bluuebunny/crossref_metadata_2025 huggingface dataset:
Test-re-test reliability and dynamics of the Fukuda–Unterberger stepping test
Authors: Hemm Simone , Baumann Denise , Duarte da Costa Vasco , Tarnutzer Alexander Andrea
Published: March 2023

Background

The Fukuda-stepping-test (FST), i.e., repetitive walking on the spot while blindfolded, has been proposed as a means to assess the integrity of the vestibular pathways. While its sensitivity to detect abnormalities in patients is limited, it may be useful in studying the physiology of the subjective-straight-ahead (SSA). Considering reported systematic shifts in SSA in humans, we hypothesize that such asymmetries arise from individual differences in the orientation/configuration of the macular organs and in central processing of vestibular input. We hypothesize that such asymmetries are stable over time in individual subjects. Alternatively, such asymmetries may arise from random noise in the sensory/motor systems involved, demonstrating low reproducibility over time.

Materials and methods

Twenty-four subjects walked on the spot over 60 s while blindfolded (n = 6 trials per subject). Using an inertial measurement unit (IMU) placed at the chest, angular deviations were recorded and compared to manually-measured final positions. Both static (direction, magnitude) and dynamic (time-to-onset of deviation, pattern of deviations) parameters were retrieved from the yaw slopes.

Results

Significant deviations were found in 15/24 participants for the manual measurements (leftwards = 8; rightwards = 7), whereas when using the IMU-sensor 13/24 participants showed significant shifts (leftwards = 9; rightwards = 4). There was a high correlation (0.98) between manually measured rotation angles (average absolute deviations = 58.0 deg ± 48.6 deg; intra-individual variability = 39 deg ± 24 deg) and sensor-based yaw slopes (1.00 deg/s ± 0.88 deg/s; 0.67 deg/s ± 0.41 deg/s). Relevant yaw deviation was detected 22.1 s ± 12.3 s (range = 5.6 s-59.2 s) after the onset of marching (no relevant yaw-deviation in 15/139 measurements), showing a mostly linear behavior over time.

Conclusion

We observed significant inter-individual variability in task performance in the FST, reproducing findings from previous studies. With test-re-test reliability being moderate only, but at the same time observing a preference in the side of shifts in most trials and subjects, we conclude that likely both individually varying estimates of straight-ahead and random noise contribute to the pattern of angular deviations observed. Using an IMU-sensory based approach, additional dynamic parameters could be retrieved, emphasizing the value of such a quantitative approach over manual measurements. Such an approach may provide useful additional information to distinguish patients from healthy controls.
INPH and parkinsonism: A positive shunt response with a negative tap test
Authors: Giannini Giulia , Jusue-Torres Ignacio , Mantovani Paolo , Mazza Liliana , Pirina Alessandro , Valsecchi Nicola , Milletti David , Albini-Riccioli Luca , Cevoli Sabina , Yasar Sevil , Palandri Giorgio
Published: March 2023

Introduction

The aim of this study was to compare clinical and functional performances of idiopathic normal pressure hydrocephalus (INPH) patients with and without parkinsonism at the initial evaluation, 72 h after the cerebrospinal fluid tap test (CSF TT), and 6 months after ventriculoperitoneal shunt (VPS) surgery.

Materials and methods

This is an observational prospective study on patients with INPH who underwent VPS. Patients were classified into INPH with parkinsonism (INPH-P+) and without parkinsonism (INPH-P−). We used the time up and go (TUG) test, Tinetti Performance-Oriented Mobility Assessment (POMA) test, INPH grading scale (INHPGS), and modified Rankin scale (mRS) at baseline, 72 h after CSF TT, and 6 months after VPS surgery.

Results

A total of 64 patients with probable INPH were included, 12 patients with INPH-P+ and 52 controls with INPH-P−. Patients with INPH showed significant improvement in all clinical and neurological parameters after VPS including TUG, Tinetti POMA, INPHGS, and mRS (p < 0.001) with the exception of mRS where there was no significant change 72 h after CSF TT compared to baseline for patients with INPH (p = 0.182). Patients with INPH-P+ performed significantly worse than patients with INPH-P− on Tinetti POMA and mRS at baseline, at 72 h post-CSF TT, and at 6 months post-VPS with INPHGS being worst at 72 h post-CSF TT. There was no difference between patients with INPH-P+ and patients with INPH-P− for TUG at baseline (p = 0.270), at 72 h post-CSF TT (p = 0.487), and at 6 months post-VPS (p = 0.182). Patients with INPH-P+ did not show any change in any of the parameters at 72 h post-CSF TT compared to baseline; however, there was a trend toward improvement on TUG (p = 0.058), Tinetti gait (p = 0.062), and Tinetti total (p = 0.067). INPH-P+ significantly improved in all parameters 6 months post-VPS compared to baseline except for mRS (p = 0.124). Patients with INPH-P− significantly improved in all parameters at 72 h post-CSF TT and at 6 months post-VPS compared to baseline, respectively, except on mRS 72 h after CSF TT (p = 0.299).

Conclusion

Patients with INPH and parkinsonism overall do worse than patients without parkinsonism. An unsatisfying response to the CSF tap test in INPH patients with parkinsonism should not be used as an exclusion criterion from VPS surgery since patients with and without parkinsonism showed significant improvement post-VPS.
Efficacy of extracellular vesicles of different cell origins in traumatic brain injury: A systematic review and network meta-analysis
Authors: Yang Zhe-Lun , Liang Ze-Yan , Lin Yi-Ke , Lin Fa-Bin , Rao Jian , Xu Xiong-Jie , Wang Chun-Hua , Chen Chun-Mei
Published: March 2023

Background

There was still no effective treatment for traumatic brain injury (TBI). Recently, many preclinical studies had shown promising efficacy of extracellular vesicles (EVs) from various cell sources. Our aim was to compare which cell-derived EVs were most effective in treating TBI through a network meta-analysis.

