bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recent updates on therapeutic targeting of lipoprotein(a) with RNA interference
Authors: Sekhar Aravind , Kuttan Ashani , Lange Richard A. 
Published: March 2024

Purpose
RNA interference (RNAi)-based therapies that target specific gene products have impacted clinical medicine with 16 FDA approved drugs. RNAi therapy focused on reducing plasma lipoprotein(a) [Lp(a)] levels are under evaluation.

Findings
RNAi-based therapies have made significant progress over the past 2 decades and currently consist of antisense oligonucleotides (ASO) and small interfering RNA (siRNA). Chemical modification of the RNA backbone and conjugation of siRNA enables efficient gene silencing in hepatocytes allowing development of effective cholesterol lowering therapies. Multiple lines of evidence suggest a causative role for Lp(a) in atherosclerotic cardiovascular disease, and recent analyses indicate that Lp(a) is more atherogenic than low density lipoprotein- cholesterol (LDL-C). These findings have led to the ‘Lp(a) hypothesis’ that lowering Lp(a) may significantly improve cardiovascular outcomes. Four RNAi-based drugs have completed early phase clinical trials demonstrating >80% reduction in plasma Lp(a) levels. Phase 3 clinical trials examining clinical outcomes with these agents are currently underway.

Summary
Currently, four RNAi-based drugs have been shown to be effective in significantly lowering plasma Lp(a) levels. Clinical outcome data from phase 3 trials will evaluate the Lp(a) hypothesis.
Management of hypertension in heart transplant recipients: an ongoing conundrum
Authors: Torres Juan Duarte , Krim Selim R. 
Published: March 2024

Purpose of review
Hypertension remains one of the most common clinical problems leading to significant posttransplant complications. This study reviews the pathophysiology of hypertension in the postcardiac transplant phase and provides an update on currently available antihypertensive therapies for heart transplant patients.

Recent findings
The true prevalence of hypertension in the heart transplant population remains unknown. Effective blood pressure (BP) control is key to prevent left ventricular remodeling, diastolic dysfunction and stroke. Calcium channel blockers (CCBs) are the most commonly and preferred agents in the early posttransplant phase and may have renal protective effects. Angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs) can all be used as second line antihypertensive agents and may have a role in preventing other long-term complications such as calcineurin-inhibitor induced nephropathy. Although more data are needed, sodium-glucose co-transporter 2 inhibitors (SGLT2i) appeared to be well tolerated and could be considered especially in the presence of type diabetes and chronic kidney disease. Conversely, angiotensin receptor-neprilysin inhibition (ARNI) have not been studied in the heart transplant population therefore cannot be recommended at this time.

Summary
Hypertension is very common after heart transplant. Early steroid wean and traditional risk factor modification play an important part in the management of post-heart transplant hypertension. CCB, ACEI, ARB are the preferred antihypertensive agents to improve postcardiac transplant complications. Novel therapies such as SGLT2i appear well tolerated and may have benefits in both BP and glycemic control in heart transplant; however, larger trials are needed.
Mechanical pain sensitivity is associated with hippocampal structural integrity
Authors: Ayoub Lizbeth J. , Honigman Liat , Barnett Alexander J. , McAndrews Mary Pat , Moayedi Massieh 
Published: March 2024

Abstract
Rodents and human studies indicate that the hippocampus, a brain region necessary for memory processing, responds to noxious stimuli. However, the hippocampus has yet to be considered a key brain region directly involved in the human pain experience. One approach to answer this question is to perform quantitative sensory testing on patients with hippocampal damage—ie, medial temporal lobe epilepsy. Some case studies and case series have performed such tests in a handful of patients with various types of epilepsy and have reported mixed results. Here, we aimed to determine whether mechanical pain sensitivity was altered in patients diagnosed with temporal lobe epilepsy. We first investigated whether mechanical pain sensitivity in patients with temporal lobe epilepsy differs from that of healthy individuals. Next, in patients with temporal lobe epilepsy, we evaluated whether the degree of pain sensitivity is associated with the degree of hippocampal integrity. Structural integrity was based on hippocampal volume, and functional integrity was based on verbal and visuospatial memory scores. Our findings show that patients with temporal lobe epilepsy have lower mechanical pain sensitivity than healthy individuals. Only left hippocampal volume was positively associated with mechanical pain sensitivity—the greater the hippocampal damage, the lower the sensitivity to mechanical pain. Hippocampal measures of functional integrity were not significantly associated with mechanical pain sensitivity, suggesting that the mechanisms of hippocampal pain processing may be different than its memory functions. Future studies are necessary to determine the mechanisms of pain processing in the hippocampus.
Elevated white blood cell count and long-term clinical outcomes of patients with vasospastic angina
Authors: Kim Dong-Yeon , Kim Sung Eun , Park Taek Kyu , Choi Ki Hong , Lee Joo Myung , Yang Jeong Hoon , Song Young Bin , Choi Jin-Ho , Gwon Hyeon-Cheol , Hahn Joo-Yong , Choi Seung-Hyuk , Cho Sung Woo 
Published: March 2024

