bluuebunny/crossref_metadata_2025 huggingface dataset:
Postoperative blood glucose increase is associated with futile recanalization in patients with successful thrombectomy: a retrospective study
Authors: Tang Tao , Li Di , Fan Tie-Ping , Bi Cong-Jie , Thomas Aline M. , Zhao Man-Hong , Li Shen
Published: December 2023

Background

Timely recognition of futile recanalization might enable a prompt response and an improved outcome in post-thrombectomy patients. This study aims to evaluate whether postoperative blood glucose increase (BGI) could act as an indicator of futile recanalization in patients receiving a successful thrombectomy.

Methods

This is a single-center, retrospective analysis of patients with anterior circulation large-vessel occlusion and successful thrombectomy between February 2019 and June 2022. BGI was defined as a higher level of blood glucose at the first postoperative morning than at admission. Futile recanalization was defined as patients with a modified Rankin Scale score of 3–6 at 90 days after onset. Multivariable binary logistic regression was used to assess the association of BGI with futile recanalization.

Results

A total of 276 patients were enrolled, amongst which 120 patients (43.5%) had BGI. Futile recanalization was more prevalent among patients with BGI compared to those without (70.0 vs. 49.4%, P = 0.001). After adjusting for potential confounders, BGI was associated with a higher likelihood of futile recanalization (adjusted OR: 2.97, 95%CI: 1.50–5.86, P = 0.002). This association was consistently observed regardless of diabetes history, occlusion site, time from symptom onset to groin puncture, or reperfusion status.

Conclusion

Our findings support BGI serving as an indicator of futile recanalization in patients with anterior circulation large-vessel occlusion and successful thrombectomy.
Video analysis of optic-haptic-interaction during hydrophobic acrylic intraocular lens implantation using preloaded injectors
Authors: Yan Weijia , Borkenstein Andreas F , Khoramnia Ramin , Borkenstein Eva-Maria , Auffarth Gerd U
Published: December 2023

Objective

To compare the optic-haptic interaction of different hydrophobic acrylic IOLs after using six preloaded injectors.

Methods

We reviewed the video-recordings of procedures on a total of 388 eyes that underwent phacoemulsification and intraocular lens (IOL) implantation. For six preloaded injectors: multiSert (Hoya Surgical Optics) [System 1], TECNIS Simplicity (Johnson & Johnson Vision) [System 2], TECNIS iTec (Johnson & Johnson Vision) [System 3], AutonoMe (Alcon, Laboratories) [System 4], Bluesert (Carl Zeiss Meditec) [System 5], and Prosert (OphthalmoPro GmbH) [System 6], we noted in each case the time of IOL delivery and made a descriptive observation of IOL insertion and optic-haptic-interaction.

Results

We defined standard haptic behavior where the haptics emerged “folded” from the injector and quickly recovered their pre-implantation appearance. The incidence where the leading haptic emerged in a deformed way for System 1 was 20%, System 2: 19%, System 3: 14%, System 4: 56%, System 5: 24% and System 6: 5%. For trailing haptic deformed behavior, the incidence was 36%, 6%, 4%, 8%, 18% and 2%, respectively for Systems 1 to 6. Optic-haptic adhesion occurred in 2% of cases for System 1, 44% for System 2, 52% for System 3, 48% for System 4, and 11% for System 6 (P < 0.05). Adhesion was not found with System 5.

Conclusions

We observed different deformed behavior for leading and trailing haptics in the six preloaded systems, some systems had as much as 52% optic-haptic adhesion.
Application of the suture needle retrograde threading method in scleral fixation of intraocular lenses
Authors: Zhou Zhou , Yao Gang , Huang Guangyi , Zhong Haibin , Chen Qi , Yang Ke , Zhong Shan , Li Min , Xu Fan
Published: December 2023

Background

Here we described a new threading technique for the universal fixation of any posterior chamber intraocular lens (IOL).

Methods

Twenty-seven eyes of 27 patients whose surgery done by Surgeon A with the needle-guided method or the suture needle retrograde threading (SNRT) method for intrascleral IOL fixation were enrolled in the first group. Thirty-four eyes of 34 patients whose surgery done by Surgeon A, Surgeon B or Surgeon C with the SNRT method for intrascleral IOL fixation were grouped into three sub-groups by surgeon. Information regarding age, sex, best-available visual acuity (BCVA), intraocular pressure (IOP), past ophthalmological history, threading time (from puncturing to externalizing suture) and complications during and after the surgery were gathered.

Results

The analysis showed that the threading time was less in the SNRT group than needle-guided group by Surgeon A. There was one eye with suture needle slipping from the guide needle when guiding out of the eye. The threading procedure was completed one time without suture ruptures or loop slippage in the SNRT group operated by Surgeon A. And using the SNRT method, Surgeon A, Surgeon B, and Surgeon C did not show any significant difference in threading time. No complications (e.g., vitreous hemorrhage, hyphemia, retinal detachment, suprachoroidal hemorrhage, or hypotony) were observed during surgery or postoperatively in all cases. No leakage occurred at the site of the puncture after the operation.

