bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anticoagulant and non-anticoagulant therapy in thrombotic antiphospholipid syndrome: old drugs and new treatment targets
Authors: Ruiz-Irastorza Guillermo , Tektonidou Maria G , Khamashta Munther 
Published: February 2024

Abstract
In this review, we discuss the current evidence on classic and newer oral anticoagulant therapy, older drugs such as HCQ and statins, and new potential treatment targets in APS. Vitamin K antagonists (VKAs) remain the cornerstone treatment for thrombotic events in APS. In patients fulfilling criteria for definite APS presenting with a first venous thrombosis, treatment with VKAs with a target international normalized ratio (INR) 2.0–3.0 is recommended. In patients with arterial thrombosis, treatment with VKA with target INR 2.0–3.0 or 3.0–4.0 is recommended by recent guidelines, considering the individual’s bleeding and thrombosis recurrence risk. A combination of VKAs and low-dose aspirin (75–100 mg/daily) may also be considered. According to available evidence direct oral anticoagulants should be avoided in patients with arterial thrombosis and/or those with triple aPL positivity. Adjunctive treatment with HCQ and/or statins can be considered, especially in anticoagulation treatment–refractory APS. Potential targeted treatments in APS include B-cell targeting, complement inhibition, mammalian target of rapamycin inhibition, IFN targeting, adenosine receptors agonists, CD38 targeting or chimeric antigen receptor T-cell therapy. The safety and efficacy of these treatment targets needs to be examined in well-designed randomized controlled trials.
New advances in genomics and epigenetics in antiphospholipid syndrome
Authors: López-Pedrera Chary , Cerdó Tomás , Jury Elizabeth C , Muñoz-Barrera Laura , Escudero-Contreras Alejandro , Aguirre M A , Pérez-Sánchez Carlos 
Published: February 2024

Abstract
APS patients exhibit a wide clinical heterogeneity in terms of the disease’s origin and progression. This diversity can be attributed to consistent aPL profiles and other genetic and acquired risk factors. Therefore, understanding the pathophysiology of APS requires the identification of specific molecular signatures that can explain the pro-atherosclerotic, pro-thrombotic and inflammatory states observed in this autoimmune disorder. In recent years, significant progress has been made in uncovering gene profiles and understanding the intricate epigenetic mechanisms and microRNA changes that regulate their expression. These advancements have highlighted the crucial role played by these regulators in influencing various clinical aspects of APS. This review delves into the recent advancements in genomic and epigenetic approaches used to uncover the mechanisms contributing to vascular and obstetric involvement in APS. Furthermore, we discuss the implementation of novel bioinformatics tools that facilitate the investigation of these mechanisms and pave the way for personalized medicine in APS.
Viewpoint: Provoked thrombosis in antiphospholipid syndrome
Authors: Wahl Denis , Pengo Vittorio 
Published: February 2024

Abstract
Unprovoked thrombosis (thrombosis occurring without an established environmental factor favouring the episode) is a classic feature of APS. In the general population, provoked venous thromboembolism (VTE) is clearly defined and has clinical and therapeutic differences compared with unprovoked VTE. Whether provoked VTE in the context of APS may lead to a limited treatment duration is not well established. Therefore, careful clinical and laboratory evaluation is needed to identify patients eligible for a limited duration of anticoagulation treatment after provoked VTE. Given the uncertainties of available data, the risks and benefits of treatment decisions should be clearly explained. Decisions should be shared by both the patient and physician. Cardiovascular risk factors are common in patients with APS with arterial thrombosis. There are insufficient data suggesting that cardiovascular risk factor control would allow the cessation of anticoagulation. In most instances, arterial thrombosis will require prolonged anticoagulants. A careful analysis of clinical characteristics and laboratory evaluation, particularly the aPL antibody profile, is needed to make decisions on a case-by-case basis.
Identification of the VLDLR locus associated with giant cell arteritis and the possible causal role of low-density lipoprotein cholesterol in its pathogenesis
Authors: Iwasaki Takeshi , Watanabe Ryu , Zhang Hui , Hashimoto Motomu , Morinobu Akio , Matsuda Fumihiko 
Published: February 2024

Abstract

Objectives
To elucidate the association between genetic variants and the risk of GCA via large-scale genome-wide association studies (GWAS). In addition, to assess the causal effect of a specific molecule by employing the obtained GWAS results as genetic epidemiological tools.