Objectives
Inflammation is known as one of key pathophysiologic mechanisms of coronary artery disease. We aimed to investigate the relationship between white blood cell (WBC) count and long-term clinical outcomes of patients with vasospastic angina (VA).

Methods
A total of 823 patients who were diagnosed as VA without significant coronary lesion by coronary angiography with ergonovine provocation test were enrolled for analysis. Patients were divided according to WBC count tertile at the time of diagnosis: group I, tertile 1 and 2 (n = 546, <7490/ml); group II, tertile 3 (n = 277, ≥7490/ml). Primary outcome was defined as major adverse cardiovascular events (MACE), a composite outcome of all-cause death, cardiac death, myocardial infarction (MI), readmission due to cardiac symptoms, and revascularization.

Results
Median follow-up duration was 4.3 years. No significant difference of primary outcome was observed between group I and group II (14.7% vs. 20.2%, hazard ratio (HR) 1.29, confidence interval (CI) 0.90–1.83, P = 0.162), while incidence of cardiac death and MI was significantly higher in group II (1.5% vs. 4.3%, HR 2.86, CI 1.14–7.17), P = 0.025). In multivariate Cox regression model, elevated WBC count at the time of diagnosis of VA was an independent predictor of MI (HR 3.43, CI 1.02–11.59, P = 0.047).

Conclusion
Elevated WBC count at the time of diagnosis was associated with a significantly increased risk of cardiac death and MI during long-term follow-up in VA patients.
The impact of Demodex blepharitis on patient symptoms and daily life
Authors: Barnett Melissa , Simmons Blake , Vollmer Patrick , Patel Assem , Whitson William E. , Berdy Gregg J. , Karpecki Paul , Periman Laura M. , Holdbrook Mark , Baba Stephanie N. , Meyer John , Yeu Elizabeth 
Published: March 2024

SIGNIFICANCE
Patients with Demodex blepharitis have a considerable symptomatic burden that negatively impacts their daily activities and well-being. Despite chronic manifestations of and problems associated with blepharitis that resulted in multiple visits to eye care providers, Demodex blepharitis remained underdiagnosed or misdiagnosed.

PURPOSE
This study aimed to evaluate the effect of Demodex blepharitis on patients' daily activities and well-being.

METHODS
This prospective, multicenter, observational study recruited 524 patients with Demodex blepharitis from 20 U.S. ophthalmology and optometry practices. Demodex blepharitis was diagnosed based on the presence of the following clinical manifestations in at least one eye: >10 collarettes on the upper lashes, at least mild lid margin erythema of the upper eyelid, and mite density of ≥1.0 mite/lash (upper and lower combined). Patients were asked to complete a questionnaire related to their symptoms, daily activities, and management approaches.

RESULTS
The proportion of patients who experienced blepharitis symptoms for ≥2 years was 67.8%, and for ≥4 years, it was 46.5%. The three most bothersome symptoms ranked were “itchy eyes,” “dry eyes,” and “foreign body sensation.” Overall, 77.4% of patients reported that Demodex blepharitis negatively affected their daily life. One-third (32.3%) of patients had visited a doctor for blepharitis at least two times, including 19.6% who visited at least four times. Despite having clinical manifestations of Demodex blepharitis confirmed by an eye care provider, 58.7% had never been diagnosed with blepharitis. Commonly used management approaches were artificial tears, warm compresses, and lid wipes. Among those who discontinued their regimen, 45.9% had discontinued because of either tolerability issues or lack of effectiveness. Among contact lens wearers, 64.3% of the patients either were uncomfortable wearing contact lenses or experienced vision changes “sometimes” or “frequently.”