Methods

We searched four databases and screened various cell-derived EVs for use in preclinical studies of TBI treatment. A systematic review and network meta-analysis were conducted for two outcome indicators, modified Neurological Severity Score (mNSS) and Morris Water Maze (MWM), and they were ranked by the surface under the cumulative ranking curves (SUCRA). Bias risk assessment was performed with SYRCLE. R software (version 4.1.3, Boston, MA, USA) was used for data analysis.

Results

A total of 20 studies were included in this study, involving 383 animals. Astrocyte-derived extracellular vesicles (AEVs) ranked first in response to mNSS at day 1 (SUCRA: 0.26%), day 3 (SUCRA: 16.32%), and day 7 (SUCRA: 9.64%) post-TBI. Extracellular vesicles derived from mesenchymal stem cells (MSCEVs) were most effective in mNSS assessment on day 14 (SUCRA: 21.94%) and day 28 (SUCRA: 6.26%), as well as MWM’s escape latency (SUCRA: 6.16%) and time spent in the target quadrant (SUCRA: 86.52%). The result of mNSS analysis on day 21 showed that neural stem cell-derived extracellular vesicles (NSCEVs) had the best curative effect (SUCRA: 6.76%).

Conclusion

AEVs may be the best choice to improve early mNSS recovery after TBI. The efficacy of MSCEVs may be the best in the late mNSS and MWM after TBI.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42023377350.
Investigating the effect of pore water composition and isosaccharinic acid (ISA) on sorption of Pu to a CEM III/C-based mortar
Authors: Coppens Erik , Wouters Katinka , de Blochouse Benny , Durce Delphine
Published: March 2023

In the frame of the safe disposal of short-lived low and intermediate level nuclear waste (SL-ILW), ONDRAF/NIRAS (Belgium) has submitted a license application for the exploitation of a near surface facility in Dessel (Belgium). A significant part of the waste intended for the surface repository is Pu-contaminated and has been conditioned by means of CEM III/C based mortar, produced in the CILVA-installation at the Belgoprocess site in Dessel. To establish more accurate data on sorption of Pu to the CILVA mortar, an experimental test set-up was designed in order to screen which factors were likely to affect Pu sorption to the mortar. The different factors of the design were variables related to the pore water composition of the mortar on the one hand (concentrations of Ca2+, Cl−, SO42−, S2−, K+ and OH− (pH)), and variables characteristic for batch sorption experiments on the other hand ([Pu], solid-to-liquid ratio and equilibration time). The results of this screening indicate that over the tested variables, only the concentration of Ca2+ in the synthetic pore water affects Pu sorption to the CILVA matrix to a significant extent. Additionally, from literature it is expected that the presence of isosaccharinic acid (ISA), a cellulose degradation product, would affect Pu sorption, with increasing concentrations of ISA frequently correlated with decreased sorption. To address the nature and extent of the impact of both [Ca2+] and [ISA] and their combined effect on sorption of Pu to the mortar, an experimental set-up for surface response measurement (SRM) was designed. A Central Composite Design (CCD) in two factors was selected for the SRM, with three test points and a four point repetition of the centre point. The execution of this experimental set-up and the resulting responses, allowed for the development of a polynomial model to predict the average response of Pu sorption (expressed as Rd) as a function of [ISA] and of [Ca2+]. In addition, the [Ca2+] in solution in equilibrium with the mortar could be assessed from the established dataset, which allowed to predict Pu sorption as a function of [ISA] at the intrinsic [Ca2+] in the mortar’s pore water.
Bridging the gap: Evidence-based practice guidelines for sports nutritionists
Authors: Ritson Alex J. , Hearris Mark A. , Bannock Laurent G.
Published: March 2023

Evidence-based practice is a systematic approach to decision-making developed in the 1990s to help healthcare professionals identify and use the best available evidence to guide clinical practice and patient outcomes amid a plethora of information in often challenging, time-constrained circumstances. Today’s sports nutrition practitioners face similar challenges, as they must assess and judge the quality of evidence and its appropriateness to their athlete, in the often chaotic, time-pressed environment of professional sport. To this end, we present an adapted version of the evidence-based framework to support practitioners in navigating their way through the deluge of available information and guide their recommendations to athletes whilst also reflecting on their practice experience and skills as evidence-based practitioners, thus, helping to bridge the gap between science and practice in sport and exercise nutrition.
Comparative cardiotoxicity risk of pembrolizumab versus nivolumab in cancer patients undergoing immune checkpoint inhibitor therapy: A meta-analysis
Authors: Ndjana Lessomo Fabrice Yves , Wang Zhiquan , Mukuka Chishimba
Published: March 2023

Objective

Recently, several researchers have reported the incidence of cardiac-related toxicities occurring with nivolumab (Opdivo) and pembrolizumab (Keytruda). There is still a need for balance between oncology treatment efficacy and reduction of cardiotoxicity burden in immune checkpoint inhibitor (ICI)-treated patients. Thus, the primary aim was to determine whether pembrolizumab or nivolumab would present with a greater risk for cardiotoxicity reports.