Conclusions

The described technique appears to be a safe, simple, easy-to-learn, and universal surgical method, which is suitable for various types of IOLs.
Incidence of non-syndromic orofacial cleft during the COVID-19 pandemic in Saudi Arabia
Authors: Sabbagh Heba Jafar , Alghamdi Sultan Musaad , Abdulhameed Fatma Dawood , Alhussain Reema Mahdi , Alrejaye Najla Sulaiman , AlGudaibi Latifa Yousef , Sallout Bahauddin Ibraheem , Albaqawi Badi Shoaib , Alnamnakani Eman Abdulbaset , Brekeit Lougin Khalid , Alsharif Mona Tala , Alshaikh Ali Bakr , Almalik Manal Ibrahim , Aburiziza Abdullah Jameel , Al Soqih Norah Suliman , Alqhtani Faisal Ali , Alghamdi Bushra Musaad , Alraddadi Asalah Khalid , Aljohar Aziza Johar , Basri Osama Adel , Alamoudi Rana Abdullah
Published: December 2023

Objectives

This is the first national study to investigate the incidence of non-syndromic oro-facial clefts (NSOFC) and Pierre-Robin-Sequence in Saudi Arabia over the Covid-19 pandemic period.

Methods

All maternity hospitals (30-hospitals) in the major regions and cities of Saudi from November 2020-to-2021 were included in the study. Patients were evaluated for cleft phenotype using the LASHAL-classification system. The incidence of NSOFC in Saudi Arabia was calculated by comparing the number of NSOFCs cases born out of all live births during the study period at the included hospitals. Clinical examination was performed and information was gathered using a validated data collection form.

Results

In one year, 140,380 live-infants were born at the selected hospitals. Of these, 177 were diagnosed with NSOFC giving an incidence of 1.26/1,000 live-births in Saudi Arabia and the highest incidence in Medina city (2.46/1000 live-births). The incidence of cleft lip-and-palate (0.67/1000 live-births) was higher than that of cleft-palate (0.37/1000 live-births) and cleft-lip (0.22/1000 live-births). Pierre-Robin Sequence incidence was (0.04/1000 live-births). There were 21(12.1) or 23(13.2%) of NSOFC’s mothers exposed or vaccinated with Covid-19, respectively.

Conclusion

The national incidence of NSOFC in Saudi Arabia was 1.26/1000 live births with variation between phenotypes and regions in the country. In addition, to reporting Covid-19 infection prevalence and vaccine exposure among NSOFC's mothers, this study represents the first of its type to evaluate NSOFC prevalence in Saudi Arabia on a national level.
Finite element analysis and a pilot study of different fixation constructs for Danis-Weber A and B lateral malleolus fractures
Authors: Huang Shuming , Zhu Junkun , Xing Hailin , Yang Ruifeng , Ye Jifei , Ye Fang , Wu Quanzhou , Lan Shuhua
Published: December 2023

Background

Displaced lateral malleolus fractures are typically stabilised through open reduction and internal fixation. The biomechanically and clinically efficacy of locking plates and lag screws, particularly in Weber A and B distal fibular fractures remains a subject of contention. This study examines two locking plate designs for lateral malleolus fractures, evaluating their performance with and without interfragmentary screws using finite element models.

Methods

Utilising CT images of a healthy adult male volunteer, a three-dimensional finite element model was constructed. The Fibula-specific Flank Multiaxial Locking Anatomic Plate (FMLP) and the Conventional Locking Plate (CLP) were subjected to stabilisation, both with and without an interfragmentary screw, mimicking the Danis-Weber A and B lateral malleolus oblique fracture fixation. Loads of 140 N and 70 N, equivalent to 20% of the body weight, were applied to simulate the single-leg and two-leg standing conditions in the axial direction. The von Mises stress (VMS) distributions and element displacements were subsequently analyzed.

Results

In the Danis-Weber A fracture model group, the FMLP with an interfragmentary screw fixation exhibited the lowest peak VMS values: 51.9 MPa in the fibula, 89.0 MPa in the plate, and 61.3 MPa in the screws for simulating single-leg conditions. Under two-leg standing conditions, these peak VMS values decreased to 25.9 MPa in the fibula, 44.5 MPa in the plate, and 30.6 MPa in the screws, respectively. Furthermore, the overall structural peak displacements during single-leg standing for both Weber-A and B fractures with different implants ranged from 1.61 to 2.54 mm. While standing on two feet, the ranged was from 0.80 to 1.27 mm. An interfragmentary screw at the oblique fracture site resulted in reduced the peak value of VMS in the fibula, plate, screws, consequently decreased the overall structural displacement for FMLP and CLP fixation in lateral malleolus fractures.

Conclusions

The current finite element analysis (FEA) demonstrates that FMLP exhibits superior mechanical characteristics in Danis-Weber A and B lateral malleolus fractures compared to CLP. The inclusion of an interfragmentary screw, combined with locking plate design, enhances stability for simple oblique distal fibular fractures. The FMLP presents itself as potential as an alternative for lateral malleolus fractures from a biomechanical perspective. Nevertheless, further verification of these results is imperative through subsequent clinical studies.
Online learning resources and social media platforms used by medical students during the COVID-19 pandemic
Authors: Azer Samy A. , Alhudaithi Deema , AlBuqami Fay , AlWaily Haifa , AlRabah Razan , AlKhashan Raghad
Published: December 2023

Background

The unprecedented COVID-19 pandemic has caused significant disruption to medical students’ education. It imposed challenges that required rapid adaptation to enforced lockdowns and remote learning and changed curriculum delivery from in-person to online learning and virtual technology.

Objective

This study aimed to determine the trends and ratings of using Internet resources and social media platforms by medical students during the COVID-19 pandemic.