Methods
We applied additional variant quality control to the publicly available GWAS results from the biobanks of the UK (UKBB) and Finland (FinnGen), which comprised 532 cases vs 408 565 controls and 884 cases vs 332 115 controls, respectively. We further meta-analysed these two sets of results. We performed two-sample Mendelian randomization (MR) to test the causal effect of low-density lipoprotein (LDL) cholesterol on the risk of GCA.

Results
The MHC class II region showed significant associations in UKBB, FinnGen and the meta-analysis. The VLDLR region was associated with GCA risk in the meta-analysis. The T allele of rs7044155 increased the expression of VLDLR, decreased the LDL cholesterol level and decreased the disease risk. The subsequent MR results indicated that a 1 s.d. increase in LDL cholesterol was associated with an increased risk of GCA (odds ratio 1.21, 95% CI 1.01–1.45; P = 0.04).

Conclusions
Our study identified associations between GCA risk and the MHC class II and VLDLR regions. Moreover, LDL cholesterol was suggested to have a causal effect on the risk of developing GCA.
Susceptibility to mycobacterial infection in VEXAS syndrome
Authors: Riescher Stanislas , Lecomte Raphael , Danic Gwenvael , Graveleau Julie , Le Bris Yannick , Hello Muriel , Guillouzouic Aurélie , Guardiolle Vianney , Garnier Alice , Grossi Olivier , Gaborit Benjamin , Néel Antoine 
Published: February 2024

Abstract

Objectives
VEXAS is a recently described acquired auto-inflammatory and haematological syndrome caused by somatic mutations in UBA1. To date, VEXAS is not a recognized cause of acquired immunodeficiency.

Methods
Two of our ten VEXAS patients developed a disseminated Mycobacterium avium infection. To shed light on this observation, we retrospectively studied all patients with disseminated non-tuberculous mycobacterial infections (NTMi) seen at our institution over 13 years. Inclusion criteria were a positive blood/bone marrow culture, or two positive cultures from distinct sites, or one positive culture with two involved sites.

Results
Patient 1 presented with fever, rash, orbital cellulitis and lung infiltrates. Patient 2 presented with fever and purpura. In both cases, Mycobacterium avium was identified on bone marrow culture. Twenty cases of disseminated NTMi were reviewed. Among 11 HIV-negative patients, three had chronic immune-mediated disease; three had untreated myeloid neoplasm; two had VEXAS; one had undergone kidney transplantation; one had GATA-2 deficiency; and one had no identified aetiology. None had lymphoid neoplasia or had undergone bone marrow transplantation. HIV-negative cases had higher CD4 counts than HIV-positive patients (median CD4: 515/mm3 vs 38/mm3, P &lt; 0.001). Monocytopenia was present in seven cases. At 2 years, six patients had died, including both VEXAS patients.

Conclusion
VEXAS patients have an intrinsic susceptibility to disseminated NTMi, which may result from monocytic dysfunction. NTMi can mimic VEXAS flare. Clinicians should maintain a high suspicion for opportunistic infections before escalating immunosuppressive therapy. Further studies are needed to confirm and better decipher the herein reported observations.
Effect of gender and age on bDMARD efficacy for axial spondyloarthritis patients: a meta-analysis of randomized controlled trials
Authors: Xie Yan , Liu Yang , Wu Qiuhong 
Published: February 2024

Abstract

Objective
To study the therapeutic variations of biologic and targeted synthetic DMARDs (b/tsDMARDs) between genders and across age stages in axial SpA (axSpA) patients through meta-analysis.

Methods
Randomized controlled trials published by PubMed, Scopus and Embase before 10 August 2023, testing the efficacy of b/tsDMARDs in axSpA, were searched and systematically reviewed. The Assessment of Spondyloarthritis International Society ≥40% improvement (ASAS40) was used as the primary outcome of treatment response.