Materials and methods

This meta-analysis was performed with respect to the MOOSE reporting guidelines. Studies were retrieved by searching PubMed, Embase, and Google Scholar; the search terms were Keytruda or Pembrolizumab, PD1 inhibitors, anti-PD1 drugs, Nivolumab or Opdivo, and cardiotoxicities or cardiac toxicity. The study was restricted to original articles investigating ICI-induced cardiac immune-related adverse events (irAEs). The targeted population was cancer patients treated with either pembrolizumab or nivolumab monotherapy, of which those with records of any cardiac events following the therapy were labeled as events. The measures used to achieve the comparison were descriptive proportions, probabilities, and meta-analysis pooled odds ratios (ORs).

Results

Fifteen studies were included in this meta-analysis. Nivolumab accounted for 55.7% cardiotoxicity and pembrolizumab, for 27.31% (P = 0.027). The meta-analysis was based on the Mantel–Haenszel method, and the random-effect model yielded a pooled OR = 0.73 (95% CI [0.43–1.23] P = 0.24), with considerable heterogeneity (I2 = 99% P = 0). Hence, the difference in cardiotoxicity odds risk between pembrolizumab and nivolumab was not statistically significant. On subgroup analysis based on cardiotoxicity type, the “myocarditis” subgroup in which there was no statistical heterogeneity was associated with a significant cardiotoxicity risk increase with pembrolizumab (OR = 1.30 [1.07;1.59], P< 0.05; I2 = 0%, Ph = 0.4).

Conclusion

To our knowledge, this is the first meta-analysis to compare the cardiotoxicity potentials of nivolumab and pembrolizumab. In contrast to previous reports, the overall findings here demonstrated that nivolumab-induced cardiotoxicity was more commonly reported in the literature than pembrolizumab; however, myocarditis seemed more likely to occur with pembrolizumab therapy.
Case report: Complete pathological admission in N3 unresectable locally advanced lung adenocarcinoma with a novel INTS10-ALK and EML4-ALK fusion after neoadjuvant crizotinib
Authors: Zhai Xiaoqian , Wang Ting , Lin Yiyun , Zhang Jiabi , Wang Yuqing , Wang Weiya , Zhou Qinghua , Zhu Daxing
Published: March 2023

Background

Although anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) have impressive response in advanced lung adenocarcinoma with anaplastic lymphoma kinase (ALK) fusion, no guidelines point to the potential benefits of neoadjuvant ALK-TKIs for N3 unresectable locally advanced lung cancer. Current ongoing clinical trials mainly focus on the efficacy of neoadjuvant ALK-TKIs in resectable locally advanced lung cancer and ignore the role of neoadjuvant ALK-TKIs in N3 unresectable locally advanced lung cancer.

Materials and methods

We report a lung cancer case with a novel INTS10-ALK and EML4-ALK rearrangement that achieved complete pathologic response to neoadjuvant crizotinib. We conducted molecular pathologic analysis by using next-generation sequencing (NGS). Genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) samples and profiled using a capture-based targeted sequencing panel consisting of 56 lung cancer-related genes.

Results

Our study reported a patient with stage IIIB-N3 lung adenocarcinoma with an unreported dual ALK rearrangement (INTS10-ALK and EML4-ALK) who received 5 months of crizotinib, followed by R0 right upper lobectomy, achieving complete pathological response (ypT0 ypN0). No recurrence of the tumor was found for 3 years postoperatively.

Conclusion

The case supports the strategy of neoadjuvant ALK inhibitors for N3 unresectable locally advanced lung cancer, expanding the spectrum of treatment of stage IIIB-N3 lung cancer.
Identifying novel biomarkers associated with bladder cancer treatment outcomes
Authors: Castaneda Peris R. , Theodorescu Dan , Rosser Charles J. , Ahdoot Michael
Published: March 2023

Bladder cancer is a complex disease with variable prognosis. Recent investigations into the molecular landscape of bladder cancer have revealed frequent genetic alterations and molecular subtypes with therapeutic implications. Consequently, a shift toward personalized treatment of bladder cancer is underway. To this end, several biomarkers have been developed and tested in their ability to predict response to treatment in patients with bladder cancer and potentially help direct therapy. We performed a search of recently published PubMed articles using terms “biomarker,” “bladder cancer,” and the respective treatment discussed (i.e., “neoadjuvant” or “BCG”). In this review, we summarize the latest studies on novel biomarkers in bladder cancer with a focus on those intended to improve risk stratification and treatment selection.
Expression and molecular regulation of non-coding RNAs in HPV-positive head and neck squamous cell carcinoma
Authors: Guo Dandan , Yang Mei , Li Shiyun , Zhu Weiwei , Chen Meixin , Pan Jiayu , Long Dan , Liu Zhaohui , Zhang Chunlin
Published: March 2023

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent malignancy worldwide. Accumulating evidence suggests that persistent HPV infection is closely related to a subset of HNSCC types, and the incidence of human papillomavirus (HPV)-positive HNSCC has been annually increasing in recent decades. Although the carcinogenesis of HPV-positive HNSCC has not been completely elucidated, it has been well confirmed that E6 and E7, the main viral oncoproteins are responsible for the maintenance of malignant transformation, promotion of cell proliferation, and increase in tumor invasion. Moreover, compared with HPV-negative HNSCC, HPV-positive HNSCC shows some special clinical-pathological features, which are possibly related to HPV infection and their specific regulatory mechanisms. Non-coding RNA (ncRNA) is a class of RNA lacking the protein-coding function and playing a critical regulatory role via multiple complex molecular mechanisms. NcRNA is an important regulatory pattern of epigenetic modification, which can exert significant effects on HPV-induced tumorigenesis and progression by deregulating downstream genes. However, the knowledge of ncRNAs is still limited, hence, a better understanding of ncRNAs could provide some insights for exploring the carcinogenesis mechanism and identifying valuable biomarkers in HPV-positive HNSCC. Therefore, in this review, we mainly focused on the expression profile of ncRNAs (including lncRNA, miRNA, and circRNA) and explored their regulatory role in HPV-positive HNSCC, aiming to clarify the regulatory mechanism of ncRNAs and identify valuable biomarkers for HPV-positive HNSCC.
Proton versus photon radiation therapy: A clinical review
Authors: Chen Zhe , Dominello Michael M. , Joiner Michael C. , Burmeister Jay W.
Published: March 2023

