgical training in urology, however, larger studies looking at more varied operations can help reinforce this viewpoint.
Clear Cell Proliferations of the Skin: A Histopathologic Review
Authors: Zaballos Pedro , Lara-Valencia Paola , Van Den Bossche Karolien , Sánchez-Martínez Eva , Roca-Gines Juncal , Vila Borja Gómez , Requena Luis
Published: August 2021

Cutaneous clear cell proliferations encompass a heterogenous group of several primary cutaneous neoplasms and metastatic tumors with different histogenesis. Many of these clear cell proliferations may seem strikingly similar under the microscope resulting in challenging diagnosis. In many of these clear cell lesions, the reason for the clear or pale appearance of proliferating cells is unknown, whereas in other ones, this clear cell appearance is due to intracytoplasmic accumulation of glycogen, mucin, or lipid. Artifacts of tissue processing and degenerative phenomenon may also be responsible for the clear cell appearance of proliferating cells. Awareness of the histopathologic findings as well as histochemical and immunohistochemical techniques are crucial to the accurate diagnosis. This review details the histopathologic features of clear cell cutaneous proliferations, classifying them according their type of differentiation and paying special attention to the histopathologic differential diagnosis among them.
Intraocular Pressure and Glaucoma in Thyroid Eye Disease
Authors: Betzler Bjorn Kaijun , Young Stephanie M. , Sundar Gangadhara
Published: August 2021

Purpose:

Current literature lacks a summary of knowledge on intraocular pressure (IOP) elevation and glaucoma in thyroid eye disease (TED). This review aims to augment existing literature by providing such a summary. It qualitatively evaluates current knowledge on the pathogenesis, prevalence, and management of concomitant ocular hypertension or glaucoma in TED patients.

Methods:

In this narrative review, relevant publications were identified through a computerized database search. Search results were screened for relevance. Correspondence, Editorials, and Letters to the Editors were excluded. References cited within the identified articles were used to further augment the search. Information extracted for qualitative analysis included epidemiologic data, methods of IOP assessment, management protocols, and response to treatment.

Results:

Studies in current literature are relatively heterogenous, differing in country of origin, TED cohort sizes, and IOP measurement techniques. Further studies are required to elucidate the true epidemiologic relationship between TED and ocular hypertension or glaucoma. Proposed models of IOP elevation include elevation of episcleral venous pressure, mucopolysaccharide deposition within the trabecular meshwork, restrictive myopathy, steroid-induced glaucoma, and secondary glaucoma. IOP-reducing effects of TED treatment options are discussed.

Conclusions:

While raised IOP in TED is a common phenomenon, the diagnosis of glaucoma in TED requires a high index of suspicion before any intervention.
Hepatotoxicity, efficacy and completion rate between 3 months of isoniazid plus rifapentine and 9 months of isoniazid in treating latent tuberculosis infection: A systematic review and meta-analysis
Authors: Tseng Shao-Yu , Huang Yi-Shin , Chang Tien-En , Perng Chin-Lin , Huang Yi-Hsiang
Published: August 2021

Background:

The mainstay therapy for latent tuberculosis infection is a 9-month regimen of daily isoniazid (9H) and a 3-month regimen of 12 once-weekly doses of isoniazid and rifapentine (3HP). We performed this updated meta-analysis to compare hepatotoxicity, efficacy and completion rate between these two regimens.

Methods:

We searched all literature in the major medical databases using the subject search terms “isoniazid” and “rifapentine”, and performed a systemic review and meta-analysis.

Results:

A total of 14 studies were eligible for the meta-analysis, which included 5600 (49%) patients who received the 3HP regimen and 5919 (51%) patients who received the 9H regimen. A total of 202 (2%) patients had a drug-induced liver injury (DILI) and 11 317 (98%) did not. The pooled odds ratio (OR) of DILI in the 3HP regimen was 0.18 (95% confidence interval [CI], 0.12-0.26; p < 0.0001), compared with the 9H regimen. This result remained consistent in subgroup analyses of ethnicity and study design. The 3HP regimen was superior to the 9H regimen in the prevention of active tuberculosis (OR, 0.38, 95% CI, 0.18-0.80, p = 0.01). Furthermore, the 3HP regimen was associated with a better completion rate than the 9H regimen (OR: 2.30, 95% CI, 2.10-2.53, p < 0.0001).