Methods

A validated questionnaire was used to explore preferences for Internet resources and social media platforms among undergraduate medical students (years 1, 3, and 5) at King Saud University. The questionnaire comprised three sections- (i) demographic information, (ii) access and use of Internet resources/social media platforms, and (iii) students’ ratings and reasons for using technology-enabled learning during the COVID-19 pandemic.

Results

A total of 320 undergraduate medical students responded to the online questionnaire. The difference in the number of students using the Internet daily across academic years increased significantly as they progressed in the medical course (p = 0.025). For learning, YouTube and Videoconferencing (e.g. Zoom) were used by 83.1% and 73.4% of students, respectively, followed by WhatsApp 198 (61.9%). For social interaction, WhatsApp, 310 (96.6%); YouTube, 296 (92.8%); Twitter, 288 (90%); and Zoom, 269 (84.1%) were the platforms used by most students. Regarding concerns about the impact of COVID-19 and social isolation, 250 (78.1%) agreed that technology helped them gain a sense of connectedness to their peers. Over half of students, 187 (58.4%) wished that technologies be integrated more often in their courses, as 245 (76.7%) agreed that it helped engage them with classes.

Conclusion

The study shows that the use of the Internet and social media resources is increasing at all levels to fill the gap in learning and social interaction because of the COVID-19 pandemic. Medical institutions should embrace the effective use of Internet resources and use the experience gained and lessons learned in guiding educators on what type of online resources should be created to add value to students learning even post-pandemic.
Trainee educational curriculum to standardize central venous catheter repair
Authors: Reppucci Marina , Prendergast Connor , Flynn Katherine , Scarbro Sharon , Derderian S. Christopher , Diaz-Miron Jose
Published: December 2023

Introduction

Children may require durable central venous catheters (CVCs) for various reasons. CVC-related integrity complications are common and can often be repaired at the bedside to increase lifetime. Variability in repair techniques can lead to complications, including the need for repeat repair and Central Line Associated Blood Stream Infection (CLABSI).

Methods

The impact of an educational curriculum to standardize tunneled CVC repairs for trainees on a pediatric surgery service was studied, focusing on comfort level with tunneled CVC repair and to determine the impact on complication rates. Rotating trainees studied a dedicated audiovisual educational curriculum comprised of a video, educational slides, and a practical component from November 2020 through January 2022. Experience and comfort level with tunneled CVC repairs were assessed before and after the rotation. CVCs repaired during the duration of the study were evaluated and compared to the period prior.

Results

Forty-nine individuals completed the pre- and post-training survey. Respondents (34.7%, n = 17) most commonly reported one year of surgical experience, and (79.6%, n = 39) had never observed or assisted in a repair previously. Following training, respondents felt more comfortable with all aspects of the CVC repair process (p < 0.001). There were no statistically significant differences in re-repair rates or CLABSI rates following the implementation of the curriculum.

Conclusions

Tunneled CVC procedural repair variability can be standardized with a dedicated educational curriculum for rotating trainees, which improves knowledge and comfort with such procedures.
Barriers to clinical nurse participation in the internet-based home visiting program: a qualitative study
Authors: Yu Jiahao , Huang Jianyuan , Li Chunlei , Zhuang Yongmei
Published: December 2023

Background

Home visits are an important part of home care. With increasing demand and the rapid development of information technology, an increasing number of regions are experimenting with the use of information technology in home visits, hoping to meet the needs of more patients through technological interventions. However, most of the current studies have focused on patient health improvement through home visits, neglecting to consider the actual experience of nurses as service providers in participating in Internet-based programs. Thus, the purpose of this research is to explore what is holding nurses back from participating after the Internet has been added to traditional home visiting programs.

Methods

This research was designed with an exploratory-descriptive qualitative analysis method. Semistructured interviews were used to collect information on barriers to nurses’ participation in the Internet-based home visiting program. Participants included 16 clinical nurses working in various hospitals in Nanjing, China. The thematic analysis method was used to analyze the information.

Results

This research identified three themes and twelve subthemes that hinder clinical nurse engagement in the Internet-based home visiting program. The three themes included multiple barriers to individuals, different service modes, and emerging organizational problems.

Conclusions

As a new form of traditional home visiting program in information society, Internet-based home visiting has many shortcomings in the overall program design and service management specifications. For more patients living at home to receive quality care services, it is necessary to take more effective measures to encourage nurses’ participation at three levels: nurse demand, service process, and organizational management.
Cultural competence in NHS hearing aid clinics: a mixed-methods case study of services for Deaf British sign language users in the UK
Authors: Hulme Celia , Young Alys , Rogers Katherine , Munro Kevin J.
Published: December 2023

Background

This study identified and explored how National Health Service (NHS) hearing aid clinics address cultural competence concerning Deaf British Sign Language (BSL) users. This was approached by (i) investigating how organisational processes meet the needs of Deaf signers from a hospital and hearing aid clinic perspective, (ii) analysing policies and guidelines to investigate if they equip practitioners to meet the needs of Deaf signers and (iii) exploring with practitioners who work in hearing aid clinics about their experiences of working with Deaf signers.

Methods

This study utilised a mixed-methods multiple case study design, incorporating documentary analysis and semi-structured interviews. Interview analysis was conducted using Reflexive Thematic Analysis (RTA). The research encompassed two hearing aid clinics in separate hospitals, producing 19 documents and eight interviews (four at each site) with audiologists ensuring a representative mix of professional experience levels.