While proton radiation therapy offers substantially better dose distribution characteristics than photon radiation therapy in certain clinical applications, data demonstrating a quantifiable clinical advantage is still needed for many treatment sites. Unfortunately, the number of patients treated with proton radiation therapy is still comparatively small, in some part due to the lack of evidence of clear benefits over lower-cost photon-based treatments. This review is designed to present the comparative clinical outcomes between proton and photon therapies, and to provide an overview of the current state of knowledge regarding the effectiveness of proton radiation therapy.
Innovative method with two-stage surgery for Ewing sarcoma with personalized distal clavicle reconstruction: A case report and diagnosis review
Authors: Arunwatthanangkul Patcharapol , Piyabenjarad Panichanok , Wisitthipakdeekul Siraprapa , Chobpenthai Thanapon
Published: March 2023

A 13-year-old boy presented with a growing lump on his left clavicle for 5 months. The plain radiograph revealed an osteolytic mass with aggressive periosteal reaction, suggesting a malignant lesion. The results of advanced imaging and histopathological examinations revealed that the patient had Ewing sarcoma without metastasis. The two-stage surgery was as follows: resection–observation–reconstruction. The underlying rationale was that Ewing sarcoma has a high recurrence. After 2 years of resection, the patient had remission, and he currently has a personal 3D-printed titanium implant with intact shoulder function.
Clinical outcome of SARS-CoV-2 infections occurring in multiple myeloma patients after vaccination and prophylaxis with tixagevimab/cilgavimab
Authors: Duminuco Andrea , Romano Alessandra , Leotta Dario , La Spina Enrico , Cambria Daniela , Bulla Anna , Del Fabro Vittorio , Tibullo Daniele , Giallongo Cesarina , Palumbo Giuseppe A. , Conticello Concetta , Di Raimondo Francesco
Published: March 2023

Introduction

Patients with multiple myeloma (MM) frequently reported immune impairment with an increased risk for infection-related mortality. We aimed to evaluate the immune response in MM patients vaccinated for SARS-CoV-2 during active treatment.

Methods

We enrolled 158 patients affected by active MM or smoldering MM (SMM) and 40 healthy subjects. All subjects received 2 or 3 doses of the BNT162b2 (Pfizer/BioNTech) vaccine, and the anti-spike IgG values were evaluated after every dose. We applied the Propensity Score Matching (PSM) as a consequence of the limited sample size and its heterogeneity to adjust for differences in baseline clinical variables between MM patients who achieved or not a vaccine response after 2 or 3 doses.

Results

At 30 days from the second dose, the median antibodies level in MM was 25.2 AU/mL, lower than in SMM and in the control group. The same results were confirmed after the third dose, with lower median anti-spike IgG levels in MM, compared to SMM and control group. Following PSM, lack of response to SARS-CoV-2 complete vaccination plus boost was associated with age more than 70 years old and use of high-dose of steroids. We failed to identify an association between specific treatment types and reduced vaccine response. The use of prophylaxis with tixagevimab/cilgavimab for 40 non-responder patients after 3 doses of vaccine has proven to be an effective and safe approach in reducing the risk of serious illness in the event of a breakthrough SARS-CoV-2 infection, faced with a mild symptomatic course, and in providing protection instead of long-term humoral immune vaccine responses. Following PSM, only the high-risk cytogenetic abnormalities were associated with an increased risk of developing a breakthrough SARS-CoV-2 infection.

Conclusion

Monitoring the immune response is fundamental in MM patients that remain highly vulnerable to SARS-CoV-2 despite the vaccine. The use of prophylaxis with tixagevimab/cilgavimab can guarantee better protection from the severe form of the disease.
Genomic landscape and survival analysis of ctDNA “neo-RAS wild-type” patients with originally RAS mutant metastatic colorectal cancer
Authors: Nicolazzo Chiara , Magri Valentina , Marino Luca , Belardinilli Francesca , Di Nicolantonio Federica , De Renzi Gianluigi , Caponnetto Salvatore , De Meo Michela , Giannini Giuseppe , Santini Daniele , Cortesi Enrico , Gazzaniga Paola
Published: March 2023

Background

The term “neo-RAS wild-type” refers to the switch to RAS wild-type disease in plasma circulating tumor DNA (ctDNA) from originally RAS mutant colorectal cancers. Consistently, the hypothesis to re-determine RAS mutational status in ctDNA at disease progression in RAS mutant mCRC opened to a new perspective for clinically-based selection of patients to be treated with EGFR inhibitors. Currently, the genomic landscape of “neo-RAS wild-type” is unknown. This is a prospective study aimed to investigate clinical and genomic features associated with RAS mutation clearance in a large cohort of RAS mutant mCRC patients who converted to RAS wild- type in liquid biopsy at failure of first-line treatments. Secondary aim was to investigate the long term prognostic significance of “true neo-RAS wild- type”.