Conclusion:

The 3HP regimen is superior to the 9H regimen, with less hepatotoxicity, and better efficacy and completion rate in treating latent tuberculosis infection.
Vitamin D in gynecological diseases
Authors: Chu Ta-Wei , Jhao Jing-Yun , Lin Ta-Jen , Lin Tzu-Wei , Wang Chia-Lin , Chang Huan-Shuo , Liu Li-Chun , Chang Cheng-Chang
Published: August 2021

Background:

Most reproductive system studies suggest the protective effects of vitamin D, but vitamin D deficiency and insufficiency are growing global health issues. The present study investigates the association between vitamin D deficiency/insufficiency and gynecologic diseases to identify illness risks at different serum vitamin D levels in Taiwan.

Methods:

A total of 7699 female adults aged ≥20 years with results for both serum vitamin D and gynecologic-associated diseases were drawn from the Taiwan MJ cohort. We analyzed the correlation between serum vitamin D levels and results from reproductive system evaluations, including history of dysmenorrhea, results of Pap smear, high-risk human papillomavirus (HPV) infection of the cervix, mammography, and ultrasound of breast and pelvis.

Results:

Over 80% of participants showed vitamin D deficiency/insufficiency. Participants with abnormal Pap smear results, high-risk HPV infection, and history of dysmenorrhea showed significantly lower levels of serum vitamin D (p < 0.001–0.05). Serum vitamin D deficiency was significantly associated with positive high-risk HPV infection of the cervix (p < 0.05) and dysmenorrhea (p < 0.001). After controlling for age as a confounding variable for each gynecologic disease, level of serum vitamin D was significantly associated with abnormal breast ultrasound (odds ratio = 0.724) and uterus ultrasound (odds ratio = 0.673 – 0.8), and dysmenorrhea (odds ratio = 0.829).

Conclusion:

Associations were found between vitamin D deficiency and endometriosis, uterine myoma, dysmenorrhea, abnormal Pap smear results, and high-risk HPV infection of the cervix. Therefore, vitamin D supplements may present a cost-effective benefit for the prevention and treatment of gynecologic diseases, and thus reduction of healthcare expenditures.
Long-term Use of Hormone Replacement Therapy is Associated With a Lower Risk of Developing High-risk Serrated Polyps in Women
Authors: O’Sullivan Dylan E. , Ruan Yibing , Forbes Nauzer , Heitman Steven J. , Hilsden Robert J. , Pader Joy , Brenner Darren R.
Published: August 2021

Goals/Background:

Hormone replacement therapy (HRT) and parity have been suggested protective factors against the development of colorectal polyps. However, there are a limited number of studies that have examined the relationship of these factors with high-risk adenomatous polyps (HRAP) or high-risk serrated polyps (HRSP), which may have different causes and therefore implications for screening programs.

Study:

Data from a cross-sectional study of 1384 women undergoing screening-related colonoscopy between 2008 and 2016 were analyzed. Modified Poisson regression models with robust error variance were used to determine the relative risk of developing adenomatous polyps, serrated polyps, HRAPs, and HRSPs associated with pregnancy, menopausal status, and the use of HRT (duration and type).

Results:

Women that used HRT for ≥6 years were at a significantly lower risk of developing a HRSP [risk ratios (RR): 0.53; 95% confidence interval (CI): 0.29-0.97]. Irrespective of the duration of use, the use of HRT that included progesterone alone or with estrogen was associated with a significantly lower risk of developing a HRSP (RR: 0.54; 95% CI: 0.30-0.95). The use HRT with progesterone for ≥6 years was associated with a nonsignificant lower risk of developing a HRSP (RR: 0.42; 95% CI: 0.17-1.04). None of the reproductive factors assessed or HRT were associated with the development of adenomatous polyps or HRAPs.