Results

Four themes emerged from the integrated analysis: (1) Understanding Deaf signers; (2) Communicating with Deaf signers; (3) Barriers and Facilitators and (4) Service improvement. A noticeable gap in understanding BSL as both a language and a cultural system was apparent across various policies, strategies, training programmes and staff expertise. Over-reliance on interpreters provided a false sense of accessibility and most participants felt tentative to engage directly with Deaf signers. Positive practices observed at Sites A and B encompassed accurate identification of patients as Deaf signers, improved interpreter availability, communication methods, enhanced training and the encouragement of professional self-awareness.

Conclusion

This is the first study that explores cultural competence of hearing aid clinics and its staff concerning Deaf signers in the UK. The results show both clinics require development to become an effective provider for culturally Deaf signers. Examples of how to design culturally competent practices have been provided to assist hearing aid clinics. The findings may be applicable to other underrepresented groups who are not typical users of conventional, acoustic hearing aids provided by the NHS.
The impact of the COVID-19 pandemic on rates and predictors of missed hospital appointments in multiple outpatient clinics of The Royal Hospital, Sultanate of Oman: a retrospective study
Authors: Alawadhi Ahmed , Palin Victoria , van Staa Tjeerd
Published: December 2023

Background

The global outbreak of the COVID-19 pandemic resulted in significant changes in the delivery of health care services such as attendance of scheduled outpatient hospital appointments. This study aimed to evaluate the impact of COVID-19 on the rate and predictors of missed hospital appointment in the Sultanate of Oman.

Methods

A retrospective single-centre analysis was conducted to determine the effect of COVID-19 on missed hospital appointments at various clinics at The Royal Hospital (tertiary referral hospital) in Muscat, Sultanate of Oman. The study population included scheduled face-to-face and virtual appointments between January 2019 and March 2021. Logistic regression models were used with interaction terms (post COVID-19) to assess changes in the predictors of missed appointments.

Results

A total of 34, 3149 scheduled appointments was analysed (320,049 face-to-face and 23,100 virtual). The rate of missed face-to-face hospital appointments increased from 16.9% pre to 23.8% post start of COVID-19, particularly in early pandemic (40.5%). Missed hospital appointments were more frequent (32.2%) in virtual clinics (post COVID-19). Increases in missed face-to-face appointments varied by clinic (Paediatrics from 19.3% pre to 28.2% post; Surgery from 12.5% to 25.5%; Obstetrics & Gynaecology from 8.4% to 8.5%). A surge in the frequency of missed appointments was seen during national lockdowns for face-to-face and virtual appointments. Most predictors of missed appointments did not demonstrate any appreciable changes in effect (i.e., interaction term not statistically significant). Distance of patient residence to the hospital revealed no discernible changes in the relative effect pre and post COVID-19 for both face-to-face and virtual clinic appointments.

Conclusion

The rate of missed visits in most clinics was directly impacted by COVID-19. The case mix of patients who missed their appointments did not change. Virtual appointments, introduced after start of the pandemic, also had substantial rates of missed appointments and cannot be viewed as the single approach that can overcome the problem of missing hospital appointments.
The HSP40 family chaperone isoform DNAJB6b prevents neuronal cells from tau aggregation
Authors: Chang Ya-Lan , Yang Chan-Chih , Huang Yun-Yu , Chen Yi-An , Yang Chia-Wei , Liao Chia-Yu , Li Hsun , Wu Ching-Shyi , Lin Chin-Hsien , Teng Shu-Chun
Published: December 2023

Background

Alzheimer’s disease (AD) is the most common neurodegenerative disorder with clinical presentations of progressive cognitive and memory deterioration. The pathologic hallmarks of AD include tau neurofibrillary tangles and amyloid plaque depositions in the hippocampus and associated neocortex. The neuronal aggregated tau observed in AD cells suggests that the protein folding problem is a major cause of AD. J-domain-containing proteins (JDPs) are the largest family of cochaperones, which play a vital role in specifying and directing HSP70 chaperone functions. JDPs bind substrates and deliver them to HSP70. The association of JDP and HSP70 opens the substrate-binding domain of HSP70 to help the loading of the clients. However, in the initial HSP70 cycle, which JDP delivers tau to the HSP70 system in neuronal cells remains unclear.

Results

We screened the requirement of a diverse panel of JDPs for preventing tau aggregation in the human neuroblastoma cell line SH-SY5Y by a filter retardation method. Interestingly, knockdown of DNAJB6, one of the JDPs, displayed tau aggregation and overexpression of DNAJB6b, one of the isoforms generated from the DNAJB6 gene by alternative splicing, reduced tau aggregation. Further, the tau bimolecular fluorescence complementation assay confirmed the DNAJB6b-dependent tau clearance. The co-immunoprecipitation and the proximity ligation assay demonstrated the protein–protein interaction between tau and the chaperone–cochaperone complex. The J-domain of DNAJB6b was critical for preventing tau aggregation. Moreover, reduced DNAJB6 expression and increased tau aggregation were detected in an age-dependent manner in immunohistochemical analysis of the hippocampus tissues of a mouse model of tau pathology.