Patients and methods

70 patients with stage IV RAS mutant colorectal cancer were prospectively enrolled. Plasma samples were collected at progression from first-line treatment. RAS/BRAF mutations in plasma were assessed by RT-PCR. In RAS/BRAF wild-type samples, ctDNA was used to generate libraries using a 17 genes panel whose alteration has clinical relevance. To investigate the prognostic significance of RAS mutation clearance, test curves for PFS and OS were represented by Kaplan-Meier estimator plot and Log-rank test.

Results

The most commonly detected actionable mutations in “neo-RAS wild-type” were: PIK3CA (35.7%); RET (11.9%); IDH1 (9.5%); KIT (7%); EGFR (7%); MET (4.7%); ERBB2 (4.7%); FGFR3 (4.7%). Both OS and post-progression survival were longer in patients with “neo-RAS wild-type” compared to those who remained RAS mutant (p<0.001 for both).

Conclusions

De-novo-targetable mutations occured in a large percentage of “neo-RAS wild-type”, being PIK3CA the most commonly detected. RAS mutation clearance in ctDNA is associated with long- term improvement of overall survival.
The nodal positivity rate in breast pCR patients with initially, clinically node-negative breast cancer after neoadjuvant systemic therapy: A systematic review and meta-analysis
Authors: Ma Le , Chen Heyan , He Jianjun , Xie Peiling , Gao Pin , Li Yijun , Zhang Huimin , Fan Zhimin
Published: March 2023

Background

The axillary lymph node positive (ypN+) rate in patients with clinically node-negative (cN0) breast cancer who have achieved breast pathologic complete response (bpCR) after neoadjuvant systemic therapy (NST) is extremely low, and this population has the potential to be exempt from sentinel lymph node biopsy (SLNB). However, an overview of the ypN+ rate in this population for different breast cancer subtypes is lacking.

Objective

To provide the pooled ypN+ rate in cN0 patients who achieved bpCR after NST in different breast cancer subtypes defined by hormone receptor (HR) status and human epidermal growth factor receptor 2 (HER2) status.

Methods

A systematic literature search was conducted in Embase and PubMed on July 20, 2022. Two authors independently selected studies that met the inclusion criteria and extracted all data. The pooled ypN+ rates for each subtype were calculated by a random-effects model using the Stata 16.0 metaprop command.

Results

The pooled analysis of 9609 cN0 patients who achieved bpCR showed that the ypN+ rate was lowest for the HR+/HER2+ (0%) subtype, followed by HR+/HER2- (5.1%), HR-/HER2+ (0.6%), and HR-/HER2- (0.3%). Additionally, 6571 cT1-T2N0 patients who achieved bpCR had a pooled ypN+ rate of 0.6%, and the ypN+ rates for different subtypes were as follows: HR+/HER2+ (1.7%), HR+/HER2- (2.7%), HR-/HER2+ (0.1%), and HR-/HER2- (0.8%).

Conclusion

Our results suggested that cN0 patients who achieve bpCR may be exempt from axillary surgery in the HR+/HER2-, HR+/HER2+, and HR-/HER2- subtypes because of the extremely low probability of residual axillary lymph node disease. However, the safety of omitting axillary surgery needs to be further confirmed by prospective studies.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42022351739.
Hereditary pulmonary arterial hypertension burden in pediatrics: A single referral center experience
Authors: Ishizuka Maki , Zou Wenxin , Whalen Elise , Ely Erin , Coleman Ryan D. , Lopez-Terrada Dolores H. , Penny Daniel J. , Fan Yuxin , Varghese Nidhy P.
Published: March 2023

Introduction

Hereditary pulmonary arterial hypertension (HPAH) is a rare yet serious type of pulmonary arterial hypertension (PAH). The burden in the pediatric population remains high yet underreported. The objective of this study is to describe the distribution of mutations found on targeted PAH panel testing at a large pediatric referral center.

Methods

Children with PAH panel administered by the John Welsh Cardiovascular Diagnostic Laboratory at Texas Children's Hospital and Baylor College of Medicine in Houston, Texas between October 2012 to August 2021 were included into this study. Medical records were retrospectively reviewed for clinical correlation.

Results

Sixty-six children with PAH underwent PAH genetic testing. Among those, 9 (14%) children were found to have pathogenic mutations, 16 (24%) children with variant of unknown significance and 41 (62%) children with polymorphism (classified as likely benign and benign). BMPR2 mutation was the most common pathogenic mutation, seen in 6 of the 9 children with detected mutations. Hemodynamic studies showed higher pulmonary vascular resistance among those with pathogenic mutations than those without (17.4 vs. 4.6 Wood units). All children with pathogenic mutations had severe PAH requiring triple therapy. There were tendencies for higher lung transplantation rate but lower mortality among those with pathogenic mutations.

Conclusions

Abnormalities on genetic testing are not uncommon among children with PAH, although majority are of unclear significance. However, children with pathogenic mutations tended to present with more severe PAH requiring aggressive medical and surgical therapies. Genetic testing should be routinely considered due to consequences for treatment and prognostic implications. Larger scale population studies and registries are warranted to characterize the burden of HPAH in the pediatric population specifically.
Effects of rhubarb peony decoction combined with antibiotics in treating pediatric periappendiceal abscess
Authors: Lin Zhixiong , Zeng Huiping , Cai Shujie , Chen Fei , Wang Xiang , Wu Dianming , Liu Mingkun , Fang Yifan
Published: March 2023

Background/purpose

Rhubarb peony decoction (RPD) is a formula of traditional Chinese medicine that has been widely used to treat intra-abdominal inflammatory diseases. To investigate the therapeutic efficacy of RPD in pediatric periappendiceal abscess, patients who received intravenous antibiotics alone were compared with those treated with intravenous antibiotics combined with RPD.