CONCLUSION

Demodex blepharitis results in a significant negative impact on daily activities, creating a psychosocial and symptomatic burden on patients.
Repeatability and agreement of the MYAH and Lenstar
Authors: Lal Barsha , Cantrell Amy , Ostrin Lisa A. 
Published: March 2024

SIGNIFICANCE
Validation of new biometry instruments against the gold standard and establishing repeatability are important before being utilized for clinical and research applications.

PURPOSE
This study aimed to investigate intersession repeatability of the MYAH optical biometer and corneal topographer and examine agreement with the Lenstar LS900 optical biometer in healthy young adults.

METHODS
Forty participants (mean age, 25.2 ± 3.1 years) presented for two visits, 2 to 4 days apart. At each visit, measurements for right eyes were collected with the MYAH and Lenstar LS 900 and included axial length, corneal power, white-to-white distance, and pupil diameter. Bland-Altman analysis was used to assess the intrasession agreement between the MYAH and Lenstar for each parameter and intersession repeatability for the two devices. For each device, coefficient of variation and intraclass correlation coefficient were calculated, and paired t tests between visits were performed to assess intersession repeatability.

RESULTS
Good agreement (mean difference [95% limits of agreement]) between the MYAH and Lenstar was found for axial length (−0.01 [−0.07 to 0.04] mm), corneal power (−0.02 D [−0.15 to 0.19 d]), white-to-white distance (−0.13 [−0.43 to 0.17] mm), and pupil diameter (−0.27 [−0.79 to 1.33] mm). The limits of agreement, coefficient of variations, and intraclass correlation coefficients for MYAH-measured parameters were −0.04 to 0.04, 0.06%, and >0.99 for axial length; −0.24 to 0.19, 0.18%, and >0.99 for corneal power; −1.05 to 1.15, 0.57%, and 0.96 for white-to-white distance; and −0.17 to 0.21, 7.0%, and 0.76 for pupil diameter, with no significant difference between visits (p>0.05 for all), indicating good intersession repeatability. Similar intersession repeatability was also noted for Lenstar.

CONCLUSIONS
Findings show good intersession repeatability of the MYAH and good agreement with the Lenstar for axial length, corneal power, and white-to-white distance in young adults. Pupil diameter was more variable, likely due to the dynamic nature of the pupil. This study provides validation and supports the use of the MYAH for ocular biometry.
Patient-Specific Le Fort I Osteotomy Plates Are More Stable than Stock Plates in Patients with Cleft Lip and Palate
Authors: Varidel Alistair , Padwa Bonnie L. , Britt Michael C. , Flanagan Sarah , Green Mark A. 
Published: March 2024

Background:
There is evidence that patient-specific plate fixation for Le Fort I osteotomies (LFI) is more stable than traditional plate fixation. The purpose of this study was to evaluate stability of LFI in patients with cleft lip and palate and determine stability differences between patient-specific and stock plates.

Methods:
Consecutive patients with cleft lip and palate who underwent isolated LFI by one surgeon (B.L.P.) between 2016 and 2021 were included. The predictor variable was type of plate used for fixation (patient-specific or stock). The outcome variable was magnitude of relapse in the vertical (nasion to A point) and horizontal planes (basion to A point) at 1 year after LFI using 3-dimensional cone beam computed tomography. Statistical analysis included independent samples t, Mann-Whitney U, Fisher exact, and chi-square tests. Values of P < 0.05 were significant.

Results:
The sample included 63 subjects; 23 in the patient-specific group (36.5%) and 40 in the stock group (63.5%). Groups were comparable by sex, race, age at surgery, cleft type, presence of pharyngeal flap, and magnitude of horizontal movement (P > 0.136 for all). Subjects who underwent patient-specific plate fixation were less likely to have greater than or equal to 1-mm change at 1 year in the horizontal (4.3% versus 50.0%; P < 0.001) and vertical planes (4.3% versus 65.0%; P < 0.001) compared with stock plates. For patients who had greater than 10-mm horizontal advancement, the patient-specific plates had significantly less relapse (patient-specific plates, 0.105 ± 0.317 mm; stock plates, 1.888 ± 1.125 mm; P = 0.003).