Conclusions:

The results of this study suggests that the long-term use of HRT, and therapies that include progesterone are associated with a lower risk of developing HRSPs. These results could have implications for targeted screening for serrated polyps among women.
Geographic disparities in transplantation
Authors: Salvalaggio Paolo R.
Published: August 2021

Purpose of review

The Final Rule clearly states that geography should not be a determinant of a chance of a potential candidate being transplanted. There have been multiple concerns about geographic disparities in patients in need of solid organ transplantation. Allocation policy adjustments have been designed to address these concerns, but there is little evidence that the disparities have been solved. The purpose of this review is to describe the main drivers of geographic disparities in solid organ transplantation and how allocation policy changes and other potential actions could impact these inequalities.

Recent findings

Geographical disparities have been reported in kidney, pancreas, liver, and lung transplantation. Organ Procurement and Transplant Network has modified organ allocation rules to underplay geography as a key determinant of a candidates’ chance of receiving an organ. Thus, heart, lung, and more recently liver and Kidney Allocation Systems have incorporated broader organ sharing to reduce geographical disparities. Whether these policy adjustments will indeed eliminate geographical disparities are still unclear.

Modern allocation policy focus in patients need, regardless of geography. Innovative actions to further reduce geographical disparities are needed.
Validation of a Tool to Assess the Multidimensional Needs of the Parents of Children With Cancer
Authors: Zucchetti Giulia , Candela Filippo , Ciappina Sabrina , Mastrazzo Camilla , Roccia Elvia , Bertolotti Marina , Fagioli Franca
Published: August 2021

Background

An assessment of the supportive care needs that parents whose children are suffering from cancer is crucial to providing maximum quality care in pediatric oncology.

Objective

To examine the psychometric properties of the Cancer Patient Needs Questionnaire (CPNQ) and validate the revised version (rCPNQ) of this multidimensional tool that evaluates the needs of parents whose child has cancer.

Methods

The original rCPNQ comprised 45 items and 6 dimensions of need. The original rCPNQ was first translated into Italian and then validated for use by performing an exploratory factor analysis with a subsequent reliability analysis for the entire scale and each factor found.

Results

One hundred forty-nine parents completed the Italian version of the rCPNQ, where a preliminary correlation analysis revealed the need for different psychometric item properties in the Italian population, with 22 items being excluded in the final model. The results of an exploratory factor analysis indicated a structure encompassing 4 factors of needs: (1) child-related emotional, (2) functional, (3) healthcare-related, and (4) emotional. The final version showed satisfactory internal consistency (subscales’ Cronbach’s α all >.80) and stability.

Conclusion

The Italian version of the rCPNQ is a shorter statistically validated version of the original scale and is a valid measure for professionals to use when assessing parents’ supportive care requirements.

Implications for Practice

The Italian version of rCPNQ can be used with professionals when assessing parents of children with cancer to assess their perceptions of their ill child’s emotional, functional, and healthcare needs.
A New Risk Assessment Model for Hospital-Acquired Venous Thromboembolism in Critically Ill Children: A Report From the Children’s Hospital-Acquired Thrombosis Consortium
Authors: Jaffray Julie , Mahajerin Arash , Branchford Brian , Nguyen Anh Thy H. , Faustino E. Vincent S. , Silvey Michael , Croteau Stacy E. , Fargo John H. , Cooper James D. , Bakeer Nihal , Zakai Neil A. , Stillings Amy , Krava Emily , Amankwah Ernest K. , Young Guy , Goldenberg Neil A.
Published: August 2021

OBJECTIVES:

To create a risk model for hospital-acquired venous thromboembolism in critically ill children upon admission to an ICU.

DESIGN:

Case-control study.

SETTING:

ICUs from eight children’s hospitals throughout the United States.