Methods

A retrospective review of children with periappendiceal abscess who received conservative treatment in our hospital between January 2013 and April 2022 was performed. The patients were divided into an intravenous antibiotic group (the control group) and an intravenous antibiotic combined with RPD group (the intervention group). Interval appendectomy (IA) was generally performed 10–12 weeks after conservative treatment. The primary outcome was the cure rate of conservative treatment, while the secondary outcomes included the recurrence rate, days of total intravenous antibiotic use, length of hospital stay (LOS), postoperative complications, and liver injury caused by RPD.

Results

A total of 142 patients (77 girls and 65 boys) were included, 52 in the control group and 90 in the intervention group. The two groups were similar in demographic data and clinical characteristics (P > 0.05). The mean total course of RPD in the intervention group was 11.82 days. The intervention group had a significantly higher cure rate than the control group (93.33% vs. 80.77%, P = 0.029), and the length of total intravenous antibiotic use (P = 0.150), LOS (P = 0.077), recurrence rate (9.52% vs. 4.76%, P = 0.439), as well as the operation time (P = 0.101), LOS (P = 0.572), and postoperative complications (P = 0.549) were not significantly different between the two groups when the patients received IA. No patient had a liver injury caused by RPD during the treatment.

Conclusion

Intravenous antibiotics combined with RPD demonstrated high effectiveness and safety for treating pediatric periappendiceal abscess.
Population pharmacokinetic analysis and dosing optimization of polymyxin B in critically ill patients
Authors: Liang Danhong , Liang Zhi , Deng Guoliang , Cen Anfen , Luo Dandan , Zhang Chen , Ni Suiqin
Published: March 2023

Objectives: Since the global broadcast of multidrug-resistant gram-negative bacteria is accelerating, the use of Polymyxin B is sharply increasing, especially in critically ill patients. Unsatisfactory therapeutic effects were obtained because of the abnormal physiological function in critically ill patients. Therefore, the determination of optimal polymyxin B dosage becomes highly urgent. This study aimed to illustrate the polymyxin B pharmacokinetic characteristics by defining the influencing factors and optimizing the dosing regimens to achieve clinical effectiveness.

Methods: Steady-state concentrations of polymyxin B from twenty-two critically ill patients were detected by a verified liquid chromatography-tandem mass spectrometry approach. The information on age, weight, serum creatinine, albumin levels, and Acute Physiology and Chronic Health Evaluation-II (APACHE-II) score was also collected. The population PK parameters were calculated by the non-parametric adaptive grid method in Pmetrics software, and the pharmacokinetic/pharmacodynamics target attainment rate was determined by the Monte Carlo simulation method.

Results: The central clearance and apparent volume of distribution for polymyxin B were lower in critically ill patients (1.24 ± 0.38 L h-1 and 16.64 ± 12.74 L, respectively). Moreover, albumin (ALB) levels can be used to explain the variability in clearance, and age can be used to describe the variability in the apparent volume of distribution. For maintaining clinical effectiveness and lowering toxicity, 75 mg q12 h is the recommended dosing regimen for most patients suffering from severe infections.

Conclusion: This study has clearly defined that in critically ill patients, age and ALB levels are potentially important factors for the PK parameters of polymyxin B. Since older critically ill patients tend to have lower ALB levels, so higher dosages of polymyxin B are necessary for efficacy.
Research progress on the utilization technology of broccoli stalk, leaf resources, and the mechanism of action of its bioactive substances
Authors: Yan Lu , Zhou Gang , Shahzad Khuram , Zhang Haoran , Yu Xiang , Wang Yusu , Yang Nan , Wang Mengzhi , Zhang Xin
Published: March 2023

Broccoli is a nutritious vegetable. It is high in protein, minerals, and vitamins. Also, it possesses antioxidant activities and is beneficial to the human body. Due to its active effect, broccoli is widely accepted by people in daily life. However, in terms of current utilization, only its florets are consumed as vegetables, while more than half of its stalks and leaves are not utilized. The stalks and leaves contain not only nutrients but also bioactive substances with physiologically regulating properties. Therefore research into the action and mechanism of its bioactive substances as well as its development and utilization technology will make contributions to the further promotion of its resource development and utilization. As a theoretical foundation for the resource utilization of broccoli stalks and leaves, this report will review the distribution and consumption of broccoli germplasm resources, the mechanism of action of bioactive substances, and innovative methods for their exploitation.
Suicidality and epilepsy: A systematic review and meta-analysis
Authors: Wang Haijiao , Zhang Yu , Tan Ge , Chen Deng , Fu Yaoqi , Liu Ling
Published: March 2023

Background

We aimed to evaluate the association between epilepsy and suicidality, including suicidal ideation, attempts and completed suicide.

Methods

We systematically searched PubMed, Embase, Cochrane Online Library, and Clinicaltrials.gov from 1946 to June 21, 2021 and assessed the quality of the studies using the Newcastle–Ottawa Scale. We calculated the pooled OR and the crude rate for suicidal ideation, suicide attempts and completed suicide in patients with epilepsy (PWE).

Results

We screened 2,786 studies and included 88 articles with 1,178,401 PWE and 6,900,657 participants as controls. Search terms included epilepsy and suicide. The pooled rates of suicidal ideation, suicide attempts and completed suicide in PWE were 19.73% (95% CI: 17.00–22.62%), 5.96% (95% CI: 4.82–7.20%), and 0.24% (95% CI: 0.11–0.42%), respectively. Compared to the control group, PWE were at a significantly higher risk of total suicidality (pooled OR, 2.60; 95%: 2.13–3.18), including suicidal ideation (pooled OR, 2.70; 95% CI, 2.21–3.30), suicide attempts (pooled OR, 2.74; 95% CI, 2.08–3.61) and completed suicide (pooled OR, 2.36; 95% CI, 1.45–3.83). Subgroup analyses showed significant differences in the subgroups of the measurement of suicidality.