Results
Only one study meet the inclusion criteria related to tsDMARDs, which was excluded from further analysis. Nine studies of bDMARDs, with 4127 patients, were included for the final analysis. When compared with placebo, both males [odds ratio (OR) 3.14 (95% CI 2.66, 3.70)] and females [OR 2.32 (95% CI 1.82, 2.82)] and younger [OR 4.00 (95% CI 2.50, 6.40)] and older [OR 2.21 (95% CI 1.15, 4.22)] patients presented significantly better responses to bDMARDs. Also, the efficacies were more evident in males [OR 1.89 (95% CI 1.56, 2.30)] and younger [OR 2.07 (95% CI 1.42, 3.02)] patients. Subgroup analysis revealed that the gender difference in efficacy was more obvious in non-radiographic axSpA (nr-axSpA) patients (Pheterogeneity = 0.03, I2 = 78.1%). Moreover, males with radiographic axSpA (r-axSpA) and nr-axSpA shared similar responses to bDMARDs (Pheterogeneity = 0.87, I2 = 0%), while females with r-axSpA showed greater response than those with nr-axSpA (Pheterogeneity = 0.005, I2 = 87.4%).

Conclusions
The bDMARDs were efficacious in all axSpA patients regardless of gender or age. However, the treatment responses were more evident in male and younger patients. Also, females with r-axSpA had greater responses than those with nr-axSpA, whereas no relevant difference was observed in males, indicating that the gender difference on efficacy was greater in nr-axSpA patients.
Dynamic analysis of an aircraft towing slip-out system considering vertical wheel constraints
Authors: Lu Xin , Sun Yuning , Tang Jie , Zhang Wei 
Published: February 2024

Abstract
To analyse the vertical dynamic characteristics of the aircraft towing system under different constraints on the nose landing gear wheels of the aircraft during the towing slip-out mode, a dynamic model of the towing system considering the constraints between the clamping mechanism and the aircraft nose landing gear wheels was established based on the general towing system dynamic model. On this basis, an analysis was conducted to determine whether considering the aircraft wheel constraints affects the vertical vibration acceleration of the towing vehicle and the nose landing gear in low-speed (10 km/h) and high-speed (40 km/h) operating conditions. With the consideration of constraints at both ends of the aircraft wheels, the vertical acceleration of the towing vehicle's centre of mass increased by 153% and 172% at low speed and high speed, respectively, compared to not considering the aircraft wheel constraints. Additionally, with the consideration of constraints at both ends of the aircraft wheels, the vertical acceleration of the nose landing gear's centre of mass decreased to 20% and 57% at low speed and high speed, respectively, compared to not considering the aircraft wheel constraints. An analysis of the vertical vibration acceleration of the towing vehicle under different wheel constraint conditions found that the Root Mean Square (RMS) value of the vertical vibration acceleration of the towing vehicle's centre of mass was minimized when the clamping angles of the clamping mechanism to the nose landing gear wheels were 63° and 64°, respectively. Under this clamping angle, the influence of the clamping forces at both ends of the clamping mechanism on the vertical vibration acceleration of the towing vehicle was minimal. The research results provide valuable reference for the direct constraints between the clamping mechanism and the nose landing gear wheels in the aircraft towing slip-out system.
Auditory Neural Responses and Communicative Functioning in Children With Microcephaly Related to Congenital Zika Syndrome
Authors: Key Alexandra P. , Powell Sarah L. , Cavalcante Juliana , Frizzo Ana , Mandra Patricia , Tavares Adriana , Menezes Pedro , Hood Linda J. 
Published: February 2024

Objectives:
Children with microcephaly exhibit neurodevelopmental delays and compromised communicative functioning, yielding challenges for clinical assessment and informed intervention. This study characterized auditory neural function and communication abilities in children with microcephaly due to congenital Zika syndrome (CZS).

Design:
Click-evoked auditory brainstem responses (ABR) at fast and slow stimulation rates and natural speech-evoked cortical auditory evoked potentials (CAEP) were recorded in 25 Brazilian children with microcephaly related to CZS (M age: 5.93 ± 0.62 years) and a comparison group of 25 healthy children (M age: 5.59 ± 0.80 years) matched on age, sex, ethnicity, and socioeconomic status. Communication abilities in daily life were evaluated using caregiver reports on Vineland Adaptive Behavior Scales-3.