Conclusion:
Patient-specific plate fixation of LFI is more stable and demonstrates less relapse after 1 year than stock plates.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
Acellular Dermal Matrix–Assisted Tissue Expansion for Giant Congenital Melanocytic Nevi of the Extremities and Trunk in Pediatric Patients
Authors: Huang Xing , Shan Shengzhou , Lu Lin , Jin Rui , Wang Xiuxia , Yuan Zhaoqi , Sun Di , Chang Mengling , Luo Xusong 
Published: March 2024

Background:
Tissue expansion for treating giant congenital melanocytic nevi (GCMN) is a commonly used surgical method. However, the procedure’s efficacy is often hindered by anatomical and histologic characteristics and blood supply, particularly in the extremities and trunk. Enhancing expansion efficiency while reducing complications is thus a topic to be investigated, especially for pediatric patients undergoing rapid physical and psychological development with higher risks of noncompliance to medical instructions. The purpose of this study was to explore the effectiveness of expansion in extremities and trunk by immobilizing the acellular dermal matrix (ADM) in the gravitational force zone of inflating expanders.

Methods:
All patients involved in this research underwent ADM-assisted tissue expansion in either the extremities or trunk. ADM was fully flattened, securely fixed to the lower pole of the expander, and subsequently attached to the inner surface of the expanding flap.

Results:
From 2021 to 2023, a total of 9 pediatric patients with GCMN underwent ADM-assisted tissue expansion. All patients achieved the desired expansion volume without experiencing petechiae, ecchymosis, or skin ulceration in the ADM-covered area. The process was well tolerated by all patients, with no reports of itching, pain, allergic reaction, or fever. During the flap transfer, the ADM was observed to be firmly adhered to the expanding flap with discernible capillary network.

Conclusions:
ADM-assisted tissue expansion demonstrates promise in augmenting expansion efficiency and reducing the time needed for surgical intervention in the extremities and trunk, thereby presenting significant clinical value for pediatric patients with GCMN.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Uncommon Anatomical Causes of Ulnar Compression
Authors: Natroshvili Tinatin , Roorda Adam , van Doorn MATS , Foumani Mahyar 
Published: March 2024

Objectives
Some patients develop ulnar nerve compression due to rare anatomical variations or malformations. The aims of this review are to provide a comprehensive overview of anatomical structures and variations that can cause ulnar nerve compression and to evaluate treatment options.

Methods
Case reports and case series about rare cases of unusual ulnar nerve compression published from January 2000 until April 2022 were obtained from databases Embase, MEDLINE, and Web of Science. A total of 48 studies describing 64 patients were included in our study.

Results
The following structures have proven to cause ulnar nerve compression: anconeus epitrochlearis, accessory abductor digiti minimi, vascular anomalies, palmaris longus, fibrous bands, and flexor carpi ulnaris. All cases except one have had a surgical release of the ulnar nerve resulting in diminished symptoms or complete recovery at follow-up.

Conclusions
In addition to considering common compression points, it is important to be aware that proximal compression symptoms, such as pain and a positive Tinel sign at the medial elbow, may be attributed to a hypertrophic AE or vascular anomaly. Distal compression symptoms encompass swelling, along with pain and a positive Tinel sign at the distal forearm. Various structures contributing to distal compression include an accessory abductor digiti minimi muscle, an accessory or anomalous palmaris longus muscle, or an accessory or hypertrophic flexor carpi ulnaris muscle. The occurrence of fibrous bands exhibits variability, manifesting in diverse locations across the arm.
Level of Evidence: IV
Intraoperative Completion Studies and their Associations with Carotid Endarterectomy Outcomes
Authors: Knappich Christoph , Bohmann Bianca , Kirchhoff Felix , Lohe Vanessa , Naher Shamsun , Kallmayer Michael , Eckstein Hans-Henning , Kuehnl Andreas 
Published: March 2024

Objective:
This study aimed at assessing outcomes after carotid endarterectomy (CEA) in dependence of center policy with respect to imaging intraoperative completion study (ICSi) usage.

Summary Background Data:
Although randomized controlled studies are missing, a beneficial effect was shown for ICSi techniques (i.e., angiography and intraoperative duplex ultrasound) after CEA.

Methods:
This secondary data analysis is based on the German statutory quality assurance database. Research was funded by Germany’s Federal Joint Committee Innovation Fund (G-BA Innovationsfonds, 01VSF19016 ISAR-IQ). According to their ICSi policy, hospitals were categorized as routine ICS

i
(>90%), selective ICS

i
(10–90%), or sporadic ICS

i
(<10%) centers. Primary study outcome was in-hospital stroke or death. Multivariable regression analyses were performed.