Conclusion

The rate of suicidal ideation, suicide attempts and completed suicide in PWE were about 19.73, 5.96, and 0.24%. And there was an increased risk of suicidality in PWE especially temporal lobe epilepsy and drug-resistant epilepsy. Clinicians need to be aware of this risk in PWE with early identification and prevention at the time of diagnosis.

Protocol Registration: PROSPERO CRD42021278220.
Association between mental health symptoms and behavioral performance in younger vs. older online workers
Authors: Mills-Finnerty Colleen , Staggs Halee , Hogoboom Nichole , Naparstek Sharon , Harvey Tiffany , Beaudreau Sherry A. , O’Hara Ruth
Published: March 2023

Background

The COVID-19 pandemic has been associated with increased rates of mental health problems, particularly in younger people.

Objective

We quantified mental health of online workers before and during the COVID-19 pandemic, and cognition during the early stages of the pandemic in 2020. A pre-registered data analysis plan was completed, testing the following three hypotheses: reward-related behaviors will remain intact as age increases; cognitive performance will decline with age; mood symptoms will worsen during the pandemic compared to before. We also conducted exploratory analyses including Bayesian computational modeling of latent cognitive parameters.

Methods

Self-report depression (Patient Health Questionnaire 8) and anxiety (General Anxiety Disorder 7) prevalence were compared from two samples of Amazon Mechanical Turk (MTurk) workers ages 18–76: pre-COVID 2018 (N = 799) and peri-COVID 2020 (N = 233). The peri-COVID sample also completed a browser-based neurocognitive test battery.

Results

We found support for two out of three pre-registered hypotheses. Notably our hypothesis that mental health symptoms would increase in the peri-COVID sample compared to pre-COVID sample was not supported: both groups reported high mental health burden, especially younger online workers. Higher mental health symptoms were associated with negative impacts on cognitive performance (speed/accuracy tradeoffs) in the peri-COVID sample. We found support for two hypotheses: reaction time slows down with age in two of three attention tasks tested, whereas reward function and accuracy appear to be preserved with age.

Conclusion

This study identified high mental health burden, particularly in younger online workers, and associated negative impacts on cognitive function.
Use of tobacco, nicotine and cannabis products among students in Switzerland
Authors: Affolter Jana , Rohland Eveline , Philippe Marc , Tal Kali , Auer Reto , Jakob Julian
Published: March 2023

Introduction

Most people who smoke cigarettes begin in their teens and teens may also be attracted to new tobacco, nicotine, and cannabis products. We describe use prevalence among upper-secondary school students in Switzerland, including daily use, of tobacco, nicotine, and cannabis products.

Methods

We invited secondary school students (age 15 to 21) in two Swiss cantons to take an online survey between October 2021 and February 2022. The survey collected demographic information and asked how frequently they used tobacco products (cigarettes in commercial packages, self-rolled cigarettes, hookahs, pipes, cigars and cigarillos, tobacco heating systems, snus, snuff), non-tobacco nicotine products (nicotine pouches, e-cigarettes with and without nicotine), and cannabis products (smoking with and without tobacco, cannabis vaping). Answers were scored on a Likert scale (no use in past month, less than weekly, weekly but not daily, daily use, prefer not to say), then tabulated and reported as descriptive statistics.

Results

Of 32,614 students in the schools we contacted, 9,515 (29.2%) completed the survey; 49.5% identified as female and 48.4% as male; 9.5% were under 16, 47% were 16–17, 27.5% were 18–19, and 16% were over 19. Reported daily use was most frequent for tobacco cigarettes in commercial packages (14.2%), snus (4.1%) and cannabis smoking with tobacco (3.6%). Most participants (54.8%) reported they had used at least one product at least once within the last month.

Conclusion

Students who used a product were most likely to smoke cigarettes, but many regularly used new tobacco, nicotine and cannabis products, though use frequency varies.
Rapid evidence review: Policy actions for the integration of public health and health care in the United States
Authors: Lin Jennifer S. , Webber Elizabeth M. , Bean Sarah I. , Martin Allea M. , Davies Melinda C.
Published: March 2023

Objective

To identify policy actions that may improve the interface of public health and health care in the United States.

Methods

A rapid review of publicly-available documents informing the integration of public health and health care, and case examples reporting objective measures of success, with abstraction of policy actions, related considerations, and outcomes.

Results

Across 109 documents, there were a number of recurrent themes related to policy actions and considerations to facilitate integration during peace time and during public health emergencies. The themes could be grouped into the need for adequate and dedicated funding; mandates and shared governance for integration; joint leadership that has the authority/ability to mobilize shared assets; adequately staffed and skilled workforces in both sectors with mutual awareness of shared functions; shared health information systems with modernized data and IT capabilities for both data collection and dissemination of information; engagement with multiple stakeholders in the community to be maximally inclusive; and robust communication strategies and training across partners and with the public.

Conclusion

While the evidence does not support a hierarchy of policies on strengthening the interface of public health and health care, recurrent policy themes can inform where to focus efforts.
Correlation analysis of anthropometric indices and type 2 diabetes mellitus in residents aged 60 years and older
Authors: Feng Xiaoyan , Wang Junyi , Wang Shupei , Wang Zhihao , Wu Shan , Wei Yuan , Li Lvrong , Shen Tianran , Chen Qingsong
Published: March 2023

Background and purpose

In recent years, the incidence of obesity in people aged 60 and over has increased significantly, and abdominal obesity has been recognized as an independent risk factor for diabetes. Aging causes physiologic decline in multiple body systems, leading to changes in obesity indicators such as BMI. At present, the relationship between abdominal obesity markers and Diabetes mellitus (DM) in people aged 60 years and older remains unclear. Therefore, it is necessary to study the correlation between anthropometric indices and diabetes and explore potential predictors.