Results:
Caregivers of children with microcephaly reported significantly lower than typical adaptive functioning in the communication and socialization domains. ABR wave I latency did not differ significantly between the groups, suggesting comparable peripheral auditory function. ABR wave V absolute latency and waves I-V interwave latency were significantly shorter in the microcephaly group for both ears and rates. CAEP analyses identified reduced N2 amplitudes in children with microcephaly as well as limited evidence of speech sound differentiation, evidenced mainly by the N2 response latency. Conversely, in the comparison group, speech sound differences were observed for both the P1 and N2 latencies. Exploratory analyses in the microcephaly group indicated that more adaptive communication was associated with greater speech sound differences in the P1 and N2 amplitudes. The trimester of virus exposure did not have an effect on the ABRs or CAEPs.

Conclusions:
Microcephaly related to CZS is associated with alterations in subcortical and cortical auditory neural function. Reduced ABR latencies differ from previous reports, possibly due to the older age of this cohort and careful assessment of peripheral auditory function. Cortical speech sound detection and differentiation are present but reduced in children with microcephaly. Associations between communication performance in daily life and CAEPs highlight the value of auditory evoked potentials in assessing clinical populations with significant neurodevelopmental disabilities.
Minimally Invasive Anterior Closing–wedge Osteotomy for Posterior Tibial Slope Correction: A Pilot Study
Authors: Baker Hayden P. , Lee Cody S. , Serotte Jordan , Poff Charles , Athiviraham Aravind , Hynes Kelly , Strelzow Jason A. 
Published: February 2024

Introduction:
The purpose of this study was to investigate the feasibility of performing a new minimally invasive technique for anterior closing–wedge high tibial osteotomy. Our hypothesis was that we would be able to successfully perform the minimally invasive osteotomy with consistent correction of the posterior tibial slope.

Materials and Methods:
Five lower limbs from cadaveric unidentified donors were obtained. Fluoroscopic imaging of the knee was obtained to determine the baseline tibial slope. A standard anterior closing–wedge osteotomy was planned to obtain the desired correction. The anterior bony segment was resected from the proximal tibia utilizing the Shannon burr under fluoroscopic guidance through a 2 cm medial incision. Fixation was completed with 2 staples positioned medial and lateral to the tibial tubercle.

Results:
The average posterior tibial slope of the 5 specimens was 8 degrees (SD: 2.3, range: 6 to 12). The average final posterior tibial was 1.8 degrees (SD: 2.1, range: −1 to 5). The average slope correction was 6.2 degrees (SD: 0.7, range: 5 to 7). Posterior tibial cortical fracture did not occur in any of the cases.

Conclusions:
Our novel minimally invasive anterior closing–wedge high tibial osteotomy technique resulted in a reproducible correction of posterior tibial slope in a cadaveric model. This is the first study to describe a minimally invasive technique for anterior closing–wedge high tibial osteotomy. Larger cadaveric studies including multiple surgeons across institutions are warranted to validate the described technique between providers.

Level of Evidence:
Level IV—Controlled laboratory study
Early Mobilization Using a Mobile Patient Lift in the ICU: A Randomized Controlled Trial
Authors: Suzuki Ginga , Kanayama Hiromi , Arai Yoshiaki , Iwanami Yuji , Kobori Toshimitsu , Masuyama Yuka , Yamamoto Saki , Serizawa Hibiki , Nakamichi Yoshimi , Watanabe Masayuki , Honda Mitsuru , Okuni Ikuko 
Published: February 2024

Objectives:
To ascertain whether a mobile patient lift facilitates early mobilization in ventilated ICU patients.

Design:
A single-center, open-label, randomized controlled trial.

Setting:
An academic ICU in Tokyo.

Patients:
Eighty patients were admitted to ICU and expected ventilation for at least 48 hours.

Interventions:
In the intervention group, in addition to the rehabilitation protocol received by the control group, patients were assisted in sitting, standing, transfers, and walking using the mobile patient lift.

Measurements and Main Results:
The intervention group predominantly stood faster than the control group (1.0 vs. 3.0 d, p < 0.01). The Intervention group also had significantly higher Functional Status Score-ICU scores at ICU discharge. However, the Medical Research Council score and Barthel index at discharge, length of ICU stay, and number of ventilator-free days did not differ between the two groups.