Results:
Between 2012 and 2016, a total of 119,800 patients underwent CEA. In-hospital stroke or death rates were lower in routine ICS

i

centers (1.7%) compared to selective (2.1%) and sporadic ICS

i

centers (2.0%). The multivariable regression analysis showed, that in routine ICS

i

centers, ICSi use was associated with lower rates of stroke or death (aOR 0.64; 95% CI 0.44–0.93). In selective ICS

i

centers, ICSi was not associated with the occurrence of either of the assessed outcomes. In sporadic ICS

i

centers, ICSi was associated with higher rates of stroke or death (aOR 1.91; 95% CI 1.26–2.91).

Conclusions:
Lowest in-hospital stroke or death rates are achieved in routine ICS

i

centers. While ICSi is associated with a lower perioperative risk in routine ICS

i

centers, it might act as a surrogate marker for worse outcomes due to intraoperative irregularities in sporadic ICS

i

centers. Routine use of ICSi is advisable.
Metallo-β-lactamase mediated rapid increase in carbapenem resistance ofPseudomonas aeruginosa
Authors: Anjum Hasnain , Mitu Shomaia Yasmin , Arefin Md. Shamsul , Mitu Meftahul Jannat , Hossain Md. Sabir , Islam Salequl , Rumi M.A. Karim , Rahman M. Hasibur 
Published: March 2024

AbstractAntibiotic-resistantPseudomonas aeruginosais a common nosocomial pathogen all over the world. We detected the presence ofP. aeruginosain 22% (53 out of 238) of the test samples collected from patients with infections including secondary wound infections, abscesses and urinary tract infections admitted to two academic hospitals in Bangladesh. Resistance to carbapenems (imipenem, and meropenem) was present among 30% (16 out of 53) of these clinicalP. aeruginosaisolates, which is more than 2-fold higher compared to that of previous studies. Such a rapid increase in carbapenem resistance was mediated by metallo-β-lactamase (MBL). Expression of MBL was detected in 90% (14 out of 16) of these resistant isolates. Molecular analyses revealed that the carbapenem-resistant isolates carried at least one of the MBL variants, eitherbla-VIM orbla-NDM-1. All thebla-NDM-1 positives carried a 0.5 MDa plasmid. ERIC-PCR revealed the highly heterogeneous nature of theP. aeruginosaisolates indicating multiple sources of infection within the hospital. However, the majority of XDR isolates belonged to a single cluster of drug-resistant bacterial infections. These findings indicate that Metallo-β-lactamase (MBL) mediated resistance to carbapenem inP. aeruginosaposes a serious threat to the spread of infections among hospitalized patients.
Clinical, psychosocial and demographic factors affect decisions in SLE people
Authors: Miguel Pedraza-Meza Luis , Laura Hernández-Ledesma Ana , Ruiz-Contreras Alejandra E , Alejandra Medina-Rivera , Domingo Martínez 
Published: March 2024

AbstractNeurological and psychiatric manifestations affect most lupus individuals and include depression, anxiety, mood disorders, and cognitive dysfunction. Although there is evidence supporting suboptimal decision-making in lupus and its association with glucocorticoids consumption, it is not clear what variables impact such decisions. The aim of this study is to explore how social, clinical, psychological, and demographic factors impact social and temporal decision-making in people with lupus. Through a within-subjects experimental-design, our participants responded to social, clinical, psychological, and demographic electronic questionnaires. Then, they participated in two behavioral economics experiments: the third-party dictator game, and the delay discounting task. Our results show that hostility, and age are essential predictors of social decisions, whereas obsessive-compulsiveness and anxiety better predict temporal decisions. These variables behave as expected, but anxiety shows unexpected results: most anxious people act patiently and prefer delayed but bigger rewards. Finally, clinical factors are critical decision predictors for social and temporal decisions. When people are in remission, they tend to impose higher punishment on those who violate the social norm, and they also tend to prefer immediate rewards. When taking glucocorticoids, they also prefer immediate rewards, and as the dosage of glucocorticoids intake increases, they tend to impose higher punishment on norm violators. Clinicians, researchers, and practitioners must consider the side effects of glucocorticoids on decision-making.