Methods

The basic demographic information of participants aged 60 and above in Zhongshan City in 2020 was collected. Physical parameters, blood glucose and other biochemical indices were measured comprehensively. Binary logistic regression analysis was used to explore the relationship between abdominal obesity indicators [Waist circumference, Neck Circumference, Waist-to-hip ratio, Chinese Visceral Obesity Index (CVAI), and visceral obesity index] and diabetes mellitus. ROC characteristic curve was used to analyze the predictive ability of abdominal obesity indicators to DM, and the non-restrictive cubic spline graph was used to visualize the screened obesity indicators and diabetes risk.

Results

Among 9,519 participants, the prevalence of diabetes was 15.5%. Compared with low CVAI, High CVAI level was significantly associated with increased prevalence of DM in males and females (all p < 0.05), in males (OR, 2.226; 95%CI: 1.128–4.395), females (OR, 1.645; 95%CI: 1.013–2.669). After adjusting for potential confounding factors, there were gender differences between neck circumference and the prevalence of DM, and above-normal neck circumference in males was significantly associated with increased prevalence of DM (OR, 1.381; 95% CI: 1.091–1.747) (p < 0.05).

Conclusion

Among these anthropometric indices, CVAI is consistent with the features of fat distribution in older individuals and shows superior discriminative power as a potential predictor of DM, compared to traditional anthropometric parameters.
Socioeconomic disparities associated with mortality in patients hospitalized for COVID-19 in Colombia
Authors: Mendoza Cardozo Oscar Ignacio , Pérez Bedoya Juan Pablo , Ruiz Galvis Lina Marcela , Pérez Aguirre Carlos Andrés , Rodríguez Rey Boris Anghelo , Barengo Noël Christopher , Cardona Jiménez Johnatan , Díaz Valencia Paula Andrea
Published: March 2023

Socioeconomic disparities play an important role in the development of severe clinical outcomes including deaths from COVID-19. However, the current scientific evidence in regard the association between measures of poverty and COVID-19 mortality in hospitalized patients is scant. The objective of this study was to investigate whether there is an association between the Colombian Multidimensional Poverty Index (CMPI) and mortality from COVID-19 in hospitalized patients in Colombia from May 1, 2020 to August 15, 2021. This was an ecological study using individual data on hospitalized patients from the National Institute of Health of Colombia (INS), and municipal level data from the High-Cost Account and the National Administrative Department of Statistics. The main outcome variable was mortality due to COVID-19. The main exposure variable was the CMPI that ranges from 0 to 100% and was categorized into five levels: (i) level I (0%−20%), (ii) level II (20%−40%), (iii) level III (40%−60%), (iv) level IV (60%−80%); and (v) level V (80%−100%). The higher the level, the higher the level of multidimensional poverty. A Bayesian multilevel logistic regression model was applied to estimate Odds Ratio (OR) and their corresponding 95% credible intervals (CI). In addition, a subgroup analysis was performed according to the epidemiological COVID-19 waves using the same model. The odds for dying from COVID-19 was 1.46 (95% CI 1.4–1.53) for level II, 1.41 (95% CI 1.33–1.49) for level III and 1.70 (95% CI 1.54–1.89) for level IV hospitalized COVID-19 patients compared with the least poor patients (CMPI level I). In addition, age and male sex also increased mortality in COVID-19 hospitalized patients. Patients between 26 and 50 years-of-age had 4.17-fold increased odds (95% CI 4.07–4.3) of death compared with younger than 26-years-old patients. The corresponding for 51–75 years-old patients and those above the age of 75 years were 9.17 (95% CI 8.93–9.41) and 17.1 (95% CI 16.63–17.56), respectively. Finally, the odds of death from COVID-19 in hospitalized patients gradually decreased as the pandemic evolved. In conclusion, socioeconomic disparities were a major risk factor for mortality in patients hospitalized for COVID-19 in Colombia.
Mechanical ventilation in snake envenomation of dogs and cats
Authors: Morris Cameron A. D. , Donaldson Rebekah E.
Published: March 2023

Envenomation by snakes inElapidaeandViperidaefamilies have been associated with respiratory failure in dogs and cats. Mechanical ventilation may be required for hypoventilation due to neuromuscular paralysis or hypoxemia due to pulmonary hemorrhage or aspiration pneumonia. Median incidence of dogs and cats with snake envenomation that require mechanical ventilation is 13% (0.06–40%). Standard treatment of snake envenomation in dogs and cats includes prompt administration of appropriate antivenom and management of envenomation complications such as coagulopathy, rhabdomyolysis and acute kidney injury. When mechanical ventilation is required, overall prognosis is good with appropriate treatment. Standard anesthetic protocols and mechanical ventilator settings are generally appropriate, with lung protective ventilation strategies typically reserved for patients with pulmonary disease. Median survival to discharge for cats and dogs with elapid envenomation is 72% (76–84%) with 33 h (19.5–58 h) median duration of mechanical ventilation and 140 h (84–196 h) median hospitalization. This article reviews indications for mechanical ventilation in cats and dogs with snake envenomation, and discusses ventilator settings, anesthetic and nursing considerations, complications and outcomes specific to this disease.