Conclusions

In summary, downregulation of DNAJB6b increases the insoluble form of tau, while overexpression of DNAJB6b reduces tau aggregation. Moreover, DNAJB6b associates with tau. Therefore, this study reveals that DNAJB6b is a direct sensor for its client tau in the HSP70 folding system in neuronal cells, thus helping to prevent AD.
The citrate transporter SLC13A5 as a therapeutic target for kidney disease: evidence from Mendelian randomization to inform drug development
Authors: Gill Dipender , Zagkos Loukas , Gill Rubinder , Benzing Thomas , Jordan Jens , Birkenfeld Andreas L. , Burgess Stephen , Zahn Grit
Published: December 2023

Background

Solute carrier family 13 member 5 (SLC13A5) is a Na+-coupled citrate co-transporter that mediates entry of extracellular citrate into the cytosol. SLC13A5 inhibition has been proposed as a target for reducing progression of kidney disease. The aim of this study was to leverage the Mendelian randomization paradigm to gain insight into the effects of SLC13A5 inhibition in humans, towards prioritizing and informing clinical development efforts.

Methods

The primary Mendelian randomization analyses investigated the effect of SLC13A5 inhibition on measures of kidney function, including creatinine and cystatin C-based measures of estimated glomerular filtration rate (creatinine-eGFR and cystatin C-eGFR), blood urea nitrogen (BUN), urine albumin-creatinine ratio (uACR), and risk of chronic kidney disease and microalbuminuria. Secondary analyses included a paired plasma and urine metabolome-wide association study, investigation of secondary traits related to SLC13A5 biology, a phenome-wide association study (PheWAS), and a proteome-wide association study. All analyses were compared to the effect of genetically predicted plasma citrate levels using variants selected from across the genome, and statistical sensitivity analyses robust to the inclusion of pleiotropic variants were also performed. Data were obtained from large-scale genetic consortia and biobanks, with sample sizes ranging from 5023 to 1,320,016 individuals.

Results

We found evidence of associations between genetically proxied SLC13A5 inhibition and higher creatinine-eGFR (p = 0.002), cystatin C-eGFR (p = 0.005), and lower BUN (p = 3 × 10−4). Statistical sensitivity analyses robust to the inclusion of pleiotropic variants suggested that these effects may be a consequence of higher plasma citrate levels. There was no strong evidence of associations of genetically proxied SLC13A5 inhibition with uACR or risk of CKD or microalbuminuria. Secondary analyses identified evidence of associations with higher plasma calcium levels (p = 6 × 10−13) and lower fasting glucose (p = 0.02). PheWAS did not identify any safety concerns.

Conclusions

This Mendelian randomization analysis provides human-centric insight to guide clinical development of an SLC13A5 inhibitor. We identify plasma calcium and citrate as biologically plausible biomarkers of target engagement, and plasma citrate as a potential biomarker of mechanism of action. Our human genetic evidence corroborates evidence from various animal models to support effects of SLC13A5 inhibition on improving kidney function.
Novel compound heterozygous pathogenic variants in the SLC3A1 gene in a Chinese family with cystinuria
Authors: Liu Danhua , Zhao Yongli , Xue Xia , Hou Xinyue , Xu Hongen , Zhao Xinghua , Tian Yongan , Tang Wenxue , Guo Jiancheng , Xu Changbao
Published: December 2023

Background

Cystinuria is an autosomal recessive disorder characterized by a cystine transport deficiency in the renal tubules due to mutations in two genes: SLC3A1 and SLC7A9. Cystinuria can be classified into three forms based on the genotype: type A, due to mutations in the SLC3A1 gene; type B, due to mutations in the SLC7A9 gene; and type AB, due to mutations in both genes.

Methods

We report a 12-year-old boy from central China with cystine stones. He was from a non-consanguineous family that had no known history of genetic disease. A physical examination showed normal development and neurological behaviors. Whole-exome and Sanger sequencing were used to identify and verify the suspected pathogenic variants.

Results

The compound heterozygous variants c.898_905del (p.Arg301AlafsTer6) is located in exon5 and c.1898_1899insAT (p.Asp634LeufsTer46) is located in exon10 of SLC3A1 (NM_000341.4) were deemed responsible for type A cystinuria family. The variant c.898_905del was reported in a Japanese patient in 2000, and the variant c.1898_1899insAT is novel.

Conclusion

A novel pathogenic heterozygous variant pair of the SLC3A1 gene was identified in a Chinese boy with type A cystinuria, enriching the mutational spectrum of the SLC3A1 gene. We attempted to find a pattern for the association between the genotype of SLC3A1 variants and the manifestations of cystinuria in patients with different onset ages. Our findings have important implications for genetic counseling and the early clinical diagnosis of cystinuria.
Prediabetes increases the risk of major limb and cardiovascular events
Authors: Hsu Jung-Chi , Yang Yen-Yun , Chuang Shu-Lin , Lee Jen-Kuang , Lin Lian-Yu
Published: December 2023

Background

Prediabetes, an intermediate stage between normal blood sugar levels and a diabetes mellitus diagnosis, is increasing in prevalence. Severe prediabetes is associated with a similar risk of complications as diabetes, but its relationship with peripheral arterial disease remains underexplored.

Methods

We conducted a retrospective cohort study involving 36,950 adult patients, utilizing electronic medical records from the National Taiwan University Hospital between 2014 and 2019. We employed multivariable Cox regression and Kaplan–Meier analysis with the log-rank test to analyze major adverse limb events (MALE) and major adverse cardiovascular events (MACE) in relation to normal glucose regulation (NGR) and prediabetes.