SUBJECTS:

Critically ill children with hospital-acquired venous thromboembolism (cases) 0–21 years old and similar children without hospital-acquired venous thromboembolism (controls) from January 2012 to December 2016. Children with a recent cardiac surgery, asymptomatic venous thromboembolism, or a venous thromboembolism diagnosed before ICU admission were excluded.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

The multi-institutional Children’s Hospital-Acquired Thrombosis registry was used to identify cases and controls. Multivariable logistic regression was used to determine the association between hospital-acquired venous thromboembolism and putative risk factors present at or within 24 hours of ICU admission to develop the final model. A total of 548 hospital-acquired venous thromboembolism cases (median age, 0.8 yr; interquartile range, 0.1–10.2) and 187 controls (median age, 2.4 yr; interquartile range, 0.2–8.3) were analyzed. In the multivariable model, recent central venous catheter placement (odds ratio, 4.4; 95% CI, 2.7–7.1), immobility (odds ratio 3.6, 95% CI, 2.1–6.2), congenital heart disease (odds ratio 2.9, 95% CI, 1.7-4.7), length of hospital stay prior to ICU admission greater than or equal to 3 days (odds ratio, 2.5; 95% CI, 1.1–5.6), and history of autoimmune/inflammatory condition or current infection (odds ratio, 2.1; 95% CI, 1.2–3.4) were each independently associated with hospital-acquired venous thromboembolism. The risk model had an area under the receiver operating characteristic curve of 0.79 (95% CI, 0.73–0.84).

CONCLUSIONS:

Using the multicenter Children’s Hospital-Acquired Thrombosis registry, we identified five independent risk factors for hospital-acquired venous thromboembolism in critically ill children, deriving a new hospital-acquired venous thromboembolism risk assessment model. A prospective validation study is underway to define a high-risk group for risk-stratified interventional trials investigating the efficacy and safety of prophylactic anticoagulation in critically ill children.
Antipsychiatric Medication Errors in Children Boarded in a Pediatric Emergency Department
Authors: Sethuraman Usha , Kannikeswaran Nirupama , Farooqi Ahmad , Richards Kimone , Chamberlain James
Published: August 2021

Objectives

Mental health visits to the pediatric emergency department (PED) have increased significantly. Our objective was to describe medication errors in children with mental health illness who were boarded in a PED for more than 6 hours.

Methods

We conducted a retrospective study from 2014 to 2015 of children 6 to 18 years with psychiatric complaints and a length of stay of more than 6 hours. Admitted patients and those not on home medications were excluded. We collected demographics, number, types, and doses of antipsychiatric medications and errors.

Results

A total of 676 patients (53.1% males) with a median age of 14 (interquartile range, 12, 15) years were included. The median length of stay was 11.7 (interquartile range, 8.5, 20.5) hours. A total of 974 medication errors occurred in 491 (72.7%) patients. Omission errors were noted in 376 patients (76.6%), commission in 44 patients (9.0%), and both in 71 patients (14.4%). Among commission errors, 8 (18.1%) were serious and 8 (18.1%) were significant. One third of patients (30.5%) had 1 medication error, 23.9% had 2, 11.7% had 3, and 5% had 4.

Medication errors were most commonly noted in antidepressant and antipsychotic classes. One third (35.8%) of errors involved 2 medication classes. Being on 3 (odds ratio, 1.8; 95% confidence interval, 1.09–2.9) or 4 or more (odds ratio, 2.81; 95% confidence interval, 1.54–5.34) antipsychiatric medications was significantly associated with a prescription error.

Conclusion

There is a high incidence of medication errors, particularly those of omission, among antipsychiatric prescriptions in children boarded in the PED. A refinement of current medication reconciliation and integration of psychiatric medication databases between the PED and pharmacies are urgently needed to reduce these errors.
Computer-Aided Three-Dimensional Virtual Surgical Planning in Complex Skull Base Reconstruction for Sphenoid Wing Dysplasia in Neurofibromatosis Type 1
Authors: Hsu Hao-Hsiang , Wong Chia-En , Lee Jing-Wei , Huang Chi-Chen , Lee Jung-Shun
Published: August 2021