Conclusions:
The use of mobile patient lifts facilitates the earlier standing of patients on ventilators. This may contribute to patients improved physical function in the ICU.

Trial Registration:
The study protocol was registered with the University Hospital Medical Information Network (UMIN) under the registration number UMIN000044965. Registered July 30, 2021.
The Keystone Perforator Island Flap: Review of Utility and Versatile Clinical Applications
Authors: Pawlak Natalie , De La Cruz Ku Gabriel , Chatterjee Abhishek , Persing Sarah , Homsy Christopher 
Published: February 2024

Background:
The keystone perforator island flap (KPIF) was described almost a decade ago. However, this flap has only recently been recognized for its advantages in various clinical applications in plastic surgery. A better understanding of the versatility of KPIFs can help promote the widespread adoption of this technique for complex wounds in various anatomical regions.

Methods:
A retrospective chart review was conducted of patients undergoing KPIFs from December 2018 to March 2022 at the authors’ home institution. The indications, surgical approaches, patient characteristics, and outcomes were extracted for review and analysis.

Results:
A total of 12 patients (ages 13–86 years) underwent reconstruction with KPIFs for oncologic and nononcologic defects. By anatomic region, three cases involved the upper back, six involved the lumbosacral region, one involved the perineum, and two involved the midfoot. Half of the patients (n = 6) had failed previous attempts at wound closure. The mean defect size was 13.8 × 10.0 cm for the upper back lesions, 13.7 × 4.8 for the lumbosacral defects, and 3.5 × 2.0 for the metatarsal wounds. Median follow-up time for all patients was 7.5 months (IQR: 4–10.5). On follow-up, there was 100% flap survival.

Conclusion:
KPIFs are a simple, safe, and suitable option for reconstructive closure of defects in many anatomical areas, including wounds complicated by previous failed closure attempts, with low complication risk profile.
Correction of Brassiere Strap Grooving with Injectable Poly-L-Lactic Acid in Plastic Surgery Resident Filler and Neuromodulator Clinic
Authors: Blanchet Nadia P. , Kelly Brooks B. 
Published: February 2024

Summary:
Poly-L-lactic acid (PLLA) is a biocompatible synthetic polymer that induces neocollagenesis by fibroblasts after placement into the reticular dermis and subcutaneous plane. We present an innovative use of this product to treat brassiere strap grooves. The size and weight of hypertrophied breasts can cause physical and psychological problems that can be corrected with reduction mammaplasty. However, bra strap grooving remains an unsightly consequence of brassiere use with large and heavy breasts. PLLA provides an innovative way to treat this deformity in a minimally invasive way, while maintaining relatively long-term results of two years or more. We studied 10 patients who presented to resident filler and neuromodulator clinic to help improve the bra strap groove deformity. The average number of clinic visits was 3.1. The average total number of vials injected was 2.58 on the right and 2.92 on the left. There were no complications or side effects, apart from one patient who reported injection site bruising. Patient surveys demonstrated 70% satisfied with the results and 30% very satisfied. We also discuss resident filler and neuromodulator clinic as an opportunity for resident research.
Pulmonary Embolism after Botulinum Toxin Treatment for Leg Muscle Hypertrophy
Authors: Wang Xiaoli , Li Xiaofei , Yu Mosheng 
Published: February 2024

Summary:
Leg muscle hypertrophy is a unique physical symptom in East Asian women. Compared with traditional surgical treatment for calf muscle hypertrophy, botulinum toxin is widely favored by East Asian women because of its minimal trauma and significant effects. We describe the case of a 22-year-old woman with pulmonary embolism because of deep vein thrombosis, who presented with hypertrophy of bilateral calf muscles, and was administered 300 U of botulinum toxin A injection in July 2022. On the third day after the injection, she experienced swelling and pain in her left leg, which gradually worsened and made walking difficult. She underwent an ultrasound examination of lower limbs, which revealed several deep and shallow vein thrombi in the left lower limb. Computed tomography arterial imaging indicated multiple embolisms in pulmonary arteries. This study aimed to explore and analyze the causes of pulmonary embolism after botulinum toxin treatment for calf muscle hypertrophy by reviewing and analyzing the patient’s symptoms, diagnosis, and treatment process to provide management strategies for treatment and prevention of this disease.