Results

During the 131,783 person-years follow-up, 17,754 cases of prediabetes and 19,196 individuals with normal glucose regulation (NGR) were identified. Kaplan–Meier analysis revealed an increased incidence of both MALE and MACE in individuals with prediabetes. (log-rank p = 0.024 and < 0.001). Prediabetes exhibited a significant association with an elevated risk of MALE (adjusted hazard ratio (aHR) 1.26 [95% CI 1.10–1.46], p = 0.001) and MACE (aHR 1.46 [1.27–1.67], p < 0.001). Furthermore, in individuals with prediabetes, the elevation in the risk of MALE commenced before HbA1c levels surpassed 5.0% (for HbA1c 5.0-5.5%: aHR 1.78 (1.04–3.04), p = 0.036; HbA1c 5.5-6.0%: aHR 1.29 [1.06–1.58], p = 0.012; aHbA1c 6.0-6.5%: aHR 1.39 [1.14–1.70], p < 0.001). Similarly, the onset of increased MACE risk was observed when HbA1c levels exceeded 5.5% (for HbA1c 5.5–6.0%: aHR 1.67 [1.39–2.01], p < 0.001; HbA1c 6.0-6.5%: HR 2.10 [1.76–2.51], p < 0.001). Factors associated with both MALE and MACE in prediabetes include advanced age, male gender, higher body mass index, and a history of heart failure or atrial fibrillation.

Conclusion

We demonstrated higher susceptibility to MALE and MACE in prediabetes compared to normoglycemic counterparts, notwithstanding lower HbA1c levels. Complications may manifest at an earlier prediabetes trajectory. Intensive lifestyle modification may improve the prognosis of severe prediabetes.
Oxygen therapy attenuates neuroinflammation after spinal cord injury
Authors: Sunshine Michael D. , Bindi Victoria E. , Nguyen Branden L. , Doerr Vivian , Boeno Franccesco P. , Chandran Vijayendran , Smuder Ashley J. , Fuller David D.
Published: December 2023

Acute hyperbaric O2 (HBO) therapy after spinal cord injury (SCI) can reduce inflammation and increase neuronal survival. To our knowledge, it is unknown if these benefits of HBO require hyperbaric vs. normobaric hyperoxia. We used a C4 lateralized contusion SCI in adult male and female rats to test the hypothesis that the combination of hyperbaria and 100% O2 (i.e. HBO) more effectively mitigates spinal inflammation and neuronal loss, and enhances respiratory recovery, as compared to normobaric 100% O2. Experimental groups included spinal intact, SCI no O2 therapy, and SCI + 100% O2 delivered at normobaric pressure (1 atmosphere, ATA), or at 2- or 3 ATA. O2 treatments lasted 1-h, commenced within 2-h of SCI, and were repeated for 10 days. The spinal inflammatory response was assessed with transcriptomics (RNAseq) and immunohistochemistry. Gene co-expression network analysis showed that the strong inflammatory response to SCI was dramatically diminished by both hyper- and normobaric O2 therapy. Similarly, both HBO and normobaric O2 treatments reduced the prevalence of immunohistological markers for astrocytes (glial fibrillary acidic protein) and microglia (ionized calcium binding adaptor molecule) in the injured spinal cord. However, HBO treatment also had unique impacts not detected in the normobaric group including upregulation of an anti-inflammatory cytokine (interleukin-4) in the plasma, and larger inspiratory tidal volumes at 10-days (whole body-plethysmography measurements). We conclude that normobaric O2 treatment can reduce the spinal inflammatory response after SCI, but pressured O2 (i.e., HBO) provides further benefit.
Combination effect of Chinese kidney-tonifying granules and platelet-rich plasma gels on enhancing bone healing in rat models with femur defects
Authors: Huo Zhiqian , Wu Feng , Lu Guoliang , Huang Feng
Published: December 2023

Background

The traditional Chinese kidney-tonifying granules, known as Bushen Zhongyao Keli (BSZYKL), have been found to stimulate calcium salt deposition, enhance bone formation, and foster bone growth within the bone matrix at sites of bone defects. On the other hand, platelet-rich plasma (PRP) is enriched with various growth factors capable of facilitating the repair of bone defects and enhancing bone strength following fractures. This study is dedicated to investigating the combined efficacy of BSZYKL and PRP gel (PRP-G) in the treatment of bone defects.

Methods

We established a femur defect model in male Sprague-Dawley (SD) rats and filled the defect areas with autologous coccygeal bone and PRP-G. For 8 consecutive weeks, those rats were given with intragastric administration of BSZYKL. Biomechanical characteristics of the femur were assessed 28 days after intramuscular administration. On day 56, bone formation was examined using X-ray, micro-CT, and transmission electron microscopy. Additionally, we analyzed the expression of bone formation markers, Runx2 and Osterix, in femur tissues through qPCR, Western blotting, and immunohistochemistry.

Results

Rats receiving the combined treatment of BSZYKL and PRP-G exhibited drastically enhanced femoral peak torsion, failure angle, energy absorption capacity, and torsional stiffness as compared to control group. This combination therapy also led to marked improvements in bone volume, mass, and microarchitecture, accompanied by elevated expressions of Runx2 and Osterix when compared to control group. Notably, the synergistic effects of BSZYKL and PRP-G in treating bone defects surpassed the effects of either treatment alone.