Unilateral sphenoid dysplasia is a rare but distinctive manifestation of neurofibromatosis type 1, causing pulsatile exophthalmos, decreased vision, and facial deformity. Surgical intervention is required to prevent visual deterioration. However, the reconstruction of a complex cranial base defect while fulfilling cosmetic needs is challenging. The asymmetric anatomy impedes identification and preservation of vital structures, and the use of bone grafts is often unsustainable due to resorption. Here we demonstrate a multimodal technique combining mirror-image-based virtual surgical planning, stereolithography, and neuronavigation to achieve skull base reconstruction and restore facial symmetry in an neurofibromatosis type 1 patient with sphenoid dysplasia. Preoperative surgical planning involved mirror-image simulation based on the unaffected contralateral counterpart and a stereolithographic skull-base model fabricated to design a patient-specific titanium mesh. Surgical reconstruction via the transcranial approach under intraoperative neuronavigation was performed. Immediate resolution of pulsatile proptosis was observed postoperatively. With the help of virtual surgical planning, stereolithography, and neuronavigation, precise and sustainable reconstruction with patient-specific implants can be tailored for a complex skull base defect.
The Relevance of Fluid and Blood Management Using Microcirculatory Parameters in Children Undergoing Craniofacial Surgery
Authors: Kilicaslan Banu , Canbay Ozgur , Saylan Alev , Akinci Seda Banu , Tuncbilek Gokhan , Ince Can
Published: August 2021

Perioperative management of bleeding in children can be challenging. Microvascular imaging techniques have allowed evaluating the effect of blood transfusion on the microcirculation, but little is known about these effects in children. We aimed to investigate the effects of blood management using macro- and micro-hemodynamic parameters measurement in children undergoing craniofacial surgery. This is a prospective observational repeated measurement study including fourteen children. The indications for blood transfusion were changes of hemoglobin/hematocrit (Hct) levels, the presence of signs of altered tissue perfusion and impaired microcirculation images. Total and perfused vessel densities, proportion of perfused vessels, microvascular flow index, and systemic parameters (hemoglobin, Hct, lactate, mixed venous oxygen saturation, K+, heart rate, mean arterial blood pressure) were evaluated baseline (T1), at the end of the surgical bleeding (T2) and end of the operation (T3). Four patients did not need a blood transfusion. In the other 10 patients who received a blood transfusion, capillary perfusion was higher at T3 (13[9–16]) when compared with the values of at T2 (11[8–12]) (P < 0.05) but only 6 patients reached their baseline values. Although blood transfusions increased Hct values (17 ± 2.4 [T2]-19 ± 2.8 [T3]) (P < 0.05), there was no correlation between microvascular changes and systemic hemodynamic parameters (P > 0.05). The sublingual microcirculation could change by blood transfusion but there was not any correlation between microcirculation changes, hemodynamic, and tissue perfusion parameters even with Hct values. The indication, guidance, and timing of fluid and blood therapy may be assessed by bedside microvascular analysis in combination with standard hemodynamic and biochemical monitoring for intraoperative bleeding in children.
Evaluating Ciliary Body Damage Induced by Blunt Low Speed Impact Using Finite Element Simulation
Authors: Cheng Qiong , Zhang Feng , Chen Zhongshan , Wu Lan , Chen Min , Xu Qiuyi , Wang Yi
Published: August 2021

Purpose:

To evaluate the ciliary body mechanical load during low speed impact using finite element method to explain the mechanism of the cause of angle recession and cyclodialysis cleft.

Methods:

Optical coherence tomography images were obtained to assess the patient's ciliary body angle recession. A finite element eye model was established based on Virginia Tech eye model with the consideration of dynamic impact of a projectile striking an eye. The mechanical properties of the ocular tissues were obtained from literatures. The stress and strain were evaluated.

Results:

The stress distribution of the eye was calculated. The stress concentration at zonules was observed after 0.75 ms of the impact. The maximum stress at the cornea reached 3.8 MPa. The maximum stress at ciliary body was 57 KPa, which has high probability to cause ciliary body injury. The maximum stress at zonules was 0.98 MPa. The lateral expansion also reduces the forces transmitted along the sclera to the rear part of the eye.

Conclusions:

The eye under frontal impact will result in lateral expansion, which increase the stretch force of the lens, zonules and ciliary body. This mechanism can be seen as the protection for retina. The boundary of ciliary body is the most vulnerable position, where angle recession and cyclodialyses cleft will occur before retina damage occurrence.

Translational Relevance:

The finite element model explains the blunt low speed impact induced ciliary body related injuries, which enables us to assess the ocular injury for low energy impact and better diagnosis and treatment in clinics.