Conclusions

These findings revealed the potential of BSZYKL in combination with PRP-G in improving bone defects.
Anesthesia management experience for pediatric day-case PDA ligation under thoracoscopy assisted by a robot: a retrospective study
Authors: Cao Huixia , Qiu Jinpeng , Hu Yaoqin , Huang Wenfang , Liu Xiwang , Jin Haiyan
Published: December 2023

Background

To summarize the anesthesia management experience for pediatric day-case patent ductus arteriosus (PDA) ligation under robot-assisted thoracoscopy and explore the key points of anesthesia management for this procedure.

Methods

The clinical data of 72 pediatric patients who underwent robot-assisted thoracoscopic day-case PDA ligation at the Children’s Hospital, Zhejiang University School of Medicine from April 2021 to February 2023 were retrospectively analyzed. 0.3% ropivacaine local infiltration combined with S-ketamine 0.2 mg/kg intravenous injection was used for postoperative analgesia The patient’s basic information and intraoperative conditions were analyzed, which included gender, age, weight, surgery time, anesthesia time, extubation time, intraoperative blood loss, MAP before pneumothorax, PaCO2 before pneumothorax, etc. Postoperative conditions were also monitored, such as PACU stay time, agitation during the recovery period, pain, and the incidence of nausea and vomiting. After discharge, the recovery status was assessed.

Results

A total of 70 pediatric patients who met the criteria for day-case PDA ligation were included in this study. Before the occurrence of pneumothorax, the mean arterial pressure (MAP) of these 70 patients was 69.58 ± 12.52 mmHg, and during controlled hypotension, the MAP was 54.96 ± 11.23 mmHg. Before the occurrence of pneumothorax, the partial pressure of carbon dioxide (PaCO2) was 38.69 ± 3.38 mmHg, and during controlled hypotension, the PaCO2 was 51.42 ± 4.05 mmHg. Three cases experienced agitation during the recovery period, and four cases had mild pain, but there was no moderate or severe pain, nausea, or vomiting. Only 1 case of postoperative respiratory tract infection and 1 case of postoperative pneumothorax occurred. Within 30 days after discharge, the unplanned revisit rate, unplanned readmission rate, and surgical wound infection rate were all 0. The residual shunt rate detected by echocardiography was 0 after 1 month.

Conclusions

The children under the robot-assisted thoracoscopic day case PDA surgeries in this study have limited trauma, little bleeding, and little postoperative pain, though still at a risk of respiratory infection and pneumothorax.
Untargeted serum metabolomics reveals novel metabolite associations and disruptions in amino acid and lipid metabolism in Parkinson’s disease
Authors: Paul Kimberly C. , Zhang Keren , Walker Douglas I. , Sinsheimer Janet , Yu Yu , Kusters Cynthia , Del Rosario Irish , Folle Aline Duarte , Keener Adrienne M. , Bronstein Jeff , Jones Dean P. , Ritz Beate
Published: December 2023

Background

Untargeted high-resolution metabolomic profiling provides simultaneous measurement of thousands of metabolites. Metabolic networks based on these data can help uncover disease-related perturbations across interconnected pathways.

Objective

Identify metabolic disturbances associated with Parkinson’s disease (PD) in two population-based studies using untargeted metabolomics.

Methods

We performed a metabolome-wide association study (MWAS) of PD using serum-based untargeted metabolomics data derived from liquid chromatography with high-resolution mass spectrometry (LC-HRMS) using two distinct population-based case-control populations. We also combined our results with a previous publication of 34 metabolites linked to PD in a large-scale, untargeted MWAS to assess external validation.

Results

LC-HRMS detected 4,762 metabolites for analysis (HILIC: 2716 metabolites; C18: 2046 metabolites). We identified 296 features associated with PD at FDR<0.05, 134 having a log2 fold change (FC) beyond ±0.5 (228 beyond ±0.25). Of these, 104 were independently associated with PD in both discovery and replication studies at p<0.05 (170 at p<0.10), while 27 were associated with levodopa-equivalent dose among the PD patients. Intriguingly, among the externally validated features were the microbial-related metabolites, p-cresol glucuronide (FC=2.52, 95% CI=1.67, 3.81, FDR=7.8e-04) and p-cresol sulfate. P-cresol glucuronide was also associated with motor symptoms among patients. Additional externally validated metabolites associated with PD include phenylacetyl-L-glutamine, trigonelline, kynurenine, biliverdin, and pantothenic acid. Novel associations include the anti-inflammatory metabolite itaconate (FC=0.79, 95% CI=0.73, 0.86; FDR=2.17E-06) and cysteine-S-sulfate (FC=1.56, 95% CI=1.39, 1.75; FDR=3.43E-11). Seventeen pathways were enriched, including several related to amino acid and lipid metabolism.

Conclusions

Our results revealed PD-associated metabolites, confirming several previous observations, including for p-cresol glucuronide, and newly implicating interesting metabolites, such as itaconate. Our data also suggests metabolic disturbances in amino acid and lipid metabolism and inflammatory processes in PD.
The association between geospatial and temporal factors and pre-hospital response to major trauma: a retrospective cohort study in the North of England
Authors: McHenry Ryan D , Smith Christopher A
Published: December 2023

Background

Major trauma is a leading cause of premature death and disability worldwide, and many healthcare systems seek to improve outcomes following severe injury with provision of pre-hospital critical care. Much research has focussed on the efficacy of pre-hospital critical care and advanced pre-hospital interventions, but less is known about how the structure of pre-hospital critical care services may influence response to major trauma. This study assessed the association between likelihood of pre-hospital critical care response in major trauma and factors important in the planning and development of those services: geographic isolation, time of day, and tasking mechanism.

Methods

A local trauma registry, supported with data from the Trauma Audit and Research Network alongside additional information regarding pre-hospital management, identified patients sustaining major trauma admitted to Major Trauma Centres in the North of England. Data was extracted on location and time of incident, mechanism of injury, on-scene times, and presence or absence of pre-hospital critical care team. An isochrone map was constructed for 30-minute intervals to regional Major Trauma Centres, defining geographic isolation. Univariate logistic regression compared likelihood of pre-hospital critical care response to that of conventional ambulance response for varying degrees of geographic isolation, day or night period, and mechanism of injury, and multiple linear regression assessed the association between geographic isolation, service response and on-scene time.

Results

2619 incidents were included, with 23.3% attended by pre-hospital critical care teams. Compared to conventional ambulance services, pre-hospital critical care teams were more likely to respond major trauma in areas of greater geographic isolation (OR 1.42, 95% CI 1.30–1.55, p < 0.005). There were significant differences in the mechanism of injury attended and no significant difference in response by day or night period. Pre-hospital critical care team response and increasing geographic isolation was associated with longer on-scene times (p < 0.005).

Conclusion

Pre-hospital critical care teams are more likely to respond to major trauma in areas of greater geographic isolation. Enhanced pre-hospital care may mitigate geographic inequalities when providing advanced interventions and transport of severely injured patients. There may be an unmet need for pre-hospital critical care response in areas close to major hospitals.
Association between allostatic load and breast cancer risk: a cohort study
Authors: Guan Yufan , Shen Jie , Lu Juan , Fuemmeler Bernard F. , Shock Lisa S. , Zhao Hua
Published: December 2023

Background

Allostatic load (AL) reflects the collective load of chronic stress during lifetime. Previous studies have shown that higher AL is associated with poor clinical outcomes among breast cancer patients. However, the relationship between AL and breast cancer risk is still unclear.

Methods

To fill the gap, we analyzed the association between AL and the development of breast cancer in 181,455 women identified from the UK Biobank.

Results

During the follow-up from 2006 to 2020, 5,701 women were diagnosed with incident breast cancer. Significantly higher AL was observed among incident breast cancer cases than all study participants (mean: 2.77 vs. 2.63, P < 0.01). Univariate Cox regression analysis indicated the risk of breast cancer was increased by 5% per one AL unit increase (hazard ratio (HR) = 1.05, 95% confidence interval (CI) 1.04, 1.07). In multivariate analyses, after adjusting demographics, family history of breast cancer, reproductive factors, socioeconomic status, lifestyle factors, and breast cancer polygenic risk score (PRS), the significant association remained (HR = 1.05, 95%CI 1.03, 1.07). The significant relationship was further confirmed in the categorical analysis. Compared with women in the low AL group (AL: 0 ~ 2), those in the high AL group (AL: 3 ~ 11) had a 1.17-fold increased risk of breast cancer (HR = 1.17, 95%CI 1.11, 1.24). Finally, in the stratified analysis, joint effects on the risk of breast cancer were observed between the AL and selected known breast cancer risk factors, including age, family history of breast cancer, PRS, income, physical activity, and alcohol consumption.

Conclusion

In summary, those findings have demonstrated that higher AL was associated with an increased breast cancer risk in women. This association is likely independent of known breast cancer risk factors. Thus, the AL could be a valuable biomarker to help breast cancer risk prediction and stratification.
Comparison of different intervention methods to reduce the incidence of venous thromboembolism: study protocol for a cluster-randomized, crossover trial
Authors: Tan Qin , Zhou Lu , Lu Yihan , Huang Weifeng
Published: December 2023

Background

Venous thromboembolism (VTE) remains a priority challenge among orthopedic trauma patients. It is crucial to further improve the prophylaxis against VTE in routine orthopedic treatment. This study aims to compare the efficacy of two low molecular weight heparin (LMWH) regimens and additional intermittent pneumatic compression in preventing VTE among orthopedic trauma patients.

Methods and analysis

This is a cluster-randomized crossover clinical study conducted in four hospitals in Shanghai from December 2019 to December 2023. The unit of randomization is orthopedic wards, and each ward will define a cluster. All clusters will implement four diverse intervention measures and one control measure in a given random sequence. Perioperative orthopedic trauma patients aged ≥ 18 years with stable vital signs, Caprini score > 2, and no contraindication of anticoagulation or intermittent pneumatic compression (IPC) devices will be eligible. The sample size will be determined to be 2590, considering cluster effect, period effect, and interactions. We will generally use the intention-to-treat (ITT) at the subject level for each outcome. For the primary outcome of the study, the incidence of VTE will be presented as risk ratio and 95% CIs. Generalized estimating equation (GEE) will be deployed to compare differences and adjust cluster effect, period effect, and interaction among interventions and periods if applicable.

Discussion

VTE is a complication that cannot be underestimated after major orthopedic surgery. Early identification, early assessment, and early prevention can significantly reduce the incidence of VTE. Most guidelines recommend both medical and physical prevention, and we hope to demonstrate how they would affect the incidence among perioperative orthopedic patients. We want to explore if there is a difference between the two types of LWMH with or without an IPC device to provide more evidence for future guidelines and prevent more patients from the threat of VTE.

Ethics and dissemination

The study received approval from the IRB of the coordinating center and all participating hospitals. Findings will be disseminated through peer-reviewed publications and conference presentations.

Trial registration

ChiCTR1900027659. Registered on 17 November 2019